3.4.21 ICH guidelines, ACRP Key Terms for CCRC exam, CCRC Exam, ACRP CCRC EXAM PREP, CCRC Exam Prep, ACRP CCRC, *CCRC Study Set

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FDA Regulation 21 CFR 314.126a

"the purpose of conducting clinical investigations of a drug is to distinguish the effect of a drug from other influences, such as spontaneous change in the course of disease, placebo effect, or biased observation."

The sponsor must submit an IND Safety Report to the FDA if an adverse event is (1) serious; (2) unexpected; and:

(3) there is a reasonable possibility that the drug caused the event

The sponsor must submit an IND Safety Report to the FDA if an adverse event is (1) serious; (2) unexpected; and:

(3) there is a reasonable possibility that the drug caused the event.

* What is a Phase II trial and what type of studies are typically seen in this phase? Why are they important?

(Most typical kind of study: Therapeutic Exploratory) - Usually considered to start with the initiation of studies in which the primary objective is to explore therapeutic efficacy in patients - Goal is to determine the doses and regimen for Phase III trials - Evaluation of potential study endpoints, therapeutic regimens and target populations for further study

Requirements of an IRB

* at least 5 members * one non-scientific member * one non-institute member

How is a monitor selected?

*Appointed by sponsor *Adequately trained & qualified *familiar with protocol, ICF, etc

What needs reported to the IRB?

*Changes / deviations from protocol due to unforeseen hazard * changes to subject risk * adverse events * new info that may impact subject safety

Sponsors role

*Complete & ensure SOPs are followed *seeks agreements from all parties *may use CRO to oversee; however, the sponsor is ultimately responsible

1.2 elements of an Investigational Brochure (IB) and/or investigational device use (instructions for use, user manual) ICH 7

*Confidentiality Statement* The sponsor may wish to include a statement instructing the investigator/recipients to treat the IB as a confidential document for the sole information and use of the investigator's team and the IRB/IEC.

1.2 elements of an Investigational Brochure (IB) and/or investigational device use (instructions for use, user manual) ICH 7

*Effects in Humans Introduction:* A thorough discussion of the known effects of the investigational product(s) in humans should be provided, including information on pharmacokinetics, metabolism, pharmacodynamics, dose response, safety, efficacy, and other pharmacological activities. Where possible, a summary of each completed clinical trial should be provided. Information should also be provided regarding results of any use of the investigational product(s) other than from in clinical trials, such as from experience during marketing.

1.2 elements of an Investigational Brochure (IB) and/or investigational device use (instructions for use, user manual) ICH 7

*Effects in Humans* a. Pharmacokinetics and Product Metabolism in Humans b. Safety and Efficacy c. Marketing Experience d. Summary of Data and Guidance for the Investigator

Purpose of Trial monitoring

*Ensure rights & safety of subjects are protected *Report on accuracy of trial data *Ensure trial is compliant (protocol, GCP, etc)

Vulnerable subjects

*Hierarchical structure employees *armed forces *detainees *incurable disease pts *homeless *poor *those in nursing home *minors *those unable to give consent

Required essential documents provided before study opens

*IB *signed protocol & amendments *CRFS *ICF *ads to promote study *financial aspects of study *agreements (signed) *Approved by IRB study materials *Composition of IRB *Signed CVs of PIs *Storing & Handling of device/drug *shipping information *Emergency decoding procedures for blinded study *Master randomization list * Pre-trial monitoring report

1.2 elements of an Investigational Brochure (IB) and/or investigational device use (instructions for use, user manual) ICH 7

*Introduction* A brief introductory statement should be provided that contains the chemical name (and generic and trade name(s) when approved) of the investigational product(s), all active ingredients, the investigational product (s ) pharmacological class and its expected position within this class (e.g., advantages), the rationale for performing research with the investigational product(s), and the anticipated prophylactic, therapeutic, or diagnostic indication(s). Finally, the introductory statement should provide the general approach to be followed in evaluating the investigational product.

Required essential documents at completion of trial

*Investigational product accountability at site (ensures products were used appropriate ensures which products were used/returned *device construction list *ID code list *audit certificate *final monitoring report *decoding document returned *final report of trial by PI *clinical study report (interpret trial)

Responsibilities of monitor

*Main line of communication b/w investigator & sponsor *Verify investigator qualifications *Verify product *Verify product storage *Verify dosing & who is receiving it *Subjects receive direction on product use *Products are accounted for appropriately *Verify protocol is being followed *verify written consent on each subject *ensure investigator has investigator brochure *ensure all staff are informed about the trial *verify only eligible subjects are being enrolled *report recruitment rate *verify source documents (CRFs match) *patient withdrawal or missed visits are reported on CRFs *notify PI of any missing data or signed edits to data *monitor reporting of AEs *report on deviations

Investigator Responsibilities

*Maintain delegation long *Ensure staff are trained/informed about the protocol (give delegated tasks) * Ascertain reason study participant withdraws consent while respecting their privacy & rights * Adhere to approved protocol *Document & explain any deviations from approved protocol * Process protocol amendments according to GCP *Manage proper storage & care for trial devices/drugs. (PI can delegate this task to trained professional - PharmD, etc)

Auditors vs Monitors vs inspectors

*Monitors - address data, storage of drug, & report to sponsor/investigator. They can be internal *Auditors - focused on compliance which is separate from routine monitoring - they should not be part of trial; independent committee reviewing data *Inspectors - IRB or regulatory body reviewing data

1.2 elements of an Investigational Brochure (IB) and/or investigational device use (instructions for use, user manual) ICH 7

*Nonclinical Studies* a. Nonclinical Pharmacology b. Pharmacokinetics and Product Metabolism in Animals c. Toxicology

1.2 elements of an Investigational Brochure (IB) and/or investigational device use (instructions for use, user manual) ICH 7

*Nonclinical Studies: Introduction* The results of all relevant nonclinical pharmacology, toxicology, pharmacokinetic, and investigational product metabolism studies should be provided in summary form. This summary should address the methodology used, the results, and a discussion of the relevance of the findings to the investigated therapeutic and the possible unfavourable and unintended effects in humans.

IRB / IEC Responsibilities

*Oversee principles of ICH/GCP *Make sure the PI / Co-Is are qualified * Review studies at least once a year

1.2 elements of an Investigational Brochure (IB) and/or investigational device use (instructions for use, user manual) ICH 7

*Physical, Chemical, and Pharmaceutical Properties and Formulation* A description should be provided of the investigational product substance(s) (including the chemical and/or structural formula(e)), and a brief summary should be given of the relevant physical, chemical, and pharmaceutical properties. Instructions for the storage and handling of the dosage form(s) should also be given. Any structural similarities to other known compounds should be mentioned.

Principles of ICH & GCP

*Protect research subjects *conduct research as it has been approved *research should be clear, organized & approved by an IRB/IEC

1.2 elements of an Investigational Brochure (IB) and/or investigational device use (instructions for use, user manual) ICH 7

*Summary* A brief summary (preferably not exceeding two pages) should be given, highlighting the significant physical, chemical, pharmaceutical, pharmacological, toxicological, pharmacokinetic, metabolic, and clinical information available that is relevant to the stage of clinical development of the investigational product.

1.2 elements of an Investigational Brochure (IB) and/or investigational device use (instructions for use, user manual) ICH 7

*Table of Contents*

1.2 elements of an Investigational Brochure (IB) and/or investigational device use (instructions for use, user manual) ICH 7

*Title Page* This should provide the sponsor's name, the identity of each investigational product (i.e., research number, chemical or approved generic name, and trade name(s) where legally permissible and desired by the sponsor), and the release date. It is also suggested that an edition number, and a reference to the number and date of the edition it supersedes, be provided.

Necessary aspects of ICF

*Trial involves research *Trial purposes *Treatments - randomization aspect if applicable * Procedures *Subject responsibilities *Experimental Aspects of trial *Risks *Benefits *Alternatives to participating *Compensation * Compensation for trial related outcomes *Voluntary nature of trial *Who has access to direct records *Confidentiality of research records *New information will be made available to subject *Who to Contact *Involuntary termination *Trial Duration *Subjects to be enrolled

Non-therapeutic trials can be conducted with consent from legal rep IF

*trial objectives cannot be met by personal subject consent *low risk *trial is not prohibited by law *IRB has approved such inclusion

Required essential documents provided during study

*updates to IB *updates to protocol / CRF, etc *approvals from IRB of updated materials *updates to any procedures / tests / shipping *records of any monitoring visits *signed ICF *completed CRFs, signed & dated *documentation of edited CRFs *source docs for completing CRFs *documentation of AEs/SAEs *subjects screening log *Subject enrollment log *subject ID code list * investigational product accountability *signature sheet (KSP) *record of samples

A witness signature is required on ICF when

*using a non-English language short-form ICF *someone who can comprehend the language, but is unable to read, write, talk or who is blind *witness MUST be impartial

Reporting for blinded studies

*when SAE occurs, it is generally suggested to break the blind for the patient unless *PI doesn't do this, the sponsor should *Blind should be maintained for research personnel, even if subject is told

* What is an IB?

- A compilation of the clinical and nonclinical data that are relevant to the study of the products in human subjects. - Purpose to facilitate understanding of & compliance with dose, method of administration, safety measures, etc.

* What is the reporting time frame for serious, unexpected ADRs that are not fatal or life-threatening?

- ASAP but no later than 15 calendar days after first knowledge by the sponsor that the case meets the minimum criteria for expedited reporting

* What is the reporting time frame for fatal or life-threatening unexpected ADRs?

- ASAP but no later than 7 calendar days after first knowledge by the sponsor that a case qualifies, followed by as complete a report as possible within 8 additional calendar days. - This report must include an assessment of the importance and implication of the findings, including relevant previous experience with the same or similar medicinal products.

* If a protocol deviation occurs to eliminate potential hazard, what should happen next?

- ASAP, the implemented deviation or change, reasons for it, and proposed amendment should be sent to... - The IRB for approval - The sponsor for agreement - Any regulatory authorities

* Should the investigator make an effort for determine reasons for early withdrawal?

- Although a subject is not obliged to give his/her reason(s) for withdrawing prematurely from a trial, the investigator should make a reasonable effort to ascertain the reasons, while fully respecting the subject's rights.

* What is a confirmatory trial?

- An adequately controlled trial in which the hypotheses are stated in advance and evaluated - Necessary to provide firm evidence of efficacy or safety

* What should definitely not be included in the oral or written information provided about the trial, pertaining to consent?

- Any language that causes the subject or LAR to waive or to appear to waive any legal rights... - or that releases or appears to release the investigator, the institution, the sponsor, or their agents from liability for negligence

* What are the most important design techniques to avoid bias in clinical trials?

- Blinding and randomization

* What are trials to show superiority? How are they best conducted?

- By demonstrating superiority to placebo in a placebo-controlled trial - By showing superiority to an active control treatment or - By demonstrating a dose-response relationship

In completing Form FDA 1572, Statement of the Investigator, the investigator agrees to:

- Conduct or supervise the investigation personally. - Report AEs to the sponsor - Retain records for two years after drug approval, disapproval, or study termination

* What are responsibilities of the IRB?

- Consider qualifications of the investigator - Conduct continuing review at least 1x/year - Request more information if it could meaningfully add to protection of rights, safety & well-being of subjects

* What are categorized variables?

- Dichotomization or other categorization of continuous or ordinal variables may sometimes be desirable

* What is a crossover design?

- Each subject is randomized to a sequence of two or more treatments, and hence acts as his own control for treatment comparisons

Per PHS, Significant Financial Interest can be defined as:

- Equity/stock interests (regardless of value) in a non-publicly traded company. - Intellectual property rights upon receipt of income related to such rights. - Consulting payments in excess of $5,000. -Includes spouses and dependent children

* What communication should be done with a subject in a therapeutic or non-therpeautic trial if only the LAR may provide consent?

- Informed about the trial to the extent compatible with the subject's understanding and, if capable, the subject should sign and personally date the written informed consent

* What should be stated about direct access in the protocol?

- Investigators/institutions will permit trial-related monitoring, audits, IRB/IEC review, and regulatory inspections, providing direct access to source data/documents

* In what phase trial may preliminary studies of activity of potential therapeutic benefit occur?

- May be conducted in Phase I as a secondary objective

* What is the purpose of multiple primary variables?

- May be desirable to use more than one primary variable, each of which could be sufficient to cover the range of effects of the therapies

* What is the purpose of an Independent Data Monitoring Committee?

- May be established by the sponsor to... - Assess trial progress (e.g., safety data, critical efficacy endpoints at intervals) - Recommend to the sponsor whether to continue, modify, or stop a trial

* What is the importance of demonstrating compliance?

- Methods used to evaluate patient usage of the test drug should be specified in the protocol and the actual usage documented

* What should be taken in to account when designing an analysis plan?

- Objectives & study design - Method of subject allocation - Measurement methods of response variables - Specific hypotheses - Analytical approaches to common problems including protocol violations & early withdrawal

* What are some possible control group options?

- Placebo - No treatment - Active control - Different dose of IP

* What is the role of an impartial witness?

- Present while the informed consent contents & other information are provided to the subject or LAR - After oral consent is completed, the witness should sign the ICF - Witness testifies that the ICF was accurately explained, was apparently understood by subject or LAR and that consent was freely given

* Before entering in to an agreement with an investigator, what should a sponsor provide?

- Protocol - Current IB - Sufficient time

* Should post-study events be reported to the sponsor?

- Serious adverse events should possibly be reported to the sponsor

* What are response variables?

- Should be defined prospectively, giving descriptions of methods of observation and quantification - Study endpoints are the response variables that are chosen to assess drug effects that are related to pharmacokinetic parameters, pharmacodynamic measures, efficacy and safety

* What is an exploratory trial?

- Should have clear and precise objectives - Objectives may not always lead to simple tests of pre-defined hypotheses - Provides rationale & design ideas for later studies

* What are trials to show dose-response relationships? What specific phase of trial are they?

- Show how response is related to the dose of a new IP is a question to which answers may be obtained in all phases of development, and by a variety of approaches

* Who is responsible for alerting the IRB to premature termination or suspension of a trial?

- Sponsor should promptly inform the investigators/institutions, and the regulatory authorities, and the reasons for the termination - The IRB should be informed & provided reasons by either the sponsor or investigator, as specified by the applicable regulatory requirements

* What factors should go in to selection of subjects?

- Stage of IP development - Condition to be studied - Prior non-clinical and clinical knowledge - Level of safety concerns

* What is a parallel group design?

- Subjects are randomized to one of two or more arms, each arm being allocated a different treatment

* With whom does the ultimate responsibility of the quality & integrity of trial data reside?

- The sponsor - The sponsor can transfer duties & functions to a CRO, but not responsibility - The CRO should always implement QA/QC (Any transferred duties should be specified in writing)

* What should happen if a monitor or auditor identifies serious or persistent noncompliance?

- The sponsor should terminate the investigator's/institution's participation in the trial. - When an investigator's/institution's participation is terminated because of noncompliance, the sponsor should notify promptly the regulatory authorities

* Why would an investigator sign the protocol?

- To document agreement to conduct the trial in compliance with the protocol agreed to by the sponsor and, if required, by the regulatory authorities

* When are deviations from or changes to the protocol acceptable without an amendment?

- To eliminate immediate hazards to the subjects - When the changes involves only logistical or administrative aspects to the trial.

* What is a factorial design?

- Two or more treatments are evaluated simultaneously through the use of varying combinations of treatments

* What are surrogate variables?

- Used in a number of indications where they are believed to be reliable predictors of clinical benefit

* What are group sequential designs?

- Used to facilitate the conduct of interim analysis

* Can the investigator delegate duties for IP accountability?

- Where allowed/required...can assign some or all of the duties to an appropriate pharmacist or other person under the investigator's supervision

* What should the IRB consider if a non-therapeutic trial is to be carrier out with the consent of a LAR?

- Whether the proposed protocol and/or other documents adequately addresses relevant ethical concerns and meets applicable regulatory requirements for such trials

* What should the IRB consider in the event consent of a subject or LAR is not possible for participation in a non-therapeutic trial?

- Whether the proposed protocol and/or other documents adequately addresses relevant ethical concerns and meets applicable regulatory requirements for such trials

Human Pharmacology Study

-Assess Tolerance -Define/Describe pharmacokinetics and pharmacodynamics -explore drug metabolism and drug interactions -estimate activity

Pharmacokinetics Study

-PI -assess the clearance of the drug and to anticipate possible accumulation of parent drug or metabolites and potential drug-drug interactions

Assessment of pharmacodynamics Study

-PI -may be conducted in healthy volunteer subjects or pt's with the target disease -can provide early estimates of activity and potential efficacy and may guide dosage and does regiment in later studies

Blinding

-Reducing or minimizing the risk of biased study outcomes - intended to limit the occurrence of conscious and unconscious bias -a procedure where one or more parties to the trial are kept unaware of the treatment assignments

* Who's responsibility is it to decide whether to report a reaction associated with an active comparator or placebo treatment?

-Sponsor's responsibility to decide whether reaction to be reported to manufacturer or to appropriate regulatory agenicies

* For what length of time should the IRB retain all relevant records for a trial after its completion?

-The IRB/IEC should retain all relevant records for a period of at least 3 years after completion of the trial and make them available upon request from the regulatory authorities

What is a development plan?

-The broad aim of the process of clinical development of a new drug is to find out whether there is a dose range and schedule at which the drug can be shown to be simultaneously safe and effective, to the extent that the risk-benefit relationship is acceptable

Single Blind Study

-Trial where the treatment assignment is not known by the study participant - The investigator and staff are aware of the treatment but the subject is not, or vice-versa

Double Blind Study

-When the study participant and the investigator and sponsor staff are unaware of the treatment assignments -Neither the subject nor any of the investigator or sponsor staff who are involved in the treatment of the subject's are aware of the treatments received

* What are the roles of the different analysis sets?

-advantageous to demonstrate a lack of sensitivity of the principal trial results to alternative choices of the set of subjects analyzed

Phase IV Study

-all studies performed after drug approval and related to the approval indication -optimizing the drug's use

Confirmatory Trial

-an adequately controlled trial in which the hypothesis are stated in advance and evaluated -necessary to provide firm evidence of safety -results should be robust

* What are the purposes of Human Pharmacology studies?

-assess tolerance -describe PK and PD -Explore drug metabolism and drug interactions -estimate activity

Serious

-based on patient outcome associated with events that pose a threat to a pt's life for functioning -serve as a guide for defining regulatory reporting obligations

E8 2.2 Type of Study: Therapeutic Confirmatory

-demonstrate/confirm efficacy -establish safety profile provide an adequate basis for assessing the benefit/risk relationship to support licensing -establish dose-response relationship

Therapeutic Confirmatory Study

-demonstrate/confirm efficacy (the ability to produce a desired or intended result). -establish safety profile -provide an adequate basis for assessing the benefit/risk relationship to support licensing -establish dose-response relationship

E8 3.1.3.1.c -- Assessment of Pharmacodynamics

-depending on the drug and the endpoint studied, pharmacodynamic studies and studies relating drug blood levels to response (PK/PD studies) may be conducted in healthy volunteer subjects or in patients with the target disease -can provide early estimates of activity and potential efficacy and may guide the dosage and dose regimen in later studies

* What are global assessment variables?

-developed to measure the overall safety, overall efficacy, and/or overall usefulness of a treatment -integrates objective variables and the investigator's overall impression about the state or change in the state of the subject, and is usually a scale of ordered categorical ratings

Exploratory Trial

-earlier clinical work -objectives may not always lead to simple tests of pre-defined hypothesis -may require a more flexible approach to design

E8 2.2 Type of Study: Therapeutic Exploratory

-explore use for the targeted indication -estimate dosage for subsequent studies -provide basis for confirmatory study design, endpoints, methodologies

Therapeutic Exploratory Study

-explore use for the targeted indication -estimate dosage for subsequent studies -provide basis for confirmatory study design, endpoints, methodologies

* What are composite variables?

-if a single primary variable cannot be selected from multiple measurements associated with the primary objective, another useful strategy is to integrate or combine the multiple measurements into a single or 'composite' variable, using a pre-defined algorithm

Randomisation

-introduces a deliberate element of chance into the assignment of treatments to subjects in a clinical trial -the process of assigning trial subjects to treatment or control groups using an element of chance to determine the assignments in order to reduce bias

E8 3.1.3.1.b --Pharmacokinetics

-may be assessed via separate studies or as a part of efficacy, safety and tolerance studies -important to assess the clearance of the drug and to anticipate possible accumulation of parent drug or metabolites and potential drug-drug interactions

Parallel Group Design

-most common clinical trial design for confirmatory trials -subject's are randomised to one of two or more arms, each arm being allocated to a different treatment -treatments include investigational product and one or more control treatments (placebo)

Phase II Study

-most typical kind of study in therapeutic exploratory -start with the initiation of studies in which the primary objective is to explore therapeutic efficacy in pt's -pt's selected by narrow criteria -Goal: determine does and regimen for PIII trials - Doses are usually less than the highest dose used in PI studies

Phase III Study

-most typical kind of study-therapeutic confirmatory study -confirm preliminary evidence accumulated in PII that a drug is safe and effective for use in intended indication and recipient population -provide an adequate basis for marketing approval

Phase I Study

-most typical kind study-human pharm. -usually have non-therapeutic objectives and may be conducted in healthy volunteer subjects or certain types of pts. involve one or more of: estimation of initial safety and tolerability, pharmacokinetics, assessment of pharmacodynamics, and early meausrment of drug activity

* In what kinds of cases would an already approved product require further studies as an IP?

-new or modified indications -new dosage regimens -new routes of administration -additional patient populations

LARs may sign for a subject if what conditions exist?

-non-therapeutic studies only -low risk to subject - cannot be conducted otherwise -IRB approves it -trial is not illegal by law

E8 2.2 Type of Study: Therapeutic Use

-refine understanding of benefit/risk relationship in general or special populations and/or environments -identify less common adverse reactions -refine dosing recommendation

Therapeutic Use Study

-refine understanding of benefit/risk relationship in general or special populations/environments -identify less common adverse reactions -refine dosing recommedation

Serious Adverse Event

-results in death -is life threatening -requires inpt. or prolonged hospitalization -results in persistent or significant disability/incapacity -is a congenital anomaly/birth defect

Primary Variable

-the variable capable of providing the most clinically relevant and convincing evidence directly related to the objective -should only be one

* What is the per protocol set?

-valid cases -efficacy sample -evaluable subjects

Which of the following are considered tasks that the CRC would complete prior to the next routine monitoring visit? 1. Review the CRF to ensure all data to date have been transcribed 2. enter all projected visit dates on the enrollment log 3. send the original CRF pages to the CRA for review 4. ensure the investigational product dispensation record is up-to-date

1 & 4

Sponsor/Investigator agreement should contain

1. Agreement to comply w/ GCP (adhere to protocol & IRB) 2. Agree to comply with data recording 3. Agree to permit monitoring 4. Agree to retain documents for specified length of time *Agreement should be signed by both parties

What are the two parts under the Principle of Beneficence?

1. Do no harm 2. Maximize possible benefits and minimize possible harms

Protocol amendments should be submitted to

1. IRB 2. Sponsor 3. Regulatory Authority

* Key Data Elements for Inclusion in Expedited Reports of Serious Adverse Drug Reactions

1. Patient Details Initials 2. Suspected Medicinal Products 3. Other Treatments 4. Details of Suspected Adverse Drug Reactions 5. Details on Reporter of Event (Suspected ADR) 6. Administrative and Sponsor/Company Details

There are two main reasons why a sponsor might audit a site:

1. To ensure that the site is complying with the regulation and protocol 2. There is evidence that the site is out of compliance and the sponsor wants to verify whether this is true or not.

The sponsor must submit an IND safety report to the FDA if an adverse event is: (3 things)

1. serious 2. unexpected 3. there is a reasonable possibility that the drug caused the event

In a drug study, what is the most important FDA document that is signed by the PI?

1572- Statement of investigator

Due to the public concern for ethical practices in research hearings were held before the Health of the US Senate Committee on Labor and Public Welfare (Kennedy Hearings), what act was passed.

1974 National Research Act

Factorial Design

2 or more treatments are evaluated simultaneously through the use of varying combinations of the treatments

According to ICH E11, what would the suggested age catagorization for children be if you were planning a study in "children"?

2 to 11 years

The PI and the CRC are reviewing a second protocol for the same therapeutic indication. Which of the following should be use to determine acceptance of the protocol by the site? 1. Protocol amendments 2. subject population 3. inclusion/exclusion differences 4. scientific merit

2, 3 & 4

Length of time a sponsor must wait before starting clinical trials after IND submission to FDA

30 calendar days

Development of most new drugs, from discovery to marketing approval, usually takes how many years?

9 or more years

Development of most new drugs from discovery to marketing approval usually takes:

9 years or more

In determining the feasibility of a hypertension study, a CC realizes that the protocol requires an automatic blood pressure machine with a measurement printout be used for all study-related blood pressures. As the site is not equipped with such a device, the FIRST action of the CRC should be to: A. ask the sponsor to supply the equipment B. perform the study without the equipment C. rent the equipment from an outside vendor D. turn the study down due to lack of equipment

The main purpose of a source document checklist is to A. ensure all study procedures have occurred B. document how data is collected C. train the CRC on how to conduct the study D. document that the study was properly conducted

A subject presents to the doctor's office with a recent onset of decreased hemoglobin at visit 4. Decreased hemoglobin is listed in the risk information contained in the investigator's brochure. Which of the following should the CRC do? A. Document decreased hgb as an AE B. Reported decreased hgb as an unexpected AE C. Complete SAE form & submit w/n 24 hours D. Add "decreased hgb" to the comments section in the CRF

A As decreased hemoglobin has its onset during the course of the study, it should be documented as an adverse event, even when consistent w/ the risks noted in the IB. Because it is a known risk, it would not be considered unexpected. It also would not be considered serious. As this meets the definition of an adverse event, it would be inappropriate to capture it solely in the comment field of a CRF.

Which of the following tasks should a CRC complete prior to the enrollment of subjects? 1. Conduct initial protocol training with site staff 2. Coordinate the process for completion of study related procedures and tests. 3. Inform primary care physician of subject's interest in the study. 4. Discontinue all excluded medications for potential subjects. A. 1 and 2 only B. 1 and 4 only C. 2 and 3 only D. 3 and 4 only

A Reason: Prior to screening subjects, site staff should be appropriately trained on the protocol and study-related procedures. In addition, the role of the CRC is to coordinate study-related testing with other departments. Informing the subject's primary care physician of the subject's interest in the study is suggested by ICH-GCP, but only with the consent of the subject, which is not presented in Option C. Finally, Option D is incorrect because it is inappropriate to discontinue medications without informed consent first being obtained from the subject.

A CRA is responsible for which of the following during a monitoring visit? 1. Verifying subject protection 2. confirming source data 3. assuring protocol compliance 4. reviewing medical charts for potential subjects A. 1, 2 & 3 B. 1, 2 & 4 C. 1, 3 & 4 D. 2, 3 & 4

A Reason: The main function of the CRA is to assure that the study is being performed according to the protocol and all applicable regulations/guidelines. CRAs can only review charts as part of source data verification after a trial subject has given his or her permission by signing an informed consent document, so Option 4 is wrong.

A study-specific flow sheet for subjects would be most appropriately stored with A. source documents B. trial protocol C. drug accountability records D. regulatory documents binder/file

A - think visit checklist

Multicentre Trial

A clinical trial conducted according to a single protocol but at more than one site, and therefore, carried out by more than one investigator.

* Coordinating Committee

A committee that a sponsor may organize to coordinate the conduct of a multicenter trial.

Coordinating Committee

A committee that a sponsor may organize to coordinate the conduct of a multicentre trial.

Coordinating Committee

A committee that sponsor may organize to coordinate the conduct of a multicentre trial

Investigator's Brochure

A compilation of the clinical and nonclinical data on the investigational product(s) which is relevant to the study of the investigational product(s) in human subjects

* Investigator's Brochure

A compilation of the clinical and nonclinical data on the investigational product(s) which is relevant to the study of the investigational product(s) in human subjects.

A subject has a suspected serious adverse drug reaction with the outcome of death. Per the ICH E2A guideline, which are items that should be submitted to the Sponsor?

A de-identified autopsy report, if available. Cause of death, and a comment on its possible relationship to the suspected drug reaction

* Audit Certificate

A declaration of confirmation by the auditor that an audit has taken place

Audit Certificate

A declaration of confirmation by the auditor that an audit has taken place.

E6(R1) 6.4.6

A description of the "stopping rules" or "discontinuation criteria" for individual subjects, parts of trial and entire trial

1.1 elements of a protocol ICH 6

A description of the "stopping rules" or "discontinuation criteria" for individual subjects, parts of trial and entire trial.

1.1 elements of a protocol ICH 6

A description of the measures taken to minimize/avoid bias, including: (a) Randomization. (b) Blinding.

1.1 elements of a protocol ICH 6

A description of the statistical methods to be employed, including timing of any planned interim analysis(ses).

1.1 elements of a protocol ICH 6

A description of the trial treatment(s) and the dosage and dosage regimen of the investigational product(s). Also include a description of the dosage form, packaging, and labelling of the investigational product(s).

E6(R1) 6.4.4

A description of the trial treatments and the dosage and dosage regimen of the investigational products. Also include a description of the dosage form, packaging, and labelling of the investigational products

1.1 elements of a protocol ICH 6

A description of the type/design of trial to be conducted (e.g., double-blind, placebo- controlled, parallel design) and a schematic diagram of trial design, procedures and stages.

1.1 elements of a protocol ICH 6

A detailed description of the objectives and the purpose of the trial.

Protocol

A document that describes the objective(s), design, methodology, statistical considerations, and organization of a trial.

Which of the following is NOT one of the required elements of an informed consent form?

A listing of all site personnel who will be involved in the research

* Contract Research Organization (CRO)

A person or an organization (commercial, academic, or other) contracted by the sponsor to perform one or more of a sponsor's trial-related duties and functions.

Contract Research Organization (CRO)

A person or an organization (commercial, academic, or other) contracted by the sponsor to perform one or more of a sponsor's trial-related duties and functions.

* Investigator

A person responsible for the conduct of the clinical trial at a trial site.

Investigator

A person responsible for the conduct of the clinical trial at a trial site. If a trial is conducted by a team of individuals at a trial site, the investigator is the responsible leader of the team and may be called the principal investigator.

* Impartial Witness

A person, who is independent of the trial, who cannot be unfairly influenced by people involved with the trial, who attends the informed consent process if the subject or the subject's legally acceptable representative cannot read, and who reads the informed consent form and any other written information supplied to the subject

Impartial Witness

* Investigational Product

A pharmaceutical form of an active ingredient or placebo being tested or used as a reference in a clinical trial, including a product with a marketing authorization when used or assembled (formulated or packaged) in a way different from the approved form, or when used for an unapproved indication, or when used to gain further information about an approved use.

Investigational Product

* Case Report Form (CRF)

A printed, optical, or electronic document designed to record all of the protocol required information to be reported to the sponsor on each trial subject.

Case Report Form (CRF)

A printed, optical, or electronic document designed to record all of the protocol required information to be reported to the sponsor on each trial subject.

* Blinding/Masking

A procedure in which one or more parties to the trial are kept unaware of the treatment assignment(s).

Blinding/Masking

A procedure in which one or more parties to the trial are kept unaware of the treatment assignment(s).

* Informed Consent

A process by which a subject voluntarily confirms his or her willingness to participate in a particular trial, after having been informed of all aspects of the trial that are relevant to the subject's decision to participate--documented by means of a written, signed and dated informed consent form

Informed Consent

* Who should be responsible for all trial-related medical decisions?

A qualified physician (or dentist when appropriate), who is an investigator or a sub-investigator for the trial

What is an unexpected Adverse Drug Reaction?

A reaction that is not consistent with the applicable product knowledge

* Interim Clinical Trial/Study Report

A report of intermediate results and their evaluation based on analyses performed during the course of a trial

Interim Clinical Trial/Study Report

A report of intermediate results and their evaluation based on analyses performed during the course of a trial.

ADR (post-marketing)

A response to a drug which is harmful and unintended and which occurs at doses normally used in man for prophylaxis, diagnoses, or therapy of disease

1.1 elements of a protocol ICH 6

A specific statement of the primary endpoints and the secondary endpoints, if any, to be measured during the trial.

* Good Clinical Practice (GCP)

A standard for the design, conduct, performance, monitoring, auditing, recording, analyses, and reporting of clinical trials that provides assurance that the data and reported results are credible and accurate, and that the rights, integrity, and confidentiality of trial subjects are protected

Good Clinical Practice (GCP)

1.1 elements of a protocol ICH 6

A summary of findings from nonclinical studies that potentially have clinical significance and from clinical trials that are relevant to the trial.

E6(R1) 7.3.6 -- Effects in Humans: Introduction -- Pharmacokinetic and Product Metabolism in Humans

A summary of information on the pharmacokinetics of the investigational products should be presented, including the following, if available: - Pharmacokinetics - Bioavailability of the investigational product - Population subgroups - Interactions - Other pharmacokinetic data

E6(R1) 7.3.6 -- Effects in Humans: Introduction -- Safety and Efficacy (Part 1)

A summary of information should be provided about the investigational products safety, pharmacodynamics, efficacy,a dn dose response that were obtained fro preceding trials in humans. The implications of this information should be discussed. IN cases where a number of clinical trials have been completed, the use of summaries of safety and efficacy across multiple trials by indications in subgroups may provide a clear presentation of the data. Tabular summaries of adverse drug reactions for all the clinical trials would be useful. Important differences in adverse drug reaction patterns/incidences across indications or subgroups should be discussed

E6(R1) 7.3.5 -- Nonclinical studies: Introduction -- Pharmacokinetics and Product Metabolism in Animals

A summary of the pharmacokinetics and biological transformation and disposition of the investigational product in all species studied should be given. The discussion of the findings should address the absorption and the local and systemic bioavailability of the investigational product and its metabolites, and their relationship to the pharmacological and toxicological findings in animal species

E6(R1) 7.3.5 -- Nonclinical studies: Introduction -- Toxicology

A summary of the toxicological effects found in relevant studies conducted in different animal species should be described under the following headings where appropriate: - Single dose - Repeated dose - Carcinogenicity - Special studies - Reproductive toxicity - Genotoxicity (mutagenicity)

Audit

A systematic and independent examination of trial related activities and documents to determine whether the evaluated trial related activities were conducted, and the data were recorded, analyzed and accurately reported according to the protocol, sponsor's standard operating procedures (SOPs), Good Clinical Practice (GCP), and the applicable regulatory requirement(s).

* Audit

A systematic and independent examination of trial related activities and documents to determine whether the evaluated trial related activities were conducted, and the data were recorded, analyzed and accurately reported according to the protocol, sponsor's standard operating procedures, (SOPs), Good Clinical Practice (GCP), and the applicable regulatory requirement(s)

According to ICH E6, an "audit" is defined as

A systematic and independent examination of trial-related activities and documents.

According to ICH E6, an "audit" is defined as:

A systematic and independent examination of trial-related activities and documents.

Double-Dummy

A technique for retaining the blind when administering supplies in a clinical trial, when the two treatments can't be made identical. Subjects take two sets of treatment; Either A (active) and B (placebo) or A (placebo) and B (active)

E6(R1) 7.3.6 -- Effects in Humans: Introduction

A thorough discussion of the known effects of the investigational products in humans should be provided, including information on pharmacokinetics, metabolism, pharmacodynamics, dose response, safety, efficacy, and other pharmacological activities. Where possible, a summary of each completed clinical trial should be provided. Information should also be provided regarding results of any use o fate investigational products other than from in clinical trials, such as from experience during marketing

Non-Inferiority Trial

A trial with the primary objective of showing that the response to the investigational product is not clinically inferior to a comparative agent (active or placebo)

Superiority Trial

A trial with the primary objective of showing that the response to the investigational product is superior to a comparative agent (active or placebo)

Equivalence Trial

A trial with the primary objective of showing the response to 2 or more treatments differs by an amount which is clinically unimportant

* Subject Identification Code

A unique identifier assigned by the investigator to each trial subject to protect the subject's identity and used in lieu of the subject's name when the investigator reports adverse events and/or other trial related data

Subject Identification Code

Surrogate Variable

A variable that provides an indirect measurement of effect in situations where direct measurement of clinical effect is not feasible or practical

Protocol Amendment

A written description of a change(s) to or formal clarification of a protocol.

* Clinical Trial/Study Report

A written description of a trial/study of any therapeutic, prophylactic, or diagnostic agent conducted in human subjects, in which the clinical and statistical description, presentations, and analyses are fully integrated into a single report

Clinical Trial/Study Report

* Audit Report

A written evaluation by the sponsor's auditor of the results of the audit

Audit Report

A written evaluation by the sponsor's auditor of the results of the audit.

* Monitoring Report

A written report from the monitor to the sponsor after each site visit and/or other trial-related communication according to the sponsor's SOPs.

Monitoring Report

A written report from the monitor to the sponsor after each site visit and/or other trial-related communication according to the sponsor's SOPs.

* Contract

A written, dated, and signed agreement between two or more involved parties that sets out any arrangements on delegation and distribution of tasks and obligations and, if appropriate, on financial matters.

Contract

Informed Consent is documented by:

A written, signed, and dated informed consent form

Clinical investigation of adverse events in clinical trials requires A) Root cause analysis B) Complete medical records review C) Investigation of potential protocol deviations D) Causality assessment

A) Root cause analysis

15 Calendar Days

ADR's that are not life-threatening must be filed no later than how many days?

Other serious, but non-fatal / life-threatening ADRs should be reported in what time frame?

ASAP, no more than 15 days

1.1 elements of a protocol ICH 6

Accountability procedures for the investigational product(s), including the placebo(s) and comparator(s), if any.

Abbreviation: "ALCOAC"

Accurate, legible, contempr

means that a known, effective treatment (as opposed to a placebo) is compared to an experimental treatment. In other words, every person in an active control clinical trial is given a treatment that works (or potentially works), instead of some receiving an inactive "sugar pill"

Active control" (or "Active Comparator")

E2CA

Addendum to E2C

Compliance (in relation to trials)

Adherence to all the trial-related requirements, Good Clinical Practice (GCP) requirements, and the applicable regulatory requirements.

ADR

Adverse Drug Reaction

Abbreviation: "ADR"

Adverse Drug Reaction

All noxious and unintended responses to a medicinal product related to any dose should be considered an ADR.

Adverse Drug Reaction

Abbreviation: "AE"

Adverse Event

Any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. Any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an IP.

Adverse Event

In pre-market approval studies, all noxious and unintended responses to a medicinal product, even possibly related to any dose, should be considered which of the following options?

Adverse drug reaction

Your third subject in a Phase III drug trial calls to report that she has developed a rash on her chest 12 hours after taking her second dose of the investigational study drug. She states that it itches and is slightly uncomfortable. She tells you that she has never had a rash and this is totally unexpected. You know from the Investigator Drug Brochure that only 12% of the patients get a rash from this drug. Which of the following options best describes this situation?

Adverse drug reaction

An untoward event in a patient or clinical investigational subject administered a pharmaceutical product which does not necessarily have a causal relationship is what?

Adverse event

Any untoward medical occurrence in a patient or clinical-trial subject administered a medicinal product and which does not necessarily have to have a causal relationship with this treatment.

Adverse event (AE)

A study subject reports that he has been having headaches for years but they seem to have become more frequent since starting the study drug. The principal investigator believes that the headaches are not related to the study medication. How should the event be reported?

Adverse event, since the headaches have become more frequent

E6(R1) 4.11.2

Adverse events and/or laboratory abnormalities identified in the protocol as critical to safety evaluations should be reported to the sponsor according to the reporting requirements and within the time periods specified by the sponsor in the protocol

Study initiation meetings are usually held:

After the site has received all study materials and is ready to start enrollment

E6(R1) 5.1.4

Agreements, made by the sponsor with the investigator/institution and any other parties involved with the clinical trial, should be in writing, as part of the protocol or in a separate agreement

Adverse Drug Reaction (ADR)

All harmful and unintended responses to a medicinal product related to any dose

* Source Data

All information in original records and certified copies of original records of clinical findings, observations, or other activities in a clinical trial necessary for the reconstruction and evaluation of the trial

Source Data

* Adverse Drug Reaction (ADR)

All noxious and unintended responses to a medicinal product related to any dose

Documentation

All records, in any form (including, but not limited to, written, electronic, magnetic, and optical records, and scans, x-rays, and electrocardiograms) that describe or record the methods, conduct, and/or results of a trial, the factors affecting a trial, and the actions taken.

* Documentation

All records, in any form that describe or record the methods, conduct, and/or results of a trial, the factors affecting a trial, and the actions taken

E6(R1) 5.2.4

All references to a sponsor in this guideline also apply to a CRO to the extent that a CRO has assumed the trial related duties and functions of a sponsor

E6(R1) 4.11.1

All serious adverse events (SAEs) should be reported immediately to the sponsor except for those SAEs that the protocol or other document identifies as not needing immediate reporting. The immediate reports should be followed promptly by detailed, written reports. The immediate and follow-up reports should identify subjects by unique code numbers assigned to the trial subjects rather than by the subjects' names personal identification numbers, and/or addresses. The investigator should also comply with the applicable regulatory requirement(s) related to the reporting of unexpected serious adverse drug reactions to the regulatory authority(its) an the IRB/IEC

* Quality Assurance (QA)

All those planned and systematic actions that are established to ensure that the trial is performed ad the data are generated, documented, and reported in compliance with GCP and the applicable regulatory requirements

Quality Assurance (QA)

All those planned and systematic actions that are established to ensure that the trial is performed and the data are generated, documented (recorded), and reported in compliance with Good Clinical Practice (GCP) and the applicable regulatory requirement(s).

The FDA's regulations related to electronic records and electronic signatures (21 CFR Part 11) are intended to:

Allow the use of electronic documents and signatures in the regulatory process for drugs and devices.

Unexpected Adverse Drug Reaction

An adverse reaction, the nature or severity of which is not consistent with the applicable product information (e.g., Investigator's Brochure for an unapproved investigational product or package insert/summary of product characteristics for an approved product)

* Unexpected Adverse Drug Reaction

An adverse reaction, the nature or severity of which is not consistent with the applicable product information.

Investigator/Institution

An expression meaning "the investigator and/or institution, where required by the applicable regulatory requirements".

* Independent Ethics Committee (IEC)

An independent body constituted of medical professionals and non-medical members, whose responsibility it is to ensure the protection of the rights, safety and well-being of human subjects involved in a trial and to provide public assurance of that protection, by, among other things, reviewing and approving / providing favorable opinion on, the trial protocol, the suitability of the investigator(s), facilities, and the methods and material to be used in obtaining and documenting informed consent of the trial subjects.

Institutional Review Board (IRB)

An independent body constituted of medical, scientific, and non-scientific members, whose responsibility is to ensure the protection of the rights, safety and well-being of human subjects involved in a trial by, among other things, reviewing, approving, and providing continuing review of trial protocol and amendments and of the methods and material to be used in obtaining and documenting informed consent of the trial subjects.

Independent Ethics Committee (IEC)

An independent body, constituted of medical professionals and non-medical members, whose responsibility it is to ensure the protection of the rights, safety and well-being of human subjects involved in a trial and to provide public assurance of that protection, by, among other things, reviewing and approving/providing favourable opinion on, the trial protocol, the suitability of the investigator(s), facilities, and the methods and material to be used in obtaining and documenting informed consent of the trial subjects.

* Independent Data-Monitoring Committee (IDMC) (Data and Safety Monitoring Board, Monitoring Committee, Data Monitoring Committee)

An independent data-monitoring committee that may be established by the sponsor to assess at intervals the progress of a clinical trial, the safety data, and the critical efficacy endpoints, and to recommend to the sponsor whether to continue, modify, or stop a trial

Independent Data-Monitoring Committee (IDMC)

Legally Authorized Representative (LAR)

An individual or judicial or other body authorized under applicable law to consent on behalf of a prospective subject to the subject's participation in the procedures involved in the research.

* Legally Acceptable Representative

An individual or juridical or other body authorized under applicable law to consent, on behalf of a prospective subject, to the subject's participation in the clinical trial.

Legally Acceptable Representative

An individual or juridical or other body authorized under applicable law to consent, on behalf of a prospective subject, to the subject's participation in the clinical trial.

* Sponsor-Investigator

An individual who both initiates and conducts, alone or with others, a clinical trial, and under whose immediate direction the investigational product is administered to, dispensed to, or used by a subject.

Sponsor-Investigator

Subject/Trial Subject

An individual who participates in a clinical trial, either as a recipient of the investigational product(s) or as a control.

* Sponsor

An individual, company, institution, or organization which takes responsibility for the initiation, management, and/or financing of a clinical trial

Sponsor

An individual, company, institution, or organization which takes responsibility for the initiation, management, and/or financing of a clinical trial.

Comparator (Product)

An investigational or marketed product (i.e., active control), or placebo, used as a reference in a clinical trial.

* Comparator (Product)

An investigational or marketed product, or placebo, used as a reference in a clinical trial.

* Coordinating Ivestigator

An investigator assigned the responsibility for the coordination of investigators at different centers participating in a multicenter trial

Coordinating Investigator

An investigator assigned the responsibility for the coordination of investigators at different centres participating in a multicentre trial.

Coordinating Investigator

An investigator who oversees multiple sites of a clinical trial (multicenter)

An investigator conducting a study of a medical device under an IDE is required to complete and sign a:

An investigator's agreement

An investigator conducting a study of a medical device under an IDE is required to complete and sign which of the following?

An investigator's agreement

According to ICH E6 GCP, an inspection is defined as:

An official review of documents, facilities, records, and any other resources related to a clinical trial.

According to ICH E6, an inspection is defined as

An official review of documents, facilities, records, and any other resources related to a clinical trial.

According to ICH E6, an inspection is defined as:

An official review of documents, facilities, records, and any other resources related to a clinical trial.

* What are analysis sets?

Analysis Sets -set of subjects whose data are to be included in the main analyses should be defined in the statistical section of the protocol -documentation for all subjects for whom trial procedures were initiated may be useful

Pre-Clinical Trials

Animal/Translational Research - 4.5 years

E6(R1) 4.9.3

Any change or correction to a CRF should be dated, initialed, and explained (if necessary) and should not obscure the original entry; this applies to both written and electronic changes or corrections. Sponsors should provide guidance to investigators and/or the investigators' designated representatives on making such corrections. Sponsors should have written procedures to assure that changes or corrections in CRFs made by sponsor's designated representatives are documented, are necessary, and are endorsed by the investigator. The investigator should retain records of the changes and corrections.

Significant Equity Interest

Any compensation whose value may be affected by study outcome, proprietary interest in the investigational product, equity interest whose value cannot be readily determined through reference to public prices, equity exceeding $50,000 in value, and significant payments of sorts (SPOOS) cumulative of $25,000

Subinvestigator

Any individual member of the clinical trial team designated and supervised by the investigator at a trial site to perform critical trial-related procedures and/or to make important trial-related decisions (e.g., associates, residents, research fellows)

* Subinvestigator

* Clinical Trial/Study

Any investigation in human subjects intended to discover or verify the clinical, pharmacological and/or other pharmacodynamic effects of an investigational product(s), and/or to identify any adverse reactions to an investigational product(s), and/or to study absorption, distribution, metabolism, and excretion of an investigational product(s) with the object of ascertaining its safety and/or efficacy

Clinical Trial/Study

* Applicable Regulatory Requirements

Any law(s) and regulation(s) addressing the conduct of clinical trials of investigational products

Applicable Regulatory Requirement(s)

Any law(s) and regulation(s) addressing the conduct of clinical trials of investigational products.

Institution (medical)

Any public or private entity or agency or medical or dental facility where clinical trials are conducted.

E6(R1) 5.5.10

Any transfer of ownership of the data should be reported to the appropriate authority(ies), as required by the applicable regulatory requirement(s)

Adverse Event

Any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product

* Adverse Event (AE)

Any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment--any unfavorable and unintended sign , symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product

Adverse Event (AE)

Any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.

Serious Adverse Event (SAE) or Serious Adverse Drug Reaction (Serious ADR)

Any untoward medical occurrence that at any dose: - results in death, - is life-threatening, - requires inpatient hospitalization or prolongation of existing hospitalization, - results in persistent or significant disability/incapacity, or - is a congenital anomaly/birth defect

* Serious Adverse Event (SAE) or Serious Adverse Drug Reaction (Serious ADR)

Any untoward medical occurrence that at any dose: -results in death -is life-threatening -requires inpatient hospitalization or prolongation of existing hospitalization -results in persistent or significant disability/incapacity -is a congenital anomaly/birth defect

Any law(s) and regulation(s) addressing the conduct of clinical trials of investigational products.

Applicable Regulatory Requirements

What is the timeframe for "expedited" reporting of serious, fatal or life-threatening, unexpected adverse drug reactions to regulatory authorities?

As soon as possible, but no later than seven calendar days after first knowledge of event

What is it called when a child is given information about a trial and asked if he or she wishes to participate?

Assent

phase 1 study

Assess safety and tolerability of a study drug in mostly healthy subjects

Feasibility of a Study

Assessment of resource needs, regulator requirements, and potential level of risk of harm for human subjects participating in study

Sub-Investigator

Assists the PI by performing delegated tasks that are outlined in the protocol.

How long must documents be retained per GCP?

At least 2 years after last approved marketing application (organizations/sponsors, etc usually set a longer required period of 5-7 years)

At least 5 members, at least one member whose primary interest is non-scientific, at least on member who is independent from the institution/trial site

The FDA requires retention of investigational drug study records for

At least two (2) years after the investigational drug's approval by the FDA

The FDA requires retention of investigational drug study records for:

At least two (2) years after the investigational drug's approval by the FDA

A systematic and independent examination of trial-related activities and documents to determine whether the evaluated trial-related activities were conducted, and the data were recorded, analyzed, and accurately reported according to protocol, sponsor standard operating procedures, GCP, and regulatory requirements.

Audit

A written evaluation by the sponsor's auditor of the results of the audit.

Audit Report

Documentation that allows reconstruction of the course of events

Audit Trail

A Phase I study protocol had a sample size of 30. Two subjects were disqualified due to protocol violations and the total number enrolled was 32. The IRB/IECC may query the investigator for which of the following reasons? A. Not informing them about the two subjects who are disqualified. B. an amendment should have been obtained and approved to increase the sample size to 32. C. No SAE reports were submitted D. The study closed sooner that anticipated

A change in weight of greater than or equal to 10% between Visits 1 and 3 is an exclusion criterion. The subject weight 130lbs at Visit 1. The subject would be excluded at what minimum weight prior to or at Visit 3? A. 135 B. 143 C. 145 D. 150

A subject arrives for a study visit on the last day of the protocol visit window. Because of bad weather, the drug re-supply shipment did not arrive. The patient must not miss any dose of the open-label study drug. Which of the following is the BEST course of action for the CRC to take? A. have the investigator write a prescription for the open-label drug B. Contact the study sponsor for permission to re-dispense leftover tablets C. Discontinue the patient and perform early-termination procedures D. Re-schedule the study visit

An acne study utilizing an oral contraceptive requires a two month washout for current oral contraceptive use, six months for injectable hormones and one month for topical antibiotics. The last day to randomize a subject is September 30th. What is the last day that a woman on birth control pills can be consented for therapy? A. March 31 B. July 31 C. August 31 D. September 30

An investigator conducts and completes the informed consent process with a subject, who then completes all of the day 1 requirements and is ready to leave. The CRC notices that the investigator neglected to sign the informed consent document, and the CRC will not be able to obtain the investigator's signature on the consent form for several hours. The protocol indicates that the ICH-GCP Guidelines will be followed throughout the study. A. Give the subject an unsigned copy of the consent form B. Mail the completely signed consent to the subject. C. Keep the subject around until the investigator is available. D. Sign for the investigator and provide the subject with a copy

During the initial review of a protocol, the CRC has questions about the study procedures. The CRC should do which of the following? A. notify the IRB/IEC of questions and concerns B. Present questions and concerns at the investigator's meeting C. Decline to participate in the study D. Discuss the questions with another CRC

A CBC is drawn on a study subject at Visit 3. The specimen cannot be transported to the central laboratory until the following day. What should the CRC do to protect the integrity of the specimen? A. Store the CBC in the refrigerator, then transport the plasma on wet ice the next day B. Store the CBC at room temperature then transport in an ambient bag the next day C. Freeze the CBC at -70 then transport frozen the next day D. Freeze at -20 then transport on dry ice the next day

B Not C & D b/c cells heomlyse when frozen; A is wrong b/c it excludes the RBC and only includes plasma

If the reference laboratory normal values change in the course of the study, which of the following actions should the CRC take? A. No action is indicated B. The new reference values are inserted in the regulatory/site file C. The PI documents the change in all subject's source documents. D. All subject's data are reviewed by the PI for significance for both pre- and post- change periods.

B Reason: A is incorrect because the new values should not be ignored. B is correct because normal ranges constitute "essential documents," according to ICH-GCP 8.2.11, C and D are not necessary because new laboratory reports will contain the new values.

In a multicenter, international clinical trial for a commercial sponsor, a principle investigator fulfills a number of responsibilities, including which of the following: 1. Updating the delegation of authority log 2. Reviewing the trial protocol as member of the IRB/IEC 3. Ensuring that he/she is aware of GCP and regulations applicable to clinical trials 4. updating the Investigator's brochure each year A. 1 & 2 B. 1 & 3 C. 2 & 4 D. 3 & 4

B Reason: Answers 1 and 3 are covered in ICH-GCP 4.1.5 & 4.1.3. Answer 2 suggests that investigators can participate in the review of protocol that he/she will subsequently conduct. However, ICH-GCP stipulates that an investigator may only provide information on the trial, but should not participate in the decision-making process of the IRB/IEC or in the vote/opinion in relation to the approval of a protocol. Updating the investigator's brochure is the responsibility of the sponsor, not the investigator, so Answer 4 is incorrect.

According to ICH-GCP, which of the following are considered SAEs? 1. Infection following surgery prolonging hospital stay 2. Pregnancy resulting in normal delivery of twins 3. Hospital admission following a motor vehicle accident 4. Use of illicit drug during the study. A. 1 & 2 B. 1 & 3 C. 2 & 4 D. 3 & 4

B Reason: By definition, ICH-GCP defines an SAE as "any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect." This definition supports Items 1 & 3 only. Neither a pregnancy resulting in normal delivery, as suggested in Item 2, nor the use of illicit drugs during the study, as suggested in Item 4, constitute an SAE.

In order to ensure that an investigative site can provide adequate storage space for the test article/investigational product and study supplies, the sponsor would conduct A. An investigator's meeting B. a pre-study site evaluation C. an initiation visit D. a telephone conference with the site

B Reason: ICH-GCP 5.6.1 and 5.18.3 suggest that, prior to the initiation of a clinical investigation, sponsors should routinely confirm the existence of adequate facilities for drug supply in their site-screening process prior to conducting the pre-study visit on-site for confirmation. Adequate storage space should continue to be verified by the sponsor at the initiation visit, as well as subsequent monitoring visits.

At the final visit, the CRC discovers that a subject has not been taking the test article/investigational product as directed. However, according to the pill counts conducted throughout the study, the subject appeared to be compliant. Which of the following should the CRC do in this situation? A. Recalculate compliance for each visit to determine a more accurate compliance percentage based on the subject's verbal account. B. Document the available information surrounding the noncompliance in the source document. C. Report the subject's noncompliance as an adverse event to the IRB/IEC. D. Classify the subject as dropped from the date at which the noncompliance began.

B Reason: In this scenario, the subject reveals that he/she was not compliant with taking the test article/investigational product as directed, despite the pill count indicating otherwise. Recalculation based on the subject's verbal account rather than amounts dispensed and returned would be inappropriate. Option C is incorrect because this is not a significant hazard, so it should not be reported to the IRB/IEC by the PI. Technically, the subject did not drop out of the study; therefore, classifying him/her as such would not be accurate. A CRC becoming knowledgeable about such noncompliance should document this information in accordance w/ GCP, as the noncompliance may have a serious and potentially significant impact on the clinical research results.

A CRC is preparing the final report to the sponsor for an osteoporosis study. He/she learns that a sub-investigator did not perform the exit physical examinations for six subjects as required by the protocol. Which of the following should the CRC do FIRST? A. Schedule the subject for an exit physical examination. B. Inform the PI of the protocol deviation. C. Complete the report and a note to file about the missing data deviation. D. Ask the sub-investigator to mark the physical exam CRF as "not done."

B Reason: The PI should be informed of these protocol deviations as the initial step. Subsequently, the CRC should ensure the sub-investigator completes the CRF as "not don't" and document the deviation with a note to file accordingly. As study subject participation has completed as this point, any opportunity to schedule those subjects for an exit physical examination has passed. According to ICH-GCP 4.13, the PI is responsible for any final report sent to the sponsor.

A response to a medical product means A) A causal relationship between drug and adverse event is established B) A causal relationship between drug and adverse event is a reasonable possibility C) The relationship of the event to drug cannot be ruled out D) An event that requires active medical intervention

B) A causal relationship between drug and adverse event is a reasonable possibility C) The relationship of the event to drug cannot be ruled out

The term, life threatening, in a serious adverse event refers to A) An event which required hospitalization B) An event where risk of death was evident at the time of the event C) An event that required treatment in an emergency room D) An event which might have caused a death if left untreated

B) An event where risk of death was evident at the time of the event

In ascertaining the basis for a serious adverse drug reaction in a randomized trial A) Care should be taken not to break the blind for the patient B) Care should be taken to break the blind only for the single patient involved C) The blind for the group of patients being treated at the site should be broken D) The blind for the single patient should be broken only if the sponsor approves

B) Care should be taken to break the blind only for the single patient involved

Following a formal investigation, a clinical investigator has been found guilty of submitting false information to the sponsor in a required clinical report. The first action the regulatory authority is likely to take is to: A. Provide the investigator oral notification B. provide the investigator written notification C. offer the investigator further opportunity to explain the matter in writing. D. offer the investigator a further opportunity to have an informal hearing to explain what has happened

B. Reason: Critical to answering this question is understanding why the regulatory authority has, at this point, decided to take or recommend formal action against a clinical investigator. This is good practice, since an investigation has already confirmed fraud, so further, formal action is required in accordance with applicable national laws.

Kidney Function

BUN (urea nitrogen) Creatinine

The packaging of investigational drugs should ideally:

Be designed to help with subject compliance

Payments to subjects in clinical trials should:

Be done only with prior IRB approval

The investigator must obtain IRB approval of the study and the consent form:

Before enrolling any patients in the study

E6(R1) 5.10 -- Notification/Submission to Regulatory Authority(ies)

Before initiating the clinical trial(s), the sponsor (or the sponsor and the investigator, if required by the applicable regulatory requirement(s)) should submit any required application(s) to the appropriate authority(ies) for review, acceptance, and/or permission (as required by the applicable regulatory requirement(s)) to begin the trial(s). Any notification/submission should be dated and contain sufficient information to identify the protocol

_____ is a principle outlined in the Belmont Report that requires researchers to protect their human subjects from any harm

Beneficence

Is a measure of how easily and quickly nutrients can be absorbed and used by the body after consumption. Simply consuming particular nutrients or taking healthy supplements does not guarantee that they will safely make their way through your intestinal tract, to your bloodstream, and ultimately to your cells.

Bioavailability

* Nonclinical Study

Biomedical studies not performed on human subjects

Nonclinical Study

Biomedical studies not performed on human subjects.

A procedure in which one or more parties to the trial are kept unaware of the treatment assignments.

Blinding

A nonspecific term for a defect in the blood

Blood dyscrasias

Regulatory Authorities

Bodies having the power to regulate.

A double-blinded trial for a new indication is conducted under an IND comparing two (2) marketed drugs, at twice the approved prescribed doses. On Day 2, subject 603 had difficulty breathing. Although it was life-threatening initially, subject 603 was treated and discharged directly from the emergency department after complete recovery. On Day 5, subject 20 had a headache, which led to hospitalization and required blood pressure lowering medications. These episodes cannot be explained on the basis of the pharmacological property of either drug or the subjects' medical histories. The investigator would submit an SAE report for:

Both Subjects

Both of the subjects

A double-blinded trial for a new indication is conducted under an IND comparing 2 marketed drugs, at twice the approved prescribed doses. On Day 2, subject 603 had difficulty breathing. Although it was life-threatening initially, subject 603 was treated and discharged directly from the emergency department after complete recovery. On Day 5, subject 20 had a headache, which led to hospitalization and required blood pressure lowering medications. These episodes cannot be explained on the basis of the pharmacological property of either drug or the subjects' medical histories. The investigator would submit an SAE report for:

Both of the subjects.

is a sudden constriction of the muscles in the walls of the bronchioles. It is caused by the release of substances from mast cells or basophils under the influence of anaphylatoxins. It causes difficulty in breathing which ranges from mild to severe

Bronchospasm or a bronchial spasm

A Phase II study involving intravenous administration of a test article/investigational product for the treatment of dyslipidemia requires that only unblinded study personnel manage the actual test article/investigational product administration. During start-up preparations, which of the following actions should be considered by study personnel? 1. Require only unblinded investigators to determine adverse event relationships 2. designate an unblinded study team member to manage the test article/investigational product administration. 3. arrange with the unblinded study pharmacist for appropriate test article/investigational product labeling. 4. Have blinded study personnel program the infusion pump settings. A. 1 & 3 B. 1 & 4 C. 2 & 3 D. 2 & 4

A subject is participating in a clinical trial where only the CRC knows the identity of the study medication. This is considered to be which of the following types of studies? A. Crossover B. Open-label C. Single-blind D. Placebo-controlled

When a subject reports an adverse event, who is responsible for determining its "relationship to study drug"? A. CRC B. CRA C. Investigator D. IRB/IEC

Which of the following is true in relation to informed consent of trial subjects in a pediatric trial of a new analgesic conducted according to ICH-GCP/ A. It can be obtained orally B. it requires two impartial witnesses C. It must be signed by the person obtaining consent D. A written summary should be provided to the subject after he/she has confirmed consent.

C *B is incorrect b/c it is a legally acceptable representative needed not two impartial witnesses*

Which of the following statements accurately reflects ICH-GCP's requirements regarding informed consent process? 1. ICH-GCP does not require that the PI personally obtain the informed consent 2. The IRB/IEC reviewing the research at a particular site should be aware of who will obtain informed consent. 3. A copy of the signed consent document must be provided to the subject. 4. ICH-GCP does not suggest that the case history for each study subject shall document consent was obtained prior to study participation. A. 1, 2 & 3 B. 1, 2 & 4 C. 1, 3 & 4 D. 2, 3 & 4

C Reason: ICH-GCP does not require that the PI personally obtain the informed consent. However, a copy shall be given to the person signing the form. It also states that it should be signed and dated. There is no requirement to document in the case history that informed consent was obtained, although this is often covered by local requirements or policies. Similarly, ICH-GCP does not require information about who is involved in obtaining consent. However, individual countries or states will have IRBs/IECs with their own local requirements and/or procedures in addition to those stipulated in ICH GCP and these may require information about who will be involved in the consent process itself.

A protocol requires that subjects in a hypertension trial have two consecutive sitting diastolic blood pressure readings performed and the average of the two recorded on the CRF. The CRA discovers that only one blood pressure reading is recorded in the source documents, which is the same as the reading recorded in the CRF for the 10 enrolled subjects. Which of the following would the CRC expect the CRA to do FIRST? A. Contac the sponsor's medical monitor to report that the investigator is noncompliant with the protocol. B. Notify the data management department that the CRF entries are incorrect and may need to be queried. C. Ask the investigator if the blood pressure procedure outlined in the protocol is being followed. D. Contact the sponsor's medical monitor to discuss closing the site due to 10 protocol violations.

C Reason: It is reasonable for the CRC to anticipate the CRA asking the investigator for an explanation regarding study procedure in this case. However, as it appears that the site is both noncompliant with the protocol (only one blood pressure check) and documenting the same result in several patient charts, falsification of data would be a legitimate concern of the CRA, who would document the finding in a routine monitoring report and closely watch it further as the study progresses. Following such a discussion with the investigator, the medical monitor may be notified so that the situation could be examined accordingly.

A CRC is reviewing a protocol for a Phase I study. The objective for conducting the study could be to determine the A. Safety and efficacy of chemotherapy "x" versus placebo in alleviating pain in osteoarthritis patients B. Dose of test articles/investigational product in reducing soft tissue inflammation following third molar extraction C. Dose at which caffeine enhances acetylsalicylic acid absorption in normal, healthy volunteers. D. Blood levels of acetaminophen in post-partum patients when taken on an empty stomach versus two hours after meal consumption.

C Reason: Phase I studies are most commonly conducted in normal, healthy volunteers, a unique characteristic of this phase of development. Theoretically, none of the other objectives stated in A, B or D contain characteristics as unique to Phase I and may, in fat, be stated as objectives of studies conducted in later phases of development.

Which of the following is a well-defined clinical study using a placebo to evaluate the treatment group? A. Open-label B. Retrospective C. Controlled D. Active concurrent controlled

C Reason: This question is based on the definition of a controlled clinical trial; however, control groups receiving no treatment or standard treatment (active concurrent control) may also be used. These trials use the randomization process to assign subjects by element of chance to either the treatment of control group (placebo in this scenario), in an effort to remove the potential of bias. In open-label trials, both trial subjects and the investigators know what treatment has been given. Retrospective trials assess results that are already known.

The CRC is preparing the budget for the protocol. The cost of the study is $12,000. The indirect cost rate for the institution is 25%. The total cost of the protocol is A. $12,000 B. $13,500 C. $15,000 D. $15,500

C Reason: To accurately project and cover costs associated w/ the conduct of a study, the site would calculate total cost by multiplying the study cost times the institution's indirect cost ($12,000 x .25 = $3,000) and summing the two for a total study cost to be submitted to the sponsor of $15,000. Failure to factor the indirect cost for the institution into the budget may result in the study being conducted at a loss.

Fatal or life threatening and unexpected adverse drug reactions in clinical investigations should be reported to the regulatory agencies ( check all that apply) A) No later than 7 days after first knowledge of event B) No later than 15 days after first knowledge of event C) By filing a complete report within 8 additional days of the initial notification D) By filing a complete report within 15 additional days of the initial notification

C) By filing a complete report within 8 additional days of the initial notification

In terms of explaining the probability of assignment to trial arms in consent forms, which is true?

CH notes that it should be included, but does not specify how the information should be presented.

a brief account of a person's education, qualifications, and previous occupations, typically sent with a job application

Fill in the blank on the following statement. You are designing a cross-over study. Cross-over designs have a number of problems that can invalidate their results. The chief difficulty concerns __________, that is, the residual influence of treatments in subsequent treatment periods.

Carryover effect

A printed, optical, or electronic document designed to record all of the protocol required information to be reported to the sponsor on each trial subject.

Case Report Form (CRF)

Investigational product dispensing or administration information for the sponsor is recorded on the:

Case report form

is the assessment of relationship between a treatment drug and the occurrence of an adverse event. It is also used to evaluate and to check that the particular treatment is the cause of an observed adverse event or not and also to understand how close is the relationship between treatment drug and event; an evaluation performed by a medical professional regarding the likelihood that a therapy or product being assessed in a clinical trial caused or contributed to an adverse event

Causality assessment

A copy of the original record that has been verified (by dated signature or by generation through a validated process) to have the same information, including data that describe the context, content, and structure of the original.

Certified Copy

* In what situations would changes in inclusion and exclusion criteria be acceptable?

Changes in Inclusion and Exclusion Criteria -should remain constant, as specified in the protocol, throughout the period of subject recruitment

E10

Choice of control group and related issues in clinical trials

ICH E6 has broader requirements than FDA or HHS concerning confidentiality of medical records and access by third parties. If investigators are complying with ICH E6 guideline, they must:

Clearly disclose to subjects in the informed consent form that the monitor, auditor, IRB/IEC, and the regulatory authorities may have access to the subject's medical records

The new ICH E6 integrated addendum (R2) requires sponsors to implement systems to manage quality throughout all stages of the trial process. The system should use a risk-based approach including which of the following?

Clearly disclose to subjects in the informed consent form that the monitor, auditor, IRB/IEC, and the regulatory authorities may have access to the subject's medical records

ICH E6 has broader requirements than FDA or HHS concerning confidentiality of medical records and access by third parties. If investigators are complying with ICH e6 guideline, they must.:

Clearly disclose to subjects in the informed consent form that the monitor, auditor, IRB/IEC, and the regulatory authorities may have access to the subject's medical records.

Open Label Trial

Clinical Trial in which investigators and participants know which intervention is being administered

Endpoint or Outcome

Clinical event, measurable indicator, subject reported response

E11

Clinical investigation of medicinal products in peds population

Studies that are performed to examine the absorption, distribution, metabolism, and excretion of a drug under investigation (investigational drug and approved drug) in healthy volunteers and/or patients. Data obtained from such studies are useful for the design and conduct of subsequent clinical trials.

Clinical pharmacokinetic

E2A

Clinical safety data management : definition and standards for expedited reporting

E2C

Clinical safety data management: Periodic safety update reports for marketed drugs

Clinical study reports

In study related inspections by the FDA, the studies audited are usually:

Closed

An investigational or marketed product, or a placebo, used as reference in a clinical trial.

Comparator

Investigator's Brochure

Compilation of data on an investigational product used in human subjects

In completing Form FDA 1572, Statement of Investigator, the investigator agrees to

Conduct or supervise the investigation personally

In completing Form FDA 1572, Statement of Investigator, the Investigator agrees to:

Conduct or supervise the investigation personally.

Prevention of disclosure, to other than authorized individuals, of a sponsor's proprietary information or of a subject's identity.

Confidentiality

Audit Certificate

Confirmation audit took place

What does CIOC stand for?

Conflict of Interest Committee

can be defined as structural or functional anomalies (for example, metabolic disorders) that occur during intrauterine life and can be identified prenatally, at birth, or sometimes may only be detected later in infancy, such as hearing defects. In simple terms, congenital refers to the existence at or before birth

Congenital anomalies

A written, dated, and signed agreement between two or more involved parties that sets out any arrangements on delegation and distribution or tasks and obligations and, if appropriate, on financial matters.

Contract

A person or organization contracted by the sponsor to preform one or more of a sponsor's trial-related duties and functions.

Contract Research Organization

CRO

Contract Research Organization

an organization hired by a company in the medical field to manage the company's clinical trials and perform other tasks to help bring a drug or device to the market

Contract Research Organization (CRO)

Clinical Trial Agreements (CTAs) are:

Contracts between industry sponsors and research sites

Types of IRB Reviews

Convened board, exempt, or expedited

1.1 elements of a protocol ICH 6

Criteria for the termination of the trial.

Is a special design in which each experimental unit receives a sequence of experimental treatments. In practice, it is not necessary that all permutations of all treatments be used. Researchers also call it switchover design, compared with a parallel group design, in which some experimental units only get a specific treatment and other experimental units get another treatment.

Crossover design

What do you call the clinical trial design in which each subject is randomized to a sequence of two or more treatments and hence acts as his or her own control for treatment comparisons.

Crossover design

A CRA has sent the site a pre-study informational packet in preparation for an upcoming site visit. For the staff to know as much about the history of the drug as possible, they should read the A. Study protocol B. Informed consent C. Investigational plan D. Investigator's brochure

A phase II clinical study is under way at a site for adult-onset diabetes. The known side effects of the study medication include fatigue, dizziness, low blood sugar, nausea & heartburn. A subject calls to report the following signs and symptoms: confusion, sweating and hand tremor. Given this information, the CRC should anticipate the PI will classify these events as: A. mild, unrelated, and not serious B. moderate, unrelated and serious C. severe, probably related and serious D. moderate, possibly related and not serious

A protocol requests a urine specimen for a routine urinalysis. A subject states she is close to the start of her menses for that month. The laboratory report for this subject subsequently indicated increased RBCs with no other abnormalities. Which of the following should the CRC do? A. write NCS on lab report B. Call lab and have sample reanalyzed C. Request the subject to return after she has completed her menses for that month and collect another specimen D. Document that the subject's comment in the course document and report this to the investigator reviewing the results.

A site is conducting a study in which Drug A is being compared to Drug B. The study medication is administered in the hospital and continued after discharge. Peak and trough blood levels are ordered to be drawn each morning while the subject is hospitalized. Upon review of the hospital records, the CRC discovers that five of the 10 subjects enrolled did not have the ordered blood work on the day of discharge. The CRC should: 1. Inform the IRB/IEC immediately 2. record the errors in the source docments 3. note "not done" on the CRF 4. Review the discharge procedures with the staff. A. 1, 2 & 3 B. 1, 2 & 4 C. 1, 3 & 4 D. 2, 3 & 4

An investigator called the sponsor's medical director about a subject who met all entry criteria except one. The sponsor's medical director gave permission to enter the subject. The BEST action for the CRC is to: A. Request an amendment to validate the subject's data B. Retrieve only the safety data for the subject C. review the previously excluded subjects for possible inclusion D. ensure the inclusion exception has been documented.

An investigator conducting a trial with seriously ill patients encounters a subject in a life-threatening situation for which no standard acceptable treatment is available. The investigator believes that the investigational drug may benefit this subject. The subject is unconscious and time is not sufficient to obtain informed consent from a legally authorized representative. The investigator solely determines that the investigational drug is the only means available to possible preserve the subject's life and decides to administer this product according to ICH-GCP provision for emergency use. Which of the following is true in relation to IRB/IEC and its approval (favorable opinion) about this emergency use: A. Under no circumstances can unconscious patients be enrolled without either their consent or that of their legally acceptable representative. B. An independent physician must confirm the need to treat the unconscious patient with the investigational product. C. the investigator is responsible for medical care of trial subjects, so can enroll unconscious patients without prior IRB/IEC approval D. Documented approval from the IRB/IEC is needed for the protocol before unconscious patients can be enrolled

During an arrhythmia study, a sponsor conducts a quality assurance audit at the site. The quality assurance officer notes that the ECG machine has had no documentation of inspection for the past three years. Which of the following is the BEST course of action for the CRC to take? A. Take no action: ECG machines do not require inspection that often B. Ask the PI if there have been any problems with the machine C. Request a replacement machine for the duration of the study D. Schedule and inspection of the machine as soon as possible

Which of the following would normally take place at a pre-study visit? 1. Evaluation of source documents 2. Review of protocol with an IRB/IEC member 3. Assessment of the site's equipment for the study 4. Discussion of the storage for the investigational product A. 1 and 2 B. 1 and 4 C. 2 and 3 D. 3 and 4

D Reason: 1. There can be no evaluation of source documentation at the pre-study visit, because the study has not yet started at the site. 2. Discussions between the CRC and the IRB/IEC are not standard practice. (3 and 4) The purpose of the visit is to decide whether a site is suitable to conduct a study. The criteria are essentially the experience and availability of the investigator and other personnel and the facilities available, including equipment required by the protocol.

The investigator must notify the IRB/IEC of any significant new findings during the course of the study after the A. Investigator has notified all subjects. B. final report is submitted to the sponsor. C. Sponsor submits the final report to the regulatory/competent authority D. information becomes available to the investigator.

D Reason: In accordance with ICH-GCP 3.3.8d, an investigator should notify the IRB/IEC about any information on significant new findings during the course of the study

An outpatient, double-blind, placebo-controlled study is being conducted at the PI's office as well as the subinvestigator's office. The offices are located across town from each other. The sponsor will only allow the test/investigational product to be stored at the PI's office. The BEST rationale for this requirement is to: A. ensure compliance with sponsor's standard operating procedure B. facilitate the monitoring process of the CRA C. limit test article/investigational product manufacturing and shipment costs. D. maintain the randomization of subjects assigned to treatment.

D Reason: the only way to maintain the randomization is to have the test article/investigational product located in one location. * I don't get it*

An adverse event is one which A) Is an unfavorable and unintended sign, symptom or disease B) Is one that is temporary associated with drug regardless of wither it is related or not C) A only D) A and B

D) A and B A) Is an unfavorable and unintended sign, symptom or disease B) Is one that is temporary associated with drug regardless of wither it is related or not

For a drug that is in a Phase IV trial and adverse drug reaction is one which A) Is noxious and unintended B) Occurs at normal doses used for prophylaxis C) A only D) A and B

D) A and B A) Is noxious and unintended B) Occurs at normal doses used for prophylaxis

Adverse drug reactions in the control group should be reported to A) The other manufacturer B) Appropriate regulatory agency C) A only D) A and B

D) A and B A) The other manufacturer B) Appropriate regulatory agency

An adverse reaction occurs in patients after the study has been completed. The appropriate action on the part of the investigator include A) Report the event to the sponsor B) Consider the event for reporting as though it was a study report C) Conduct causality assessment and determination of expectedness prior to expedited reporting D) All of the above

D) All of the above A) Report the event to the sponsor B) Consider the event for reporting as though it was a study report C) Conduct causality assessment and determination of expectedness prior to expedited reporting

Adverse events of marketed drug usually imply A) Multi drug reactions B) Unreliable subjective measures C) Psychosomatic factors D) Causality

D) Causality

A patient in a clinical I trial for joint pain experiences a bronchospasm while at home The event would be A) Not reportable because it occurred in a home setting B) An adverse event which does not require reporting C) An unexpected adverse event which does not require expedited reporting D) May be considered serious and should be considered for expedited reporting

D) May be considered serious and should be considered for expedited reporting

The Code of Federal Regulations at 45 CFR 46 describes the regulation requirements for the protection of human subjects. This regulation require that research involving human participants be subject to oversight by an IRB to ensure that the rights and welfare of research participants are protected.

DDHS Regulations (the Department of Health and Human Services)

1.1 elements of a protocol ICH 6

Data Handling and Record Keeping

What does DSMB stand for?

Data Safety Monitoring Board

An independent group of experts that advises NIDCR. The members of this group serve in an individual capacity and provide their expertise and recommendations.

Data and Safety Monitoring Board (DSMB)

What does DSMP stand for?

Data and Safety Monitoring Plan

What does "DSMB" stand for?

Data and safety monitoring board

Which of the following brought increased public attention to the problems with the IRB system

Death of research subject (Jesse Gelsinger)

One of the primary purposes of a Phase II study is to:

Demonstrate efficacy within the established safe dose range

What does DHHS stand for?

Department of Human and Health Services

1.1 elements of a protocol ICH 6

Description of and justification for the route of administration, dosage, dosage regimen, and treatment period(s).

1.1 elements of a protocol ICH 6

Description of ethical considerations relating to the trial.

1.1 elements of a protocol ICH 6

Description of the population to be studied.

The packaging of investigational drugs should ideally be:

Designed to help with subject compliance

ICH E6 Guidelines provides a harmonized standard for _________ clinical trials involving human subjects

Designing, recording, reporting, and conducting

* Standard Operating Procedures (SOPs)

Detailed, written instructions to achieve uniformity of the performance of a specific function

Standard Operating Procedures (SOPs)

Detailed, written instructions to achieve uniformity of the performance of a specific function.

Coverage Analysis

Determination of which, if any, subject care costs in a clinical trial must be covered by a study sponsor.

Example of how the Principle of Beneficence can be applied to the a study employing human subjects.

Determine that the study has maximized benefits and minimized risks.

Permission to examine, analyze, verify, and reproduce any records and reports that are important to evaluation of a clinical trial.

Direct Access

A 46-year-old man is currently enrolled in a Phase III study of a drug for severe diabetic neuropathy. While the study is ongoing, a new drug becomes commercially available that may have equal or greater benefit to the subject. The investigator should do which of the following?

Discuss the pros and cons of both the investigational drug and the commercially available drug and then allow the subject to decide whether to withdraw from the research to take the new drug.

By regulation, an investigator must keep records relating to:

Disposition of the study drug, case histories, care report forms, and signed ICFs

A subject, who has been 100% compliant thus far, has forgotten to bring her medication back to the clinic for her regular visit. She reports that she has not missed any doses and has been fully compliant with the protocol. What is the most appropriate action for the investigator or clinical research coordinator to take?

Document that the subject has forgotten to return her medication in the source document and ask her to bring the medication back to the clinic as soon as possible or during her next visit

Audit Trail

Documentation of audit events

* Audit Trail

Documentation that allows reconstruction of the course of events

Audit Trail

Documentation that allows reconstruction of the course of events.

* Essential Documents

Documents which individually and collectively permit evaluation of the conduct of a study and the quality of the data produced

Essential Documents

Documents which individually and collectively permit evaluation of the conduct of a study and the quality of the data produced

Dose response

Refers to the subject, investigator, monitor, and sometimes analyst being unaware of the treatment.

Double Blind

Is a technique for retaining the blind when administering supplies in a clinical trial, when the two treatments cannot be made identical. Supplies are prepared for Treatment A (active and indistinguishable placebo) and for Treatment B (active and indistinguishable placebo). A double blind study is a randomized clinical trial in which: You as the patient don't know if you're receiving the experimental treatment, a standard treatment or a placebo

Double dummy

What term is used to describe the biotransformation of pharmaceutical substances in the body so that they can be eliminated more easily. The majority of metabolic processes that involve drugs occur in the liver, as the enzymes that facilitate the reactions are concentrated there.

Drug metabolism

What is an important component of drug accountability?

Drug shipping and disposition records

Which of the following is an important component of drug accountability?

Drug shipping and disposition records

* Who is responsible for ensuring that adequate medical care is provided to a subject for any adverse events?

During and following a subject's participation in a trial, the investigator/institution should ensure that adequate medical care is provided to a subject for any adverse events, including clinically significant laboratory values, related to the trial. The investigator/institution should inform a subject when medical care is needed for intercurrent illness(es) of which the investigator becomes aware

When must the investigator update the IRB about the progress of a trial?

During the conduct of the study and at termination

Efficacy

E1 to E12 , wherein GCP E6

Clinical Safety

E1 to E2E

Guideline for Clinical Investigation of Medicinal Products in the Pediatric Population

E11

Guideline for Definitions and Standards for Expedited Reporting

E2A

Guideline for Good Clinical Practice

E6(R2)

Guideline for General Considerations for Clinical Trials

Guideline for Statistical Principles for Clinical Trials

Is the ability to perform a task to a satisfactory or expected degree. The word comes from the same roots as effectiveness, and it has often been used synonymously, although in pharmacology a distinction is now often made between that word and effectiveness.

Efficacy

21 CFR 11

Electronic Records; Electronic Signatures

The overall goal of monitoring, audits, and inspection activities is to:

Ensure the protection of human research subjects and data integrity

The overall goal of monitoring, audits, and inspection activities is to

Ensure the protection of human research subjects and data integrity.

Accurate reporting of adverse events is most important for

Ensuring subject safety

Accurate reporting of adverse events is most important for:

Ensuring subject safety.

studies that measure the risk of illness or death in an exposed population compared to that risk in an identical, unexposed population (for example, a population the same age, sex, race and social status as the exposed population)

Epidemiological studies

Documents that individually and collectively permit evaluation of the conduct of a study and the quality of the data produced

Essential Documents

* What are essential documents?

Essential Documents are those documents which individually and collectively permit evaluation of the conduct of a trial and the quality of the data produced. These documents serve to demonstrate the compliance of the investigator, sponsor and monitor with the standard of Good Clinical Practice and with all applicable regulatory requirements

E6(R1) 4.9.5

Essential documents should be retained until at least 2 years after the last approval of a marketing application in an ICH region and until there are no pending or contemplated marketing applications in an ICH region or at least 2 years have elapsed since the formal discontinuation of clinical development of the investigational product. These documents should be retained for a longer period however if required by the applicable regulatory requirements or by an agreement with the sponsor. It is the responsibility of the sponsor to inform the investigator/institution as to when these documents no longer need to be retained.

Ethnic factors in the acceptability of foreign clinical data

Factorial Design

Evaluates two or more treatments simultaneously *Drug A *Drug B *Drug A & B *Neither Drug A or B

Which of the following is required at a prestudy site visit?

Evaluation of the site's capacity to conduct the study

Events that should be reported expeditiously

Events that are BOTH serious and unexpected (does not include events that are not study related, non-serious events and serious, but expected events)

Therapeutic Confirmatory Study

Examples: -adequate and well controlled studies to establish efficacy -randomized parallel dose-response studies -clinical safety studies - studies of mortality/morbidity outcomes -large simple trials -comparative studies

Therapeutic Use Study

Examples: -comparative effectiveness studies -studies of mortality/morbidity outcomes -studies of additional endpoints -large simple trials -pharmacoeconomic studies

Therapeutic Exploratory Study

Examples: -earliest trials of relatively short duration in well-defined narrow pt. populations, using surrogate or phamalogical endpoints -does-response exploration studies

Human Pharmacology Study

Examples: -dose tolerance studies -single and multiple does pharmacokinetics and pharmacodynamic studies -drug interaction studies

Language in the consent document through which the subject is made to waive or appear to waive any of his/her legal rights, or releases or appears to release the investigator, the sponsor, the institution, or its agents from liability for negligence.

Exculpatory language

Form FDA 1572, Statement of Investigator, is legally binding between the Investigator and the:

FDA

Form FDA 1572, Statement of Investigator, is legally binding between the investigator and the:

FDA

Form FDA 1572, Statement of the Investigator, is legally binding between the Investigator and the:

FDA

Statement of Investigator

FDA 1572-Must be signed by all investigators participating under the clinical trial under the IND. This is an agreement by the investigator to conduct the study in compliance with FDA regulations

Phase 4 Study

FDA has approved a drug and it is commercially available, but may be necessary to gather more information about product through controlled clinical trial, also known as a post market trial.

Premarket Review

FDA process to evaluate the safety and effectiveness of devices that support or sustain human life, or which present a potential, unreasonable risk of illness or injury

Which trial design is used for the specific purpose of examining the interaction of A and B?

Factorial Design

45 CFR 46 requires Federal Departments and Agencies to rely solely on IRBs to evaluate risks to subjects, protection against these risks, potential benefits of the research and the importance of the knowledge to be gained.

False

A subject in your diabetes research study developed colon cancer, which the Investigator has determined to be unrelated to the study. The subject is currently asymptomatic. This will be considered a serious adverse event because it is life threatening. Is this a true or false statement?

False

T/F: Investigator meetings are a requirement for any multi-center study with six or more sites?

False

T/F: It is a regulatory requirement to have source document for every data item collected on case report forms?

False

T/F: Patient compliance with study drug dosing is a statistical issue, so site personnel do not have to be concerned about it?

False

T/F: The investigator's signature must be on the consent form?

False

True or False? Due to low blood volumes researchers should not do pharmacokinetic studies in the pediatric population.

False

True or False? Pharmacokinetic Phase 1 studies in the pediatric population are generally conducted in healthy pediatric subjects.

False

7 Calendar Days

Fatal or life-threatening, unexpected ADR's occurring in clinical investigations qualify for rapid reporting no later than how many days?

Reporting time frame for events

Fatal/Life threatening unexpected = ASAP; no more than 7 days after event Non fatal/Life threatening = 15 days *ok if not all info is available --> submit what you have

What does FWA stand for?

Federal Wide Assurance (for protection of human subjects)

Observational Study monitoring board (OSMB)

Federal agency within the Department of Health and Human Services (DHHS) charged with the protection of human subjects participating in government funded research. It issues assurances and oversees compliance of regulatory guidelines by research institutions.

GCPs are derived from all the following:

Federal regulations, ethical codes, ICH guidelines, official guidance documents

Is an assurance of compliance with the U.S. federal regulations for the protection of human subjects in research. It is approved by the Office for Human Research Protections (OHRP) for all human subjects research conducted or supported by the U.S. Department of Health and Human Services (HHS).

Federalwide Assurance (FWA)

1.1 elements of a protocol ICH 6

Financing and insurance if not addressed in a separate agreement.

Phase 2 study

Focuses on obtaining evidence of therapeutic efficacy indicating that the molecule has the desired effect. Performed in subjects with specific condition targeted by investigational product.

How long is an investigator required to keep consent documents, IRB correspondence, and research records?

For a minimum of three years after completion of the study

Protocol

Formal document containing details of the study design and all the associated procedures to be followed during the course of the study. Deviations from this can risk subject safety, damage integrity of trial data, and jeopardize regulatory approval of product.

* What is the full analysis set?

Full Analysis Set -the analysis set which is as complete as possible and as close as possible to the intention-to-treat ideal of including all randomized subjects

GCP!!!

General considerations for clinical trials

Good Clinical Practice (GCP)

Abbreviation: "GCP"

Good Clinical Practices

defines quality measures for both production and quality control and defines general measures to ensure that processes necessary for production and testing are clearly defined, validated, reviewed, and documented, and that the personnel, premises and materials are suitable for the production of pharmaceuticals and biologicals including vaccines

Good Manufacturing Practice (GCP)

Coordinating Committee

Group a sponsor comprises to coordinate multi-center trials

What Type of Study is this? Objective of Study • Assess tolerance • Define/describe PK1 and PD2 • Explore drug metabolism and drug interactions • Estimate activity Study Examples • Dose-tolerance studies • Single and multiple dose PK and/or PD studies • Drug interaction studies

Human Pharmacology (Phase I Study)

Phase I Trials

Human Pharmacology; assess safety & tolerability *usually non-therapeutic in nature *may use healthy volunteers unless its cancer *PKs & PDs 15-30 patients Goals: figure out if its safe and best administration Population: normal, healthy adults; if cancer --> end stage

Non-clinical studies refer to studies that do not involve:

Human subjects

What does HDE stand for?

Humanitarian Device Exemption

What does HUD stand for?

Humanitarian Use Device

Statement in a consent form that is an example of exculpatory language?

I waive any possibility of compensation for injuries that I may receive as a result of participation in this research

During the course of a clinical trial the CRC notices that the HCT values have been consistently low in several subjects. Upon further investigation it was discovered that the lab assistant was storing the samples under his desk and sending the entire batch for analysis once every week. The CRC should g) Immediately inform the Pl h) File a protocol deviation with the IRB i) Inform the sponsor j) Arrange to have the lab assistant retrained or disciplined k) Initiate a CAPA plan I) All of the above

I) All of the above g) Immediately inform the Pl h) File a protocol deviation with the IRB i) Inform the sponsor j) Arrange to have the lab assistant retrained or disciplined k) Initiate a CAPA plan

What ICH Guideline is this? Clinical Investigation of Pediatric Population The guidance provides an outline of critical issues in pediatric drug development and approaches to the safe, efficient, and ethical study of medicinal products in the pediatric population.

ICH E11

Which ICH Guidance pertains to the Pediatric Population?

ICH E11

What ICH Guideline is this? Clinical safety data management: definitions and standards for expedited reporting Keywords: Clinical development, clinical safety reporting, expedited reports, adverse drug reaction (ADR) This document aims to develop standard definitions and terminology for key aspects of clinical safety reporting. IT also provides guidance on the appropriate mechanism for handling expedited (rapid) reporting, in the investigational (i.e. pre-approval) phase. Clinical Safety Data Management - a document which describes the sponsor's responsibilities pertaining to safety and reporting AEs (Adverse Events)

ICH E2A

What ICH Guideline is this? Guideline for good clinical practice - falls under the "efficacy" category. It pertains specifically to the conduct of clinical research to support marketing applications for drugs. "discusses approaches to clinical trial design, conduct, oversight, recording, and reporting as well as updated standards regarding electronic records and essential documents."

ICH E6

"discusses approaches to clinical trial design, conduct, oversight, recording, and reporting as well as updated standards regarding electronic records and essential documents."

ICH E6(R2) The International Conference on Harmonisation's (ICH) Guideline for Good Clinical Practice (GCP; document E6) is currently being revised. The FDA published the new version, which will be called E6 (R2), as a draft document in the Federal Register in June 2015 E6(R2)Good Clinical Practice (GCP) The first version of the ICH E6 Good Clinical Practice (GCP) Guideline was finalised in 1996 describing the responsibilities and expectations of all participants in the conduct of clinical trials, including investigators, monitors, sponsors and IRBs.

What ICH Guideline is this? General considerations for clinical studies This document sets out the general scientific principles for the conduct, performance and control of clinical trials. ... The Guideline addresses a wide range of subjects in the design and execution of clinical trials.

ICH E8

What ICH Guideline is this? Statistical Principles for Clinical Trials This document provides guidance on the design, conduct, analysis and evaluation of clinical trials of an investigational product in the context of its overall clinical development. ... It presents a structured framework for clinical trial planning, conduct, data collection and interpretation of data analyses.

ICH E9

What ICH Guideline on Good Clinical Practice is this? The principles and practices concerning protection of trial subjects in which are stated. These principles have their origins in The Declaration of Helsinki and should be observed in the conduct of all human drug investigations.

ICH Guideline on Good Clinical Practice (ICH E6).

Before any clinical trial is carried out, results of non-clinical investigations or previous human studies should be sufficient to indicate that the drug is acceptably safe for the proposed investigation in humans. The purpose and timing of animal pharmacology and toxicology studies intended to support studies of a given duration are discussed in ICH M3. The role of such studies for biotechnology products is cited in in which ICH Guideline and GoodClinical Practice?

ICH S6

In terms of explaining the probability of assignment to trial arms in consent forms, what are the specification about how it must be stated?

ICH notes that it should be included, but does not specify how the information should be presented.

In terms of explaining the probability of assignment to trial arms in consent forms, which is true?

ICH notes that it should be included, but does not specify how the information should be presented.

When the sponsor-investigator holds the IND for an investigational drug he or she is responsible for annual reporting of which one of the following to FDA?

IND Report

ICH E6 Section 5.1 requires the investigator to obtain a statement from who to show compliance with ICH?

IRB

An institutional review board, also known as an independent ethics committee, ethical review board, or research ethics board, is a type of committee that applies research ethics by reviewing the methods proposed for research to ensure that they are ethical. Under FDA regulations, that is group that has been formally designated to review and monitor biomedical research involving human subjects. In accordance with FDA regulations, this group has the authority to approve, require modifications in (to secure approval), or disapprove research.

IRB (Institutional Review Board)

The affirmative decision of the IRB that the clinical trial has been reviewed and may be conducted at the institution site within the constraints set forth by the IRB, the institution, GCP, and the applicable regulatory requirements.

IRB Approval

Which of the following should take place during periodic site visits?

Identification of protocol violations

Identification of study risks to determine which may safely be omitted from continual monitoring.

The new ICH E6(R2) integrated addendum requires sponsors to implement systems to manage quality throughout all stages of the trial process. The system should use a risk-based approach including which of the following?

Identification of study risks to determine which may safely be omitted from continual monitoring.

E6(R1) 5.5.4

If data are transformed during processing, it should always be possible to compare the original data and observations with the processed data

E6(R1) 5.8.1

If required by the applicable regulatory requirement(s), the sponsor should provide insurance or should indemnify the investigator/ the institution against claims arising fro the trial, except for claims that arise from malpractice and/or negligence

E6(R1) 5.13.5

If significant formulation changes are made in the investigational or comparator product(s) during the course of clinical development, the results of any additional studies of the formulated product(s) needed to assess whether these changes would significantly alter the pharmacokinetic profile of the product should be available prior to the use of the new formulation in clinical trials

E6(R1) 5.11.2

If the IRB/IEC conditions its approval/favorable opinion upon change(s) in any aspect of the trial, such as modification(s) of the protocol, written informed consent form and any other written information to be provided to subjects, and/or other procedures, the sponsor should obtain from the investigator/institution a copy of the modification(s) made and the date approval/favorable opinion was given bytes IRB/IEC

E6(R1) 4.12.3

If the IRB/IEC terminates or suspends its approval/favorable opinion of a trial, the investigator should inform the institution where applicable and the investigator/institution should promptly notify the sponsor and provide the sponsor with a detailed written explanation of the termination or suspension.

E6(R1) 4.12.1

If the investigator terminates or suspends a trial without prior agreement of the sponsor, the investigator should inform the institution where applicable, and the investigator/institution should promptly inform the sponsor and the IRB/IEC, and should provide the sponsor and the IRB/IEC a detailed written explanation of the termination or suspension

E6(R1) 5.5.8

If the sponsor discontinues the clinical development of an investigational product, the sponsor should maintain all sponsor-specific essential documents for at least 2 years after formal discontinuation or in conformance with the applicable regulatory requirement(s)

E6(R1) 4.12.2

If the sponsor terminates or suspends a trial, the investigator should promptly inform the institutions where applicable and the investigator/institution should promptly inform the IRB/IEC and provide the IRB/IEC a detailed written explanation of the termination or suspension

E6(R1) 4.12--Premature Termination or Suspension of a Trial

If the trial is prematurely terminated or suspended for any reason, the investigator/institution should promptly inform the trial subjects, should assure appropriate therapy and follow-up for the subjects, and where required by the applicable regulatory requirement(s), should inform the regulatory authority(ies)

When to submit SAE to sponsor?

Immediately (usually within 24 hours)

A person, who is independent of the trial, who cannot be unfairly influenced by people involved with the trial, who attend the informed consent process if the subject's or the subject's legally acceptable representative cannot read, and who reads the informed consent form and any other written information supplied to the subject

Impartial Witness

E6(R1) 5.13.4

In blinded trials, the coding system for the investigational product(s) should include a mechanism that permits rapid identification of the product(s) should include a mechanism that permits rapid identification of the product(s) in case of a medical emergency, but does not permit undetectable breaks of the blinding

E6(R1) 4.8.15

In emergency situations, when prior consent of the subject is not possible, the consent of the subject's legally acceptable representative, if present, should be requested. When prior consent of the subject is not possible, and the subject's legally acceptable representative is not available, enrollment of the subject should require measures described in the protocol and/or elsewhere, with documented approval/favorable opinion by the IRB/IEC, to protect the rights, safety and well-being of the subject and to ensure compliance with applicable regulatory requirements. The subject or the subject's legally acceptable representative should be informed about the trial as soon as possible and consent to continue and other consent as appropriate should be requested

E6(R1) 4.8.1

In obtaining and documenting informed consent, the investigator should comply with the applicable regulatory requirement(s), and should adhere to GCP and to the ethical principles that have their origin in the Declaration of Helsinki. Prior to the beginning of the trial, the investigator should have the IRB/IEC's written approval/favorable opinion of the written informed consent form and any other written information to be provided to subjects.

Adverse Drug Reaction (ADR)

In the pre-approval clinical experience with a new medicinal product or its new usages, particularly as the therapeutic dose(s) may not be established: all noxious and unintended responses to a medicinal product related to any dose should be considered adverse drug reactions.

Where is information on storage requirements for the investigational product usually found?

In the study protocol

Placebo

Inactive substance that looks the same as, and is administered in the same way as , a drug in a clinical trial.

Post Award Process

Includes establishing an account, purchasing equipment and supplies, controlling expenses to ensure compliance with the grant or contract terms, reallocations of funds, cost sharing, effort reporting, financial reporting to study sponsor and closeout activities

Necessary controls in Clinical trials

Inclusion/ exclusion criteria(identify target), randomization(avoid bias), Blinding(avoid observation bias), Primary and secondary endpoints(prove hypothesis)

Any amendment that _____________ must be approved by the IRB prior to implementation

Increases the risks to subjects

IDMC

Independent Data Monitoring Committee, Data & Safety Monitoring Board (DSMB), Data Monitoring Committee: Oversee safety & progress; make recommendations to continue, modify or stop

An independent body constituted of medical professionals of non-medical members, whose responsibility is to ensure the protection of the rights, safety, and well-being of human subjects involved in a trial and to provide public assurance of that protection, by reviewing and approving favorable opinion on the trial protocol, the suitability of the investigator facilities, and the methods and materials to be used in obtaining and documenting ICF of subjects.

Independent Ethics Committee

IEC

Independent Ethics Committee; group who oversees protection, rights, safety & well-being of human subjects

* What is the purpose of an audit?

Independent of and separate from routine monitoring or quality control functions, should be to evaluate trial conduct and compliance with the protocol, sops, GCP, and the applicable regulatory requirements

The cost of renting additional clinic space for clinical research is an example of:

Indirect Costs

Vulnerable Subjects

Individuals whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate.

* Vulnerable Subject

Individuals whose willingness to volunteer in a clinical trial may be unduly influenced by... - Expectation of participation - Benefits associated with participation - Fear of a retaliatory response

The principle of informed consent as described in the Belmont Report has three parts. List these three parts.

Information, comprehension, and voluntariness

What describes the principle of informed consent as described by the Belmont Report.

Information, comprehension, voluntariness

The process by which a subject voluntarily confirms his or her willingness to participate in a clinical trial is known as:

Informed Consent

The process by which a subject voluntarily confirms his or her willingness to participate in a clinical trial is best described as which of the following options?

Informed Consent Process

Study sponsor

Initiator of clinical investigation, overseeing entire process, develops regulatory strategies, funding source, and manages interactions with regulatory authorities.

An independent body constituted of medical, scientific, and non-scientific members, whose responsibility is to ensure the protection of the rights, safety, and well-being of human subjects involved in the trial.

Institutional Review Board

* What is interim analysis?

Interim Analysis and Early Stopping -an analysis intended to compare treatment arms with respect to efficacy or safety at any time prior to formal completion of a trial

ICH

International Conference on Harmonization

What document makes recommendations on information that should be included in a core clinical study report of an individual study of any therapeutic, prophylactic, or diagnostic agent conducted in human subjects.

International Conference on Harmonization (ICH)

E6(R1) 7.3.3

Introduction -- A brief introductory statement should be provided that contains the chemical name of the investigational products, all active ingredients, the investigational products pharmacological class and its expected position within their class, the rationale for performing research with the investigational products, and the anticipated prophylactic, therapeutic, or diagnostic indications. Finally, the introductory statement should provide the general approach to be followed in evaluating the investigational product

What does IDE stand for?

Investigation Device Exemption

What does IND stand for?

Investigational New Drug

A pharmaceutical form of an active ingredient or placebo being tested or used as reference in a clinical trial

Investigational Product

The FDA is the regulatory agency in the US that oversees the approval process for drugs, biologics, and medical devices. What form needs to be submitted to the FDA before starting a clinical trial with unapproved drug?

Investigational new Drug (IND)

A person responsible for the conduct of the clinical trial at a trial site. If a trial is conducted by a team of individuals at the site, the investigator is the responsible leader. Also called PI

Investigator

According to ICH-GCP, who has the responsibility for creating the subject identification code list?

Investigator

Who has ultimate responsibility for an investigational product?

Investigator

What financial considerations should be included in developing a budget for a pharmaceutical company sponsored study?

Investigator oversight, study specific procedures and exams, training, pharmacy, site overhead, subject stipends, data collection, AE and SAE handling, monitoring visits, regulatory an IRB prep, and other activities associated with the study.

A compilation of the clinical and non-clinical data on the investigational product(s) which is relevant to the study of the investigational product(s) in human subjects.

Investigator's Brochure

In drug development, this comprehensive document summarizing the body of information about an investigational product ("IP" or "study drug") obtained during a drug trial. This document is a document of critical importance throughout the drug development process and is updated with new information as it becomes available.

Investigator's Brochure (IB)

In drug development, what is a comprehensive document summarizing the body of information about an investigational product ("IP" or "study drug") obtained during a drug trial. It is a document of critical importance throughout the drug development process and is updated with new information as it becomes available.

Investigator's Brochure (IB)

ICH E6 describes standards that apply to:

Investigators, sponsors, and IRBs

The ICH E6 GCP describes standards that apply to:

Investigators, sponsors, and IRBs.

Radiation Safety Committee review is required for studies that:

Involve investigational imaging studies and studies that are not clinically indicated

Institutional Biosafety Committees (IBCs) are always responsible for review of research:

Involving recombinant or synthetic nucleic acids regardless of funding

Advocate

Is a witness assigned as a monitor to attest to consenting process

The Belmont Report is significant because:

It articulated ethical principles that formed the basis for the HHS Human Subjects Regulations.

What is the legal status of ICH in U.S.?

It is a FDA guidance

What is the status of ICH in the U.S?

It is a FDA guidance

What did Henry Beecher's article about Ethics and Clinical research demonstrate?

It showed that unethical research was not confined to the Nazis atrocities.

Comparator

Item used as an active control references in a clinical trail

What is the status of ICH in U.S.?

Its an FDA guidance

1.2 elements of an Investigational Brochure (IB) and/or investigational device use (instructions for use, user manual) ICH 7

Its purpose is to provide the investigators and others involved in the trial with the information to facilitate their understanding of the rationale for, and their compliance with, many key features of the protocol, such as the dose, dose frequency/interval, methods of administration: and safety monitoring procedures.

The two main aspects of a study that will be looked at by the FDA during an inspection are:

Just starting to enroll

In order to document the delegation of study related tasks, the PI should:

Keep a signed and dated delegation log that describes the delegated tasks, identifies that study staff have received training that qualifies them to perform the tasks, and documents dates of involvement in the study.

Clinical Trial Agreement (CTA)

Legal contract between the clinical site, investigator and sponsor. Regulatory, financial and ethical implications will be included.

Any individual or juridical or other body authorized under applicable law to consent, on behalf of a prospective subject, to the subject's participation in the trial.

Legally Acceptable Representative

LFTs

Liver Function Tests Total Protein Albumin Bilirubin ALP (Alk Phos) AST/ALT

Multidisciplinary

M1, M2, M4

E2B

Maintenance of clinical safety data management

1.1 elements of a protocol ICH 6

Maintenance of trial treatment randomization codes and procedures for breaking codes.

* What is the role of the Independent Data Monitoring Committee (IDMC)

May be established by the sponsor to assess at intervals the progress of a clinical trial, safety data, and critical efficacy variables and recommend to the sponsor whether to continue, modify or terminate a trial

1.1 elements of a protocol ICH 6

Medication(s)/treatment(s) permitted (including rescue medication) and not permitted before and/or during the trial.

As per ICH E6 GCP, which groups of potential subjects could be defined as "vulnerable subjects"?

Members of armed forces, patients with incurable diseases, persons in nursing homes

1.1 elements of a protocol ICH 6

Methods and timing for assessing, recording, and analysing of efficacy parameters.

What is the medicinal product dosing in the pediatric population usually based on when developing a pediatric heart disease study involving an adult approved drug?

Milligram (mg)/kilogram (kg) body weight

A primary purpose of the ICH is to:

Minimize the need for redundant research

The primary purpose of the ICH is to:

Minimize the need for redundant research

A primary purpose of the ICH is to:

Minimize the need for redundant rsearch

Who is ultimately responsible for Source Data Verification or SDV?

Monitor

The act of overseeing the progress of a clinical trial, and of ensuring that it is conducted, recorded, and reported in accordance with the protocol, SOP, GCP, and the applicable regulatory requirements.

Monitoring

Any proposed advertising for the study:

Must be submitted to the IRB and approved before it can be used

1.1 elements of a protocol ICH 6

Name and address of the sponsor and monitor (if other than the sponsor).

1.1 elements of a protocol ICH 6

Name and description of the investigational product(s).

1.1 elements of a protocol ICH 6

Name and title of the investigator(s) who is (are) responsible for conducting the trial, and the address and telephone number(s) of the trial site(s).

1.1 elements of a protocol ICH 6

Name and title of the person(s) authorized to sign the protocol and the protocol amendment(s) for the sponsor.

1.1 elements of a protocol ICH 6

Name(s) and address(es) of the clinical laboratory(ies) and other medical and/or technical department(s) and/or institutions involved in the trial.

1.1 elements of a protocol ICH 6

Name, title, address, and telephone number(s) of the qualified physician (or dentist, if applicable), who is responsible for all trial-site related medical (or dental) decisions (if other than investigator).

1.1 elements of a protocol ICH 6

Name, title, address, and telephone number(s) of the sponsor's medical expert (or dentist when appropriate) for the trial.

is the federal government's lead agency for scientific research on dental, oral, and craniofacial health and disease.

National Institute of Dental and Craniofacial Research (NIDCR) Scientific Director

Double-blind randomized trial

Neither study staff, nor the subject know the assignment until study is completed

An informed consent form is changed to reflect an additional interim visit at month 6. Current subjects have completed the month 8 visit. Which subjects should sign the new consent document?

New subjects

Does the PI need to notify sponsor of administrative changes to protocol, ICF, etc

The terms "serious" and "severe" are synonymous according to ICH?

a study that may include studies using human materials derived from clinical trials (such as primary, metastatic, or circulating tumor cells), normal tissue, blood and any of its components). This defined term shall be limited to studies under this CRADA

Non-Clinical Studies

Trials are ones which do not provide a treatment to patients, but instead study important factors which help advance the understanding of cancer and its impact. For example, of those studies collect tissue specimens to examine the cellular structure of a cancer tumor.

Non-therapeutic trials

Biomedical studies not performed on human subjects

Nonclinical Study

E6(R1) 8.3.16 -- Notification by Originating Investigator to Sponsor of Serious Adverse Events and Related Reports

Notification by originating investigator to sponsor of serious adverse events and related reports in accordance with 4.11 LOCATION: -Investigator/Institution -Sponsor

E6(R1) 8.3.17 -- Notification by Sponsor and/or Investigator, Where Applicable, to Regulatory Authorities and IRB/IECs of Unexpected Serious Adverse Drug Reactions and of Other Safety Information

Notification by sponsor and/or investigator where applicable, to regulatory authorities and IRB/IECs of unexpected serious adverse drug reactions in accordance with 5.17 and 4.11.1 and of other safety information in accordance with 5.16.2 and 4.11.2 LOCATION: -Investigator/Institution -where required -Sponsor

* What variables should go in to sample size calculation?

Number of Subjects - Condition in question - Study objectives - Study endpoints

Basic elements of a protocol

Objectives, scientific background, Trial design, Selection and enrollment of subjects, procedure and research events, management of AEs, Statistical considerations, Data collection and recordkeeping, Quality control, assurance of safety of patients is protected.

IRB continuing review of a greater than minimal risk approved protocol that is currently enrolling subjects must:

Occur at least annually.

What does OHRP stand for?

Office for Human Research Protection

What is OHRP and what is their main purpose?

Office of Human Research Protections. It oversees the safety of participants in federally funded research

Financial disclosure applies to:

Only the people listed on the 1572

Source Documents

Original documents, data, and records (e.g., hospital records, clinical and office charts, laboratory notes, memoranda, subjects' diaries or evaluation checklists, pharmacy dispensing records, recorded data from automated instruments, copies or transcriptions certified after verification as being accurate copies, microfiches, photographic negatives, microfilm or magnetic media, x-rays, subject files, and records kept at the pharmacy, at the laboratories and at medico-technical departments involved in the clinical trial).

* Source Documents

Original documents, data, and records.

US Public Health Service

PHS

A subject presents to the emergency department (ED) with complaints of chest pain and shortness of breath. Blood studies are positive for a heart attack and the subject is hospitalized. The subject has a history of coronary artery disease. The subject reports to the ED nurse that he is currently enrolled in a Phase I study of a new lipid lowering agent. Which individual should determine causality of the serious adverse event?

Ascertaining that the subject has understood the information presented in the informed consent form is the responsibility of:

Overall responsibly for personally conducting or supervising the conduct of human subjects research and for protecting the rights, safety, and welfare of the subjects enrolled in the research lies with the:

Who is ultimately responsible for staff training?

Termination Vortex

PI -----> Subjects Below is a triangle of communication - two way streets with all parties PI <------> Sponsor PI <-----> IRB IRB <------>Sponsor

Who reports AEs & SAEs / to whom & in what order?

PI to 1. sponsor and then 2. IRB

Who reports change of risks to subjects & to whom?

PI to sponsor & IRB & site

If unblinding occurs who reports & to whom?

PI to sponsor only

Who has responsibility for investigational product accountability?

PI/Site

"A design in which subjects are randomized to one of two or more arms, each arm being allocated a different treatment" is a description of what kind of trial design?

Parallel group design

The FDA considers advertising for study subjects to be:

Part of the consent process

At which study visits can the site expect the sponsor to review subjects' signed informed consent forms?

Periodic and termination site visits

Which of the following best describes when the majority of case report form (CRF) data are verified against source record information?

Periodic site visits

* Direct Access

Permission to examine, analyze, verify, and reproduce any records and reports that are important to evaluation of a clinical trial

Direct Access

Permission to examine, analyze, verify, and reproduce any records and reports that are important to evaluation of a clinical trial.

The Belmont Report's principle of respect for persons incorporates at least two ethical convictions: first, that individuals should be treated as autonomous agents, and second, that:

Persons with diminished autonomy are entitled to protection.

the science of measuring costs and outcomes associated with the use of pharmaceuticals in health-care delivery. Its objective is to improve public health through rational decision making when selecting among alternative therapies, e.g., for formularies and their impact on costs and outcomes

Pharmacoeconomics

Characterisation of a drug's absorption, distribution, metabolism, and excretion that continues throughout the development plan is defined as what?

Pharmacokinetics

E8 3.1.1.2

Pharmacological and Pharmacokinetic Studies -- includes information such as: a) pharmacological basis of principal effects b) dose-response or concentration-response relationships and duration of action c) study of the potential clinical routes of administration d) systemic general pharmacology, including pharmacological effects on major organ systems and physiological responses e) studies of absorption, distribution, metabolism and excretion

E2E

Pharmacovigilance planning

The type of study that investigates human pharmacology and is the initial administration of the investigational new drug in humans.

Phase 1

New Drug Application (NDA)

Phase 1-3 clinical trials prove drug is effective and safe, this application is submitted to the FDA.

The main goal of which phase of drug development is to explore therapeutic efficacy in patients? It is important during this phase to determine the dose and regimens that will be used for later trials.

Phase 2

Adults with more than a twelve (12)-month history of migraines were assigned randomly in a double-blinded study to receive treatment with experimental drug X (10 or 20 mg/day) or placebo. The primary efficacy measure was the reduction in severity of the migraine attacks. Enrollment was twelve-hundred (1200) subjects. Which of the following best describes the clinical phase of this study?

Phase 3

Which phase of clinical research has a primary objective to demonstrate or confirm therapeutic benefit?

Phase 3

Which phase of clinical research is often called "Therapeutic Use". It begins after drug approval.

Phase 4

In which development phase might normal, healthy volunteers be given a new drug?

Phase I

Pharmacokinetics and pharmacodynamics of a new formulation of an investigational drug most likely refers to which clinical phase of a study in humans?

Phase I

What clinical trial phase is that you could be one of the first people to get the new drug or treatment. That clinical trial last several months to a year. They usually have 10 to 30 volunteers. The treatment might help the cancer. Dose-ranging on healthy volunteers for safety Often subtherapeutic, but with ascending doses 20-100 normal healthy volunteers (or cancer patients for cancer drugs) Determines whether drug is safe to check for efficacy. Human Pharmacology: • Assess tolerance, Define/describe PK1and PD2, Explore drug metabolism and drug interactions, Estimate activity Dose-tolerance studies, Single and multiple dose PK and/or PD studies, Drug interaction studies

Phase I Study

The first randomized, controlled study of an experimental drug versus aspirin for postoperative pain control will enroll 55 subjects in each arm. Which of the following best describes the clinical phase of this study?

Phase II

Usually enrolls a limited number of patients in a controlled study to determine a drug's short term risks (safety) at the optimal drug dose established in a Phase 1 trial.

Phase II Trial

Adults with more than a 12-month history of migraines were assigned randomly in a double-blinded study to receive treatment with experimental drug X (10 or 20 mg/day) or placebo. The primary efficacy measure was the reduction in severity of the migraine attacks. Enrollment was 1200 subjects. Which of the following best describes the clinical phase of this study?

Phase III

Large multi-center studies are usually done in which phase?

Phase III

* What is a Phase III trial and what type of studies are typically seen in this phase? Why are they important?

Phase III (Most typical kind of study: Therapeutic Confirmatory) - Primary objective is to demonstrate, or confirm therapeutic benefit - Intended to provide an adequate basis for marketing approval - Further explore the dose-response relationship or explore the drug's use in wider populations, in different stages of disease, or in combination with another drug - Complete the information needed to support adequate instructions for use of the drug

Testing of drug on participants to assess efficacy and side effects Therapeutic dose 100-300 participants with a specific disease Determines whether drug can have any efficacy; at this point, the drug is not presumed to have any therapeutic effect Therapeutic Exploratory: • Explore use for the targeted indication, Estimate dosage for subsequent studies, Provide basis for confirmatory study design, endpoints, methodologies • Earliest trials of relatively short duration in well- defined narrow patient populations, using surrogate or pharmacological endpoints or clinical measures, Dose-response exploration studies

Phase III Study

Testing of drug on participants to assess efficacy, effectiveness and safety Therapeutic dose Clinical researcher and personal physician300-3,000 people with a specific disease Determines a drug's therapeutic effect; at this point, the drug is presumed to have some effect Therapeutic Confirmatory: • Demonstrate/confirm efficacy, Establish safety profile, Provide an adequate basis for assessing the benefit/risk relationship to support licensing, Establish dose-response relationship • Adequate, and well controlled studies to establish efficacy, Randomised parallel dose response studies, Clinical safety studies, Studies of mortality/ morbidity outcomes, Large simple trials, Comparative studies

Phase III Study

Phase III trials usually include from several hundred to several thousand subjects determining the drug's effectiveness.

Phase III Trial

What phase study looks at drugs that have already been approved by the FDA. The drugs are available for doctors to prescribe for patients, but this study might still be needed to answer important questions. These studies may involve thousands of people.

Phase IV

* What is a Phase IV trial and what type of studies are typically seen in this phase? Why are they important?

Phase IV (Variety of Studies: Therapeutic Use) - Begins after drug approval - All studies performed after drug approval and related to the approved indication - Important for optimizing the drug's use

looks at drugs that have already been approved by the FDA. The drugs are available for doctors to prescribe for patients, but this phase in the studies might still be needed to answer important questions. These studies may involve thousands of people. Post marketing surveillance in public Therapeutic dose Personal physician Anyone seeking treatment from a physician Monitor long-term effects Therapeutic Use: • Refine understanding of benefit/risk relationship in general or special populations and/or environments, Identify less common adverse reactions, Refine dosing recommendation • Comparative effectiveness studies, Studies of mortality/morbidity outcomes, Studies of additional endpoints, Large simple trials, Pharmacoeconomic studies

Phase IV Study

E6(R1) 7.3.4

Physical, Chemical, and Pharmaceutical Properties and Formulation -- A description should be provided of the investigational product substances , and a brief summary should be given of the relevant physical, chemical, and pharmaceutical properties. To permit appropriate safety measures to be taken in the course of the trial, a description of the formulations to be used, including excipients, should be provided and justified if clinically relevant. Instructions for the storage and handling of the dosage forms should also be given. Any structural similarities to other known compounds should be mentioned

Preliminary studies that are small-scaled which aim to investigate whether crucial components of a main study - usually a randomized controlled trial (RCT) - will be feasible. The reporting of these studies must be of high quality to allow readers to interpret the results and implications correctly.

Pilot studies

A quality assurance program should include:

Policies and procedures, training, audits, and corrective action plans

What are the three ways to minimize the number of samples obtained from each pediatric patient?

Population PK, sparse sampling, use of indwelling catheters

E2D

Post approval safety data management

What does PMA stand for?

Pre-Market Approval

Long-term toxicology of an experimental drug in animals most likely refers to which part of drug development?

Pre-clinical

Long term toxicology of an experimental drug in animals most likely refers to which part of drug development?

Preclinical

For Phase I new drug study in humans, what is the primary source of the data included in the initial Investigator's Brochure?

Preclinical Data

For a Phase I new drug study in humans, what is the primary source of the data included in the initial Investigator's Brochure?

Preclinical Data

For a phase I new drug study in humans, what is the primary source of the data included in the initial Investigator's Brochure?

Preclinical data

Which monitoring visit would not include an inventory of investigational agents?

Prestudy site visit

* Confidentiality

Prevention of disclosure, to other than authorized individuals, of a sponsor's proprietary information or of a subject's identity.

Confidentiality

Prevention of disclosure, to other than authorized individuals, of a sponsor's proprietary information or of a subject's identity.

* What is a primary variable?

Primary and Secondary Variables -the primary variable should be the variable capable of providing the most clinically relevant and convincing evidence directly related to the primary variable -should be specified in the protocol, along with the rationale for its selection

Which variable in a study should be used to determine the sample size?

Primary variable

Principal Investigator

A subject presents to the emergency department (ED) with complaints of chest pain and shortness of breath. Blood studies are positive for a heart attack and the subject is hospitalized. The subject has a history of coronary artery disease. The subject reports to the ED nurse that he is currently enrolled in a phase I study of a new lipid lowering agent. Which individual should determine causality of the serious adverse event?

Principal Investigator

E12A

Principles for clinical evaluation of new antihypertensives

Which of the following is not a special population mentioned in ICH E8?

Prisoners

The use of prisoners in research is a concern under the Belmont principle of Justice because:

Prisoners may be used to conduct research that only benefits the larger society

1.1 elements of a protocol ICH 6

Procedure for accounting for missing, unused, and spurious data.

1.1 elements of a protocol ICH 6

Procedures for eliciting reports of and for recording and reporting adverse event and intercurrent illnesses.

1.1 elements of a protocol ICH 6

Procedures for monitoring subject compliance.

1.1 elements of a protocol ICH 6

Procedures for reporting any deviation(s) from the original statistical plan (any deviation(s) from the original statistical plan should be described and justified in protocol and/or in the final report, as appropriate).

E6(R1) 6.9.6

Procedures for reporting any deviations from the original statistical plan (any deviations from the original statistical plan should be described and justified in protocol and/or in the final report as appropriate

If a sponsor's attempts to secure compliance have failed, and the monitoring/auditing identifies serious and/or persistent noncompliance on the part of an investigator or institution, the sponsor should implement which of the following actions?

Promptly notify regulatory authority(ies), terminate the investigator's/institution's participation in the trial

Primary purpose of a Certificate of Confidentiality (COC) is to:

Protect identifiable research information from forced disclosure

The purpose of an IRB is to:

Protect the rights and welfare of human subjects of research.

OHRP is an oversight body primarily concerned with

Protection of human research subjects

OHRP is an oversight body primarily concerned with:

Protection of human research subjects

A document that describes the objective(s), design, methodology, statistical considerations, and organization of a trial.

Protocol

A written description of a change(s) to or formal clarification of a protocol

Protocol Amendment

1.1 elements of a protocol ICH 6

Protocol title, protocol identifying number, and date. Any amendment(s) should also bear the amendment number(s) and date(s).

Medicare Clinical Trials Policy (CTP)

Provides Medicare coverage for Routine costs or qualifying clinical trials when the routine costs are otherwise billable to Medicare outside of a clinical trial.

Office for Human Research Protections (OHRP)

Provides leadership in the protection of the rights, welfare, and well-being of subjects involved in research conducted or supported by the US Department of Health and Human Services (HHS). Ensure this by providing clarification and guidance, developing educational programs and materials, maintaining regulatory oversight, and providing advice on ethical and regulatory issues in biomedical and social-behavioral research

1.1 elements of a protocol ICH 6

Publication policy, if not addressed in a separate agreement.

Quality

Q1 to Q6

means relating to, measuring, or measured by the quality of something rather than its quantity

Qualitative

All those planned and systematic actions that are established to ensure that the trial is performed and the data are generated, documented, and reported in compliance with GCP and o requirements.

Quality Assurance

1.1 elements of a protocol ICH 6

Quality Control and Quality Assurance

E8 3.1.2

Quality of Investigational medicinal Products -- formulations used in clinical trials should be well characterized, including information on bioavailability wherever feasible

Which of the following choices "Introduces a deliberate element of chance into the assignment of treatments to subjects in a clinical trial"?

Randomization

Study Designs

Randomized, controlled, double blind, Observational, Retrospective, Historical

Gold standard of Study Design

Randomized, controlled, double-blind

One of the most difficult aspects of conducting clinical trials is:

Recruiting sufficient subjects

The pediatric population represents a vulnerable subgroup. Therefore, special measures are needed to protect the rights of pediatric study participants and to shield them from undue risk. Which of the following should be taken into consideration?

Recruitment, Consent and Assent, Minimizing Risk, Minimizing Distress

1.1 elements of a protocol ICH 6

References to literature and data that are relevant to the trial, and that provide background for the trial.

A subject of research is involved in a motor vehicle crash. The subject sustained a broken wrist and mild concussion. The subject was treated and released from the emergency department. What should be done after learning of the crash?

Report AEs of the broken wrist and mild concussion.

A subject is a passenger in a car involved in a motor vehicle crash. The subject sustained a broken wrist and mild concussion. The subject was treated and released from the emergency department. What should the investigator do when learning of the crash?

Report adverse events of both a broken wrist and a mild concussion.

A subject of a research study is a passenger in a car involved in a motor vehicle crash. The subject sustained a broken wrist and mild concussion. The subject was treated and released from the emergency department. What should the investigator do when learning of the crash?

Report adverse events of both a broken wrist and a mild concussion.

A subject in a clinical research trial experiences a serious, unanticipated adverse drug experience. How should the investigator proceed, with respect to the IRB, after the discovery of the adverse event occurrence?

Report the adverse drug experience in a timely manner, in keeping with the IRB's policies and procedures, using the forms or the mechanism provided by the IRB.

Subject 311 has had elevated white blood cell (WBC) counts for the past 2 study visits, with no clinical signs or symptoms. "Increased WBC count" is not listed in the Investigator's Brochure (IB) as an adverse event. The investigator should:

Report the elevated WBC to the sponsor as an unexpected adverse effect.

Subject 311 has had elevated white blood cell (WBC) counts for the past two (2) study visits, with no clinical signs or symptoms. "Increased WBC count" is not listed in the Investigator's Brochure (IB) as an adverse event. The investigator should:

Report the elevated WBC to the sponsor as an unexpected adverse event

Subject 311 has had elevated WBCs for the past 2 study visits, with no clinical signs or symptoms. "Increased WBC count" is not listed in the IB as an adverse event. The investigator should:

Report the elevated WBCs to the sponsor as an unexpected adverse event

Two weeks after starting an investigational therapy, a subject is rushed to the hospital after experiencing a heart attack. The subject is currently being treated in the Intensive Care Unit (ICU). The ICU doctor has noticed that the subject was enrolled in the trial and has contacted the trial Principal Investigator. Heart attack is not described in the Investigator's Brochure. What actions must be taken by the Principal Investigator?

Report to the Sponsor per the protocol timelines for serious, unexpected events. Report to the IRB/IEC per their event reporting requirements for serious, unexpected events

Informed consent is considered an application of which Belmont principle?

Respect for Persons

What are the three principles of the Belmont Report?

Respect for Persons, Beneficence, Justice

What are the three principles of the Belmont Report?

Respect for persons, beneficence, justice

Study Endpoint

Response variables that are chosen to assess drug effects

A serious adverse event is any untoward medical occurrence which at any dose is best described by which of the following statements?

Results in death, is life threatening, is a congenital anomaly

E6(R1) 8.4.6 -- Treatment Allocation and Decoding Documentations

Returned to sponsor to document any decoding that may have occurred LOCATION: -Sponsor

When the FDA conducts an inspection, the inspectors will

Review regulatory records.

When the FDA conducts an inspection, the inspectors will:

Review regulatory records.

Audit

Reviews how the research was conducted; takes into account SOPs, IRB requirements & GCP (ensures compliance)

What are the two main themes covered by the formal ICH definition of "Good Clinical Practice"?

Rights and well-being of study subjects and credibility of the data

You are in the role of Study Manager for the Sponsor. One of your monitors reports significant noncompliance at a site. Which of the following options would be the first course of action for you to implement.

Root cause analysis

In science and engineering, it is a method of problem solving used for identifying the root causes of faults or problems. It is widely used in IT operations, telecommunications, industrial process control, accident analysis (e.g., in aviation, rail transport, or nuclear plants), medicine (for medical diagnosis), healthcare industry (e.g., for epidemiology), etc.

Root cause analysis (RCA)

Safety

S1 to S7 and M3

Carcinogenicity

S1A- S1Cr

Genotoxicity

S2A- S2B

Toxicokinetics and Pharmacokinetics

S3A- S3B

Toxicity Testing

S4-S4A

Reproductive testing

S5A- S5B( M)

Biotech products

Pharmacology studies

S7-S7b

Monitor should conduct monitoring visits according to what, created by whom?

SOPs / monitoring specifics, by the sponsor

What is the purpose of the IRB/IEC?

Safeguard the rights, safety, and well-being of all trial subjects

E8 3.1.1.1

Safety Studies -- early non-clinical studies should provide sufficient information to support selection of the initial human dose and safe duration of exposure and to provide information about physiological and toxicological effects of a new drug

* What is sample size and how is the number usually decided?

Sample Size -the number of subjects in a clinical trial should always be large enough to provide a reliable answer to the questions addressed -number is usually determined by the primary objective of the trial

Expedited reporting of AEs is necessary when what 2 things exist?

Serious & unexpected

Any untoward medical occurrence that at any dose:- results in death,- is life-threatening,- requires inpatient hospitalization or prolongation -results in persistent or significant disability/incapacity

Serious Adverse Event (SAE)

SAE

Serious Adverse Event - Results in death, is life-threatening, requires long-term hospitalization, results in long term disability/hospitalization incapacitation or is a congenital birth defect

Subject 3826 had to stay in the hospital for three extra days when his legs started swelling after participation in a cardiac drug study. Swelling of the legs was listed in the Investigator's Brochure as a possible side effect. Which of the following options best describes this situation?

Serious adverse drug reaction

The ICH GCP Guidelines:

Set standards for the design, conduct, monitoring and reporting of clinical research.

The ICH GCP guidelines:

Set standards for the design, conduct, monitoring and reporting of clinical research.

The ICH GCP Guidelines are:

Set standards for the design, conduct, monitoring, and reporting of clinical research.

Serious vs Severe events

Severe = degree of event (mild/moderate, etc) Serious = overall event outcome; dictates regulatory documentation & reporting

those that may be life threatening (such as liver failure, abnormal heart rhythms, certain types of allergic reactions), that result in persistent or significant disability or hospitalization, and that cause a birth defect and are relatively rare

Severe adverse drug reactions

What details need to be document in the source documentation when and AE occurs?

Severity of event, when event occurred, setting in which event occurred

Refers to the subject being unaware of the treatment assignment

Single Blind

a single-blind study is a type of experiment or clinical trial in which the experimenters are aware of which subjects are receiving the treatment or independent variable, but the participants of the study are not

Single-Blind Study

When should the sponsor-monitor conduct the most detailed review of the study protocol with the site's study staff?

Site initiation visit

Original documents, data, records

Source Document

All information in original records and certified copies of original records of clinical findings, observations, or other activities in a trial necessary for the reconstruction and evaluation of the trial.

Source data

1.1 elements of a protocol ICH 6

Specification of safety parameters.

1.1 elements of a protocol ICH 6

Specification of the efficacy parameters.

Per ICH E8, methods used to evaluate patient usage of the test drug should be what?

Specified in the protocol and actual usage documented

* Who is responsible to update the IB as new information becomes available?

Sponsor

An individual, company, institution, or organization which takes responsibility for the initiation, management, and/or financing of a clinical trial.

Sponsor

Evaluation of Unanticipated Adverse Device Effects (UADEs) must be reported to the FDA by the:

Sponsor

Identify which party is responsible for reporting directly to the FDA the investigator's financial interests with the sponsor:

Sponsor

The investigator must report adverse events to the:

Sponsor

Who is responsible for designing the clinical trial protocol?

Sponsor

Who is responsible for establishing a study's data safety monitoring plan (DSMP)

Sponsor

Who is responsible for ongoing safety evaluation of the IP?

Sponsor

* Who is responsible for providing the investigator with the IP?

Sponsor (once investigator has provided all necessary documentation)

The investigator must report adverse events to the:

Sponsor.

Direct Costs

Staffing, pharmacy, IRB, advertising, storage

Detailed, written instructions to achieve uniformity of the performance of a specific function.

Standard Operating Procedures (SOPs)

Stat principles

Parallel Trial Design

Study Group ----------------> END Control Group --------------> END

Crossover Trial Design

Study Group ----------> Control Group ------> END Control Group --------> Study Group ------> END *main issue is ample wash out time b/w crossovers

According to ICH E8, which of the following are response variables that are chosen to assess the drug's effects?

Study endpoints

2 Types of FDA inspections

Study oriented, and Investigator oriented

During the course of administration of an investigational drug, the following events occurred: On Day 7, subject 603 had an unexpected stroke that requires hospitalization; On Day 15, subject 415 complained of nausea, vomiting, and headache relieved by aspirin; On Day 21, subject 20 has brief dizzy spells upon trying to stand. Which of these subject's events meets the FDA definition of "serious" and "unexpected" and would require the sponsor to file an IND Safety Report with the FDA?

Subject 603 Only

During the course of administration of an investigational drug, the following events occur: On Day 7, subject 603 has an unexpected stroke that requires hospitalization. On Day 15, subject 415 complains of nausea, vomiting, and headache relieved by aspirin. On Day 21, subject 20 has brief dizzy spells upon trying to stand. An IND Safety Report is most likely filed by the sponsor with the FDA for the observations associated with:

Subject 603 only

1.1 elements of a protocol ICH 6

Subject exclusion criteria.

1.1 elements of a protocol ICH 6

Subject inclusion criteria.

Which of the following is necessary to waive consent:

Subject is unable to give consent, no time or unable to contact next of kin, life-threatening condition, no other treatment available.

1.1 elements of a protocol ICH 6

Subject withdrawal criteria (i.e., terminating investigational product treatment/trial treatment) and procedures specifying: (a) When and how to withdraw subjects from the trial/ investigational product treatment. (b) The type and timing of the data to be collected for withdrawn subjects. (c) Whether and how subjects are to be replaced. (d) The follow-up for subjects withdrawn from investigational product treatment/trial treatment.

E6(R1) 6.5.3

Subject withdrawal criteria and procedure specifying a) when and how to withdraw subjects from the trial/investigational product treatment b) the type and timing of the data to be collected for withdrawn subjects c) whether and how subjects are to be replaced d) the follow-up for subjects withdrawn from investigational product treatment/trial treatment

Double Blind Study

Subjects & Researchers are unaware

Single Blind Study

Subjects Unaware

Investigational Device Exemption (IDE)

Submission to FDA for significant risk device before a clinical trial can begin, that allows the investigational device to be used to collect safety and effectiveness data required to support Premarket Approval application (PMA)

Which of the following is an investigator's commitment to the sponsor?

Submit a new Form FDA 1572 to sponsor as needed

What is an example investigator's commitment to the sponsor?

Submit a new Form FDA 1572 to the sponsor as needed

An investigator proposes to study a marketed product sold to treat high blood pressure in individuals over age 12 using a liquid formulation for children under age 12. The drug sponsor hopes that the information from the research can be used to change the labeling for use of the drug in younger children. Which of the following is the investigator's most appropriate course of action?

Submit the research protocol to the IRB for review and submit an IND application to the FDA before conducting the research

E6(R1) 4.8.14--Non-therapeutic trials may be conducted in subjects with consent of a legally acceptable representative provided the following conditions are fulfilled. . .Part 2

Such trials, unless an exception is justified, should be conducted in patients having a disease or condition for which the investigational product is intended. Subjects in these trials should be particularly closely monitored and should be withdrawn if they appear to be unduly distressed.

E6(R1) 7.3.2

Summary -- a brief summary should be given, highlighting the significant physical, chemical, pharmaceutical, pharmacological, toxicological, pharmacokinetic, metabolic, and clinical information available that is relevant to the stage of clinical development of the investigational product

1.1 elements of a protocol ICH 6

Summary of the known and potential risks and benefits, if any, to human subjects.

Identify the most influential event that led to the HHS Policy for Protection of Human Research Subjects:

Syphilis Study at Tuskegee

Blood pressure

Systolic/Diastolic

The current protocol for a study in pediatrics is asking for all new patients to have stages of pubertal development assessed. What is this assessment called?

Tanner Staging

Premature trial termination should be reported using what schematic?

Termination Vortex

All unused investigational agents are expected to be returned to the sponsor at the

Termination site visit

All unused investigational agents are expected to be returned to the sponsor at the:

Termination site visit

Data and Safety Monitoring Boards or DSMBs, have the power to recommend which of the following?

That the sponsor should continue the trial, that the sponsor should modify the trial, that the sponsor should stop the trial

A report created by the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. Its full title is Ethical Principles and Guidelines for the Protection of Human Subjects of Research, Report of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research.

The Belmont Report

is set in an appropriate context the challenges of present-day clinical research, by addressing complex issues including HIV/AIDS research, availability of study treatments after a study ends, women as research subjects, safeguarding confidentiality, compensation for adverse events, as well guidelines on consent Also plays an important role within contemporary pharmacovigilance practice.

The CIOMS guidelines is an abbreviation for the "Council for International Organizations of Medical Sciences"

Case report forms are completed by:

The CRC

In general, corrections to case report forms should be made by:

The CRC or the investigator

E6(R1) 5.23.2

The CRFs are designed to capture the required data at all multi center trial sites. For those investigators who are collecting additional data, supplemental CRFs should also be provided that are designed to capture the additional data

The FDA will apply:

The Code of Federal Regulations.

represents a substantial proportion of the biomedical scientific community through its member organizations, which include many of the biomedical disciplines, national academies of sciences and medical research councils

The Council for International Organizations of Medical Sciences (CIOMS)

a set of ethical principles regarding human experimentation developed for the medical community by the World Medical Association (WMA). It is widely regarded as the cornerstone document on human research ethics.

The Declaration of Helsinki

E6(R1) 7.3.6 -- Effects in Humans: Introduction -- Marketing Experience

The IB should identify countries where the investigational product has been marketed or approved. Any significant information arising from eh marketed use should be summarized. The IB should also identify all the countries where the investigational product did not receive approval/registration for marketing or was withdrawn from marketing/registration

E6(R1) 7.3.6 -- Effects in Humans: Introduction -- Safety and Efficacy (Part 2)

The IB should provide a description of the possible risks and adverse drug reactions to be anticipated on the basis of prior experiences with the product under investigation and with related products. A description should also be provided of the precautions or special monitoring to be done as part of the investigational use of the products

What ICH guidelines is the Studies in Support of Special Populations: Geriatrics provides recommendations on special considerations that apply in the design and conduct of clinical trials of medicines that are likely to have significant use in the elderly.

The ICH guidance E7

* Describe the recommended composition of the IRB

The IRB/IEC should consist of a reasonable number of members, who collectively have the qualifications and experience to review and evaluate the science, medical aspects, and ethics of the proposed trial. It is recommended that the IRB/IEC should include: a) at least five members b) at least one member whose primary area of interest is in a nonscientific area c) at least one member who is independent of the institution/trial site. Only those IRB/IEC members who are independent of the investigator and the sponsor of the trial should vote/provide opinion on a trial-related matter. A list of IRB/IEC members and their qualifications should be maintained. (Can invite nonmembers with special expertise)

is the primary agency of the United States government responsible for biomedical and public health research

The National Institutes of Health (NIH)

is a set of research ethics principles for human experimentation created as a result of the Nuremberg trials at the end of the Second World War

The Nuremberg Code

a scale that is used for physical development in children, adolescents and adults

The Tanner scale (also known as the Tanner stages)

* Inspection

The act by a regulatory authority of conducting an official review of documents, facilities, records, and any other resources that are deemed by the authorities to be related to the clinical trial and that may be located at the site of the trial, at the sponsor's and/or contract research organization's (CRO's) facilities, or at other establishments deemed appropriate by the regulatory authorities

Inspection

The act by a regulatory authority(ies) of conducting an official review of documents, facilities, records, and any other resources that are deemed by the authority(ies) to be related to the clinical trial and that may be located at the site of the trial, at the sponsor's and/or contract research organization's (CRO's) facilities, or at other establishments deemed appropriate by the regulatory authority(ies).

* Monitoring

The act of overseeing the progress of a clinical trial, and of ensuring that it is conducted, recorded, and reported in accordance with the protocol, Standard Operating Procedures (SOPs), Good Clinical Practice (GCP), and the applicable regulatory requirement(s).

Monitoring

Approval (in relation to IRB)

Approval (in relation to Institutional Review Boards)

Amendments involving changes to IRB-approved protocols do NOT need prior IRB approval if:

The changes must be immediately implemented for the health and well-being of the subject.

1.1 elements of a protocol ICH 6

The expected duration of subject participation, and a description of the sequence and duration of all trial periods, including follow-up, if any.

The extent of population EXPOSURE to assess clinical safety

For initial approval of proposed research, the investigator must submit to the IRB:

The full protocol and the informed consent

1.1 elements of a protocol ICH 6

The identification of any data to be recorded directly on the CRFs (i.e., no prior written or electronic record of data), and to be considered to be source data.

Which of the following options describes the term "severe" in regards to ICH?

The intensity of a specific event

E6(R1) 5.13.3

The investigational product(s) should be packaged to prevent contamination and unacceptable deterioration during transport and storage

An investigator is confronted with a life-threatening situation that necessitates using a test article in a human subject who is unable to provide informed consent and there is no time to obtain consent for the individual's legal representative. Under the FDA regulations, what should the investigator action be?

The investigator and another physician not part of the study team agree that the situation necessitates the use of the test article and the IRB will be notified later.

Randomization Procedures and Unblinding

The investigator should follow the trial's randomization procedures, if any, and should ensure that the code is broken only in accordance with the protocol. If the trial is blinded, the investigator should promptly document and explain to the sponsor any premature unblinding of the investigational product(s)

E6(R1) 4.10.2

The investigator should promptly provide written reports to the sponsor, the IRB/IEC and, where applicable, the institution on any changes significantly affecting the conduct of the trial, and/or increasing the risk to subjects

E6(R1) 4.6.6

The investigator, or a person designated by the investigator/institution, should explain the correct use of the investigational product(s) to each subject and should check, at intervals appropriate for the trial, that each subject is following the instructions properly

* Who is responsible for IP accountability at trial sites?

The investigator/institution

E6(R1) 4.6.3

The investigator/institution and/or a pharmacist or other appropriate individual, who is designated by the investigator/institution, should maintain records of the product's delivery to the trial site, the inventory at the site, the use by each subject, and the return to the sponsor or alternative disposition of unused product(s). These records should include dates, quantities, batch/serial numbers, expiration dates (if applicable), and the unique code numbers assigned to the investigational product(s) and trial subjects. Investigators should maintain records that document adequately that the subjects were provided the doses specified by the protocol and reconcile all investigational product(s) received from the sponsor

Opinion (in relation to Independent Ethics Committee)

The judgement and/or the advice provided by an Independent Ethics Committee (IEC).

1.1 elements of a protocol ICH 6

The level of significance to be used.

Trial Site

The location(s) where trial-related activities are actually conducted.

An academic medical center is selecting a new database system for clinical research. The system needs to be "Part 11 compliant" in order to allow:

The medical center to replace the use of paper records with electronic records for its research

1.1 elements of a protocol ICH 6

The methods and timing for assessing, recording, and analysing safety parameters.

Unexpected Adverse Reaction

The nature of severity is not consistent with the applicable product information

Visit Windows

The number of days around a specific date that the patient may come in for a study visit.

1.1 elements of a protocol ICH 6

The number of subjects planned to be enrolled. In multicentre trials, the numbers of enrolled subjects projected for each trial site should be specified. Reason for choice of sample size, including reflections on (or calculations of) the power of the trial and clinical justification.

* Quality Control (QC)

The operational techniques and activities undertaken within the quality assurance system to verify that the requirements for quality of the trial-related activities have been fulfilled

Quality Control (QC)

The operational techniques and activities undertaken within the quality assurance system to verify that the requirements for quality of the trial-related activities have been fulfilled.

Principal Investigator (PI)

The person who is primarily in charge of research on a project that is sponsored or funded by an organization. Also responsible for all study conduct, including protecting human subjects and ensuring the integrity of the data obtained during the course of the trial.

* Well-being (of the trial subjects)

The physical and mental integrity of the subjects participating in a clinical trial

Well-being (of the trial subjects)

The physical and mental integrity of the subjects participating in a clinical trial.

Pharmacokinetics

The process by which drugs are absorbed, distributed within the body, metabolized, and excreted.

Randomization

The process of assigning trial subjects to treatment or control groups using an element of chance to determine the assignments in order to reduce bias.

The investigator and sponsor share responsibility for the protection of clinical trial subjects together with the Institutional Review Board/Independent Ethics Committee. The responsibilities are described in what ICH section

The responsibilities are described in ICH E6

E6(R1) 7.3.5 -- Nonclinical studies: Introduction

The results of all relevant nonclinical pharmacology, toxicology, pharmacokinetic, and investigational product metabolism studies should be provided in summary form. This summary should address the methodology used, the results, and a discussion of the relevance of the findings to the investigated therapeutic and the possible unfavorable and unintended effects in humans.

Two important goals of ICH E6 are to assure that:

The rights, well-being, and confidentiality of trial subjects are protected and trial data are credible.

1.1 elements of a protocol ICH 6

The selection of subjects to be included in the analyses (e.g., all randomized subjects, all dosed subjects, all eligible subjects, evaluable subjects).

Identify which party is responsible for reporting directly to the FDA the investigator's financial interests with the sponsor:

The sponsor

Identify which party is responsible for reporting directly to the FDA the investigator's financial interests with the sponsor?

The sponsor

By regulation, investigators are required to make a final study report to:

The sponsor and the IRB

E6(R1) 5.1.1

The sponsor is responsible for implementing and maintaining quality assurance and quality control systems with written SOPs to ensure that trials are conducted and data are generated, documented (recorded), and reported in compliance with the protocol, GCP, and the applicable regulatory requirement(s)

E6(R1) 5.1.2

The sponsor is responsible for securing agreement from all involved parties to ensure direct access to all trial related sites, source data/documents, and reports for the purpose of monitoring and auditing by the sponsor, and inspection by domestic and foreign regulatory authorities

E6(R1) 5.6.1

The sponsor is responsible for selecting the investigator(s)/institution(s). Each investigator should be qualified by training and experience and should have adequate resources to properly conduct the trial for which the investigator is selected. If organization of a coordinating committee and/or selection of coordinating investigator(s) are to be utilized in multi center trials, their organization and/or selection are the sponsor's responsibility

E6(R1) 7.2.2 -- Confidentiality Statement

The sponsor may wish to include a statement instructing the investigator/recipients to treat the IB as a confidential document for the sole information and use of the investigator's team and the IRB/IEC

E6(R1) 5.3 -- Medical Expertise

The sponsor should designate appropriately qualified medical personnel who will be readily available to advise on trial related medical questions or problems. If necessary, outside consultant(s) may be appointed for this purpose.

E6(R1) 5.13.2

The sponsor should determine, for the investigational product(s), acceptable storage temperatures, storage conditions, storage times, reconstitution fluids and procedures, and devices for product infusion, if any. The sponsor should inform all involved parties of these determinations.

E6(R1) 5.15.1

The sponsor should ensure that it is specified in the protocol or other written agreement that the investigator(s)/institution(s) provide direct access to source data/documents for trial-related monitoring, audits, IRB/IEC review, and regulatory inspection

1.1 elements of a protocol ICH 6

The sponsor should ensure that it is specified in the protocol or other written agreement that the investigator(s)/institution(s) will permit trial-related monitoring, audits, IRB/IEC review, and regulatory inspection(s), providing direct access to source data/documents.

E6(R1) 5.13.1

The sponsor should ensure that the investigational product(s) is characterized as appropriate to the stage of development of the product(s), is manufactured in accordance with any applicable GMP, and is coded and labelled in a manner that protects the blinding, if applicable. In addition, the labelling should comply with applicable regulatory requirement(s)

E6(R1) 5.18.3 -- Extent and Nature of Monitoring

The sponsor should ensure that the trials are adequately monitored. The sponsor should determine the appropriate extent and nature of monitoring. The determination of the extent and nature of monitoring should be based on consideration such as the objective, purpose, design, complexity, blinding, size, and endpoints of the trial. In general there is a need for on-site monitoring, before, during, and after the trial; however in exceptional conjunction with procedures such as investigators' training and meetings, and excessive written guidance can assure appropriate conduct of the trial in accordance with GCP. Statistically controlled sampling may be an acceptable method for selecting the data to be verified

E6(R1) 5.14.3

The sponsor should ensure that written procedures include instructions that the investigator/institution should follow for the handling and storage of investigational product(s) for the trial and documentation thereof. The dispensing, retrieval of unused product from subjects, and return of unused investigational product(s) to the sponsor (or alternative disposition if authorized by the sponsor and in compliance with the applicable regulatory requirement(s))

E6(R1) 5.17.1

The sponsor should expedite the reporting to all concerned investigator(s)/institution(s), to the IRB(s)/IEC(s), where required, and to the regulatory authority(ies) of all adverse drug reactions (ADRs) that are both serious and unexpected

E6(R1) 5.5.12

The sponsor should inform the investigator(s)/institution(s) in writing of the need for record attention and should notify the investigator(s)/institution(s) in writing when the trial related records are no longer needed

E6(R1) 5.16.2

The sponsor should promptly notify all concerned investigator(s)/institution(s) and the regulatory authority(ies) of findings that could affect adversely the safety of subjects, impact the conduct of the trial, or alter the IRB/IEC's approval/favorable opinions to continue the trial

E6(R1) 5.5.7

The sponsor should retain all sponsor-specific essential documents in conformance with the applicable regulatory requirement(s) of the country(ies) where the product is approved, and/or where the sponsor intends to apply for approval(s)

E6(R1) 5.17.3

The sponsor should submit to the regulatory authority(ies) all safety updates and periodic reports, as required by applicable regulatory requirement(s).

E6(R1) 5.15.2

The sponsor should verify that each subject has consented, in writing, to direct access to his/her original medical records for trial-related monitoring, audit, IRB/IEC review, and regulatory inspection

E6(R1) 5.5.11

The sponsor specific essential documents should be retained until at least 2 years after the last approval of a marketing application in an ICH region and until there are no pending or contemplated marketing applications in an ICH region or at least 2 years have elapsed since the formal discontinuation of clinical development of the investigational product. These documents should be retained for a longer period however if required by the applicable regulatory requirement(s) or if needed by the sponsor

E6(R1) 5.8.2

The sponsor's policies and procedures should address the costs of treatment of trial subjects in the event of trial-related injuries in accordance with the applicable regulatory requirements

Who is responsible for making the initial risk determination for a device being used in a study?

The sponsor-investigator

Who is responsible for making the initial risk determination for a device being used in the study?

The sponsor-investigator

According to federal regulations, which of the following best describes when expedited review of a new, proposed study may be used by the IRB?

The study involves no more than minimal risk and meets one of the allowable categories of expedited review specified in federal regulations

Under which circumstance does the FDA allow verbal consent prior to participation in a research study?

The study is minimal risk

Under which circumstance does the FDA allow verbal consent prior to participation in a research study?

The study is minimal risk.

One of the acceptable criterion for determining that a study of an approved drug does not require an IND?

The study is not intended to be reported to FDA to support a new indication or support a labeling change

What is an acceptable criterion for determining that a study of an approved drug does not require an IND?

The study is not intended to be reported to FDA to support a new indication or support a labeling change.

Pharmacogenomics

The study of the influence of genetic factors on drug response that result in the absence, overabundance, or insufficiency of drug-metabolizing enzymes

Pharmacodynamics

The study of what the drug does to the body

Which signatures are required by regulation to be on the consent form?

The subject

Potential reasons to discontinue a subject in a trial are:

The subject is not compliant, Pregnancy, and the subject has intolerable medical events during treatment

Bias

The systematic tendency of any factors associated with the design, conduct, analysis, and interpretation of the results of clinical trials to make the estimate of a treatment effect deviate from its true value

When writing an early phase clinical study plan, which of the following do you want to pay attention to, if you wish to maximize the chance of observing specific clinical effects of interest?

The target population

When evaluating causality of an adverse event, what should be a consideration?

The timing of the event in relation to administration of the investigational agent

When evaluating the causality of an adverse event, which of the following should be a consideration?

The timing of the event in relation to administration of the investigational agent

1.1 elements of a protocol ICH 6

The treatment(s) to be administered, including the name(s) of all the product(s), the dose(s), the dosing schedule(s), the route/mode(s) of administration, and the treatment period(s), including the follow-up period(s) for subjects for each investigational product treatment/trial treatment group/arm of the trial.

1.1 elements of a protocol ICH 6

The type and duration of the follow-up of subjects after adverse events.

Nuremburg Code

The voluntary consent of the human subject is absolutely essential

What type of study is this? Objective of Study • Demonstrate/confirm efficacy • Establish safety profile • Provide an adequate basis for assessing the benefit/risk relationship to support licensing • Establish dose-response relationship Study Examples • Adequate, and well controlled studies to establish efficacy • Randomised parallel doseresponse studies • Clinical safety studies • Studies of mortality/ morbidity outcomes • Large simple trials • Comparative studies

Therapeutic Confirmatory (Phase III Study)

Phase III

Therapeutic Confirmatory; confirm early findings; *establish efficacy *establish drug as beneficial to treat condition *set stage for marketing approval 100-1000's of patients Goals: confirm drug works, control & investigational group, double-blinded controlled studies

What type of study is this? Objective of Study • Explore use for the targeted indication • Estimate dosage for subsequent studies • Provide basis for confirmatory study design, endpoints, methodologies Study Examples • Earliest trials of relatively short duration in well- defined narrow patient populations, using surrogate or pharmacological endpoints or clinical measures • Dose-response exploration studies

Therapeutic Exploratory (Phase II Study)

What type of study is this? Objective of Study • Refine understanding of benefit/risk relationship in general or special populations and/or environments • Identify less common adverse reactions • Refine dosing recommendation Study Examples • Comparative effectiveness studies • Studies of mortality/morbidity outcomes • Studies of additional endpoints • Large simple trials • Pharmacoeconomic studies

Therapeutic Use (Phase IV)

Phase II Trials

Therapeutic exploratory; explore medications - establish dose for phase III *begin to test drug therapeutically *Typically enrolls a very specific criteria on patients *may help lay groundwork for endpoints in phase III Fewer than 100 patients Goals: determines short term risks, examine preliminary effectiveness Population: controlled study with limited population

Note about Phase IV trials

Therapeutic use is never in phase I, II or II, but others can fall into continuum.

Phase IV

Therapeutic use; outcomes of use, multiple endpoints, large trials *comes after drug approval (Think LINX PAS but for meds) *Basically confirms dosing, safety & effectiveness

What is the most important factor to consider in a sites decision to participate in competing clinical trials?

There is an imminent risk for struggle in prioritizing study related activities when a site is involved in similar clinical trials for different sponsors.

Global Variables

These assess the overall outcomes in objective terms. The PI may give impressions regarding the study

CRCs should cultivate professional relationships with clinic administrators and laboratory directors because:

These relationships allow the CRC to solicit assistance with operational issues as they arise

E6(R1) 7.3.7 -- Summary of Data and Guidance for the Investigator

This section should provide an overall discussion of the nonclinical and clinical data, and should summarize the information from various sources on different aspects of the investigational products, wherever possible. In this way, the investigator can be provided with the most informative interpretation of the available data and with an assessment of the implications of the information for future clinical trials. Where appropriate, the published reports on related products should be discussed. This could help the investigator to anticipate adverse drug reactions or other problems in clinical trials

E6(R1) 7.2.1 -- Title Page

This should proved the sponsor's name, the identity of each investigational product (research number, chemical or approved generic name, the trade names where legally permissible and desired by the sponsor), and the release date. It is also suggested that an edition number, and a reference to the number and date of the edition it supersedes, be provided.

What is the purpose of the "Data and Safety Monitoring Board (DSMB)"?

To assess the progress of a clinical trial, the safety data, and the critical efficacy endpoints

E6(R1) 8.3.15 -- Documentations of CRF Corrections

To document all changes/additions or corrections made to CRF after initial data were recorded LOCATION: -Investigator/Institution -copy -Sponsor -original

E6(R1) 8.3.11 -- Relevant Communications Other than Site Visits: letters, meeting notes, notes of telephone calls

To document any agreements or significant discussions regarding trial administration, protocol violations, trial conduct, adverse event (AD) reporting LOCATION: -Investigator/Institution -Sponsor

E6(R1) 8.4.7 -- Final Report by Investigator to IRB/IEC Where Required, and Where Applicable, to the Regulatory Authorities

To document completion of the trial LOCATION: -Investigator/Institution

* Essential Document - Sample of Labels Attached to Investigational Product Containers

To document compliance with applicable labeling regulations and appropriateness of instructions provided to the subjects LOCATION: -Sponsor

E6(R1) 8.3.4 -- Regulatory Authorities Authorization/Approvals/Notifications Where Required for Protocol Amendments and Other Documents

To document compliance with applicable regulatory requirements LOCATION: -Investigator/Institution -where required -Sponsor

E6(R1) 8.4.2 -- Documentation of Investigational Product Destruction

To document destruction of unused investigational products by sponsor or at site LOCATION: -Investigator/Institution -if destroyed at site -Sponsor

* Decoding Procedures for Blinded Trials

To document how, in case of an emergency, identity of blinded investigational product can be revealed without breaking the blind for the remaining subjects' treatment LOCATION: -Investigator/Institution -Sponsor -Third Party -if applicable

E6(R1) 8.3.20 -- Subject Screening Log

To document identification of subjects who entered pre-trial screening LOCATION: -Investigator/Institution -Sponsor -where required

* Essential Document - Certificates of Analysis of Investigational Products Shipped

To document identity, purity, and strength of investigational products to be used in the trial LOCATION: -Sponsor

E6(R1) 8.3.9 -- Certificates of Analysis for New Batches of Investigational Products

To document identity, purity, and strength of investigational products to be used in the trial LOCATION: -Sponsor

* Essential Document - Instructions for Handling of Investigational Products and Trial-Related Materials

To document instructions needed to ensure proper storage, packaging, dispensing and disposition of investigational products and trial related materials LOCATION: -Investigator/Institution -Sponsor

E6(R1) 8.3.25 -- Record of Retained body Fluids/Tissue Samples (If Any)

To document location and identification of retained samples if assays need to be repeated LOCATION: -Investigator/Institution -Sponsor

* Master Randomization List

To document method for randomization of trial population LOCATION: -Sponsor -Third Party -if applicable

E6(R1) 8.4.8 -- Clinical Study Report

To document results and interpretations of trial LOCATION: -Investigator/Institution -if applicable -Sponsor

* Essential Document - Shippng Records for Investigational Products and Trial-Related Materials

To document shipment dates, batch numbers and method of shipment of investigational products and trial-related materials. Allows tracking of product batch, review of shipping conditions, and accountability LOCATION: -Investigator/Institution -Sponsor

E6(R1) 8.3.8 -- Documentation of Investigational Products and Trial-Related Materials Shipment

E6(R1) 8.3.24 -- Signature Sheet

To document signatures and initials of all persons authorized to make entries and/or corrections on CRFs LOCATION: -Investigator/Institution -Sponsor

E6(R1) 8.3.10 -- Monitoring Visit Reports

To document site visits by, and findings of, the monitor LOCATION: -Sponsor

E6(R1) 8.4.5 -- Final Trial Close-Out Monitoring Report

To document that all activities required for trial close-out are completed, and copies of essential documents are held in the appropriate files LOCATION: -Sponsor

E6(R1) 8.4.4 -- Audit Certificate (if available)

To document that audit was performed LOCATION: -Sponsor

E6(R1) 8.3.12 -- Signed Informed Consent Forms

To document that consent is obtained in accordance with GCP and protocol and dated prior to participation of each subject in trial. Also to document direct access permission LOCATION: -Investigator/Institution

E6(R1) 8.3.23 -- Investigational Products Accountability at the Site

To document that investigational products have been used according to the protocol LOCATION: -Investigator/Institution -Sponsor

E6(R1) 8.3.21 -- Subject Identification Code List

To document that investigator/institution keeps a confidential list of names of all subjects allocated to trial numbers on enrolling in the trial. Allows investigator/institution to reveal identity of any subject LOCATION: -Investigator/Institution

E6(R1) 8.3.14 -- Signed, Dated and Completed Case Report Forms (CRF)

To document that the investigator or authorized member of the investigator's staff confirms the observations recorded LOCATION: -Investigator/Institution -copy -Sponsor -original

E6(R1) 8.2.20 -- Trial Initiation Monitoring Report

To document that trial procedures were reviewed with the investigator and the investigator's trial staff LOCATION: -Investigator/Institution -Sponsor

E6(R1) 8.3.13 -- Source Documents

To document the existence of the subject and substantiate integrity of trial data collected. To include original documents related to the trial, to medical treatment, and history of subject LOCATION: -Investigator/Institution

E6(R1) 8.4.3 -- Completed Subject Identification Code List

To permit identification of all subjects enrolled in the trial in case follow-up is required. List should be kept in a confidential manner and for agreed upon time LOCATION: -Investigator/Institution

What is the main objective of a phase 2 clinical trial?

To test a new molecule in subjects with the disease of interest to obtain safety information and preliminary evidence of efficacy.

Non-significant Risk Devices

Tongue depressor, adhesive bandages

Conflict of Interest (COI)

Training required every 4 years

An adult with attention deficit hyperactivity disorder (ADHD) presents to a physician. To date, no behavioral or drug interventions have proven useful. The physician has just read several reports about a drug that is approved and marketed for another indication, but has shown some benefit for ADHD. The physician wants to prescribe this drug, in the labeled marketed dose, for the individual patient. Which of the following would be the most appropriate course of action?

Treat the patient with the drug based on physician's best medical judgment

Adherence to all trial-related requirements, GCP, and the applicable regulatory requirements.

Trial Compliance

E9 3.3.2

Trials to Show Equivalence or Non-inferiority -and investigational product is compared to a reference treatment without the objective of showing superiority -divided by two major categories according to its objective; one is an 'equivalence' trial and the other is a 'non-inferiority' trial

An intuitionally designated authority, other than the investigator, should determine that proposed studies are exempt from regulatory requirements

True

T/F: The FDA regulations allow subjects or the legally acceptable representatives to receive either a signed or unsigned copy of the ICF?

True

True or False? Medicinal products may affect physical and cognitive growth and development, and the adverse event profile may differ in pediatric patients.

True

True or False? The Data and Safety Monitoring Board (DSMB) is a separate entity from an Institutional Review Board (IRB) or an Independent Ethics Committee (IEC)?

True

True or False? The intention of ICH E8 is to describe internationally accepted principles and practices in the conduct of both individual clinical trials and overall development strategy for new medicinal products.

True

Is a statistical term that is also known as a "false positive": the error of rejecting a null. Hypothesis when it is actually true. In other words, this is the error of accepting an. alternative hypothesis (the real hypothesis of interest) when the results can be. attributed to chance.

Type I Error

Is a statistical term used within the context of hypothesis testing that describes the error that occurs when one accepts a null hypothesis that is actually false, because we accept the conclusion of the test as negative, even though it is incorrect.

Type II Error

Study Monitor or CRA

Typically employed by the sponsor or CRO and is responsible for evaluating the overall conduct of the trial at a research site.

An "autonomous person" is someone who:

Understands the risks and benefits of his or her participation and is able to make a voluntary decision if adequate information is provided.

refers to an event or reaction that is not listed in the investigator's brochure or is not listed at the specificity or severity that has been observed; or, if an investigator's brochure is not required or available, is not consistent with the risk information

Unexpected adverse event or suspected adverse reaction

Most sponsors will expect an investigative site to keep all study records for how long?

Until the sponsor says they may be destroyed.

E6(R1) 4.13 -- Final Report(s) by Investigator

Upon completion of the trial, the investigator, where applicable, should inform the institution; the investigator/institution should provide the IRB/IEC with a summary of the trial's outcome, and the regulatory authority(its) with any reports required

Phase 3 Study

Uses information gathered from Phase 1 and 2 studies to determine safety and effectiveness.

A classification of FDA audits that says the deviations found were not serious is:

VAI A VAI inspection classification indicates that, although investigators found and documented objectionable conditions during the inspection, FDA will not take or recommend regulatory or enforcement action because the objectionable conditions do not meet the threshold for action at this time. Despite this facility inspection classification, FDA recommends that you address any observations noted on the Form FDA 483 issued at the conclusion of the inspection or otherwise conveyed to you following the inspection. If not corrected, the same or similar conditions could lead to a future inspection being classified as "official action indicated" ("OAI").

A process of establishing and documenting that the specified requirements of a computerized system can be consistently fulfilled from design until decommissioning of the system or transition to a new system.

Validation of Computerized Systems

Peak

Varies, but usually around 30 mins to several hours after dosing, depends on administration

What are the rules of the Nuremberg Code

Voluntary consent, scientific merit, benefits outweigh the risks, subjects can terminate research at any time.

In the US, following the ICH E6 guideline is:

Voluntary for FDA-regulated drug studies

In the U.S, following the ICH E6 GCP is:

Voluntary for FDA-regulated drug studies.

In the United States, following the ICH E6 GCP is:

Voluntary for FDA-regulated drug studies.

Individuals whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation. Examples: patients with incurable diseases, patients in nursing homes, patients in emergency situations, refugees, minors, pregnant women.

Vulnerable Subjects

E6(R1) 5.12.1

When planning trials, the sponsor should ensure that sufficient safety and efficacy data from nonclinical studies an/or clinical trials are available to support human exposure by the route, at the dosages, for the duration, and in the trial population to be studied

A 510(k) Premarket Notification is submitted

When the new device to be marketed is substantially similar (equivalent) to one already on the market

A 510(k) Premarket Notification is submitted:

When the new device to be marketed is substantially similar (equivalent) to one already on the market

When is a 510(k) Premarket Notification submitted?

When the new device to be marketed is substantially similar to one already on the market

The study subject asks you why the study is called a double blind study. You explain double blind as what?

When the subject and the Investigator and sponsor staff who are involved in the treatment or clinical evaluation of the subjects are unaware of the treatment assignments

What does WMA stand for?

World Medical Association

Audit Report

Written Evaluation - not regularly made available to regulatory body; only when serious evidence exists concerning non-compliance

The IRB must inform the investigator the study has been approved by:

Written notification saying it has been approved

* Should an investigator inform a subject's primary care physician about the trial?

Yes if the subject has a PCP and consents to this.

Exploratory trials (select all that apply) a) Explore a wide range of hypotheses b) Provide formal proof of efficacy c) Need flexible designs d) Are designed to explore new uses for an approved drug

a and c a) Explore a wide range of hypotheses c) Need flexible designs

Fatal or life threatening and unexpected adverse drug reactions in clinical investigations should be reported to the regulatory agencies (check all that apply) a) No later than 7 days after first knowledge of event b) No later than 15 days after first knowledge of event c) By filing a complete report within 8 additional days of the initial notification d) By filing a complete report within 15 additional days of the initial notification

a and c a) No later than 7 days after first knowledge of event c) By filing a complete report within 8 additional days of the initial notification

Office for Human Research Protections (OHRP)

a branch of the U.S. Department of Health and Human Services that provides leadership regarding protection of human subjects involved in research activities

Multicentre Trial

a clinical trial conducted according to a single protocol but at more than once site, and therefore, carried out by more than one investigator

Investigator's Brochure

a compilation of the clinical and nonclinical data on the investigational product which is relevant to the study of the investigational product in human subjects

Audit Certificate

a declaration of confirmation by the auditor that an audit has taken place

Humanitarian Use Device (HUD)

a device that is intended to benefit patients in the treatment or diagnosis of a disease or condition affecting fewer than 8,000 individuals in the U.S. per year.

Protocol

a document that describes the objectives, design, methodology, statistical consideration, and organization of a trial

Contract Research Organization (CRO)

a person or an organization contracted by the sponsor to perform one or more of a sponsor's trial-related duties and functions

Investigator

a person responsible for the conduct of the clinical trial at a trial site.

Impartial Witness

a person, who is independent of the trial, who cannot be unfairly influenced by people involved with the trial, who attends the informed consent process if the subject cannot read, and who reads the informed consent form and any other written information supplied to the subject

Investigational Product

a pharmaceutical form of an active ingredient or placebo being tested or used as a reference in a clinical trial, including a product with a marketing authorization when used or assembled in a way different from the approved form, or when used for an unapproved indication, or when used to gain further information about an approved use

Case Report Form (CRF)

a printed, optical, or electronic document designed to record all of the protocol required information to be reported to the sponsor on each trial subject

Informed Consent

a process by which a subject voluntarily confirms their willingness to participate in a particular trial, after having been informed of all aspects of the trial that are relevant to the subject's decision to participate. Documented by means of a written, signed, and dated form

Unrestricted Randomization

a randomization method in which all subjects have the same chance to receive each treatment

Block Randomization

a randomization method in which subjects are randomized in blocks, each containing a predefined combination of treatments

Stratified Randomization

a randomization method in which subjects with shared characteristics are divided into strata; each stratum is then randomized seperatley

Dynamic Randomization

a randomization method in which the likelihood of subsequent assignments changes based on previous ones

Central Randomization

a randomization method used in multcenter trials to obtain the desired overall distribution across treatment arms

Interim Clinical Trial/Study Report

a report of intermediate results and their evaluation based on analysis performed during the course of a trial

Global Assessment Variable

a single variable, usually a scale of ordered categorical ratings, which integrates objective variables and the investigator's overall impression about the state or change in state of a subject

Global Assessment Variables

a single variable, usually a scale of ordered categorical ratings, which integrates objective variables and the investigator's overall impression about the state or change in the subject

Dropout

a subject in a clinical trial who for any reason fails to continue in the trial until the last visit required of him/her by the study protocol

E6(R1) 7.3.5 -- Nonclinical studies: Introduction -- Nonclinical Pharmacology

a summary of the pharmacological aspects of the investigational product and, where appropriate, its significant metabolites studied in animals, should be included. Such a summary should incorporate studies that assess potential therapeutic activity as well as those that assess safety

Audit

a systematic and independent examination of trial related activities and documents to determine whether the evaluated trial related activities were conducted, and the data were recorded, analyzed and accurately reported according the protocol

Open-label Study

a trial in which treatment identities are known to everyone involved

Protocol Amendment

a written description of a change to or formal clarification of a protocol

Clinical Trial/Study Report

a written description of a trial/study of any therapeutic, prophylactic, or diagnostic agent conducted in human subjects, in which the clinical and statistical description, presentations, and analyses are fully integrated into a single report

Audit Report

a written evaluation by the sponsor's auditor of the results of the audit

Monitoring Report

a written report from the monitor to the sponsor after each site visit and other trial related communication according to the sponsor's SOPs

A control group may consist of all of the following except a) A group of a distinct age composition b) A placebo c) Active control d) Different doses of the drug

a) A group of a distinct age composition

In ICH-GCP an investigator is defined as a) A person responsible for the conduct of the clinical trial b) An individual supervised by the team leader c) A person responsible for initiation, management and financing of a clinical trial d) A person responsible for overseeing the progress of a clinical trial

a) A person responsible for the conduct of the clinical trial

A subject in an IND protocol misses a study visit because of a work related engagement and shows up for the scheduled visit two days after the due date. There are no medical consequences. The event is a) A protocol deviation b) A serious adverse event c) An unanticipated event of risk to self or others d) Regulatory non-compliance

a) A protocol deviation

The protocol should include all of the following except a) A section for assessment of conflict of interest b) Analysis plan appropriate to objectives and design c) Statistical methods d) Plans for interim analysis

a) A section for assessment of conflict of interest

A drug manufacturer has developed a new drug for hypertension. There are currently 15 drugs available for the treatment of hypertension. The trial design that would be most favored would be a) A superiority trial with the best performing drug as comparator control b) A non-inferiorly trial with an "average" performing drug as comparator control c) An equivalence trial with an "average" performing drug as a control d) A placebo control trial with high statistical power.

a) A superiority trial with the best performing drug as comparator control

In ICH-GCP an audit is defined as a) A systematic and independent examination of trial related activities and documents b) An investigation intended to discover and verify the clinical effects of an investigational product c) Official review of documents facilities records and any other resources d) Overseeing of the progress of a clinical trial

a) A systematic and independent examination of trial related activities and documents

Which of the following is a liver function test? a) AST b) BUN c) Serum Creatinine d) GFR

a) AST

a) Acting as the main line of communication between the sponsor and the investigator b) Verifying that the investigator has adequate qualifications and resources and remain adequate throughout the trial period, that facilities, including laboratories, equipment, and staff, are adequate too sales and properly conduct the trial and remain adequate throughout the trial period.

A subject in an arthritis clinical trial develops a severe cold and flu like symptoms. This event is most likely classified as a) An adverse event b) An adverse drug reaction c) An unexpected adverse drug reaction d) A serious adverse event

a) An adverse event

The Hawthorne effect is a) An effect caused in a treatment group because of the special attention paid to it by the investigator b) The participants form an interpretation of the experiment's purpose and modify their behavior accordingly c) Occurs in cognitive trial where the perception of one trait is influenced by the perception of another trait. d) An effect ,caused by psychological influence, experienced by the patient when they are unaware that they are not being administered the medication for the clinical trial e) The investigator's paradigm in experimental design and analysis predetermines the interpretation of the results. f) Patients in the control group become aware of group membership and tum rebellious and alter behavior to contradict the experiment's purpose

a) An effect caused in a treatment group because of the special attention paid to it by the investigator

In a clinical trial, reports of adverse events from the investigator to the sponsor should include a) Any adverse event observed in the subject b) Only events which meet the definition of a serious event c) Only events which are unanticipated d) Only events which meet the definition of possibly related to drug

a) Any adverse event observed in the subject

An IRB reviews a study which has two treatment groups one involving adults over the age of 18 and the other involving children under the age of 18. The IRB has reservations about the adequacy of the protocol for the inclusion of children. The IRB may a) Approve the study for adults and defer the study for children b) Approve the study with conditions for both groups c) Disapprove the study for both groups since one group does not qualify d) Defer the study for both groups.

a) Approve the study for adults and defer the study for children

An IRB conducting a continuing review of a research study requiring a fully convened IRB determines that changes in the protocol, not previously specified are needed to ensure the safety of the subjects. The IRB may require all of the following except a) Approve the study to prevent disruption of the research protocol b) Require that the altered protocol be put into effect only for newly enrolled subject c) Require changes to the informed consent and reconsent of the subjects d) Require appropriate changes to the long term follow up of current and future enrollees.

a) Approve the study to prevent disruption of the research protocol

According to ICH in multi-center trials the sponsor should a) Carefully define the responsibilities of the coordinating site principal investigator b) Delegate monitoring to the coordinating site c) Allow different standards of compliance depending on the site d) Permit changes in the CRFs for sites that may suggest these

a) Carefully define the responsibilities of the coordinating site principal investigator

The sponsor in a phase 2 clinical trial may a) Choose to delegate evaluations of safety at the site to the principal investigator b) Carry out all evaluations of SAEs itself c) Delegate the evaluation of SAEs to the CRO d) Choose not to report an SAE to the FDA

a) Choose to delegate evaluations of safety at the site to the principal investigator

Statistical assessment of sample size should include assessments of all of the following except a) Clinical trial logistics and cost controls b) Treatment effect and data variability c) Probability of error d) Information in population subsets or secondary endpoints

a) Clinical trial logistics and cost controls

An HUD requires all of the following except a) Collecting research data for effectiveness b) Safety reports to the FDA c) Annual report to the FDA d) Informed consent only if the IRB requires one

a) Collecting research data for effectiveness

A major problem in the DSMBs for a sponsor- investigator clinical trial is a) Conflict of interest with the principal investigator b) Unavailability of qualified members c) Difficulty in IRB approval of the DSMB members d) Difficulty in convening the DSMB and keeping minutes

a) Conflict of interest with the principal investigator

The DSMB can recommend a) Continuation, modification or termination of a sponsor's trial b) The continued enrollment of patients in light of safety events c) The submission of serious adverse safety events for regulatory review d) The submission of serious adverse safety events to the IRB.

a) Continuation, modification or termination of a sponsor's trial

Study design considerations should include all of the following except a) Cost assessment of proposed clinical trial b) Primary and secondary endpoints and associated analyses c) Methods to monitor adverse events d) Use of appropriate comparators and adequate sample size

a) Cost assessment of proposed clinical trial

Respect for persons in the Belmont report relates to a) Decision on the part of subjects to voluntarily participate or not in the research b) Protection from harms c) Sharing benefits with others d) Legal protection in the event of medical injury

a) Decision on the part of subjects to voluntarily participate or not in the research

The ethical framework cited in ICH-GCP as the framework for conducting clinical trials is a) Declaration of Helsinki b) Belmont report c) Nuremberg Code d) CIOMS guidelines

a) Declaration of Helsinki

The ethical principles underlying clinical study management are stated in a) Declaration of Helsinki b) Belmont report c) Nuremberg Code d) CIOMS guidelines

a) Declaration of Helsinki

A child seven years old is being consented for a juvenile arthritis clinical trial for a new oral medication. The question that would be important to ask the child would include all of the following except a) Do you understand juvenile arthritis symptoms and causes b) Do you have difficulty swallowing c) What oral medications have you take before d) Do you prefer to have a liquid formulation

a) Do you understand juvenile arthritis symptoms and causes

The primary concern in a confirmatory trial is a) Efficacy b) Safety c) Pharmacodynamics d) Pharmacokinetics

a) Efficacy

E6(R1) 5.5.3 When using electronic trial data handling and/or remote electronic trial data systems, the sponsor should:

a) Ensure and document that the electronic data processing system(s) conforms to the sponsor's established requirements for completeness, accuracy, reliability, and consistent intended performance b) Maintains SOPs for using these systems c) Ensure that the systems are designed to permit data changes in such a way that the data changes are documented and that there is no deletion of entered data d) Maintain a security system that prevents unauthorized access to the data e) Maintain a list of the individuals who are authorized to make data changes f) Maintain adequate backup of the data g) Safeguard the blinding, if any

When reviewing studies involving a vulnerable population the IRB should a) Ensure protective measures relevant to the population b) Appoint a subject advocate for the vulnerable group c) Require continuing reviews more frequently than annually d) Mandate post approval monitoring for such studies

a) Ensure protective measures relevant to the population

E6(R1) 5.14.4 -- The sponsor should . . .

a) Ensure timely delivery of investigational product(s) to the investigator(s) b) Maintain records that document shipment, receipt, disposition, return, and destruction of the investigational product(s). c) Maintain a system for retrieving investigational products and documenting this retrieval d) Maintain a system for the disposition of unused investigational product(s) and for the documentation of this disposition

Which of the following is simple test for rheumatoid arthritis or joint disease? a) Erythrocyte Sedimentation Rate b) AST c) Serum creatinine d) Urine microalbumin

a) Erythrocyte Sedimentation Rate

The investigator's brochure is a central part of the submission of an IND a) Form 1571 b) Form 1572 c) Form 3455 d) Med watch Form 3500 A

a) Form 1571

The sponsor's decision to use a CRO should be declared in a) Form 1571 b) Form 1572 c) Form 3455 d) Medwatch Form 3500 A

a) Form 1571

In confirmatory trials, it is usual to analyze a) Full analysis set only b) Per protocol Set only c) Full analysis and per protocol sets d) Null hypothesis analysis set

a) Full analysis set only

Before an HUD is used in a hospital the application must a) Have review and approval from the IRB b) Have institutional approval c) Have only the sponsor's approval d) Have an approved HOE from the FDA only

a) Have review and approval from the IRB

Which of the following is a test for Type II diabetes? a) HbA1c b) ALT c) BUN d) Anti-nuclear antigen

a) HbA1c

In a clinical trial under an IND the investigator determines that a protocol procedure should be changed immediately in consideration of patient safety. He does not inform the IRB or the sponsor a) His action is approvable under regulations b) His action constitutes serious noncompliance c) His action merits study suspension d) His action merits disciplinary action from the institution

a) His action is approvable under regulations

Studies which examine dose tolerance, PK and PD aspects of a drug are likely to be a) Human Pharmacology b) Therapeutic Exploratory c) Therapeutic Confirmatory d) Therapeutic use

a) Human Pharmacology

Protocol deviations are reportable to the FDA a) If the event is associated with a serious adverse event b) Routinely c) Only if the OHRP recommends it d) Never

a) If the event is associated with a serious adverse event

Serious adverse events in a clinical trial should be reported to the sponsor according to ICH a) Immediately b) Within one day c) Within one week d) As time permits

a) Immediately

Late reporting of a protocol deviation a) Is itself a protocol deviation b) Is a serious adverse event c) Is of no consequence because DHHS regulations do not specify a time period for reporting protocol deviations d) Is an event of interest only to the sponsor

a) Is itself a protocol deviation

According to the FDA guidance on recruitment a web listing of a clinical trial does not need IRB review if a) It lists title, protocol summary, basic eligibility criteria, location and contact information b) It discusses benefits in detail c) It provides payment incentive information d) It provides a list of free medical services beyond that in the consent document

a) It lists title, protocol summary, basic eligibility criteria, location and contact information

Approaches to minimize risks in pediatric clinical trials include all of the following except a) Minimize the number of study subjects b) Maximize the number of study subjects c) Minimize study procedures d) Employ good study designs

a) Minimize the number of study subjects

One of the most common protocol deviations is a) Missed or late study visit because of patient non-compliance b) Missed or late study visit because of mistakes in scheduling of the Pl c) Drug dose related miscalculations d) Failure to maintain a delegation of authority log for the clinical trial.

a) Missed or late study visit because of patient non-compliance

The principal investigator's wife owns equity interest greater than $50,000 directly in the sponsor's stock. The principal investigator a) Must disclose this to the FDA on form 3455 b) Need not disclose this to the FDA on Form 3455 c) Must disclose this to the institutional conflict of interest committee d) Must disclose this on the consent form

a) Must disclose this to the FDA on form 3455

If the DSMB suspends a clinical trial the IRB a) Must suspend the clinical trial at its site b) May still keep the trial open if it deems the trial is important c) May postpone the decision to suspend until it observes what the DSMB has observed d) May suspend new enrollment but permit continued treatment of current subjects.

a) Must suspend the clinical trial at its site

The amount of blood volume that may be obtained form a child in the United States is set at a) No more than 50 ml in an eight week period b) No more than a 100 ml in one month c) No more than 20 ml in one week d) No more than one unit in four weeks

a) No more than 50 ml in an eight week period

The inclusion criterion for a clinical trial sates that the subject should not have a liver or renal function test outside the normal range. His values are 1. AST 20 2. ALT 10 3. Serum creatinine 2.0 The subject should a) Not be enrolled in the clinical trial at the time of presentation b) Be enrolled in a clinical trial c) Should be evaluated in another month to see if the lab values were stable d) Should be evaluated clinically by the Pl

a) Not be enrolled in the clinical trial at the time of presentation

In determining the extent of monitoring the sponsor should consider a) Objective, design, complexity, blinding and size b) Objective, payments, complexity, blinding, cost c) Objective, drug supply, payments, complexity, cost d) Objective, site support, payments, complexity, blinding

a) Objective, design, complexity, blinding and size

The requirements for a screening consent would be indicated for all of the following except a) Obtaining information about demographics, medical history and lab tests for the subject b) Conducting a CT scan prior to progression in the clinical trial c) Initiating a washout of current drug treatments d) Administering a diagnostic drug for a thyroid condition

a) Obtaining information about demographics, medical history and lab tests for the subject

An IRB reviewing an IND study must according to FDA guidelines have at least a) One physician present b) A specialist in the study topic present c) A community member preset d) Only the nonscientific member present

a) One physician present

The most commonly used study design in clinical trials is a) Parallel design b) Crossover design c) Pre-Post design d) Factorial design

a) Parallel design

The site monitor's findings should be summarized in a) Periodic site monitoring reports b) E-mails to the investigator c) Verbal communication with research coordinators d) Summarized at the close out visit

a) Periodic site monitoring reports

The studies designed to first introduce a drug in human beings are a) Phase 1 b) Phase2 c) Phase 3 d) Phase 4

a) Phase 1

The studies most likely to use healthy volunteers are likely to be a) Phase 1 b) Phase 2 c) Phase 3 d) Phase 4

a) Phase 1

The studies with lowest number of subjects is likely to be a) Phase 1 b) Phase 2 c) Phase 3 d) Phase 4

a) Phase 1

The studies with the highest risk to benefit ratio are a) Phase 1 b) Phase2 c) Phase 3 d) Phase 4

a) Phase 1

Dose escalation is most likely to be used in a) Phase 1 trials b) Phase 2 trials c) Phase 3 trials d) Phase 4 trials

a) Phase 1 trials

About 15 subjects were enrolled in a clinical trial. The trial is most likely a) Phase I b) Phase II c) Phase III d) Phase IV

a) Phase I

ICH defined Human pharmacology trial are a) Phase I b) Phase II c) Phase Ill d) Phase IV

a) Phase I

In a sponsored clinical trial the path to reporting serious adverse events is a) Pl to CRO to sponsor to DSMB b) Pl to CRO to DSMB c) Pl to DSMB d) Pl to IRB to DSMB

a) Pl to CRO to sponsor to DSMB

In ICH-GCP quality assurance is defined as a) Planned and systematic action to ensure that the data is generated ,recorded and reported according to GCP b) The act of overseeing the progress of a clinical trial c) The act of performing inspections of a clinical trial d) The act of performing an official review of a clinical trial

a) Planned and systematic action to ensure that the data is generated ,recorded and reported according to GCP

The sequence of regulatory events for approval of marketing for a device is a) Preclinical studies- IDE-PMA b) Preclinical studies- PMA-IDE c) 510K-IDE-PMA d) HDE-510K-PMA

a) Preclinical studies- IDE-PMA

In a clinical trial a serious adverse event should be reported by the investigator to the sponsor within a) Promptly b) Seven days c) Fifteen days d) One month

a) Promptly

During the study monitoring visit it was noted that the sample for laboratory analysis were being shipped long after the required shipment date. Many of the samples were deemed non evaluable. The event is a) Protocol deviation b) Serious adverse event c) An unanticipated event of risk to self or others d) Nor reportable because the lab measurements were not of central importance to the study outcome.

a) Protocol deviation

According to the FDA guidance on recruitment for studies under an IND, the following information needs to be reviewed by the IRB: a) Protocol, consent forms, recruiting scripts, investigator's brochure b) Protocol, debriefing forms, conflict of interest information, recruitment scripts c) Protocol, research monitoring plans, recruitment scripts, consent forms d) Protocol, enrollment bonuses, consent forms and investigator's brochure

a) Protocol, consent forms, recruiting scripts, investigator's brochure

According to ICH the IRB should obtain the following documents from the investigator a) Protocol, consent, recruitment procedures, investigator's brochure, payments b) Protocol , consent, case report forms , payments, CV c) Protocol, consent, monitoring plan, payments, CV, recruitment d) Protocol, monitoring plan, investigator's brochure, payments, CV

a) Protocol, consent, recruitment procedures, investigator's brochure, payments

In a parallel group design the subjects a) Randomized to two arms each with a different treatment b) Are evaluated before and after drug administration c) Are randomized to a sequence of two treatments d) Are evaluated simultaneously for varying combinations of treatments

a) Randomized to two arms each with a different treatment

With regard to access to the sponsor's audit report by regulatory authority ICH advises a) Regulatory authority should not routinely request access to the audit report b) Require the audit report to be part of he study binder c) Ask to see the internal audit reports prior to commencing their audits d} Record the absence of an internal audit report a deficiency

a) Regulatory authority should not routinely request access to the audit report

With regard to reporting serious adverse events to the DSMB the sponsor should a) Report all serious events to the DSMB b) Forward only the IND safety reports sent to the REGULATORY AGENCY to the DSMB c) Forward only the events reported to the IRB d) Forward only the events to be reported to the funding agency

a) Report all serious events to the DSMB

A research subject enrolled in a clinical trial is involved in a car accident and suffers significant physical injuries. The event occurs while the drug administration phase of the protocol is still ongoing. The investigator should a) Report the event to the sponsor and the IRB b) Not report the event c) Report the event to the REGULATORY AGENCY d) Report the event to OHRP

a) Report the event to the sponsor and the IRB

A protocol deviation should be a) Reported to the IRB on forms designated for such reports b) Reported directly to OHRP by the investigator c) Reported to the FDA d) Not reportable as this is not addressed in DHHS regulations.

a) Reported to the IRB on forms designated for such reports

IRB records must include a) Research proposals reviewed, approved consent documents, continuing review activities and significant new findings provided to subjects b) Significant new findings provided to subjects, conflict of interest documents, continuing review activities, progress reports submitted by investigators c) Financial disclosure forms, reports of FDA audits of the studies, conflict of interest documents, reports of injuries to subjects d) Significant new findings provided to subjects, conflict of interest documents, scientific evaluations of studies, reports of FDA audits

a) Research proposals reviewed, approved consent documents, continuing review activities and significant new findings provided to subjects

If an investigator does not obtain consent from his subjects the principle in Belmont that is violated is a) Respect for persons b) Principle of justice c) Beneficence d) Privacy and confidentiality

a) Respect for persons

The study monitor reviews case report forms during a) Routine site visits b) Site initiation visit c) Study close out visit d) Pre-study visit

a) Routine site visits

An adverse event in a device study is reported to the FDA if it is a) Serious b) Serious and unanticipated c) Serious and unanticipated and possibly related d) Serious and unanticipated and probably related.

a) Serious

The sponsor must report a serious adverse event in an IND safety report to the regulatory agency if the event is a) Serious, unanticipated and possibly related to the drug b) Serious regardless of anticipatedness or proof of relatedness c) Mentioned as a high risk event in the investigator's brochure d) Stated in the informed consent

a) Serious, unanticipated and possibly related to the drug

Agreements between the sponsor and the investigator: a) Should be in writing as part of the protocol or in a separate agreement b) May be verbally implemented c) Must be provided to the IRB prior to study approval d) May be signed by the CRO on behalf of the sponsor

a) Should be in writing as part of the protocol or in a separate agreement

Response variables are closely related to a) Study endpoints b) Primary objectives c) Secondary Objectives d) Statistical Plan

a) Study endpoints

In a single blind trial the person who is unaware of the treatment is a) Subject b) Investigator c) Monitor d) Clinical coordinator

a) Subject

In clinical trial under an IND Subject A experiences difficulty breathing and self admits to the emergency room. Subject S experiences nausea and vomiting which is resolved by home rest for a day. Which event should be reported as "serious" to the regulatory agency? a) Subject A b) Subject S c) Subjects A and S d) Neither subject.

a) Subject A

In an open label trial the persons who should be aware that the treatment is being administered are a) Subject and investigator b) Pharmacist and investigator c) Sponsor and investigator d) Monitor and investigator

a) Subject and investigator

Which of the following is an FDA mandated responsibility that represents the investigator's responsibility to the sponsor? a) Submission of an updated 1572 b) Completion of a delegation log c) Retention of records for three years d) Update the investigator's CV annually

a) Submission of an updated 1572

A Data and Safety Monitoring Board does all of the following except a) Supports SAE review by the IRB b) Assesses progress of a clinical trial and critical efficacy endpoints c) Monitors all aspects of data safety for a clinical trial d) Recommends to the sponsor whether a trial should be continued , modified or stopped.

a) Supports SAE review by the IRB

E6(R1) 5.14.5 -- Th sponsor should

a) Take steps to ensure that the investigational product(s) are stable over the period of use b) maintain sufficient quantities of the investigational product(s) used in the trials to reconfirm specifications, should this become necessary, and maintain records of batch sample analysis and characteristics. To the extent stability permits, samples should be retained either until the analyses of the trial data are complete or as required but he applicable regulatory requirement(s), whichever represents the longer retention period.

E6(R1) 4.8.10 Both the informed consent discussion and the written informed consent form and any other written information to be provided to subjects should include explanations of. . .Part 1

a) That the trial involves research b) The purpose of the trial c) The trial treatment(s) and the probability for random assignment to each treatment d) The trial procedures to be followed, including all invasive procedures e) The subject's responsibilities f) Those aspects of the trial that are experimental g) The reasonably foreseeable risks or inconveniences to the subject and, when applicable to an embryo, fetus, or nursing infant h) the reasonably expected benefits. When there is no intended clinical benefit to the subject, the subject should be made aware of this

With regard to electronic trial data the sponsor should ensure all of the following except a) The EDC vendor is approved by the IRB b) The data changes are documented c) There is no deletion of entered data d) An audit, data and edit trials are maintained .

a) The EDC vendor is approved by the IRB

An important affirmation regarding the ICH guidelines for the IRB which differ from DHHS regulation is that a) The IRB should comply with GCP b) Should have at least five members c) Should have a non-scientific member d) Should have a non-affiliated member

a) The IRB should comply with GCP

The Belmont report was formulated by a) The National Commission for the protection of human subjects in biomedical and behavioral research b) The National Commission for protection of families in biomedical research c) The National Commission for the medical protection of human subjects in research d) The National Commission for the study of medical research of human subjects in biomedical and behavioral research

a) The National Commission for the protection of human subjects in biomedical and behavioral research

Reporting a health related adverse event in clinical trial as serious, unanticipated and possibly related are criteria required by a) The REGULATORY AGENCY and the IRB b) OHRP c) The sponsor's instruction to the investigator d) The subject's personal physician

a) The REGULATORY AGENCY and the IRB

A placebo controlled trial would be considered unethical if a) The drug has been shown to be efficacious in a superiority trial b) The drug has been shown equivalent to active control in a non-inferiority trial c) Drug has shown serious side effects in preclinical studies d) All of the above

a) The drug has been shown to be efficacious in a superiority trial

E6(R1) 5.11.1--The sponsor should obtain from the investigator/institution

a) The name and address of the investigator's/institution's IRB/IEC b) A statement obtained from the IRB/IEC that it is organized and operates according to GCP and the applicable laws and regulations c) Documented IRB/IEC approval/favorable opinion and, if requested by the sponsor, a current copy of protocol, written informed consent form and any other written information to be provided to subjects, subject recruiting procedures, and documents related to payments and compensation available to the subjects, and any other documents that the IRB/IEC may have requested

Non-therapeutic trials should only be conducted in subjects who can personally give consent except under the following conditions...

a) The objectives of the trial can not be met by means of a trial in subjects who can give informed consent personally b) The foreseeable risks to the subjects are low c) The negative impact on the subject's well-being is minimized and low d) The trial is not prohibited by law e) The approval/favorable opinion of the IRB/IEC is expressly sought on the inclusion of such subjects, and the written approval/favorable opinion covers this aspect

The person who the subject should contact for research subject rights is a) The person noted in the consent form for such contact b) A person other than the principal investigator c) Usually an IRB appointed Research Subject Advocate described in the consent form d) All of the above

a) The person noted in the consent form for such contact

A research subject enrolled in a clinical trial experiences significant chest pain and is admitted to the emergency department for the possible evaluation of a cardiac event. The event occurs while the drug administration is still ongoing in the clinical trial. The causality of the event should be determined by a) The principal investigator b) The study sponsor c) The IRB d) The subject's personal physician

a) The principal investigator

The DSMB monitors a) The safety data b) Patient accrual c) Data accuracy d) Missing data

a) The safety data

A subject on a test drug experiences a hospitalization while on the drug for a period of four weeks at a hospital other than the site's hospital. The CRC learns of it though a family member. The CRC should report it immediately to a) The sponsor b) The IRB c) The regulatory agency d) The relevant family members

a) The sponsor

In a single blind trial the person unaware of the treatment assignment is a) The subject b) The investigator c) The monitor d) The data analyst

a) The subject

Phase IV studies in the pediatric population differ from those in adult populations because a) They are required to assess the effects on development b) They are less likely to yield safety information because of age variation c) The large samples required for such studies are hard to find in pediatric populations d) Unlike adult populations regulations do not require Phase IV pediatric studies

a) They are required to assess the effects on development

Payments to research subjects should be based on a) Time and inconvenience b) Risk and discomfort c) Ensuring participation d) Satisfying the needs of study participants

a) Time and inconvenience

A washout in clinical trial denotes a) Treatment drugs are discontinued prior to study drugs for a period of time b) Special hygiene measures are used in the clinical trial c) Physician consultation is used prior to administration of study drug d) All of the above

a) Treatment drugs are discontinued prior to study drugs for a period of time

Clinical trial records should be preserved for at least a) Two years post marketing approval b) Two years post study closure c) Four years after the filing of marketing application d) As long as sponsor wants

a) Two years post marketing approval

The probability of erroneously rejecting the null hypothesis is described as a) Type I error b) Type II error c) Type Ill error d) Risk assessment

a) Type I error

A pharmacist makes a dosing error in a clinical trial that results in no harm to any subject. The event is a) Unanticipated problem that does not involve an adverse event and needs to be reported to the IRB under regulations b) Adverse event that does not represent an unanticipated problem and does not need to be reported under DHHS regulations c) Adverse event that does represent an unanticipated problem that needs to be reported under DHHS regulations d) DHHS regulations do not apply

a) Unanticipated problem that does not involve an adverse event and needs to be reported to the IRB under regulations

An investigator conducting a study of illicit drug behavior has the data on a laptop in an unencrypted fashion. The laptop is stolen. The event is a) Unanticipated problem that does not involve an adverse event and needs to be reported to the IRB under regulations b) Adverse event that does not represent an unanticipated problem and does not need to be reported under DHHS regulations c) Adverse event that does represent an unanticipated problem that needs to be reported under DHHS regulations d) DHHS regulations do not apply

a) Unanticipated problem that does not involve an adverse event and needs to be reported to the IRB under regulations

Subjects in a cancer trial received serum that was not screened for the hepatitis virus. No illness in subjects is reported. The event is a) Unanticipated problem that does not involve an adverse event and needs to be reported to the IRB under regulations b) Adverse event that does not represent an unanticipated problem and does not need to be reported under DHHS regulations c) Adverse event that does represent an unanticipated problem that needs to be reported under DHHS regulations d) DHHS regulations do not apply

a) Unanticipated problem that does not involve an adverse event and needs to be reported to the IRB under regulations

With regard to the investigator the monitor should a) Verify that the investigator has adequate qualifications, resources, facilities and staff b) Verify whether the investigator meets regularly with staff c) Verify whether the investigator is delivering on all 1572 commitments d) Check on the Pl's characteristics by talking to staff.

a) Verify that the investigator has adequate qualifications, resources, facilities and staff

The most important consideration in reporting and adverse event in a clinical trial is a) Whether the event occurred in the time frame of drug administration b) Whether the event is reported as drug related by the research subject c) Whether the event is listed as an adverse event in the investigator's brochure d) Whether the event is listed as an adverse event in the protocol.

a) Whether the event occurred in the time frame of drug administration

* What are the minimum criteria for reporting?

a) an identifiable patient; b) suspect medicinal product; c) identifiable reporting source; d) event or outcome that can be identified as serious and unexpected, and for which, in clinical investigation cases, there is a reasonable suspected causal relationship. -Follow-up information should be actively sought and submitted as it becomes available.

* What is the investigator obliged to report promptly to the IRB?

a) deviations from, or changes of, the protocol to eliminate immediate hazards to the trial subjects b) changes increasing the risk to subjects and/or affecting significantly the conduct of the trail c) all adverse drug reactions (ADRs) that are both serious ad unexpected d) new information that may affect adversely the safety of the subjects or the conduct of the trial.

* Apart from serious & unexpected ADRs, what other 3 types of events should be reported in an expedited fashion?

a) for an "expected," serious ADR, an increase in the rate of occurrence which is judged to be clinically important b) a significant hazard to the patient population, such as lack of efficacy with a medicinal product used in treating life-threatening disease c) a major safety finding from a newly comleted animal study

E6(R1) 5.18.2 -- Selection and Qualifications of Monitors

a) monitors should be appointed by the sponsor b) Monitors should be appropriately trained, and should have the scientific and/or clinical knowledge needed dod monitor the trial adequately. A monitor's qualifications should be documented c) monitors should be thoroughly familiar with the investigational product(s) the protocol, written informed consent form and any other written information to be provided to subjects, the sponsor's SOPs, GCP, and the applicable regulatory requirement(s)

E6(R1) 5.18.6 -- Monitoring Report

a) the monitor should submit a written report to the sponsor after each trial site visit or trial related communication b) reports should include the date, site, name of the monitor, and name of the investigator or the other individual(s) contacted c) reports should include a summary of what the monitor reviewed and the monitor's statements concerning the significant findings/facts, deviations and deficiencies, conclusions actions taken or to be taken and/or nations recommended to secure compliance d) the review and follow-up of the monitoring report with the sponsor should be documented by the sponsor's designated representative

* What are the purposes of trial monitoring?

a) the rights and well-being of human subjects are protected b) the reported trial data are accurate, complete, and verifiable from source documents c) the conduct of the trial is in compliance with the currently approved protocol/amendment(s), with GCP, and with the applicable regulatory requirement(s)

* How should auditors be selected?

a) the sponsor should appoint individuals, who are independent of the clinical trials/systems, to conduct audits b) The sponsor should ensure that the auditors are qualified by training and experience to conduct audits properly. An auditor's qualifications should be documented

E6(R1) 5.19.3 -- Auditing Procedures

a) the sponsor should ensure that the auditing of clinical trials/systems is conducted in accordance with the sponsor's written procedures on what to audit, how to audit, the frequency of audits, and the form and content of audit reports. b) the sponsor's audit plan and procedures for a trial audit should be guided by the importance of the trial to submissions to regulatory authorities, the number of subjects in the trial, the type and complexity of the trial, the level of risks to the trial subjects, and any identified problem(s) c) the observations and findings of the auditor(s) should be documented d) to preserve the independence and value of the audit functions, the regulatory authorities should not routinely request the audit reports. Regulatory authorities may seek access to an audit report on a case by case basis when evidence of serious GCP non-compliance exists, or in the course of legal proceedings e) when required by applicable law or regulation, the sponsor should provide an audit certificate

E6(R1) 5.6.3 -- The sponsor should obtain the investigator's/institution's agreement. . .

a) to conduct the trial in compliance with GCP, with th applicable regulatory requirement(s), and with the protocol agreed to by the sponsor and given approval/favorable opinion by the IRB/IEC b) to comply with procedures for data recording/reporting c) to permit monitoring, auditing and inspection d) to retain the trial related essential documents until the sponsor informs the investigator/institution these documents are no longer needed

Which of the following is a liver function test? a. ALT b. BUN c. Serum Creatinine d. GFR

a. ALT

Which of the following is a liver function test? a. AST b. BUN c. Serum Creatinine d. GFR

a. AST

Which of the following is simple test for rheumatoid arthritis or joint disease? a. Erythrocyte Sedimentation Rate b. AST c. Serum creatinine d. Urine microalbumin

a. Erythrocyte Sedimentation Rate

Inspection

act by a regulatory authority(ies) of conducting an official review of documents, facilities, records, and any other resources that are deemed by the authority(ies) to be related to the clinical trial and that may be located at the site of the trial, at the sponsor's and/or contract research organization's (CRO) facilities, or at other establishments deemed appropriate by the regulatory authority

Compliance

adherence to all the trial-related requirements, GCP requirements, and the applicable regulatory requirements

response to a drug which is noxious and unintended, and which occurs at doses normally used in man for the prophylaxis, diagnosis, or therapy of disease, or for the modifications of physiological function

adverse drug reaction

an unwanted or harmful reaction experienced following the administration of a drug or combination of drugs under normal conditions of use and is suspected to be related to the drug and will usually require the drug to be discontinued or the dose reduced

adverse drug reaction (ADR)

Any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.

adverse event

What does ALP lab test stand for?

alkaline phosphatase

Source Data

all information in original records and certified copies of original records of clinical findings, observations, or other activities in a clinical trial necessary for the reconstruction and evaluation of the trial--contained in source documents

Documentation

all records, in any form that describe or record the methods, conduct, and/or results of a trial, the factors affecting a trial, and actions taken

Quality Assurance (QA)

all those planned and systematic actions that are established to ensure that the trial is performed and the data are generated, documented, and reported in compliance with GCP and the applicable regulatory requirements

often affects people with asthma and allergies. It contributes to asthma symptoms like wheezing and shortness of breath; your chest also feels tight, and it can be hard to catch your breath

allergic bronchospasm

Independent Ethics Committee (IEC)

an independent body constituted of medical professionals and non-medical members, whose responsibility is to ensure the protection of the rights, safety, and well-being of human subjects involved in a trial and to provide public assurance of that protection.

Institutional Review Board (IRB)

an independent body constituted of medical, scientific, and non-scientific members, whose responsibility is to ensure the protection of the rights, safety, and well-being of human subjects involved

Data Safety Monitoring Board (DSMB)

an independent committee, composed of community representatives and clinical research experts, that reviews data while a clinical trial is in progress to ensure that participants are not exposed to undue risk

Legally Acceptable Representative

an individual or juridical or other body authorized under applicable law to consent, on behalf of a prospective subject, to the subject's participation in the clinical trial

Sponsor-Investigator

an individual who both initiates and conducts a clinical trial and under whose immediate direction the investigation product is administered to, dispensed to, or used by a subject

Subject/Trial Subject

an individual who participates in a clinical trial, either as a recipient of the investicational product or as a control

Sponsor

an individual, company, institution, or organization which takes responsibility for the initiation, management, and financing of a clinical trial

Comparator (product)

an investigational or marketed product (i.e. active control) or placebo, used as reference in a clinical trial

Coordinating Investigator

an investigator assigned the responsibility for the coordination of investigators at different centres participating in a multcentre trial

Certificates of Confidentiality (CCoon

another way to protect confidential information by allowing researchers to refuse to disclose research data for use in "civil, criminal, administrative, legislative or other proceedings. Will be issued by NIH or HHS agency

Interim Analysis

any analysis intended to compare treatment arms with respect to efficacy or safety at any time prior to the formal completion of a trial

Subinvestigator

any individual member of the clinical trial team designated and supervised by the investigator at a trial site to perform critical trial-related procedures and to make important trial-related decisions

Clinical Trial/Study

any investigation in human subjects intended to discover or verify the clinical, pharmacological and/or other pharmacodynamic effects of an investigational product and/or to study absorption, distribution, metabolism, and excretion of an investigational product with the object of ascertaining its safety.

clinical trial

any investigation in human subjects intended to discover or verify the clinical, pharmacological, and/or other pharmacodynamic effects of an investigational product(s), whether approved for marketing or not, and/or to identify any adverse reactions to an investigational product(s), and/or to study absorption, distribution, metabolism, and excretion of an investigational product(s) with the object of ascertaining its efficacy and/or safety

Applicable Regulatory Requirements

any laws and regulations addressing the conduct of clinical trials of investigational products

Institution (medical)

any public or private entity or agency or medical or dental facility where clinical trials are conducted

Unanticipated Adverse Device Effect

any serious adverse effect on health or safety or any life-threatening problem or death caused by, or associated with, a device, if that effect, problem, or death was not previously identified in nature, severity, or degree of incidence in the investigational plan or application (including a supplementary plan or application), or any other unanticipated serious problem associated with a device that relates to the rights, safety, or welfare of subjects (Investigational Device Exemptions 2014). The investigator reports UADEs to the sponsor and the local IRB. The sponsor transmits evaluations of these reports to the FDA.

42 CFR 11

applicable clinical trials must be registered and have results submitted to the ClinicalTrials.gov databank

Humanitarian Device Exemption (HDE)

application that is similar to a premarket approval (PMA) application, but for which the manufacturer does not need to provide evidence of efficacy. HDEs are subject to restrictions on profitability and can only be used in a facility after an IRB/IEC has approved their use in that facility, except in certain emergencies.

Investigational New Drug (IND)

application to the FDA that contains all the animal and cell testing data

Bayesian Approaches

approaches to data analysis that provide a posterior probability distribution for some parameter, derived from the observed data and a prior probability distribution for the parameter

find (something) out for certain; make sure of

ascertaining

the expression of approval or agreement

assent

Intent-To-Treat Priciple

asserts that the effect of a treatment policy can be best assessed by evaluating on the basis the intention to treat a subject rather than the actual treatment given

A response to a medical product means (check all options that apply) a) A causal relationship between drug and adverse event is established b) A causal relationship between drug and adverse event is a reasonable possibility c) The relationship of the event to drug cannot be ruled out d) An event that requires active medical intervention

b and c b)A causal relationship between drug and adverse event is a reasonable possibility c)The relationship of the event to drug cannot be ruled out

The minimum number of subjects that can be enrolled in a clinical trial is a) 0 b) 1 c) 10 d) 100

b) 1

In screening for eligibility for a clinical trial 50 medical records were screened. Of these, 50% were screened failures. Of the remaining 10 failed the lab tests at visit 0. The number who proceeded to be evaluable is a) 30 b) 15 c) 10 d) 5

b) 15

A drug with a half-life of one day is initiated at 100mg. The subject does not take the drug for three days. The minimum effective concentration is 50 mg. The maintenance dose that should be administered is a) 50 mg b) 25 mg c) 75 mg d) 12.5mg

b) 25 mg 1 day=100mg 2 day=50mg 3 day=25mg 4 day=12.5

An adverse drug reaction is one which a) Results in death or hospitalization b) A noxious and unintended response to a drug c) Occurs frequently and with greater severity than usual d) Likely occurs at normal doses of the drug

b) A noxious and unintended response to a drug

A subject in a psychology study requires sequestration in small space and develops claustrophobia which is described as one of the risks in the IRB approved protocol. The event is a) Unanticipated problem that does not involve an adverse event and needs to be reported under DHHS regulations b) Adverse event that does not represent an unanticipated problem and does not need to be reported under regulations c) Adverse event that does represent an unanticipated problem that needs to be reported under DHHS regulations d) DHHS regulations do not apply

b) Adverse event that does not represent an unanticipated problem and does not need to be reported under regulations

A subject in an oncology trial develops multi organ failure and dies. The event is a known complication of the disease and standard therapy and is described in an IRB approved protocol. The event is a) Unanticipated problem that does not involve an adverse event and needs to be reported under DHHS regulations b) Adverse event that does not represent an unanticipated problem and does not need to be reported under regulations c) Adverse event that does represent an unanticipated problem that needs to be reported under DHHS regulations d) DHHS regulations do not apply

b) Adverse event that does not represent an unanticipated problem and does not need to be reported under regulations

An investigator carries out prospective chart reviews of neonates in the intensive care unit. One of the neonates dies. The event is a) Unanticipated problem that does not involve an adverse event and needs to be reported under DHHS regulations b) Adverse event that does not represent an unanticipated problem and does not need to be reported under regulations c) Adverse event that does represent an unanticipated problem that needs to be reported under DHHS regulations d) DHHS regulations do not apply

b) Adverse event that does not represent an unanticipated problem and does not need to be reported under regulations

Which of the following is true? a) All adverse events are adverse drug reactions b) All adverse drug reaction may be classified as adverse events c) An adverse event is never classified as an adverse drug reaction d) An adverse drug reaction excludes mild adverse events

b) All adverse drug reaction may be classified as adverse events

The term, life threatening, in a serious adverse event refers to a) An event which required hospitalization b) An event where risk of death was evident at the time of the event c) An event that required treatment in an emergency room d) An event which might have caused a death if left untreated

b) An event where risk of death was evident at the time of the event An adverse event or suspected adverse reaction is considered "life-threatening" if, in the view of either the investigator or sponsor, its occurrence places the patient or subject at immediate risk of death. ... Serious adverse event or serious suspected adverse reaction.

In ICH-GCP a sub-investigator is defined as: a) A person responsible for the conduct of the clinical trial b) An individual supervised by the team leader c) A person/entity responsible for initiation, management and financing of a clinical trial. d) A person responsible for overseeing the progress of a clinical trial

b) An individual supervised by the team leader

In ICH-GCP a clinical trial is defined as a) A systematic and independent examination of trial related activities and documents b) An investigation intended to discover and verify the clinical effects of an investigational product c) Official review of documents, facilities, records and any other resources d) Overseeing of the progress of a clinical trial

b) An investigation intended to discover and verify the clinical effects of an investigational product

An IRB reviewing a study of surgical procedures requires that a change be made in the protocol to ensure that the informed consent is done at a prior clinical visit and not be scheduled on the day of the surgery. The action taken by the IRB would be a) Approve the study with the optional recommendation b) Approve the study with the condition c) Defer the study d) Disapprove the study

b) Approve the study with the condition

An IRB reviewing a study requires the investigator to obtain a certificate of confidentiality and a letter of approval from the radiation safety committee. The action taken by the IRB would be a) Approve the study with the optional recommendation b) Approve the study with the condition c) Defer the study d) Disapprove the study

b) Approve the study with the condition

An IRB reviewing a study requires the investigator to specify which procedures are standard of care and which are research related. The action taken by the IRB would be: a) Approve the study with the optional recommendation b) Approve the study with the condition c) Defer the study d) Disapprove the study

b) Approve the study with the condition

An IRB reviewing a study which requires radiographic imaging requires the investigator to confirm that the contrast agent used in the imaging be confined to the type and dose of the reagent specified by the IRB. The action taken by the IRB should be a) Approve the study with the optional recommendation b) Approve the study with the condition c) Defer the study d) Disapprove the study

b) Approve the study with the condition

In a pre-post design the subjects a) Randomized to two arms each with a different treatment b) Are evaluated before and after drug administration c) Are randomized to a sequence of two treatments d) Are evaluated simultaneously for varying combinations of treatments

b) Are evaluated before and after drug administration

The institutional review board in the United States sets the blood volume that can be obtained from a child a) Based on institutional policy b) Based on guidelines in DHHS regulations c) Based on disease severity d) Based on the age of the child.

b) Based on guidelines in DHHS regulations

ICH defines an adolescent as a person who is a) Between 14 and 18 years of age b) Between 12 to 16-18 years of age c) Between 13 and 17 years of age d) Between 16 to 18 years of age

b) Between 12 to 16-18 years of age

Formulations of the drug should be characterized on a) Maximum tolerated dose b) Bioavailability C) Half -life d) Drug clearance

b) Bioavailability

In an open label trial a) The investigator knows whether the treatment is placebo or treatment b) Both the investigator and the subject know that the treatment drug is being administered c) Neither the investigator not the subject knows whether drug or placebo is being administered d) The investigator knows that the drug is being administered but the subject does not

b) Both the investigator and the subject know that the treatment drug is being administered.

In ascertaining the basis for a serious adverse drug reaction in a randomized trial a) Care should be taken not to break the blind for the patient b) Care should be taken to break the blind only for the single patient involved c) The blind for the group of patients being treated at the site should be broken d) The blind for the single patient should be broken only if the sponsor approves

b) Care should be taken to break the blind only for the single patient involved

An MRI machine and a thermometer are examples of a) Class I devices b) Class II devices c) Class 111 devices d) Class IV devices

b) Class II devices

A trial designed on the basis of some evidence of benefits is likely to be a) Exploratory trial b) Confirmatory trial c) Phase IV trial d) Open label trial

b) Confirmatory trial

Oversight of the quality of a trial involves review of all of the following except a) Protocol adherence b) Conflict of interest c) Patient accrual and retention d) Review of design assumptions

b) Conflict of interest

Regarding costs of the research to the subject the consent form should a) Assume the subject knows that the institution will pay for all research costs b) Disclose any additional costs as this is an additional element of consent c) Provide detailed analysis of the study's cost structure d) Transfer as much of the costs to the subject as possible

b) Disclose any additional costs as this is an additional element of consent

In a two group parallel design trial neither the investigator nor the subject is aware of whether the group is the treatment drug or a placebo. This is an example of a) Single blinding b) Double blinding c) Open label d) None of the above

b) Double blinding

A clinical trial in which the only the research pharmacist knows the identity of the test article being given to subjects is a a) Single-blind trial b) Double-blind trial c) Open label trial d) Crossover design trial

b) Double-blind trial

Special populations to be considered in clinical trial is defined in ICH ES to include all except a) Pregnant women b) Elderly c) Nursing women d) Children

b) Elderly

Primary endpoints should have all of the following features except a) Reflect clinically relevant effects b) Exclude safety considerations c) Be based on the principal objective d) Be clearly distinguishable from secondary endpoints

b) Exclude safety considerations

The ability of the investigator to retain and analyze the data of a withdrawn subject even if the data includes identifiable information is permitted in a) DHHS regulations, but not the FDA regulations b) FDA regulations, but not in DHHS regulations c) Neither FDA nor DHHS regulations d) Both FDA and DHHS regulations

b) FDA regulations, but not in DHHS regulations

In a phase 3 trial four treatment groups are identified Placebo X and active group X, Placebo Y and active group Y. The subjects are randomized to all four groups. The study design is an example of a) Parallel design b) Factorial design c) Crossover design d) Withdrawal trial design

b) Factorial design

Breaking the blind for a single patient in randomized clinical trial a) Has negative implications for data integrity at the site level b) Has little or no significant implication for the investigation or final data analysis c) May compromise drug approval because of implications for final data analysis d) Provides no significant information regarding the safety of the patient

b) Has little or no significant implication for the investigation or final data analysis

In a clinical trial of schizophrenia the study design calls for a washout of the current treatment drug prior to administration of the study drug. The sponsor should a) Inform the subject's physician prior to administration of the study drug b) Have an SOP for monitoring the subjects during the washout period c) Allow a subject to self-administer any drug during the washout period d) Make the washout period as short as possible regardless of the drug's half-life.

b) Have an SOP for monitoring the subjects during the washout period

Description of the investigator's brochure is included in a) DHHS regulations b) ICH c) FDA regulations and guidance d) OHRP regulations and guidance

b) ICH

The role specifically of medical physician as responsible for medical decisions is affirmed in a) DHHS only b) ICH and DHHS c) ICH only d) OHRP

b) ICH and DHHS

Crossover studies are particularly favored in a) Where the placebo group shows large variations b) In phase one bioequivalence trials c) Where long acting drugs are involved d) When a short treatment time is desired for the clinical trial.

b) In phase one bioequivalence trials

Regarding the risks of pregnancy and harm to the fetus during the research study, the consent form requires that it a) Mention the procedure may involve such risks that are unforeseeable b) Include the need for contraception c) Provide specific instructions regarding the efficacy of specific contraceptive methods d) Advise subjects that only women need to be aware of such risks

b) Include the need for contraception

A subject in a clinical trial is late for a critical visit scheduled for the study. The CRC should a) Reschedule the visit immediately b) Inform the sponsor prior to rescheduling the visit c) Inform the IRB d) Immediately report the event as an SAE

b) Inform the sponsor prior to rescheduling the visit

A 1572 is a contract between a) IRB and FDA b) Investigator and FDA c) Sponsor and FDA d) Sponsor and institution

b) Investigator and FDA

An unexpected adverse drug reaction is a reaction a) Happens immediately after drug administration b) Is inconsistent with the documented product information in the investigator's brochure or other source document c) Known to occur frequently in preclinical studies d) Dependent on the dose the drug

b) Is inconsistent with the documented product information in the investigator's brochure or other source document

According to the FDA guidance on payments which of the following applies a) May be viewed as a recruitment incentive or a benefit b) It is not uncommon for subjects to be paid for their participation in research c) May be considered as coercion d) Is higher in phase 1 studies

b) It is not uncommon for subjects to be paid for their participation in research

With regard to keeping the IRB informed about the Investigator's brochure ICH states that a) It is the sponsor's responsibility b) It is the investigator's responsibility c) It is not needed d) Updates to the brochure need not be provided.

b) It is the investigator's responsibility

Regarding the informed consent process the Declaration of Helsinki does not include which of the following: (Check all that apply) a) Participation by individuals giving consent must be voluntary b) It may be appropriate to consult with family members or community leaders regarding the informed consent process c) The informed consent must include sources of funding and conflicts of interest and institutional affiliations of the researcher. d) The dependent relationship with a physician should be avoided in a consent situation e) The refusal of consent should not affect the patient physician relationship. f) Payment information must be included. g) The ability of external regulatory bodies to audit the study must be included in the consent. h) For medical research on data or material to be contained in biobanks or similar repositories informed consent must be obtained regarding collection, storage, use and reuse.

b) It may be appropriate to consult with family members or community leaders regarding the informed consent process

Withdrawal of pediatric subject from a clinical trail a) Is always permitted b) May be overridden by the investigator or parent for serious or life threatening diseases c) Depends on the regulations of the country d) Requires the consent of both parents

b) May be overridden by the investigator or parent for serious or life threatening diseases

According to OHRP guidance the informed consent element that the subject may "discontinue participation at any time" a) Can be stated without any reservations b) Must be explained with regard to data retention in light of the prevailing FDA, DHHS and HIPAA regulations c) Will be honored by destroying all data d) Can be overruled by the investigator even if the subject requests it

b) Must be explained with regard to data retention in light of the prevailing FDA, DHHS and HIPAA regulations

The principal investigator in an IND study owns shares in a mutual fund that invests in the stock of the sponsor as one of its holdings. The investigator a) Must disclose this to the FDA on form 3455 b) Need not disclose this to the FDA on Form 3455 c) Must disclose this to the institutional conflict of interest d) Must disclose this on the consent form

b) Need not disclose this to the FDA on Form 3455

The typical restriction on blood draws form children in the United States is set at a) No more than once weekly b) No more than twice weekly c) No more than three time weekly d) No more than four times weekly

b) No more than twice weekly

An unexpected adverse reaction is one which is a) Not expected by the investigator b) Not mentioned in the investigator's brochure or relevant source document c) Classified as such by the IRB d) Classified as such by the sponsor's medical safety officer

b) Not mentioned in the investigator's brochure or relevant source document

According to OHRP guidance unanticipated problems which are serious should be reported to the IRB within a) One day b) One week c) Two weeks d) One month

b) One week

During a study monitoring visit the monitor observes the following documents are incomplete or missing: the investigator's CV, the delegation of authority log, IRB approval letters. This should be a) Reported as a protocol deviation b) Part of study monitoring, immediately remediable and not reportable to the IRB c) Reportable as an adverse event to the sponsor d) An unanticipated event reportable by the IRB to OHRP.

b) Part of study monitoring, immediately remediable and not reportable to the IRB

During a study monitoring visit the study monitor observes several errors in the case report forms and a failure to attach source documents in support of the data recorded. The event should be a) Reported as a protocol deviation b) Part of study monitoring, immediately remediable and not reportable to the IRB c) Reportable as an adverse event to the sponsor d) An unanticipated event reportable by the IRB to OHRP.

b) Part of study monitoring, immediately remediable and not reportable to the IRB

A study enrolls 100 subjects is most likely to be a) Phase 1 b) Phase 2 c) Phase 3 d) Phase 4

b) Phase 2

The studies which are likely to provide the earliest reliable information about efficacy are a) Phase 1 b) Phase 2 c) Phase 3 d) Phase 4

b) Phase 2

ICH defined Therapeutic Exploratory studies are likely to be a) Phase I b) Phase II c) Phase Ill d) Phase IV

b) Phase II

Trials of short duration in narrow patient populations using pharmacological endpoints or clinical measures are likely to be a) Phase I b) Phase II c) Phase Ill d) Phase IV

b) Phase II

In a phase 2 design of hypertensive drugs the following protocols implemented. The patient's blood pressure is taken and the blood pressure is measured. The treatment drug is then given and the blood pressure is measured again. This is an example of a) Factorial design b) Pre post design c) Parallel design d) Crossover design

b) Pre post design

For expedited reporting and event must be a) Serious b) Serious and unexpected c) Only temporally associated with drug administration d) Causally related to drug administration

b) Serious and unexpected

According to FDA guidance information on payments to subjects a) Need not be disclosed to the subjects until the first visit b) Should be disclosed in detail in the consent form c) May be verbally communicated to the subject d) May be disclosed in general terms in the consent form without committing to a dollar amount

b) Should be disclosed in detail in the consent form

Planning of clinical trials with children a) Should await the results of a trials in adults b) Should be planned with children in mind from the very outset c) Should exclude children ages d) Should be planned predominantly in adolescents

b) Should be planned with children in mind from the very outset

The study monitor reviews the protocol and schedule of assessments with the staff during a) Routine site visits b) Site initiation visit c) Study close out visit d) Pre-study visit

b) Site initiation visit

Responsibility for the investigational product rests with the a) Monitor b) Sponsor c) CRO d) Investigator

b) Sponsor

Pharmacokinetic studies of a pediatric drug requires a) Studies in adults with the disease b) Studies in pediatric populations with the disease c) Studies in healthy children d) Studies preferably carried out in older children or adolescents

b) Studies in pediatric populations with the disease

Phase 1 studies of a cancer drug are done in a) Healthy volunteers b) Subjects with cancer c) Subjects with cancer who have failed conventional therapy d) Subjects with cancer with more than a year's anticipated survival

b) Subjects with cancer

In a confirmatory trial the following apply a) Phase 1 results are verified in phase 2 trials b) Test the key hypothesis, effect size and clinical significance c) Conduct the trial in a large sample of subjects d) The design is that described for the use of an approved drug

b) Test the key hypothesis, effect size and clinical significance

A subject on a test drug for allergic rhinitis reports to the CRC that he was hospitalized for respiratory distress because the test drug is not working. The CRC should immediately inform a) The sponsor b) The PI c) The IRB d) The regulatory agency

b) The PI

The most likely person to contact for a trial related injury would be a) The IRB b) The investigator or other designated person for medical safety c) The sponsor d) The institution

b) The investigator or other designated person for medical safety

An example of demand characteristics in an experimental study is a) An effect caused in a treatment group because of the special attention paid to it by the investigator b) The participants form an interpretation of the experiment's purpose and modify their behavior accordingly c) Occurs in cognitive trial where the perception of one trait is influenced by the perception of another trait. d) An effect ,caused by psychological influence, experienced by the patient when they are unaware that they are not being administered the medication for the clinical trial e) The investigator's paradigm in experimental design and analysis predetermines the interpretation of the results. f) Patients in the control group become aware of group membership and turn rebellious and alter behavior to contradict the experiment's purpose

b) The participants form an interpretation of the experiment's purpose and modify their behavior accordingly

In pediatric clinical trials a) The assent of the child always overrides the permission of the parent b) The pediatric subject is usually legally incapable of providing informed consent c) The approval of both parents is required d) A witness to the consent process is mandatory

b) The pediatric subject is usually legally incapable of providing informed consent

In assessing the payments to subjects in light of the Belmont report the IRB should be concerned about a) Respect for persons b) The principle of justice c) The principle of beneficence d) Loss of dignity

b) The principle of justice

A medically competent subject who has recently undergone physical injury in an accident to his writing hand signs the consent form with an "x" The consent process should include a) An impartial witness b) The signature of a legal guardian c) A medical counselor d) The signature of a family member

b) The signature of a legal guardian

Regarding withdrawals or drop outs among study subjects, ICH recommends that a) They be reported to the IRB. b) They be recorded and explained on the appropriate CRFs c) Notifications be sent to the regulatory authorities d) Notification be sent to the institution.

b) They be recorded and explained on the appropriate CRFs

If the sponsor discontinues clinical development of a drug the records of a clinical trial should be retained for a) One year b) Two years c) Three years d) Four years

b) Two years

Payment in a lump sum at the beginning of the research study may be viewed as--------- ; while payment in a lump sum at the end of the visit schedule may constitute --- a) Convenient; a late payment b) Undue influence; coercion c) Beneficence; disrespect for persons d) Justice; maleficence

b) Undue influence; coercion

Under ICH guidelines approaches to minimize distress in pediatric clinical studies include all of the following except a) Use of personnel skilled in pediatric procedures b) Use of age appropriate gifts as compensation c) A setting with furniture and play equipment appropriate to the age d) Use of an environment familiar to the child where they have received clinical care

b) Use of age appropriate gifts as compensation

What are the kidney function tests? (check all the apply) a. AST b. BUN c. Serum Creatinine d. GFR

b, c, d b. BUN c. Serum Creatinine d. GFR

The minimum number of subjects that can be enrolled in a clinical trial is a. 0 b. 1 c. 10 d. 100

b. 1

The probability of erroneously failing to reject the null hypothesis is described as a. Type I error b. Type II error c. Type Ill error d. Risk assessment

b. Type II error

The packaging of investigational drugs should ideally

be designed to help with subject compliance

Nonclincal Study

biomedical studies not performed on human subjects

Methods to avoid bias

blinding randomization

Regulatory Authorities

bodies having the power to regulate- the authorities that review submitted clinical data and those that conduct inspections

Double Dummy

both groups of patients in a placebo controlled study take

FDA requires the disclosure by the principal investigator of financial payments of an amount greater than a) $5000 b) $10,000 c) $25000 d) $50000

c) $25000

The costs of a clinical trial are apportioned so that the following procedure will be reimbursed 1. One MRI at $100 2. Lab tests for the initial visit $50 3. One ECG at $50 A patient undergoing three visits each with an MRI a lab tests and an ECG would-be liable for a) $200 b) $300 c) $400 d) $500

c) $400

FDA requires disclosure by the principal investigator of equity interest greater than a) $10000 b) $25000 c) $50000 d) $75000

c) $50000

The serum creatinine values for a subject on three consecutive visits are 1.6, 1.4, and 1.2. the mean value which can be used to determine if the subject should proceed in the clinical trial is a) 1.1 b) 1.3 c) 1.4 d) 1.5

c) 1.4

1.1 A monitor assessing drug accountability makes a note of the following • The sponsor has mailed 50 vials to the site research pharmacist • Thirty vials were dispensed to patients • Of the ones dispensed 20 were used The number of vials eligible for drug destruction is a) 10 b) 20 c) 30 d) 40

c) 30

A subject has to take his medication twice a day and is given a pill box with a counter to assess compliance for the week. The pill count at the end of the week shows one tablet left on Monday, Tuesday, Wednesday, Thursday and Friday and two pills left on Saturday. The compliance rate is a) 20% b) 40% c) 50% d) 80%

c) 50%

The subject's weight in his medical record is reported at 150 lbs. What would be his approximate weight in kg? a) 175 kg b) 100kg c) 75kg d) 35 kg

c) 75kg

A response to a medical product in the context of an adverse drug reaction is best defined as a) An event documented in the medical record b) A death c) A causal relationship between a drug and an adverse event that is possible d) An event that occurs in the time frame of drug administration

c) A causal relationship between a drug and an adverse event that is possible

An active control is best represented by a) Any drug that has shown activity against the disease b) A drug that has been shown to be non-inferior in an equivalence trial c) A drug that has shown efficacy in a superiority trial d) All of the above

c) A drug that has shown efficacy in a superiority trial

In ICH-GCP a co-investigator is defined as a) A person responsible for overseeing the progress of a clinical trial b) An individual supervised by the team leader c) A person responsible for assuming, when needed, the responsibilities of an investigator/team leader d) A person responsible for funding the clinical trial.

c) A person responsible for assuming, when needed, the responsibilities of an investigator/team leader

In ICH-GCP a sponsor is defined as a) A person responsible for the conduct of the clinical trial b) An individual supervised by the team leader c) A person/entity responsible for initiation, management and financing of a clinical trial. d) A person/ entity responsible for overseeing the progress of a clinical trial

c) A person/entity responsible for initiation, management and financing of a clinical trial.

In a study under an IND involving an oral drug the subject misses two doses and takes an extra-large dose on the third day to make up for the missed doses. She suffers a serious medical event which needs hospitalization. The vent is a) A protocol deviation only b) A serious adverse event only c) A protocol deviation that is also a serious adverse event d) Not reportable because this is a patient error and not an investigator error.

c) A protocol deviation that is also a serious adverse event

In a clinical trial of congestive heart failure a hospitalization for one day until acute symptoms resolve is considered usual. Patient X was hospitalized for a period for five days. This event a) Is an adverse event b) Unexpected adverse drug reaction c) A serious adverse drug reaction d) Cannot be characterized as serious as it is reflective of the disease and not the drug

c) A serious adverse drug reaction

A subject in clinical trial for GI reflux disease develops renal failure, an event not described in the protocol or informed consent. The event is a) Unanticipated problem that does not involve an adverse event and needs to be reported under DHHS regulations b) Adverse event that does not represent an unanticipated problem and does not need to be reported under DHHS regulations c) Adverse event that does represent an unanticipated problem that needs to be reported under regulations d) Regulations do not apply

c) Adverse event that does represent an unanticipated problem that needs to be reported under regulations

The bias on part of a subject in a clinical trial would best be represented by a) Complaints to OHRP regarding the IRB b) Noncompliance with the visitation schedule c) Altered behavior which may subvert the objective of the trial d) Non-authorized variation in the drug dosing schedule.

c) Altered behavior which may subvert the objective of the trial

An investigator participating in a device study must complete a) A 1572 b) A1571 c) An investigator agreement d) A form from Appendix M

c) An investigator agreement

The IRB has a non-scientific member whose attendance at meetings is erratic and leads to loss of quorum. The IRB may address this situation by a) Firing the non-scientific member b) Meet without the member c) Appoint approved matching alternates for this member d) Write institutional policy for disciplining unruly IRB members

c) Appoint approved matching alternates for this member

The threshold payment amounts to be disclosed to the institutional conflict of interest committees in most institutions a) ·'Are the same as the FDA guidelines b) Are greater than the FDA guidelines c) Are less than the FDA guidelines d) Are greater than the NIH guidelines

c) Are less than the FDA guidelines

In a crossover design the subjects a) Randomized to two arms each with a different treatment b) Are evaluated before and after drug administration c) Are randomized to a sequence of two treatments d) Are evaluated simultaneously for varying combinations of treatments

c) Are randomized to a sequence of two treatments

Serious adverse drug reactions must be filed with regulatory agencies a) As soon as possible, but not later than 8 days of first knowledge b) As soon as possible, but not later than 10 days of first knowledge c) As soon as possible, but not later than 15 days of first knowledge d) As soon as possible, but not later than 1 month of first knowledge

c) As soon as possible, but not later than 15 days of first knowledge

During a monitoring visit the monitor would do all of the following except a) Review discrepancies in CRFs and source documents with the Pl or CRC b) Review informed consent forms signed by new enrollees c) Ask for updates on the Pl's conflict of interest d) Update the regulatory document binder

c) Ask for updates on the Pl's conflict of interest

During the informed consent process the Pl receives an emergency call from a patient and has to curtail the conference. The CRC should a) Ask the subject to sign the consent as most of the conference was conducted b) Take over the conference himself and complete it c) Ask the subject to take the consent form with him and bring it back for another scheduled consent conference d) Report the incident as a protocol deviation to the IRB

c) Ask the subject to take the consent form with him and bring it back for another scheduled consent conference

In the United States pediatric clinical research studies are designated different categories based on a) Disease severity b) Complexity of study design c) Assessment of the level of risk d) Age range of the study participants

c) Assessment of the level of risk

For a subject who has had a consent form emailed to him the CRC should ensure all except a) The subject brings the consent form to the conference b) Supply a new consent form if the subject has forgotten to bring the consent form with him c) Assume that the subject has read and understood the form d) Have the subject sign and date the form while the CRC is present

c) Assume that the subject has read and understood the form

Which of the following statements is true of auditing and monitoring of a clinical trial? a) Audits often occur prior to clinical trial enrollment as do monitoring visits b) Audits and monitoring visit are both periodic in nature and occur throughout the progress of a clinical trial c) Audits are generally performed by a regulatory authority whereas monitoring is done by a CRO or sponsor d) Both audits and monitoring visits involve necessary assessments at study close out

c) Audits are generally performed by a regulatory authority whereas monitoring is done by a CRO or sponsor

According to federal regulations, recruitment related activities for a clinical trial a) Should be free of bias b) Should provide payment related incentives c) Be free of coercion and undue influence d) Imply the possibility of a cure

c) Be free of coercion and undue influence

A pharmacist providing an investigational drug for a Phase I protocol makes an error in the dosing which is not associated with any adverse event in the subject. The event is a) A protocol deviation b) An unanticipated event of risk to self or others c) Both a and b d) Neither because it is not a serious adverse event

c) Both a and b a) A protocol deviation b) An unanticipated event of risk to self or others

In a study under an IND an investigator enrolls a patient without informed consent which is done after the patient's first visit. Later the informed consent undergoes a change which requires reconsent. The investigator fails to obtain reconsent. The event is a) A protocol deviation b) Serious or continuing non-compliance c) Both a and b d) Not reportable because such an event is not described in the DHHS regulations

c) Both a and b a) A protocol deviation b) Serious or continuing non-compliance

An IDE is required before a new device a) Can be evaluated in a clinical trial b) Shipped across state lines c) Both a and b d) Neither a nor b

c) Both a and b a) Can be evaluated in a clinical trial b) Shipped across state lines

With regard to randomization the investigator should: a) Follow the sponsor's randomization plan b) Explain to the sponsor any premature unblinding due to an adverse event c) Both a and b d) Neither a nor b

c) Both a and b a) Follow the sponsor's randomization plan b) Explain to the sponsor any premature unblinding due to an adverse event

A high risk protocol deviation would be one with a) High risk to patient b) High risk to the study c) Both a and b d) High risk to the institution

c) Both a and b a) High risk to patient b) High risk to the study

Blinding is not advised in the evaluation of a significant risk device in a clinical trial because a) Installation of sham device would be unacceptable. b) The choice between surgery and no surgery for the two groups may mask the real risks of the device to the subject c) Both a and b d) Neither a nor b

c) Both a and b a) Installation of sham device would be unacceptable. b) The choice between surgery and no surgery for the two groups may mask the real risks of the device to the subject

In order to distinguish an event as being probably versus possibly related to a drug it is important to eliminate a) Natural progression of disease or disease related events b) Contributions from concomitant medications c) Both a and b d) Neither a nor b

c) Both a and b a) Natural progression of disease or disease related events b) Contributions from concomitant medications

During a study under an IND the investigator places the data on a lap top and the lap top is stolen. The data was not encrypted. The event is a) Protocol deviation b) Unanticipated event of risk to self or others c) Both a and b d) Serious adverse event

c) Both a and b a) Protocol deviation b) Unanticipated event of risk to self or others

The final report of the investigator should be provided to a) The IRB b) The regulatory authority c) Both a and b d) The institution

c) Both a and b a) The IRB b) The regulatory authority

According to HIPAA if the research subject revokes a HIPAA authorization: a) The revocation has to be in writing b) The revocation does not affect the use or disclosure of data prior to the revocation c) Both a and b d) Neither a nor b

c) Both a and b a) The revocation has to be in writing b) The revocation does not affect the use or disclosure of data prior to the revocation

A protocol deviation should be reported to the IRB a) Promptly b) Within the prescribed institutional guidelines c) Both a and b may apply d) According to the investigator's convenience as the time period is not specified in DHHS regulations.

c) Both a and b may apply a) Promptly b) Within the prescribed institutional guidelines

Safety and tolerability of the drug are best assessed in a) Phase I trials b) Phase 11 trials c) Continuously during drug development d) Phase Ill trials

c) Continuously during drug development

Missing values in a data set a) Are generally discounted in data analysis b) Are eliminated by extrapolation c) Contribute to bias d) Have no effect on hypothesis testing

c) Contribute to bias

In a phase 3 trial the following treatment scheme is adopted. Group A patients are started on the treatment drug and after a period of time switched over to the control drug. Group B patients are started on the control drug and then switched over to the treatment drug. This study design is an example of a) Parallel design b) Factorial design c) Crossover design d) Matched pair design

c) Crossover design

The guidelines for IRB composition in ICH are the same as those in a) DHHS only b) FDA only c) DHHS and FDA d) CIOMS

c) DHHS and FDA

That the investigator may make changes in a protocol without IRB approval to eliminate an immediate hazard is stated in a) DHHS only b) ICH only c) DHHS and ICH d) Not stated exactly in either DHHS or ICH.

c) DHHS and ICH

The decision to stop a Phase 2 or Phase 3 trial at all sites is the responsibility of a) FDA b) IRB c) DSMB d) The investigator at the coordinating center

c) DSMB

An IRB reviewing a study requires the investigator to replace the placebo group with a comparator drug. The likely action taken by the IRB would be a) Approve the study with the optional recommendation b) Approve the study with the condition c) Defer the study d) Disapprove the study

c) Defer the study

Delegation of authority to the staff at the site level should be a) Done independently by the investigator b) Approved by the IRB c) Defined established and allocated by the sponsor d) Delegated to the CRO

c) Defined established and allocated by the sponsor

Bias is defined as a) Error in miscalculation of the final drug effect b) Trend to extrapolation in missing values c) Deviation in the estimation of a treatment effect from its true value d) Failure to use a complete data set for analysis

c) Deviation in the estimation of a treatment effect from its true value

The Belmont report addresses a) Compensation for medical injury b) Guidelines for conflict of interest c) Differences between practice and research d) Disclosure of incidental findings

c) Differences between practice and research

The principle of justice in the Belmont report relates to a) Payment to subjects b) Protection of vulnerable subjects c) Distribution of burdens and benefits d) Compensation for injuries

c) Distribution of burdens and benefits

The primary role of the witness is to ensure that a) Provide emotional support to the subject b) Satisfy the IRB that the informed consent process is adequate c) Ensure that the information was understood and consent freely given by the subject d) Verify that signatures and dates on the consent are adequate.

c) Ensure that the information was understood and consent freely given by the subject

The Per protocol analysis data set includes a) All randomized subjects b) All subjects who have not undergone SAEs c) Evaluable subjects compliant with the protocol d) Subjects with no missed visits as specified in the schedule of assessments

c) Evaluable subjects compliant with the protocol

A sponsor investigator must complete the following forms for the FDA at the initiation of a clinical trial I a) Form 1571 only b) Form 1572 only c) Form 1571 and Form 1572 d) Medwatch form 3500 A

c) Form 1571 and Form 1572

Financial disclosure in clinical trial under an IND is done on a) Form 1571 b) Form1572 c) Form 3455 d) Medwatch 3500 A

c) Form 3455

According to FDA regulations the investigator brochure must be a) Given by the sponsor to the IRB b) Given by the investigator to the IRB c) Given by the sponsor to the investigator d) Given by the sponsor to the CRO

c) Given by the sponsor to the investigator

An adverse drug reaction is one which a) Always associated with a hospitalization b) Qualifies for expedited reporting c) Has a reasonable suspected causal relationship to the drug d) Can usually be characterized as severe

c) Has a reasonable suspected causal relationship to the drug

The requirement that each individual involved in conducting a clinical trial should be qualified by education and training is affirmed in a) ICH only b) ICH and the FWA only c) ICH, FWA and NIH guidelines d) Not explicitly stated in the regulations

c) ICH, FWA and NIH guidelines

In frequently reviewing studies involving vulnerable subjects the IRB should consist of a) Community members sympathetic to these groups b) Attorneys who specialize in legal issues that pertain to these groups c) Individuals who are knowledgeable and experienced in working with these groups d) Subject advocates for each vulnerable group

c) Individuals who are knowledgeable and experienced in working with these groups

Regarding informed consent in clinical trials ICH states that a) Waivers of informed consent are possible b) Waiver of documentation of informed consent may be given c) Informed consent should be obtained from every subject d) Parental permission should be given only when it is a reasonable protection

c) Informed consent should be obtained from every subject

Investigator in institution A is carrying out an IRB approved studies and wishes to post flyers for his study in Institution B. According to OHRP guidance a) Institution B must carry out an IRB review of the study. b) Only the institution B's institutional official needs to be notified c) Institution B is not engaged in the research d) Institution B needs to have an FWA

c) Institution B is not engaged in the research

When reviewing studies in specialized areas the IRB should a) Consider written review only from outside consultants b) Rely on the expertise of its voting members and need not use consultants c) Invite competent consultants but not have them vote d) Invite consultants and include them in the vote

c) Invite competent consultants but not have them vote

The population of a clinical trial reflects all of the following except a) My be narrow in early trials to maximize effects b) Tend to mirror the target disease population in later trials c) Is always significantly large in Phase 1 trials to ensure reliable toxicology results d) Must balance eligibility criteria and treatment effects

c) Is always significantly large in Phase 1 trials to ensure reliable toxicology results

An adverse event is defined as one which a) Results in hospitalization b) Causes a disability c) Is not necessarily causally related to drug d) Is life threatening

c) Is not necessarily causally related to drug

A physician wishes to inform his patients about a clinical trial for which he is the principal investigator. He should a) Present the information in person to the patient b) Ask his nursing staff to present information to the patients c) Leave the clinical trial brochures in his waiting room and provide his research staff member as the contact for further information d) E-mail the information to his patients with a recommendation for enrollment thus avoiding direct patient contact

c) Leave the clinical trial brochures in his waiting room and provide his research staff member as the contact for further information

An adverse event that is severe in intensity a) May qualify for expedited reporting b) Could be classified as a serious adverse event c) May not meet the definition of a serious adverse event d) Need not be reported to the sponsor if it is part of the disease condition

c) May not meet the definition of a serious adverse event

The primary variable reflects all of the following except a) Must provide convincing evidence for the primary objective b) Is usually the efficacy variable c) Must provide significant support for secondary variables d) May be restricted in some trials only to safety and tolerability

c) Must provide significant support for secondary variables

An IRB member with a conflict of interest should a) Not participate in the discussion of the study in question b) Not participate in vote for the study in question c) Not participate in the initial discussion or vote for the study d) May be present if the IRB chair overrules the conflict of interest consideration

c) Not participate in the initial discussion or vote for the study

Which of the following is cited as an influence in the Belmont Report? a) The Milgram study b) The tea room trade study c) Nuremberg war crimes trial involving Nazi medical experiments d) The Guatemala Syphilis study

c) Nuremberg war crimes trial involving Nazi medical experiments

An example of a halo effect in a psychosocial study is a) An effect caused in a treatment group because of the special attention paid to it by the investigator b) The participants form an interpretation of the experiment's purpose and modify their behavior accordingly c) Occurs in cognitive trial where the perception of one trait is influenced by the perception of another trait d) An effect ,caused by psychological influence, experienced by the patient when they are unaware that they are not being administered the medication for the clinical trial e) The investigator's paradigm in experimental design and analysis predetermines the interpretation of the results. f) Patients in the control group become aware of group membership and turn rebellious and alter behavior to contradict the experiment's purpose

c) Occurs in cognitive trial where the perception of one trait is influenced by the perception of another trait

In ICH-GCP an inspection is defined as a) A systematic and independent examination of trial related activities and documents b) An investigation intended to discover and verify the clinical effects of an investigational product c) Official review of documents, facilities, records and any other resources d) Overseeing of the progress of a clinical trial

c) Official review of documents, facilities, records and any other resources

If a regular voting member and his alternate both attend the meeting then a) Only the voting member can present the study b) Only the voting member can participate in the motion c) Only the voting member can count towards the quorum d) Only the voting member can be shown as attending the meeting in the minutes

c) Only the voting member can count towards the quorum

In a phase 3 trial subjects are randomized to a treatment group and a control (drug) group. The assignments remain unchanged for the duration of the trial. This is an example of what study design a) Pre-post design b) Crossover design c) Parallel design d) Matched pair design

c) Parallel design

In a phase 1 oncology study in adults the subjects are likely to be a) Healthy volunteers b) Patients in remission c) Patients with cancer who have failed standard therapy d) Patients who are terminally ill.

c) Patients with cancer who have failed standard therapy

When a subject voluntarily withdraws from participation in a research study: a) Payments for past visits should be withheld b) The rate of payment should be recalculated based on the completed visits c) Payments should be made up to and including the latest visit d) Payments should be made for all visits regardless

c) Payments should be made up to and including the latest visit

The studies most likely to influence the labeling of the drug and its approval by the FDA are a) Phase 1 studies b) Phase 2 c) Phase 3 d) Phase 4

c) Phase 3

The trial which would most influence FDA approval and the final product label for a drug is a) Phase 1 b) Phase 2 c) Phase 3 d) Phase 4

c) Phase 3

ICH defined Therapeutic Confirmatory studies re likely to be a) Phase I b) Phase II c) Phase III d) Phase IV

c) Phase III

Studies which provide the most information for risk benefit relationship of a drug are likely to be a) Phase I b) Phase II c) Phase III d) Phase IV

c) Phase III

Adverse events encompass a) Physical harms only b) Psychological harms only c) Physical and psychological harms d) Harms determined as relevant and serious by the investigator.

c) Physical and psychological harms

ICH advises that in terms of compensation for claims arising during a clinical trial the sponsor should a) Not provide any assurances to the site b) Assume negligence on the part of the Pl c) Provide insurance or indemnify the investigator d) Compensate only life threatening emergencies on the part of the subject.

c) Provide insurance or indemnify the investigator

An additional element of consent to be disclosed to subjects in the consent form if appropriate, is the number of subjects involved in the study. The likely reason behind this requirement is a) Satisfy the subject's curiosity b) The sponsor's desire to impress the subject with the enrollment numbers c) Provide the subject with an idea of how risks and burdens are being shared d) Assure subjects that they are not alone in their decision to enroll

c) Provide the subject with an idea of how risks and burdens are being shared

Among the various models proposed for payments to research subjects the IRB is most likely to favor a) The Market model which suggests that payments be regulated by the laws of supply and demand b) A wage payment model in which payment would be based on reimbursement for wages for time involved but close to the minimum wage. c) Reimbursement model to cover a subject's reasonable expenses d) A benefit model which views the payment as a supplemented benefit

c) Reimbursement model to cover a subject's reasonable expenses

The three principles in the Belmont report relate to a) Privacy, confidentiality, conflict of interest b) DHHS regulations, IRB procedures, FDA guidance's c) Respect for persons, beneficence, justice d) Informed consent, Debriefing forms, deception

c) Respect for persons, beneficence, justice

The IRB should refer to the principle of beneficence in the Belmont report when it is evaluating a) Payment to subjects b) Study populations c) Risk benefit ratio d) Informed consent

c) Risk benefit ratio

DSMB's primary responsibility is to review a) Protocol deviations b) The informed consent c) Safety and efficacy at defined intervals d) Monitoring data quality and integrity

c) Safety and efficacy at defined intervals

For an adverse event to be reported to the FDA it must be a) Serious b) Serious and unanticipated c) Serious , unanticipated and possibly related d) Serious, unanticipated and probably related

c) Serious , unanticipated and possibly related

Breaking the blind for a single subject a) Implies breaking the blind for the study group b) May be done at the discretion of the monitor c) Should be implemented when deemed essential for subject's care d) Always involves a serious adverse event

c) Should be implemented when deemed essential for subject's care

Nonclinical studies a) Should be performed in at least three species b) Must include a disease animal model c) Should be sufficient to indicate safety in human studies d) Are not needed before some human studies

c) Should be sufficient to indicate safety in human studies

IRBs reviewing pediatric clinical trials a) Are required to have a pediatrician according to the regulations b) May review the studies without a pediatrician c) Should have a member or experts consulted who are knowledgeable in pediatric ethics and psychosocial issues d) Should have pediatrician who is trained in the disease subspecialty of the clinical trial.

c) Should have a member or experts consulted who are knowledgeable in pediatric ethics and psychosocial issues

Inclusion and exclusion criteria a) Can be set to maximize enrollment b) Are independent of preclinical studies c) Should remain constant during a clinical trial d) May change as needed during a clinical trial

c) Should remain constant during a clinical trial

According to ICH the informed consent should be a) Signed but not dated by the subject b) Signed and dated by the subject only c) Signed and dated by the subject and the person obtaining consent d) Witnessed for all consent situations

c) Signed and dated by the subject and the person obtaining consent

Methods to avoid the bias in a clinical trial generally involve a) Single-blind only b) Double-blind only c) Single or double blind d) Open label

c) Single or double blind

Clinical trial protocols should reflect a) Reasonable costs for the clinical trial b) Minimize sample sizes to reduce risks c) Sound scientific design d) The use of control groups whenever possible.

c) Sound scientific design

An independent DSMB for a clinical trial reaches a decision communicated in its report that the clinical trial be stopped for safety. The DSMB report should be sent to a) FDA b) IRB c) Sponsor d) OHRP

c) Sponsor

When the DSMB suspends a clinical trial it is customary for the principal investigator a) To keep the commitment to treat new enrollees because they have signed the informed consent b) Keep the treatment schedule for currently enrolled subjects c) Stop new enrollment and treatments and keep the study open only for long term follow up of existing subjects d) Ignore the dictates of the DSMB as it does not know the events at the site in any detail.

c) Stop new enrollment and treatments and keep the study open only for long term follow up of existing subjects

The term non-clinical studies refers to a) Studies in vitro cell culture models b) Studies in organ culture c) Studies in animal models d) Pilot human studies

c) Studies in animal models

The study monitor verifies final disposition of unused drug during a) Routine site visits b) Site initiation visit c) Study close out visit d) Pre-study visit

c) Study close out visit

According to ICH serious unexpected reaction to a drug should be a) Submitted to the appropriate regulatory authority within one week b) Submitted to the appropriate regulatory authority within 15 days c) Submitted to the appropriate regulatory authority on an expedited basis d) Submitted promptly to the IRB

c) Submitted to the appropriate regulatory authority on an expedited basis

The minutes of the IRB meeting should record a) A detailed account of the discussion for every study b) The reasons for members voting against the motion c) Summary of the discussion of controverted issues d) An account of the scientific evaluations for each study

c) Summary of the discussion of controverted issues

The term double dummy refers to a) Double blinded trial b) Placebo controlled trial c) Technique to retain the blind when administering supplies to non-identical groups d) All of the above

c) Technique to retain the blind when administering supplies to non-identical groups

An essential element of informed consent affirmed in most ethical frameworks is a) That the research should bear fruitful results b) That the risk of the research should always be minimal c) That participation is voluntary, without penalty or loss of benefits d) That compensation for research is fair

c) That participation is voluntary, without penalty or loss of benefits

The sponsor should ensure that in planning for a clinical trial the sponsor should ensure all of the following except a) Sufficient safety and efficacy data is available from non clinical studies b) Pilot studies in human subjects have been performed c) That the drug will be safe in pregnant women and children d) Data to support route, dosage and duration of treatment is available.

c) That the drug will be safe in pregnant women and children

The Commission that formulated the Belmont report was created as a part of a) The National Research Act of 1985 b) The Biomedical Research Act of 1977 c) The National Research Act of 1974 d) The National Commission of 1979

c) The National Research Act of 1974

Regarding recruitment of in pediatric clinical trials all of the following are true except a) Inappropriate inducements should be avoided b) Reimbursements and subsistence costs may be covered c) The compensation should be divided between the parent and the child d) Any level of compensation no matter how small should be reviewed by the IRB.

c) The compensation should be divided between the parent and the child

An IRB recommends that a research study be approved with conditions. The investigator submits the revised study and it is approved by the IRB chair. The approval date for the study would be a) The date of the initial review b) The date of submission of the revision by the investigator c) The date of approval by the IRB chair d) The date the letter of approval is mailed out.

c) The date of approval by the IRB chair

In a single blind trial a) Both the investigator and the subject know that the treatment drug is being administered. b) Neither the investigator nor the subject knows whether drug or placebo is being administered c) The investigator knows that the drug is being administered but the subject does not d) The subject knows that the drug is being administered but the investigator does not

c) The investigator knows that the drug is being administered but the subject does not

In a questionnaire study of homeless subjects the investigator wishes to pay each subject $10. The IRB could be concerned about this payment because a) The payment could be used to pay for drugs b) The payment violates the principle of justice in the Belmont report because non study participants are not being paid c) The payment may constitute undue influence d) The payment may be too small in consideration of the principle of beneficence in the Belmont report

c) The payment may constitute undue influence

In assessing sample size the items that need to be specified include all except a) The primary variable and test statistic b) The null and alternative hypothesis c) The projected cost of the trial for the designated sample size d) Type I and Type II errors

c) The projected cost of the trial for the designated sample size

Which of the following regarding the protocol for a clinical trial is correct a) The protocol should reflect sound design is affirmed in DHHS but not ICH b) The protocol should reflect sound design is reflected in ICH but not DHHS c) The protocol should reflect sound design is affirmed in both ICH and DHHS d) There is no reference to sound design in either DHHS or ICH.

c) The protocol should reflect sound design is affirmed in both ICH and DHHS

Regarding the reporting of serious adverse events which of the following statements is included in the Declaration of Helsinki: a) Serious adverse events need to be reported only if they are unanticipated and possibly related to the research. b) The data and safety monitoring board should send reports directly to the research ethics committee c) The researcher must provide monitoring information to the committee especially information about any serious adverse events d) The research ethics committee should review all adverse events from all participating sites in a clinical trial.

c) The researcher must provide monitoring information to the committee especially information about any serious adverse events

A CRC is preparing a project tracker for following the progress of enrolled subjects in a clinical trial for study initiation to study close out. He should follow a) The protocol b) The enrollment log c) The schedule of assessments d) The screening log

c) The schedule of assessments

In ICH the consent form should explain the responsibilities of a) The sponsor b) The investigator c) The subject d) The IRB and other regulatory agencies

c) The subject

An essential element of consent that is affirmed in most ethical frameworks is that a) There should be compensation for medical injury b) There should be no deception used in the study c) The subject may discontinue participation at any time without penalty d) Drugs which might diminish the quality of life not be used.

c) The subject may discontinue participation at any time without penalty

The IRB records must be maintained for how long after the completion of the research a) One year b) Two Years c) Three years d) Five years

c) Three years

The Declaration of Helsinki advises this design for clinical trials whenever possible: a) Double blinded placebo control b) Single blinded placebo control c) Treatment drug with a comparator control d) Open label treatment

c) Treatment drug with a comparator control

According to OHRP guidance unanticipated problems which are other than serious should be reported to the IRB within a) One day b) One week c) Two weeks d) One month

c) Two weeks

The timing of pediatric studies of a drug is dependent on a) Completion of Phase 1 trials in adults b) Successful non clinical studies c) Type of disease and safety and efficacy of alternate treatments d) Known safety profile of the drug in the adult population

c) Type of disease and safety and efficacy of alternate treatments

A subject in a clinical trial experiences severe diarrhea, which requires hospitalization an event not described in the investigator's brochure. The event is a) Not serious because it is not life threatening b) Expected by the Pl and not reportable to the IRB c) Unexpected and serious and should be reported to the IRB d) Should be reported as an adverse event to the sponsor, but not the IRB

c) Unexpected and serious and should be reported to the IRB

For identification of all subject data the sponsor should a) Use the medical record number b) Use the name c) Use an identification code d) Use a social security number or driver's license number

c) Use an identification code

Approaches to minimize discomfort of procedures in pediatric clinical trials includes all of the following except a) Topical anesthesia to place IV catheters b) Use of indwelling catheters c) Use of anesthesia in MRI procedures d) Collection of research samples at the same time as clinical care samples are collected.

c) Use of anesthesia in MRI procedures

The definition of a child as classified by age in the United States a) Is specified in the Federal regulations b) Is designated as being the same in countries that are signatories to ICH guidelines c) Varies by state in the United States d) Is set at 18 years as a universal standard

c) Varies by state in the United States

In a clinical trial the following design is followed. All subjects are placed on the treatment drug for a period of time. The baseline measure is then taken. Then they are randomized into two groups. One group receives the treatment drug and the other group receives a placebo. The patients are then reevaluated for the outcome measure. This design is an example of a) Crossover design b) Parallel design c) Withdrawal trial d) Factorial design

c) Withdrawal trial

Development of drug for a disease exclusively affecting the pediatric population requires a) The entire development program in children only b) Safety and tolerability data obtained in adults c) a only d) a and b

c) a only a) The entire development program in children only

The subject's weight in his medical record is reported at 150 lbs. What would be his approximate weight in kg? a. 175 kg b. 100kg c. 75kg d. 35 kg

c. 75kg You divide by 2.2

Current Good Manufacturing Practices

cGMP

is a paper or electronic questionnaire specifically used in clinical trial research, is the tool used by the sponsor of the clinical trial to collect data from each participating patient

case report form (or CRF)

E7-E11

clinical trials

Institutional Review Board (IRB)

committee of administrators, scientists, and community members that reviews proposals for research involving human participants. Oversees the ethical and scientific aspects of a study, with special focus on risk of harm vs benefit assessment for participating subjects.

A trial that is an adequately controlled trial where hypotheses are stated in advance and evaluated according to a protocol. This type of trial may be implemented when it is necessary to provide additional or firm evidence of efficacy or safety. They can be used to demonstrate or confirm efficacy, establish a safety profile, investigate benefit/risk, or establish dose- response.

confirmatory clinical trial

The drug concentration used in preclinical studies is likely to higher than in human studies by a) 5 fold b) 10 fold c) 100fold d) 1000 fold

d) 1000 fold

A drug with a half-life of 1 day is initiated at 100mg dose. How much drug would be left in the subject's blood stream after four days? a) 50 mg b) 75 mg c) 35 mg d) 12.5 mg

d) 12.5 mg 1 day=100mg 2 day=50mg 3 day=25mg 4 day=12.5mg

In ICH children are defined as between the ages of a) 7-13years b) 2-6 years c) 4-11 years d) 2-11 years

d) 2-11 years

A drug has a half- life of one day and a Minimum Effective Concentration (MEG) of 12.5 mg. It has an initial concentration of 100 mg. The drug will stop being effective after a) 1 day b) 2days c) 3 days d) 4 days

d) 4 days

A drug has a half-life of one day and has an initial plasma concentration of 100 mg. The concentration after four days is a) 50 b) 25 c) 12.5 d) 6.25

d) 6.25

The sequence of clinical trials for a device study a) Phase 1- 2-3-4 b) Phase 1-2-3 c) A single clinical trial d) A feasibility study followed by a pivotal study.

d) A feasibility study followed by a pivotal study.

1.1 When an IRB approves a study with conditions the subsequent review is likely done by any of the following except a) IRB chair b) IRB member reviewer designated by the chair c) Review by an IRB consultant followed by the review of an IRB designated reviewer d) A fully convened IRB

d) A fully convened IRB

An adverse event is defined as a) A mild clinical event not associated with hospitalization b) An episode that interrupts a daily activity c) An event that requires a doctor's visit d) A medical occurrence which may not be causally related to a drug

d) A medical occurrence which may not be causally related to a drug

An adverse drug reaction is a) A congenital birth defect caused by a drug b) An event described in the Adverse Drug Reaction Tabulation at the FDA c) A repeat hospitalization caused by progression of disease d) A noxious and unintended response to a drug at any dose

d) A noxious and unintended response to a drug at any dose

In ICH-GCP a monitor is defined as: a) A person responsible for the conduct of the clinical trial b) An individual supervised by the team leader c) A person/entity responsible for initiation, management and financing of a clinical trial d) A person responsible for overseeing the progress of a clinical trial

d) A person responsible for overseeing the progress of a clinical trial

According to ICH the following statements about the involvement of a CRO in a clinical trial are correct: a) A sponsor may transfer any or all of the trial related duties and functions to a CRO b)The CRO should implement quality assurance and quality control c)The delegated CRO responsibilities should be specified in writing d) AII of the above

d) AII of the above a) A sponsor may transfer any or all of the trial related duties and functions to a CRO b)The CRO should implement quality assurance and quality control c)The delegated CRO responsibilities should be specified in writing

The IRB staff should maintain a) Complete copies of all IRB activities b) Copies of all external audits of the IRB c) Financial records of IRB charges to sponsors for IRB reviews d) Adequate documentation of IRB activities

d) Adequate documentation of IRB activities

Regarding the storage and handling of investigational products ICH a) Assigns the responsibility to the principal investigator only b) Assigns responsibility to the CRO and study monitor c) Does not mention storage and handling d) Affirms that handling and storage be in accordance with GMP.

d) Affirms that handling and storage be in accordance with GMP.

Regarding the protection of privacy and confidentiality, ICH: a) States that specific guidelines be followed for the protection of confidentiality b) Affirms the principles of HIPAA in privacy and confidentiality c) Does not mention privacy and confidentiality explicitly in its guidelines d) Affirms that privacy and confidentiality be protected in accordance with applicable regulatory requirements

d) Affirms that privacy and confidentiality be protected in accordance with applicable regulatory requirements

According to the FDA when a subject withdraws from a clinical trial: a) All data should be destroyed related to that individual b) Only data related to serious adverse events be retained c) The data be kept only if the IRB recommends it d) All data collected up to the time of withdrawal must remain in the trial data base in order for the study to be scientifically valid

d) All data collected up to the time of withdrawal must remain in the trial data base in order for the study to be scientifically valid

An IRB must maintain written procedures for a) Conducting initial and continuing review b) Determining which projects require review more often than annually c) Ensuring prompt reporting of proposed changes in research d) All of the above

d) All of the above

Disadvantages of a crossover design include a) A carryover effect from one treatment to the other b) Often not possible for acute disease c) Cannot be used when the initial treatment has long term or permanent effect (e.g. vaccine trials) d) All of the above

d) All of the above a) A carryover effect from one treatment to the other b) Often not possible for acute disease c) Cannot be used when the initial treatment has long term or permanent effect (e.g. vaccine trials)

Which of the following is an unexpected adverse event a) A report which adds significant information to an already documented serious adverse event b) A report of interstitial nephritis in a patient with acute renal failure c) A report of fulminant hepatitis in patient with an initial report of hepatitis d) All of the above

d) All of the above a) A report which adds significant information to an already documented serious adverse event b) A report of interstitial nephritis in a patient with acute renal failure c) A report of fulminant hepatitis in patient with an initial report of hepatitis

The essential basic elements of consent include a) A statement that the study involves research and its purpose b) A description and identification of experimental procedures c) The duration of the study d) All of the above

d) All of the above a) A statement that the study involves research and its purpose b) A description and identification of experimental procedures c) The duration of the study

Withdrawal of subjects from a research study implies that a) Activities involving interaction or intervention must cease b) Accessing identifiable private information about the subject be discontinued c) Observation or recording of private behavior must be stopped d) All of the above

d) All of the above a) Activities involving interaction or intervention must cease b) Accessing identifiable private information about the subject be discontinued c) Observation or recording of private behavior must be stopped

A subject withdrawing from a primary intervention component may still opt to continue secondary interventions which can include a) Activities that involve interventions other than those of the primary student interaction, including radiography and venipuncture b) Accessing private information including medical, educational or social service agency records c) Participation in studies required to monitor the long term safety of the subject d) All of the above

d) All of the above a) Activities that involve interventions other than those of the primary student interaction, including radiography and venipuncture b) Accessing private information including medical, educational or social service agency records c) Participation in studies required to monitor the long term safety of the subject

Events which may be classified as serious even though they do not result in hospitalization include a) Allergic bronchospasm b) Blood dyscrasias c) Convulsions d) All of the above

d) All of the above a) Allergic bronchospasm b) Blood dyscrasias c) Convulsions

A serious adverse event which has resulted in death requires a) An autopsy report b) A detailed account of relationship to drug c) A definitive exclusion of the effects of concomitant drugs d) All of the above

d) All of the above a) An autopsy report b) A detailed account of relationship to drug c) A definitive exclusion of the effects of concomitant drugs

An institution (medical) is defined as a site for clinical trials and includes a) Any public or private entity or agency b) A medical facility c) A dental facility d) All of the above

d) All of the above a) Any public or private entity or agency b) A medical facility c) A dental facility

An HUD is a device a) Applicable to less than 4000 individuals b) A device for which a clinical trial to prove effectiveness is not required c) For which no comparable device exists on the market d) All of the above

d) All of the above a) Applicable to less than 4000 individuals b) A device for which a clinical trial to prove effectiveness is not required c) For which no comparable device exists on the market

With regard to the training of monitors ICH states that they should be a) Appropriately trained with documented qualifications b) Have the needed scientific and clinical knowledge c) Familiar with the protocol and the consent form d) All of the above

d) All of the above a) Appropriately trained with documented qualifications b) Have the needed scientific and clinical knowledge c) Familiar with the protocol and the consent form

According to ICH the investigator should a) Ascertain the reason for withdrawal of a subject b) Inform a subject's physician about subject participation in a clinical trial c) Ensure that adequate care is provided for any adverse event experienced by the subject d) All of the above

d) All of the above a) Ascertain the reason for withdrawal of a subject b) Inform a subject's physician about subject participation in a clinical trial c) Ensure that adequate care is provided for any adverse event experienced by the subject

A subject being screened for a clinical trial of a drug for allergic rhinitis presents with a heart rate of 110 beats per minute. Tachycardia is not an exclusion criterion for the study. The CRC should a) Ask the sponsor's medical safety officer if the subject should be enrolled b) Do a repeat measurement of heart rate, in two weeks or more, to see if the symptom is repeatable c) Ask the subject if he has experienced any symptoms of a rapid heart beat d) All of the above

d) All of the above a) Ask the sponsor's medical safety officer if the subject should be enrolled b) Do a repeat measurement of heart rate, in two weeks or more, to see if the symptom is repeatable c) Ask the subject if he has experienced any symptoms of a rapid heart beat

Bias in a clinical trial can result from a) Aspects of trial design b) Operational aspects of the trial c) Statistical analysis and evaluation of the results d) All of the above

d) All of the above a) Aspects of trial design b) Operational aspects of the trial c) Statistical analysis and evaluation of the results

The essential documents for a clinical trial should be retained for a) At least two years after discontinuation of clinical development of the drug b) For a period of longer than two years if applicable regulatory requirements demand it c) As long as the sponsor deems it necessary d) All of the above

d) All of the above a) At least two years after discontinuation of clinical development of the drug b) For a period of longer than two years if applicable regulatory requirements demand it c) As long as the sponsor deems it necessary

The features of a source document should include their being a) Attributable and legible b) Contemporaneous c) Original and accurate d) All of the above

d) All of the above a) Attributable and legible b) Contemporaneous c) Original and accurate

Steps to reduce bias in clinical trial include a) Blinding b) Masking c) Randomization d) All of the above

d) All of the above a) Blinding b) Masking c) Randomization

In ICH, with regard to the retention of records by the investigator, the sponsor a) Can request retention for as long as the sponsor needs the data b) Can request retention for at least two years post NOA approval, according to FDA guidelines c) Should notify the investigator in writing when the records are no longer needed d) All of the above

d) All of the above a) Can request retention for as long as the sponsor needs the data b) Can request retention for at least two years post NOA approval, according to FDA guidelines c) Should notify the investigator in writing when the records are no longer needed

For a successful crossover design a) Carryover from a pervious treatment should be minimized b) The disease should be chronic and stable c) Drug effects should develop fully within the treatment period d) All of the above

d) All of the above a) Carryover from a pervious treatment should be minimized b) The disease should be chronic and stable c) Drug effects should develop fully within the treatment period

According to the FDA guidance on recruitment the following do not need IRB review a) Communications intended to be seen or heard by health professionals b) New stories c) Publicity such as financial page advertisements intended for investors d) All of the above

d) All of the above a) Communications intended to be seen or heard by health professionals b) New stories c) Publicity such as financial page advertisements intended for investors

IRB concerns about recruitment activities may include a) Completeness of information provided. b) Subtle coercion of the subjects in advertisements c) Compromised confidentiality in the initial recruitment process. d) All of the above

d) All of the above a) Completeness of information provided. b) Subtle coercion of the subjects in advertisements c) Compromised confidentiality in the initial recruitment process.

Criteria used for inclusion of data in the per protocol data set include a) Completion of minimal exposure to treatment b) Available measure of the primary variables c) Absence of protocol violations and eligibility criteria d) All of the above

d) All of the above a) Completion of minimal exposure to treatment b) Available measure of the primary variables c) Absence of protocol violations and eligibility criteria

For a patient with dementia the informed consent process should ensure that a) Consent of the legally acceptable representative should be obtained b) The subject should be informed about the trial to the extent compatible with understanding c) If capable the subject should sign and personally date the written informed consent d) All of the above

d) All of the above a) Consent of the legally acceptable representative should be obtained b) The subject should be informed about the trial to the extent compatible with understanding c) If capable the subject should sign and personally date the written informed consent

According to ICH the case report forms should be a) Consistent with source documents b) Dated, initialed and explained when needed c) Show the original when corrections are made d) All of the above

d) All of the above a) Consistent with source documents b) Dated, initialed and explained when needed c) Show the original when corrections are made

An SAE is a medical event associated with a) Death b) Life threatening event c) Hospitalization or increased hospitalization stay d) All of the above

d) All of the above a) Death b) Life threatening event c) Hospitalization or increased hospitalization stay

Drug accountability for the investigational product includes a) Delivery and inventory at the trial site b) Use and return of the product c) Batch ,serial numbers and expiration dates d) All of the above

d) All of the above a) Delivery and inventory at the trial site b) Use and return of the product c) Batch ,serial numbers and expiration dates

According to ICH the investigator should a) Demonstrate the potential for recruiting the required number of subjects b) Have sufficient time and staff to conduct the trial c) Ensure that the delegated staff be informed about the protocol, duties and product d) All of the above

d) All of the above a) Demonstrate the potential for recruiting the required number of subjects b) Have sufficient time and staff to conduct the trial c) Ensure that the delegated staff be informed about the protocol, duties and product

Drug efficacy is best established by a) Demonstrating superiority to placebo in a placebo control trial b) Demonstrating superiority in an active control trial c) Demonstrating a dose -response relationship d) All of the above

d) All of the above a) Demonstrating superiority to placebo in a placebo control trial b) Demonstrating superiority in an active control trial c) Demonstrating a dose -response relationship

The ICH guidelines differ from DHHS guidelines in that they a) Describe in detail the features of a non-therapeutic trial b) Describe the process of managing non-therapeutic trials c) Affirm the need for signed and dated consent and IRB approval of non-therapeutic trials d) All of the above

d) All of the above a) Describe in detail the features of a non-therapeutic trial b) Describe the process of managing non-therapeutic trials c) Affirm the need for signed and dated consent and IRB approval of non-therapeutic trials

The goals of a phase 4 trial include a) Detection of rare side effects b) Detection of side effects associated with chronic use of the drug c) Desensitization and loss of effect of the drug upon continued treatment d) All of the above

d) All of the above a) Detection of rare side effects b) Detection of side effects associated with chronic use of the drug c) Desensitization and loss of effect of the drug upon continued treatment

With respect to financial disclosure by the principal investigator in a clinical trial the FDA requires a) Disclosure of any financial arrangement b) Financial arrangements that could influence the outcome of the study c) Financial arrangements that meet the threshold requirements set forth in Form 3455 d) All of the above

d) All of the above a) Disclosure of any financial arrangement b) Financial arrangements that could influence the outcome of the study c) Financial arrangements that meet the threshold requirements set forth in Form 3455

When a subject withdraws from the research study, the investigator should according to OHRP guidance: a) Document whether the withdrawal was a decision of the subject or the investigator b) Document whether the withdrawal applied to both the primary and secondary components of the research c) Report the matter to the IRB depending on the prevailing institutional policy d) All of the above

d) All of the above a) Document whether the withdrawal was a decision of the subject or the investigator b) Document whether the withdrawal applied to both the primary and secondary components of the research c) Report the matter to the IRB depending on the prevailing institutional policy

The appropriate documents to send to the sponsor for a study close out visit include a) Drug accountability records b) Remaining data clarification forms c) The key to the coded samples d) All of the above

d) All of the above a) Drug accountability records b) Remaining data clarification forms c) The key to the coded samples

Considerations for determining the nature and timing of non-clinical studies include a) Duration and total exposure prosed in individual patients b) Long half life c) Route of administration d) All of the above

d) All of the above a) Duration and total exposure prosed in individual patients b) Long half life c) Route of administration

In a double blind trial the person who should be unaware of the treatment should not be involved in assessing a) Eligibility b) Endpoints c) Compliance d) All of the above

d) All of the above a) Eligibility b) Endpoints c) Compliance

Pre analysis review should include considerations of a) Exclusion of subjects from the data set b) Transformation of the variables c) Impact an statistical treatment of outliers d) All of the above

d) All of the above a) Exclusion of subjects from the data set b) Transformation of the variables c) Impact an statistical treatment of outliers

In response to new preclinical studies a sponsor revises the Investigator's Brochure which leads to changes in the inclusion and exclusion criteria and informs the Pl of these changes. The Pl or CRC should a) File an amendment to the IRB detailing the change b) Make revisions in the informed consent c) Reconsent existing enrolled subjects d) All of the above

d) All of the above a) File an amendment to the IRB detailing the change b) Make revisions in the informed consent c) Reconsent existing enrolled subjects

According to ICH the additional documents to be included on file after completion of the trial are a) Final close out study monitoring report b) Final report to IRB c) Clinical study report to document results and interpretation of trial d) All of the above

d) All of the above a) Final close out study monitoring report b) Final report to IRB c) Clinical study report to document results and interpretation of trial

1.1 The following agreements between sponsor and investigator should be documented in writing a) Financial arrangements and contracts b) Protocol agreement document c) Investigator's brochure receipt and confidentiality document d) All of the above

d) All of the above a) Financial arrangements and contracts b) Protocol agreement document c) Investigator's brochure receipt and confidentiality document

A development plan purpose is to a) Find a dose range that is simultaneously safe and effective b) Prove that the risk benefit relationship is acceptable c) Identify the subjects who would most benefit and indications for the use d) All of the above

d) All of the above a) Find a dose range that is simultaneously safe and effective b) Prove that the risk benefit relationship is acceptable c) Identify the subjects who would most benefit and indications for the use

The inclusion criteria for a clinical trial indicate that the serum creatinine should not exceed 1.2 mg. A subject repents with a serum creatinine of 1.25 and meets all the other inclusion criteria. The Pl feels that the subject is appropriate for the trial. The CRC should a) First indicate to the Pl that the inclusion criterion has not been met b) Permit the Pl to request a medical waiver of eligibility for the subject c) Not consent the subject until the sponsor has approved the medical waiver d) All of the above

d) All of the above a) First indicate to the Pl that the inclusion criterion has not been met b) Permit the Pl to request a medical waiver of eligibility for the subject c) Not consent the subject until the sponsor has approved the medical waiver

In a matched pair design a) For every subject assigned to treatment group A a matched subject on given characteristics is assigned to treatment group B b) Intergroup variability is reduced thus lowering the influence of confounding factors c) May be difficult to implement relative to unmatched parallel group design d) All of the above

d) All of the above a) For every subject assigned to treatment group A a matched subject on given characteristics is assigned to treatment group B b) Intergroup variability is reduced thus lowering the influence of confounding factors c) May be difficult to implement relative to unmatched parallel group design

For a surrogate variable to be reliable, they should a) Have a plausible relationship to clinical outcome b) Be supported by epidemiologic evidence c) Reflect a treatment effect that corresponds to clinical outcome d) All of the above

d) All of the above a) Have a plausible relationship to clinical outcome b) Be supported by epidemiologic evidence c) Reflect a treatment effect that corresponds to clinical outcome

A placebo control design is justified when a) High placebo response is expected b) Treatment drug is anticipated to have fluctuating outcomes c) There is mixed data on the effectiveness of the current standard treatment d) All of the above

d) All of the above a) High placebo response is expected b) Treatment drug is anticipated to have fluctuating outcomes c) There is mixed data on the effectiveness of the current standard treatment

If the investigator terminates a trial at the site without prior approval from the sponsor he should inform the following in writing of this decision a) IRB b) Institution c) Sponsor d) All of the above

d) All of the above a) IRB b) Institution c) Sponsor

The responsibility for the protection of clinical trial subjects rests with a) IRB/IEC b) Investigator c) Sponsor d) All of the above

d) All of the above a) IRB/IEC b) Investigator c) Sponsor

FDA requires reporting of any financial interest of the principal investigator in the sponsor a) Immediately before the trial begins b) During the clinical trial c) For a period of one year after study closure at the site. d) All of the above

d) All of the above a) Immediately before the trial begins b) During the clinical trial c) For a period of one year after study closure at the site.

An SAE experienced by a subject on a test drug for a clinical trial should be reported to a) Immediately to the sponsor b) To the regulatory agency within 7 calendar days c) To the IRB usually in five days or sooner depending on institutional policy d) All of the above

d) All of the above a) Immediately to the sponsor b) To the regulatory agency within 7 calendar days c) To the IRB usually in five days or sooner depending on institutional policy

Rapid communication of single case reports of serious adverse events is merited if the information a) Influences risk benefit assessment b) Implies a change need in drug administration c) A change in the conduct of the clinical investigation d) All of the above

d) All of the above a) Influences risk benefit assessment b) Implies a change need in drug administration c) A change in the conduct of the clinical investigation

A sponsor investigator of a clinical trial increases the number of sites to enhance enrollment . The sponsor investigator should a) Inform the IRB b) Arrange for monitoring of the added sites c) Arrange for the new sites to be updated on any new findings and IND safety reports d) All of the above

d) All of the above a) Inform the IRB b) Arrange for monitoring of the added sites c) Arrange for the new sites to be updated on any new findings and IND safety reports

Regarding the issuance of a final report by the investigator the ICH advises that the investigator should a) Inform the institution b) Provide the IRB with a summary of the trial's outcome c) Provide regulatory authorities with any reports that may be required, if applicable. d) All of the above

d) All of the above a) Inform the institution b) Provide the IRB with a summary of the trial's outcome c) Provide regulatory authorities with any reports that may be required, if applicable.

In a clinical trial for an oral anti-inflammatory drug the CRC notices that the patients have consistently misunderstood the instructions to take the drug. The CRC should a) Investigate who has been doing the informed consent conferences b) Arrange to retrain the individuals administering consent c) Reconsent the subjects d) All of the above

d) All of the above a) Investigate who has been doing the informed consent conferences b) Arrange to retrain the individuals administering consent c) Reconsent the subjects

The advantages of a disease registry over a specific drug registry in a phase 4 trial is a) It provides insights into comparative side effects b) It provides assessments of cost effectiveness of the different drugs c) It may allow for comparative assessments of efficacy in the long run d) All of the above

d) All of the above a) It provides insights into comparative side effects b) It provides assessments of cost effectiveness of the different drugs c) It may allow for comparative assessments of efficacy in the long run

Regarding the use of the investigational product the investigator should a) Maintain records that the subjects were provided with the doses stated in the protocol b) Ensure that the drug was used only as described in the protocol c) Should ensure that the drug use is explained to the subject and compliance is verified d) All of the above

d) All of the above a) Maintain records that the subjects were provided with the doses stated in the protocol b) Ensure that the drug was used only as described in the protocol c) Should ensure that the drug use is explained to the subject and compliance is verified

The decision to approve with conditions implies: a) Make specified changes to the protocol b) Make specified changes to the informed consent c) Submit specific clarifications or specified additional documents d) All of the above

d) All of the above a) Make specified changes to the protocol b) Make specified changes to the informed consent c) Submit specific clarifications or specified additional documents

During a clinical trial the Pl has to leave the country to take care of a relative abroad. The CRC should a) Make sure either the co-investigator or sub investigator takes over for the Pl per written instructions from the Pl b) Update the delegation log to reflect the new situation c) File and amendment with the IRB indicating a temporary change of personnel d) All of the above

d) All of the above a) Make sure either the co-investigator or sub investigator takes over for the Pl per written instructions from the Pl b) Update the delegation log to reflect the new situation c) File and amendment with the IRB indicating a temporary change of personnel

The types of bias on the part of the investigator that are reduced or eliminated by blinding may include a) Making Changes in the protocol eligibility criteria that may favor the sponsor b) Data falsification and fabrication c) Lack of Reporting of protocol deviations and serious adverse events d) All of the above

d) All of the above a) Making Changes in the protocol eligibility criteria that may favor the sponsor b) Data falsification and fabrication c) Lack of Reporting of protocol deviations and serious adverse events

The monitoring report should include a) Name of the investigator b) Significant findings, deviations and deficiencies c) Actions needed to secure compliance d) All of the above

d) All of the above a) Name of the investigator b) Significant findings, deviations and deficiencies c) Actions needed to secure compliance

For an adverse event to be characterized as unexpected OHRP guidance advises that the event should be in nature, severity or frequency be a) Not listed in the research protocol b) Not listed in the informed consent c) Not a characteristic of the study population d) All of the above

d) All of the above a) Not listed in the research protocol b) Not listed in the informed consent c) Not a characteristic of the study population

The monitoring of blood pressure prior to taking the drug is required in a clinical trial. The CRC notices that the blood pressure readings have been recording abnormally low blood pressures and suspects the blood pressure monitors may not be adequate. The CRC should a) Notify the sponsor b) First notify the Pl c) Notify the IRB by filing a protocol deviation d) All of the above

d) All of the above a) Notify the sponsor b) First notify the Pl c) Notify the IRB by filing a protocol deviation

A subject being consented for a clinical trial is blind. The CRC should a) Obtain a Braille version of the consent form b) A legally acceptable guardian help the subject sign and the LAR should sign the consent form as well c) Have the complete consent form read to the subject d) All of the above

d) All of the above a) Obtain a Braille version of the consent form b) A legally acceptable guardian help the subject sign and the LAR should sign the consent form as well c) Have the complete consent form read to the subject

In conducting an audit of source documents the auditor would look for a) Original entries that were clearly visible, including alterations b) Traceable or attributable documents c) An audit trail of access to or alteration of the source documents d) All of the above

d) All of the above a) Original entries that were clearly visible, including alterations b) Traceable or attributable documents c) An audit trail of access to or alteration of the source documents

Data collection in a clinical trial usually employs a) Paper case record forms b) Remote site monitoring c) Medical computer systems and electronic transfer d) All of the above

d) All of the above a) Paper case record forms b) Remote site monitoring c) Medical computer systems and electronic transfer

FDA requires disclosure by the principal investigator of proprietary interest which includes a) Patents b) Copyright or trademark c) Intellectual property d) All of the above

d) All of the above a) Patents b) Copyright or trademark c) Intellectual property

For first in human studies the administered dose should be determined by a) Pharmacokinetics b) Drug pharmacology c) Toxicological evaluations d) All of the above

d) All of the above a) Pharmacokinetics b) Drug pharmacology c) Toxicological evaluations

Statistical principles are relevant to a) Phase I trials b) Phase II trials c) Phase III trials d) All of the above

d) All of the above a) Phase I trials b) Phase II trials c) Phase III trials

A placebo design in a clinical trial is contraindicated when a) Placebo may cause serious harm to the subject b) When a good comparator drug exists for the trial c) Where a high rate of morbidity exists for the patients with the disease d) All of the above

d) All of the above a) Placebo may cause serious harm to the subject b) When a good comparator drug exists for the trial c) Where a high rate of morbidity exists for the patients with the disease

Procedures to minimize the amount of blood sampled in pediatric clinical trials include a) Population PK sampling b) Sparse sampling c) In dwelling catheters d) All of the above

d) All of the above a) Population PK sampling b) Sparse sampling c) In dwelling catheters

Age classifications of pediatric subjects in ICH includes a) Preterm newborn infants b) Term newborn infants c) Infants and toddlers d) All of the above

d) All of the above a) Preterm newborn infants b) Term newborn infants c) Infants and toddlers

In a double blinded placebo control design the reasons for the blinding of the investigator include a) Prevent the investigator from reviewing the treatment group more strenuously b) Prevent the investigator from not recording or reporting serious adverse events in the treatment group c) Prevent the investigator from making protocol changes which favor the treatment group d) All of the above

d) All of the above a) Prevent the investigator from reviewing the treatment group more strenuously b) Prevent the investigator from not recording or reporting serious adverse events in the treatment group c) Prevent the investigator from making protocol changes which favor the treatment group

The ideal data analysis set is one in which a) Procedures are followed perfectly b) Data records are complete c) There is no loss to patient follow up d) All of the above

d) All of the above a) Procedures are followed perfectly b) Data records are complete c) There is no loss to patient follow up

According to ICH the purpose of monitoring is a) Protect the rights and well-being of human subjects b) Ensure data are accurate complete and verifiable c) The conduct of the trial is in agreement with the protocol, GCP and regulatory requirements d) All of the above

d) All of the above a) Protect the rights and well-being of human subjects b) Ensure data are accurate complete and verifiable c) The conduct of the trial is in agreement with the protocol, GCP and regulatory requirements

Irregularities in the data analysis set may arise from a) Protocol violations b) Patient withdrawals c) Missing values d) All of the above

d) All of the above a) Protocol violations b) Patient withdrawals c) Missing values

With regard to liability claims that may arise against the investigator/institution the sponsor should a) Provide indemnification b) Provide insurance where possible c) Specify compensation for trial subjects in the event of trial related injury d) All of the above

d) All of the above a) Provide indemnification b) Provide insurance where possible c) Specify compensation for trial subjects in the event of trial related injury

According to ICH, for an investigator to be eligible to conduct a clinical trial he should be a) Qualified by education, training and experience b) Meet the qualification specified by regulatory authorities and the IRB c) Should provide documentary evidence of his qualifications to the sponsor and the IRB d) All of the above

d) All of the above a) Qualified by education, training and experience b) Meet the qualification specified by regulatory authorities and the IRB c) Should provide documentary evidence of his qualifications to the sponsor and the IRB

Methods to minimize bias include a) Randomization b) Blinding c) Compliance measures d) All of the above

d) All of the above a) Randomization b) Blinding c) Compliance measures

In consenting an adult illiterate subjects who cannot read or write English the consent process should include a) Reading the consent form to the subject b) Having the subject make a mark "X" on the subject signature line c) Have an impartial witness present d) All of the above

d) All of the above a) Reading the consent form to the subject b) Having the subject make a mark "X" on the subject signature line c) Have an impartial witness present

An adverse reaction occurs in patients after the study has been completed. The appropriate action on the part of the investigator include a) Report the event to the sponsor b) Consider the event for reporting as though it was a study report c) Conduct causality assessment and determination of expectedness prior to expedited reporting d) All of the above

d) All of the above a) Report the event to the sponsor b) Consider the event for reporting as though it was a study report c) Conduct causality assessment and determination of expectedness prior to expedited reporting

If a potential subject cannot speak or write English and an informed consent conference has to be held the investigator should a) Request the appropriate foreign language form from the sponsor b) Follow IRB procedures, including the use of a consent short form of the foreign language c) Utilize a qualified and certified interpreter for the communication of the foreign language consent form d) All of the above

d) All of the above a) Request the appropriate foreign language form from the sponsor b) Follow IRB procedures, including the use of a consent short form of the foreign language c) Utilize a qualified and certified interpreter for the communication of the foreign language consent form

Regarding protocol and GCP deviations observed by the monitor in a periodic site visit the sponsor may a) Require that these be reported promptly to the IRB b) Institute a corrective measure promptly c) Develop a CAPA plan as needed d) All of the above

d) All of the above a) Require that these be reported promptly to the IRB b) Institute a corrective measure promptly c) Develop a CAPA plan as needed

Study objectives in clinical trial design may include a) Safety and efficacy characterization b) Pharmacokinetic and pharmacological studies c) Physiological and biochemical studies d) All of the above

d) All of the above a) Safety and efficacy characterization b) Pharmacokinetic and pharmacological studies c) Physiological and biochemical studies

According to DHHS regulations IRB records must include a) Scientific evaluations that accompany each proposal b) Reports of injuries to subjects c) Copies of all correspondence between the IRB and investigators d) All of the above

d) All of the above a) Scientific evaluations that accompany each proposal b) Reports of injuries to subjects c) Copies of all correspondence between the IRB and investigators

A double blind trial is one in which the following are unaware of the treatment received a) Sponsor b) Investigator c) Subject d) All of the above

d) All of the above a) Sponsor b) Investigator c) Subject

The essential basic elements of consent include a) Statements about the risk, benefits and alternate procedures b) Any compensation for injury c) Confidentiality of records and contact information regarding subject's rights d) All of the above

d) All of the above a) Statements about the risk, benefits and alternate procedures b) Any compensation for injury c) Confidentiality of records and contact information regarding subject's rights

Factors associated with bias can include a) Study design b) Study conduct c) Data analysis and interpretation d) All of the above

d) All of the above a) Study design b) Study conduct c) Data analysis and interpretation

Double blind study design entails that the following are unaware of the treatment assignment a) Subject b) Investigator c) Monitor d) All of the above

d) All of the above a) Subject b) Investigator c) Monitor

According to ICH when non-compliance which is serious or persistent is observed the sponsor should a) Terminate the investigator's participation in the clinical trial b) Inform the IRB c) Inform the regulatory authorities d) All of the above

d) All of the above a) Terminate the investigator's participation in the clinical trial b) Inform the IRB c) Inform the regulatory authorities

For a CRC to file SAE reports to the IRB it would be advised that a) The CRC is a qualified physician b) The CRC is delegated this function in the investigators' delegation log c) This function be approved by the sponsor and the IRB d) All of the above

d) All of the above a) The CRC is a qualified physician b) The CRC is delegated this function in the investigators' delegation log c) This function be approved by the sponsor and the IRB

If the investigator implements a change in the protocol to eliminate an immediate hazard the following entities should be informed: a) The IRB b) The sponsor c) Regulatory authority if applicable d) All of the above

d) All of the above a) The IRB b) The sponsor c) Regulatory authority if applicable

Regarding the use of placebos in clinical trials the Declaration of Helsinki states that a) The benefits risks and burdens of a new intervention must be tested against the best proven intervention. b) Placebo may be used when for sound methodological reasons it is important to determine safety and efficacy of the intervention c) The use of placebo will not result in additional risks of serious or irreversible harm to the subject relative to not receiving the best possible intervention d) All of the above

d) All of the above a) The benefits risks and burdens of a new intervention must be tested against the best proven intervention. b) Placebo may be used when for sound methodological reasons it is important to determine safety and efficacy of the intervention c) The use of placebo will not result in additional risks of serious or irreversible harm to the subject relative to not receiving the best possible intervention

Which of the following statements regarding informed consent are true? a) The consent form should have a signature and date of the subject and the person obtaining consent b) The source documents or note to the informed consent should document that consent was obtained prior to the trial related procedures c) Where the informed consent is administered in an emergency setting both the date as well as the time of the consent relative to the first trial related procedure should be documented d) All of the above

d) All of the above a) The consent form should have a signature and date of the subject and the person obtaining consent b) The source documents or note to the informed consent should document that consent was obtained prior to the trial related procedures c) Where the informed consent is administered in an emergency stetting both the date as well as the time of the consent relative to the first trial related procedure should be documented

When the IRB suspends a clinical trial it should inform a) The institution b) The sponsor c) OHRP d) All of the above

d) All of the above a) The institution b) The sponsor c) OHRP

The investigator brochure is a living document that is continually updated in a clinical trial to include a) The latest nonclinical studies b) Changes in chemistry of the product c) The latest results from completed clinical trials d) All of the above

d) All of the above a) The latest nonclinical studies b) Changes in chemistry of the product c) The latest results from completed clinical trials

In order to avoid serious harm to subjects in phase 1 studies a) The lowest doses of drugs are tested initially b) Cohorts with the lowest doses are evaluated before dose is escalated gradually in later cohorts. c) Subjects are frequently located in an observation center to monitor serious adverse events d) All of the above

d) All of the above a) The lowest doses of drugs are tested initially b) Cohorts with the lowest doses are evaluated before dose is escalated gradually in later cohorts. c) Subjects are frequently located in an observation center to monitor serious adverse events

During a meeting a voting member has a conflict of interest for a study being reviewed. The minutes must indicate a) The name of the conflicted member b) The name of the alternate who substituted for the conflicted member if applicable c) The study for which the conflict was recorded d) All of the above

d) All of the above a) The name of the conflicted member b) The name of the alternate who substituted for the conflicted member if applicable c) The study for which the conflict was recorded

The minutes of the IRB meeting should include sufficient detail to show attendance. In practice this involves showing a) The names of the attendees and their representative roles b) The earned degrees of the members attending c) The alternate members and who they are the alternates for d) All of the above

d) All of the above a) The names of the attendees and their representative roles b) The earned degrees of the members attending c) The alternate members and who they are the alternates for

A monitor ensures that a clinical trial is being performed as specified in a) The protocol b) Standard operating procedures c) Good Clinical Practice and other regulatory requirements d) All of the above

d) All of the above a) The protocol b) Standard operating procedures c) Good Clinical Practice and other regulatory requirements

At a site initiation visit the sponsors CRA reviews a) The protocol b) The schedule of assessments and associated CRFs c) The site' SOPs d) All of the above

d) All of the above a) The protocol b) The schedule of assessments and associated CRFs c) The site' SOPs

A clinical trial requires five CT scans in the period of one year. For the disease condition only one CT scan per year is indicated . The situation requires a) The radiation safety committee evaluation and approval prior to IRB approval b) Statement about radiation risk in the consent form c) A consideration of an alternative imaging technique if possible. d) All of the above

d) All of the above a) The radiation safety committee evaluation and approval prior to IRB approval b) Statement about radiation risk in the consent form c) A consideration of an alternative imaging technique if possible.

Premature termination of a clinical trial should be reported by the investigator to a) The research subjects b) The regulatory authority if applicable c) The IRB d) All of the above

d) All of the above a) The research subjects b) The regulatory authority if applicable c) The IRB

In describing the risks of a clinical trial the informed consent should detail the risks to a) The subject b) Embryo or fetus c) Nursing infant d) All of the above

d) All of the above a) The subject b) Embryo or fetus c) Nursing infant

The informed consent should be signed by a) The subject b) The legally acceptable representative if applicable c) The person conducting the consent discussion d) All of the above

d) All of the above a) The subject b) The legally acceptable representative if applicable c) The person conducting the consent discussion

With regard to access to medical records during a clinical trial a) The subject should consent in writing to medical record access b) Access should be guaranteed for monitoring, audits, IRB review and regulatory inspection c) Access should be in accord with prevailing federal and state laws d) All of the above

d) All of the above a) The subject should consent in writing to medical record access b) Access should be guaranteed for monitoring, audits, IRB review and regulatory inspection c) Access should be in accord with prevailing federal and state laws

With respect to monitoring of adverse events in a clinical trial the IRB should consider a) The type of data, events and the entity responsible for reporting b) The time frame and frequency of assessments of events and their relationship to stopping rules c) The appropriate procedures for timely communication of the monitoring results to the IRB and sponsor d) All of the above

d) All of the above a) The type of data, events and the entity responsible for reporting b) The time frame and frequency of assessments of events and their relationship to stopping rules c) The appropriate procedures for timely communication of the monitoring results to the IRB and sponsor

Expedited reporting of serious adverse events may be considered if a) There is an increased rate of occurrence in the serious adverse drug reaction b) A lack of efficacy is evident in treating a life-threatening disease c) A new safety consideration is evident from a new animal study d) All of the above

d) All of the above a) There is an increased rate of occurrence in the serious adverse drug reaction b) A lack of efficacy is evident in treating a life-threatening disease c) A new safety consideration is evident from a new animal study

The IRS may not approve a study if it is unable a) To make determinations about research risks b) To determine the adequacy of privacy and confidentiality agreements c) To determine the adequacy of the informed consent or the informed consent process d) All of the above

d) All of the above a) To make determinations about research risks b) To determine the adequacy of privacy and confidentiality agreements c) To determine the adequacy of the informed consent or the informed consent process

Non-monetary reward for recruitment offered to investigators by sponsors may include a) Token gifts b) Promise of authorship of the clinical trial findings c) Post study rewards including speakership bureau assignments d) All of the above

d) All of the above a) Token gifts b) Promise of authorship of the clinical trial findings c) Post study rewards including speakership bureau assignments

Which of the following statements is true a) Trial subjects should not enroll in more than one trial at any given time b) Women of childbearing potential should use highly effective contraception measures c) Male subjects should be made aware of hazard of drug exposure to their sexual partners or progeny d) All of the above

d) All of the above a) Trial subjects should not enroll in more than one trial at any given time b) Women of childbearing potential should use highly effective contraception measures c) Male subjects should be made aware of hazard of drug exposure to their sexual partners or progeny

Enrollment bonuses paid to investigators in a clinical trial represent a) Undue influence in the recruitment process b) Are not addressed in DHHS regulations c) Reflect the sponsor's pressure to increase enrollment d) All of the above

d) All of the above a) Undue influence in the recruitment process b) Are not addressed in DHHS regulations c) Reflect the sponsor's pressure to increase enrollment

The amount of blood obtained from a child in a clinical trial may be minimized by the following methods a) Use of sensitive assays and indwelling catheters for sampling and analyzing drugs and metabolites b) Use of laboratories specialized in handling small blood volumes c) Collection of research samples at the same time as clinical care samples d) All of the above

d) All of the above a) Use of sensitive assays and indwelling catheters for sampling and analyzing drugs and metabolites b) Use of laboratories specialized in handling small blood volumes c) Collection of research samples at the same time as clinical care samples

Covariates in a statistical analysis may include a) Variation in populations between centers in a multi-center trail b) Variations in age subgroups c) Variations by gender d) All of the above

d) All of the above a) Variation in populations between centers in a multi-center trail b) Variations in age subgroups c) Variations by gender

A protocol deviation is a) Any departure from the procedures and practices described in an IRB approved protocol b) Any action associated with regulatory non-compliance c) Failure to follow the appropriate procedure or protocol for the informed consent process d) All of the above.

d) All of the above. a) Any departure from the procedures and practices described in an IRB approved protocol b) Any action associated with regulatory non-compliance c) Failure to follow the appropriate procedure or protocol for the informed consent process

The frequency of meetings of the DSMB may be a) Based on a specified frequency in time (every six or twelve months for example) b) Based on the number of serious adverse events observed c) Based on the number of patients enrolled d) All of the above.

d) All of the above. a) Based on a specified frequency in time (every six or twelve months for example) b) Based on the number of serious adverse events observed c) Based on the number of patients enrolled

Secondary variables must a) Be supportive measurements related to the primary objective b) Need to have their role and importance defined carefully in a clinical trial c) Should be limited to answering a limited number of questions in the trial. d) All of the above.

d) All of the above. a) Be supportive measurements related to the primary objective b) Need to have their role and importance defined carefully in a clinical trial c) Should be limited to answering a limited number of questions in the trial.

The principal investigator receives a cash payment for consultation from the sponsor in the amount of $10000. This amount is a) Below the threshold amount for disclosure to the FDA b) May have to be disclosed to the conflict of interest committee c) May have to be disclosed to the IRS if required by the institutional guidelines d) All of the above.

d) All of the above. a) Below the threshold amount for disclosure to the FDA b) May have to be disclosed to the conflict of interest committee c) May have to be disclosed to the IRS if required by the institutional guidelines

Formulation of pediatric drugs may require the need for a) Chewable tablets and liquid formulations b) Safe and easily injectable formulations c) Frequent use of suspensions d) All of the above.

d) All of the above. a) Chewable tablets and liquid formulations b) Safe and easily injectable formulations c) Frequent use of suspensions

A Phase 1 study is likely to evaluate a) DLT (dose limiting toxicity) b) MTD (maximum tolerated dose) C) Half -life d) All of the above.

d) All of the above. a) DLT (dose limiting toxicity) b) MTD (maximum tolerated dose) C) Half -life

When an IRB approves a study with conditions the IRB must a) Document the date of the acceptance of the changes by the IRB reviewer, the date of approval if different from this date and the date of continuing review b) Document conditions for partial approval with conditions c) Document all appropriate events and reviews in the minutes and IRB records d) All of the above.

d) All of the above. a) Document the date of the acceptance of the changes by the IRB reviewer, the date of approval if different from this date and the date of continuing review b) Document conditions for partial approval with conditions c) Document all appropriate events and reviews in the minutes and IRB records

The conflict of interest committee reviewing the disclosure of a Pl on an FDA clinical trial in the amount of $10000 a) May require the Pl to transfer consenting responsibilities to others on the research team b) May require the Pl to transfer the principal investigator duties to the co-investigator who does not have a conflict of interest c) May develop a customized conflict of interest management plan specific to this situation. d) All of the above.

d) All of the above. a) May require the Pl to transfer consenting responsibilities to others on the research team b) May require the Pl to transfer the principal investigator duties to the co-investigator who does not have a conflict of interest c) May develop a customized conflict of interest management plan specific to this situation.

According to OHRP guidance corrective actions which may be needed in response to an unexpected problem include a) Modification of the research protocol including eligibility criteria b) Modification of informed consent and reconsent of currently enrolled subjects c) Suspension of new enrollment and of current procedures in enrolled subjects d) All of the above.

d) All of the above. a) Modification of the research protocol including eligibility criteria b) Modification of informed consent and reconsent of currently enrolled subjects c) Suspension of new enrollment and of current procedures in enrolled subjects d) All of the above.

With regard to payments to subjects ICH indicates that a) Payments be free of coercion and undue influence b) Payments should be prorated c) Methods, amounts and schedule of payments be set forth in the informed consent. d) All of the above.

d) All of the above. a) Payments be free of coercion and undue influence b) Payments should be prorated c) Methods, amounts and schedule of payments be set forth in the informed consent.

The Medical Safety Officer at the sponsor carries out which of the duties listed below? a) Providing medical advice during the clinical trial b) Assessing medical waivers of eligibility c) Review of SAEs and continuance of subjects on the study d) All of the above.

d) All of the above. a) Providing medical advice during the clinical trial b) Assessing medical waivers of eligibility c) Review of SAEs and continuance of subjects on the study

The essential elements of a Corrective and Preventive Action Plan (CAPA plan) developed in response to repeat protocol deviations might include a) Root cause analysis b) Training and education needs to ensure repeat events do not occur c) System changes to ensure future prevention d) All of the above.

d) All of the above. a) Root cause analysis b) Training and education needs to ensure repeat events do not occur c) System changes to ensure future prevention

An IDE exemption may be granted if a) The device has a 510K b) The study uses an approved device on label c) The device is a non-significant risk device d) All of the above.

d) All of the above. a) The device has a 510K b) The study uses an approved device on label c) The device is a non-significant risk device

In a sponsored clinical trial the IRB should review a) The sponsor's recruitment efforts b) Differences between the principal investigator's recruitment efforts and the sponsor's. c) Only a summary of the media advertisements being used by the Pl d) All of the investigator's recruitment materials

d) All of the investigator's recruitment materials

The intention to treat analysis set includes a) All treated subjects b) Only subjects with complete drug treatments c) Subjects who have undergone the minimum number of acceptable trial visits d) All randomized subjects

d) All randomized subjects

An abbreviated IDE is a) A shorter IDE application to the FDA b) A variation on a 51OK application c) An alternative to the FDA IDE application process d) An IRB SR/NSR determination for a device

d) An IRB SR/NSR determination for a device

The placebo effect in experimental studies is a) An effect caused in a treatment group because of the special attention paid to it by the investigator b) The participants form an interpretation of the experiment's purpose and modify their behavior accordingly c) Occurs in cognitive trial where the perception of one trait is influenced by the perception of another trait. d) An effect ,caused by psychological influence, experienced by the patient when they are unaware that they are not being administered the medication for the clinical trial e) The investigator's paradigm in experimental design and analysis predetermines the interpretation of the results. Patientsinthecontrolgroupbecomeawareofgroupmembershipandturnrebellious and alter behavior to contradict the experiment's purpose

d) An effect ,caused by psychological influence, experienced by the patient when they are unaware that they are not being administered the medication for the clinical trial

A possible relationship of an adverse drug reaction to a drug may be defined as one a) Reported by the patient b) Suspected by the Principal investigator c) An event that is discontinued when the drug is discontinued d) An event in which the relationship cannot be ruled out

d) An event in which the relationship cannot be ruled out

An adverse event is one which occurs a) Within ten days of drug administration b) An event which may occur after study treatments have been completed c) An event which occurs immediately after drug administration d) An event temporally associated with drug use which may or may not be drug related.

d) An event temporally associated with drug use which may or may not be drug related.

If the subject or the LAR is unable to read the informed consent a) The subject should not be considered for enrollment b) Written permission should be obtained from the IRB prior to enrollment c) A family member should be recruited to explain the consent d) An impartial witness should be present

d) An impartial witness should be present

A controverted issue is one in which a) There was a tie vote for the study b) One or more members abstained from the vote c) A motion to defer the study was approved d) Any issue that caused a debate among the members

d) Any issue that caused a debate among the members

Mutlicenter trials can be implemented for a) Open label trials b) Exploratory trials c) Confirmatory trials d) Any stage of clinical drug development

d) Any stage of clinical drug development

Phase IV protocols generally follow a) Phase I protocols b) Phase II protocols c) Phase III protocols d) Approved use by the regulatory agency

d) Approved use by the regulatory agency

Multi center trials have the following features except a) They are more efficient as they accrue sufficient subjects b) May facilitate generalization of findings c) May present the only method for accruing subjects in rare diseases d) Are easily administered for uniform implementation of the protocol

d) Are easily administered for uniform implementation of the protocol

In a factorial design the subjects a) Randomized to two arms each with a different treatment b) Are evaluated before and after drug administration c) Are randomized to a sequence of two treatments d) Are evaluated simultaneously for varying combinations of treatments

d) Are evaluated simultaneously for varying combinations of treatments

Global assessment variables reflect all of the following except a) They are developed to measure the overall usefulness of treatment b) Require that a scale be developed and detailed in the protocol c) Should define how to assign subjects to a unique category on a scale d) Are never used as a primary variable in most clinical trials

d) Are never used as a primary variable in most clinical trials

Phase IV studies in pediatric populations a) Are not required as there is no regulation that outlines the need b) Are rarely done because safety information is already documented in Phase III trials c) Are recommended only if Phase IV studies in the adult population have not been done d) Are particularly important as the pediatric database is limited at the time of approval

d) Are particularly important as the pediatric database is limited at the time of approval

If an investigator terminates a subject's participation in a clinical trial, according to OHRP guidance the investigator should a) Terminate all study activities and make sure that no involvement with the subject is ongoing b) Include activities which are non-interventional only c) Consult with their private physician about activities which might continue d) Ask the subject if participation in secondary interventional components should continue

d) Ask the subject if participation in secondary interventional components should continue

The language of the informed consent should be all of the following except a) Non technical b) Practical c) Understandable to legally acceptable representative d) At the high school level

d) At the high school level

The IRB should a) Have a physician as the IRB chair b) Have at least one member who is an attorney c) Have specialists in the areas which it might review d) Be sufficiently qualified through the experience and expertise of its members

d) Be sufficiently qualified through the experience and expertise of its members

Blind review occurs a) At various stages of a clinical trial b) After study close out visit for all sites has been completed c) At pre-specified intervals d) Between trial completion and breaking of the blind

d) Between trial completion and breaking of the blind

In pediatric clinical trials a) Participants should sign assent or consent depending on their intellectual maturity b) Participants should always be made aware of their right to decline c) a only d) Both a and b

d) Both a and b a) Participants should sign assent or consent depending on their intellectual maturity b) Participants should always be made aware of their right to decline

In children 2-11 years of age factors to consider in clinical trials include a) Tanner staging for puberty b) Recreational use of drugs, alcohol and tobacco c) a only d) Both a and b

d) Both a and b a) Tanner staging for puberty b) Recreational use of drugs, alcohol and tobacco

If the IRB suspends a clinical trial the investigator should report it to a) The sponsor b) The institution c) The regulatory authority d) Both a and b

d) Both a and b a) The sponsor b) The institution

Adverse events of marketed drugs usually imply a) Multi-drug interactions b) Unreliable subjective measures c) Psychosomatic factors d) Causality

d) Causality

Clinical investigation of adverse events in clinical trials requires a) Root cause analysis b) Complete medical records review c) Investigation of potential protocol deviations d) Causality assessment

d) Causality assessment

The following reports should be filed as needed or promptly with the FDA by the sponsor except a) Annual report b) Adverse event report c) Protocol amendments d) Change in the IRB roster

d) Change in the IRB roster

A research study would most likely be approved with conditions in all of the following scenarios except a) Submission of additional documents b) Making precise language changes in the protocol or informed consent c) Confirmation of the specific assumptions and understandings on the part of the IRB regarding the application d) Changes in the exclusion criteria for the study

d) Changes in the exclusion criteria for the study

In designing a study in which participants have mature hepatic and renal function you would choose a) Neonates b) Preterm infants c) Participants between the ages of 1-2 years d) Children

d) Children

A phase I oncology study for lymphoma in children should enroll a) Healthy adults b) Healthy children c) Children with any known cancer d) Children with lymphoma who have failed standard treatment

d) Children with lymphoma who have failed standard treatment

A subject who has withdrawn from a research study requests that all of their data be destroyed. According to OHRP guidance the investigator should a) Destroy the data immediately b) Refuse categorically to destroy the data c) Refer the matter to the IRB d) Choose to honor the request after consultation with NIH, FDA and the appropriate regulatory agency

d) Choose to honor the request after consultation with NIH, FDA and the appropriate regulatory agency

In infants and toddlers features of drug metabolism include a) Hepatic and renal clearance are stable b) Oral absorption is as unreliable as in newborns c) The CNS maturation is nearly complete d) Clearance of drugs on a mg/kg basis may exceed adult values

d) Clearance of drugs on a mg/kg basis may exceed adult values

Pharmacokinetic studies include all except a) Dose response studies b) Absorption, distribution and metabolism studies c) Studies of the route of administration d) Comparative bioavailability studies

d) Comparative bioavailability studies

If a sponsor finds in an audit an action of the investigator which compromises human subject protection or reliability of the trial the sponsor should a) Immediately terminate the investigator's involvement b) Notify the regulatory agency c) Notify the IRB d) Conduct a root cause analysis

d) Conduct a root cause analysis

According to ICH all of the following are essential documents except a) Delegation of authority forms b) Certificates of analysis for new batches of investigational drugs c) Normal values for the analytes being tested d) Conflict of interest information for core team members

d) Conflict of interest information for core team members

With regard to ICH, conflict of interest on the IRB, which of the following is not correct: a) The IRB may invite non-members but only members can vote b) The investigator may not participate in deliberations or the vote c) There is no provision for non-tangible conflict of interest d) Conflict of interest is defined as financial interest greater than $10000.

d) Conflict of interest is defined as financial interest greater than $10000.

In terms of earning the respect for its advice and counsel from the community the IRB should a) Consider a highly educated membership b) Consider only those individuals who are members of professional societies c) Consider the inclusion of one or more attorneys d) Consider a diversity of membership in race, gender, cultural backgrounds

d) Consider a diversity of membership in race, gender, cultural backgrounds

Characterization of drug's absorption, metabolism and excretion a) Are confined to Phase I studies b) Cab be conducted in Phase II studies if Phase I studies are inconclusive c) Are never studied in Phase Ill studies d) Continue throughout the development plan

d) Continue throughout the development plan

The term CRO stands for a) Certified Research Organization b) Certified Research Officer c) Contract Research Official d) Contract Research Organization

d) Contract Research Organization

According to ICH the copy of the CV given to the IRB should be a) No more than a year old b) No more than two years old c) No date on the CV is required d) Current

d) Current

The statement that continuing review be carried out at least once annually is affirmed by a) ICH only b) DHHS and ICH only c) DHHS only d) DHHS, ICH, and FDA

d) DHHS, ICH, and FDA

According to the FDA guidance on recruitment which of the following does not need IRB review a) Brochures to be confined to the clinic waiting room b) Flyers posted only in the institution c) E-mails sent to potential community participants d) Dear doctor letters even when soliciting for study subjects

d) Dear doctor letters even when soliciting for study subjects

When a protocol deviation is observed on several occasions the investigator should a) Batch the reporting of the protocol deviations for reporting to the IRB b) Report it directly to institutional officials c) Report it to the IRB only after it has been corrected d) Develop a comprehensive Corrective and Preventive Action Plan (CAPA plan)

d) Develop a comprehensive Corrective and Preventive Action Plan (CAPA plan)

When a study is reviewed under an expedited procedure the IRB may do all of the following except a) Approve the study without conditions b) Approve the study with conditions c) Defer the study pending major modifications d) Disapprove the study

d) Disapprove the study

Phase 1 studies are likely to provide the least reliable data on efficacy because a) They are always conducted in healthy subjects b) They are not measuring efficacy c) They are too long in duration d) Effects are unlikely at the lowest doses tested

d) Effects are unlikely at the lowest doses tested

Regulations provide which of the following guidelines regarding data monitoring a) Specific guidelines for data and safety monitoring board b) Describes the need of a DSMB in the review of serious adverse events c) Guidelines that the IRB may substitute for a DSMB if the conditions require it. d) Ensure that the research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects

d) Ensure that the research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects.

In ICH a clinical trial with randomization should a) Explain the reasons for the use of control groups b) Provide a justification for why an active control group is or is not being used c) Should describe the need for placebo controlled design d) Explain the probability for random assignment to each treatment group

d) Explain the probability for random assignment to each treatment group

A sponsor who makes a cardiac pacemaker has secured a PMA for the device. The sponsor decides to make a minor modification to the pacemaker. The sponsor must a) Notify the FDA by letter of his decision b) Make the modification if it is minor without notification c) File for a 510K d) File an IDE because it is significant risk device.

d) File an IDE because it is significant risk device.

A CRC has scheduled a first visit for a subject for an IRB approved study. When the patient arrives the CRC notices that the IRB approval letter is missing a date. The CRC should do all of the following except a) Reschedule the visit b) Contact the IRB and ask for a dated letter c) Inform the Pl d) File an unanticipated event report with the IRB

d) File an unanticipated event report with the IRB

ICH advises that the following individuals may be utilized in trial design except a) Biostatisticians b) Clinical pharmacologists c) Physicians d) Financial analysts

d) Financial analysts

In reviewing matters of state law the IRB should a) Appoint a lawyer certified to practice in the state as a member b) Get advice form OHRP on state law matters c) Follow the federal guidelines regardless d) Follow state law if it provides more stringent protections than federal law.

d) Follow state law if it provides more stringent protections than federal law.

During a study monitoring visit the study monitor observes that the revised versions of the investigator's brochure are not being kept in the regulatory binder for the study. The sponsor asks the investigator to report this as a protocol deviation to the IRB. The investigator should a) Not report it because it is not within institutional guidelines for a protocol deviation b) Not reportable because it was corrected by the investigator c) Not reportable because it is a minor event of no risk to patient or study d) Follow the sponsor's instructions and report it to the IRB.

d) Follow the sponsor's instructions and report it to the IRB.

Regarding ICH provisions for emergency use of an investigational article which of the following is applicable? a) ICH describes guidelines for emergency use similar to those required by the FDA. b) ICH makes a provision for emergency medical care similar to that provided in DHHS c) ICH describes guidelines for use of an investigational article in an emergency setting d) ICH states that if consent of subject or LAR cannot be obtained then relevant ethical concerns and applicable regulatory requirements be addressed.

d) ICH states that if consent of subject or LAR cannot be obtained then relevant ethical concerns and applicable regulatory requirements be addressed.

In term new born infants features of drug metabolism include a) Stable renal and hepatic clearance compared to preterm newborns b) Oral administration of the drug is predictable and preferred c) Dose adjustments are unlikely to be needed in the course of a clinical trial d) Immaturity of the blood brain barrier may give rise to CNS toxicity

d) Immaturity of the blood brain barrier may give rise to CNS toxicity

Methods to be used in assessing patient drug use and compliance are best a) Discussed verbally with the subject b) Need not be mentioned in the informed consent c) Need not be discussed with subjects d) Included in the study protocol

d) Included in the study protocol

The informed consent defines significant new information that should be updated in the informed consent as including a) Other new clinical trials on the same drug b) Other new drugs that have come on the market c) New side effects of the most commonly used alternative medication d) Information relevant to the continued participation of the subject in the clinical trial

d) Information relevant to the continued participation of the subject in the clinical trial

Factors to consider in measuring the effect of a pediatric drug to children between 2 and 11 years of age include all of the following except a) Skeletal muscle growth b) Weight gain c) School attendance and school performance d) Interpersonal interactions with other children

d) Interpersonal interactions with other children

The statement that significant new findings, which may affect participation will be provided to subjects a) Is required in all consent forms b) Is an essential element of consent c) Is only required for risks and not benefits d) Is an added element included on the consent form only if the IRB deems it appropriate to do so

d) Is an added element included on the consent form only if the IRB deems it appropriate to do so

Under ICH GCP all of the following apply to a legally authorized representative (LAR) except: a) Is an individual authorized to consent on behalf of a trial subject b) Juridical or other body authorized under applicable law to consent on behalf of a trial subject c) Often consents in situations where the trial subject is unable to consent for himself because of physical or mental limitations d) Is authorized to make financial decisions on behalf of the trial subject if hospitalized.

d) Is authorized to make financial decisions on behalf of the trial subject if hospitalized.

Payments to children for research participation a) Is prohibited under DHHS regulations b) Should be given only to the parent c) Must be in the form of a gift certificate d) Is not addressed in the DHHS regulations

d) Is not addressed in the DHHS regulations

Randomization entails all of the following except a) Use of a computer generated number system b) Use of an Interactive Voice recognition System c) Involves assignments to treatment and control groups d) Is often decided by a coin toss

d) Is often decided by a coin toss

Regarding final report on completion of the clinical trial the investigator should according to ICH do all of the following except a) Provide the IRB with a summary of the trials' outcome b) Provide a report to regulatory authorities c) Should inform the institution d) Is similar to DHHS in its requirements

d) Is similar to DHHS in its requirements

An impartial witness is all of the following except a) A person who cannot be unfairly influenced b) Attends the informed consent conference when the subject or LAR cannot read c) Reads any written information supplied to the subject d) Is usually certified by the institution

d) Is usually certified by the institution

An inspection of a clinical trial is all of the following except a) Usually performed by a regulatory authority b) Consists of a review of documents, facilities, records and any other resources at the site c) May occur at the site or at the sponsor or CRO location d) Is usually integrated into the monitoring schedule.

d) Is usually integrated into the monitoring schedule.

With regard to a quorum for the IRB ICH specifies that a) It is majority of members b) It is more than 50% of the roster c) It is governed by a specified formula d) It should be stipulated in the written procedures

d) It should be stipulated in the written procedures

A non-significant risk determination for a study planned by an investigator is a) Made by the sponsor b) Made by the FDA c) Made by OHRP d) Made by the IRB

d) Made by the IRB

A non clinical study is one which is all of the following except a) Includes all animal studies b) Any non human study c) Usually precedes human studies d) May apply to human studies with high risk and no benefit

d) May apply to human studies with high risk and no benefit

A patient in a clinical I trial for joint pain experiences a bronchospasm while at home, The event would be a) Not reportable because it occurred in a home setting b) An adverse event which does not require reporting c) An unexpected adverse event which does not require expedited reporting d) May be considered serious and should be considered for expedited reporting

d) May be considered serious and should be considered for expedited reporting

A small hospital without an IRB has an urgent need to use a HUD. The hospital a) May file for an HOE b) Use the device anyway c) Inform the FDA of its intent to use the device d) May not use the device as it does not have an IRB.

d) May not use the device as it does not have an IRB.

A patient in a rheumatoid arthritis clinical trial is required to keep a pain and symptom diary. Which of the following measures would be considered objective in evaluating the trial's efficacy variable a) Number of sleepless nights due to joint pain b) Ability to go for a run c) Number of days off work d) Measures using tape of swelling size in key joints

d) Measures using tape of swelling size in key joints

Regarding compensation for trial-related injury the informed consent should a) Provide no fault insurance b) Always state that no compensation will be provided c) State that medical care but no compensation is available d) Merely state if compensation is available

d) Merely state if compensation is available

Dosing recommendations for pediatric drugs are based on a) Body area b) Renal clearance c) Liver metabolism d) Mg/kg body weight

d) Mg/kg body weight

A listing of a clinical trial on clincaltrials.gov a) ls regarded by the IRB as a recruitment tool b) Must be approved by the institution c) Can be approved by the expedited process d) Must be declared in the consent form

d) Must be declared in the consent form

A major problem in studies with adolescents is a) Drug addiction b) Peer pressure c) Conflicting school and personal schedules d) Noncompliance

d) Noncompliance

Which of the following statements is correct? a) An adverse event is one that is always viewed as potentially serious b) An adverse event is an adverse drug reaction c) An adverse event qualifies for expedited reporting d) None of the above

d) None of the above

ICH-GCP requires that a regulatory authority be given direct access to a clinical trial records. Direct access includes the ability to do all except a) Examine and analyze all clinical trial records b) Verify the clinical trial records c) Reproduce any records as needed d) Not assume responsibility during an audit for the confidentiality of the clinical trial records.

d) Not assume responsibility during an audit for the confidentiality of the clinical trial records.

Which of the following is not a commitment made by the investigator on a 1572 form to the FDA? a) Supervise all associates and colleagues b) Adhere to the IRB approved protocol c) Ensure IRB review of protocol and any changes d) Not enter into any financial arrangement with the sponsor e) Inform patients that the drugs are investigational

d) Not enter into any financial arrangement with the sponsor

IRB minutes should record a) Number of members voting for and against the motion b) Names of members voting for and against the motion c) Names of members voting for, against and abstaining from the motion d) Number of members voting for, against and abstaining from the motion

d) Number of members voting for, against and abstaining from the motion

An IND is needed for all of the following except a) A new chemical entity b) A new or unapproved indication c) A new dosage form or dosage level or new drug combination d) Off label use at the discretion of a physician

d) Off label use at the discretion of a physician

Which of the following statements regarding surrogate variables is false? a) They are used when direct observation of clinical efficacy is not practical b) May show an effect in the absence of a clinical outcome c) May not yield a quantitative measure of clinical benefit d) Often allow for an assessment of benefits relative to adverse effects.

d) Often allow for an assessment of benefits relative to adverse effects.

In ICH-GCP monitoring is defined as a) A systematic and independent examination of trial related activities and documents b) An investigation intended to discover and verify the clinical effects of an investigational product c) Official review of documents, facilities, records and any other resources d) Overseeing of the progress of a clinical trial

d) Overseeing of the progress of a clinical trial

Under ICH the sponsor's responsibilities for electronic data handling includes all of the following except a) Accuracy, reliability and consistent performance guided by SOPs b) Security and backup of the system and access to authorized individuals only c) Safeguarding of the blinding d) Part 11 compliance

d) Part 11 compliance

According to FDA guidance the payment of a completion bonus for a clinical trial is a) Undue influence b) Constitutes coercion c) Violates the principle of justice in the Belmont report d) Permitted under the guidance

d) Permitted under the guidance

The studies most likely to employ the use of a drug registry are likely to be a) Phase 1 b) Phase 2 c) Phase 3 d) Phase 4

d) Phase 4

The studies which are likely to have the longest duration are a) Phase 1 b) Phase 2 c) Phase 3 d) Phase 4

d) Phase 4

The studies which do not require an IND are a) Phase 1 studies b) Phase 2 studies c) Phase 3 studies d) Phase 4 studies

d) Phase 4 studies

Epidemiologic and pharmacoeconomic studies are likely to be a) Phase I b) Phase II c) Phase III d) Phase IV

d) Phase IV

ICH defined Therapeutic Use studies are likely to be a) Phase I b) Phase II c) Phase Ill d) Phase IV

d) Phase IV

Studies on which marketing approval hinges are likely to be a) Phase I b) Phase II c) Phase III d) Phase IV

d) Phase IV

The decision to proceed with a pediatric drug development program includes all of the following except a) Novel or unique features of the proposed drug b) The age ranges of the likely pediatric patients c) Non clinical safety issues and implications for formulation development d) Pilot studies in a small relevant group of children.

d) Pilot studies in a small relevant group of children.

The investigator's brochure should include all of the following except a) Marketing experience in foreign countries b) Summary and data Guidance for the investigator c) Discussion of published reports on related products d) Potential costs of the clinical trial.

d) Potential costs of the clinical trial.

The study monitor assesses the investigator's qualification, resources and facilities during a) Routine site visits b) Site initiation visit c) Study close out visit d) Pre-study visit

d) Pre-study visit

Timely and accurate reporting of an adverse event is most important for a) Ensuring drug approval by the regulatory agency b) Prevention of study suspension by the IRB c) Updating the consent form d) Protection of subject safety

d) Protection of subject safety

Regarding the monitor's reports ICH advises that they include all of the following except a) They be in written form, dated and signed b) Include a summary of what was reviewed, deviations and deficiencies and actions to be taken c) Review and follow up of the report with the sponsor d) Punitive actions to be taken against the Pl or study coordinator

d) Punitive actions to be taken against the Pl or study coordinator

Measurements of subjective and objective endpoints should be all of the following except a) Accurate and precise b) Reproducible and reliable c) Responsive d) Qualitative

d) Qualitative

The most common techniques utilized to prevent bias in a clinical trial are a) Small sample sizes and frequent measurements b) Large sample sizes but low statistical power c) Large sample sizes and high p values d) Randomization and blinding

d) Randomization and blinding

A patient with a history of migraines in a clinical trial reports a migraine episode of greater frequency than usuals the investigator should a) Report the event as an SAE to the IRB b) Notify the sponsor of an SAE and do so promptly c) Neither report nor record the event d) Record and report the episode as an adverse event to the sponsor

d) Record and report the episode as an adverse event to the sponsor

The purpose of a double blind design is to ensure a) Deceive the subject b) Reduce the bias on the part of the investigator c) Reduce the bias on the part of the subject d) Reduce bias on the part of subject and investigator

d) Reduce bias on the part of subject and investigator

A research subject in clinical trial under IND experiences difficulty breathing and self admits to the emergency department. The investigator should a) Submit the SAE report to the sponsor only b) Not report the event as the admission to the emergency department was self-reported c) Report the event to the IRS but not the study sponsor d) Report the event to the study sponsor and the IRS

d) Report the event to the study sponsor and the IRS

The IRB requirements in ICH differ from DHHS requirements in a) Requiring annual continuing review b) Ability for approval or disapproval c) Ability for termination or suspension d) Requirements for review of non-therapeutic trials.

d) Requirements for review of non-therapeutic trials.

The sponsor's SOP requires the Pl to be present for a site initiation visit but scheduling prevents the Pl form being present for the date set by the sponsor. The CRC should a) Sign for the Pl b) Proceed with the site initiation visit c) Schedule the meeting and subsequently train the Pl himself d) Reschedule the meeting

d) Reschedule the meeting

The decision to proceed with a pediatric drug development program includes all of the following except a) Prevalence and seriousness of the condition b) The availability and suitability of alternative treatment c) The adverse event profile of alternative treatments d) Results of phase I trials in adults

d) Results of phase I trials in adults

A CRC wishes to be ready for potential enrollment into a clinical trial. The study application is still under review with the IRB. In this situation the most that he can do is a) Call potential subjects and discuss enrollment b) Review the proposed informed consent form with potential subjects c) Review the medical records of potential subjects for eligibility d) Review the Pl's previous list of treated subjects to assess if enrollment targets will be met

d) Review the Pl's previous list of treated subjects to assess if enrollment targets will be met

Regarding the sponsor's audits of a clinical trial ICH advises all of the following except a) Written procedures to be followed in the event of an audit b) The audit plan takes into account the complexity and importance of the clinical trial c) Where applicable an audit certificate should be issued d) Send the audit report to the IRB.

d) Send the audit report to the IRB.

Which of the following is a renal function test? a) AST b) ALT c) ALP d) Serum creatinine

d) Serum creatinine

The monitor should a) Serve as the person who decides on whether a trial should continue at the site b) List complaints about Pl behavior c) Train the research coordinator in their daily duties d) Serve as the main line of communication between the sponsor and the investigator.

d) Serve as the main line of communication between the sponsor and the investigator.

Which of the following would not be classified as an SAE? a) An anaphylactic event which needed an emergency room visit b) An acute renal failure, which resulted in an increased hospitalization stay of one day c) A stroke which occurred during a clinical trial d) Severe hallucinations caused by the ingestion of a recreational drug

d) Severe hallucinations caused by the ingestion of a recreational drug

According to FDA guidance the payments to research subjects should be a) An upfront payment b) A lump sum given at the end of the study c) Should be prorated in accordance with the research related visits d) Should be given as gift certificates only

d) Should be given as gift certificates only

Enrollment bonuses paid to investigators by sponsors a) Are regulated by the FDA b) Are described in DHHS regulations c) Should be declared to the IRB by the sponsors of the clinical trial d) Should be reported to the IRB and the Conflict of Interest Committee in the initial IRB application

d) Should be reported to the IRB and the Conflict of Interest Committee in the initial IRB application

The monitor is responsible for a) Verifying conflict of interest information on the part of the investigator b) Facilitating recruitment at the site c) Assisting the local CRC in scheduling patients d) Source document verification

d) Source document verification

Regarding the subjects's expenses the informed consent should state a) That every effort to cover all expenses will be made b) Detail the expenses which will or will not be covered c) Make no commitment regarding expenses d) State the anticipated expenses, if any

d) State the anticipated expenses, if any

Central features of a vulnerable subject in ICH GCP include all except a) Subject influenced by the benefits of participation b) Subjects influenced by a retaliatory response by a senior member of a hierarchy c) Subjects of an ethnic minority group d) Subjects enrolled in more than one clinical trial at the same time

d) Subjects enrolled in more than one clinical trial at the same time

A research study would most likely be deferred in all of the following scenarios except a) Justification of the use of placebo b) Justification for the enrollment of children c) Alteration of the protocol or study design and hypothesis d) Submission of additional specified documents

d) Submission of additional specified documents

A subject in a clinical trial who has been through two earlier visits develops hives and calls the CRC. The CRC should do all of the following except a) Schedule the subject for an additional visit b) First notify the Pl c) Ask the Pl if an SAE report to the IRB is indicated d) Tell the subject that it is not serious

d) Tell the subject that it is not serious

Sample populations in device studies a) Tend to be derived from a single site b) Must have at least 100 subjects c) Must be at least 1% of the target disease population d) Tend to be much smaller than in drug studies.

d) Tend to be much smaller than in drug studies.

To be characterized as severe an adverse event is one a) That qualifies for expedited reporting b) Is always life threatening c) Is always one that can be characterized as serious d) That merely describes the intensity of the medical event

d) That merely describes the intensity of the medical event

Which of the following ethical frameworks has been revised on several occasions? a) The Belmont report b) The Nuremberg Code c) ICH-GCP d) The Declaration of Helsinki

d) The Declaration of Helsinki

With regard to quality assurance in clinical trials ICH affirms of all of the following except a) States that systems with procedures that assure quality be implemented for every aspect of the clinical trial b) The sponsor is responsible for implementing and maintain quality assurance and quality control with written SOPs c) Quality control be applied to every stage of data handling d) The IRB should review the quality control measures of a clinical trial

d) The IRB should review the quality control measures of a clinical trial

Regarding access to the subject's medical records the informed consent should state a) That the original medical record will be abstracted but not directly accessed for cellular trial data b) The monitor will always have access to the medical record c) That signing of the informed consent automatically authorizes public release of the medical record d) The access to the medical record should be limited to protect the confidentiality of the subject and permitted by applicable laws and regulations

d) The access to the medical record should be limited to protect the confidentiality of the subject and permitted by applicable laws and regulations

Regarding payments in the informed consent ICH implies that a) A statement that fair payment is being made should be included b) The payment will be based on the risk and discomfort of the clinical trial c) The payment will be based on time and inconvenience d) The anticipated prorated payment will be stated

d) The anticipated prorated payment will be stated

The IRB minutes should contain a) Records of the scientific evaluations of the studies presented b) Reasons behind the votes for abstention c) Reasons behind a tie vote d) The basis for requiring changes in or disapproving the research

d) The basis for requiring changes in or disapproving the research

Robustness refers to all of the following except a) Sensitivity of the conclusions to various limitations of data b) Sensitivity to the conclusions data to various limitations of assumptions c) Lack of an effect of study conclusions to alternative analytic approaches d) The health status of the subjects in the clinical trial

d) The health status of the subjects in the clinical trial

Which of the following statements about risk in clinical trials does not apply to ICH-GCP? a) Foreseeable risk should be weighed against anticipated benefit b) Anticipated benefit should justify the risk c) The well-being of the subject should prevail over the interests of science and society d) The importance of the objective may in certain circumstances outweigh the risk to the subject

d) The importance of the objective may in certain circumstances outweigh the risk to the subject

With regard to obtaining continued approval of a clinical trial the IRB has the authority to require additional detailed information from a) The investigator only b) The investigator and the sponsor c) The study coordinating center d) The investigator, the sponsor, the coordinating center and the DSMB.

d) The investigator, the sponsor, the coordinating center and the DSMB.

Before entering an agreement with the investigator/institution the sponsnor should provide a) The IRB with the protocol b) The investigator/institution with the protocol only c) The investigator/institution with investigator's brochure d) The investigator/institution with protocol and the investigator's brochure

d) The investigator/institution with protocol and the investigator's brochure

The person who should be contacted regarding a medical emergency experienced at home by a clinical trial subject is a) Always the principal investigator b) The sponsor's medical safety officer c) The research coordinator d) The person designated for contact for medical matters on the consent form

d) The person designated for contact for medical matters on the consent form

Regarding contact information about the rights of a trial subject the informed consent should mention a) The institution b) The investigator c) The IRB d) The person or persons to contact

d) The person or persons to contact

ICH recommends that responsibility for the investigational product and its accountability be assigned to a) The sub-investigator b) The research coordinator c) The study monitor d) The pharmacist

d) The pharmacist

Which of the following statements about the relationship of the IRB to the DSMB is NOT ACCURATE? a) The IRB is not a DSMB because it only reviews serious adverse events at the institutional site whereas the DSMB reviews serious adverse events from all sites b) The IRB is not a DSMB because it does not have the authority to unblind a subject's identity in a clinical trial to analyze a serious adverse event whereas the DSMB does c) The IRB can suspend a clinical trial at its own site regardless of the DSMB but the DSMB can stop the clinical trial at all sites d) The relative duties of the DSMB and the IRB are described in regulations

d) The relative duties of the DSMB and the IRB are described in regulations

When an IRB defers a research project: a) The research can proceed in the interim b) The research may not proceed until reviewed by the IRB chair c) The research may not proceed until reviewed by a qualified consultant to the IRS d) The research may not proceed until reviewed again and approved by a fully convened IRB.

d) The research may not proceed until reviewed again and approved by a fully convened IRB.

According to ICH the ultimate responsibility for the quality and integrity of the data rests with a) The investigator b) The research coordinator c) The site monitor and CRO d) The sponsor

d) The sponsor

An important rare side effect is observed for a drug in phase 4 trial. The likely outcome would be a) The sponsor ignores the effect because it is rare b) The sponsor decides not to report it to the FDA c) The sponsor reports it to the FDA which then imposes a black box warning on the product label d) The sponsor reports it to the FDA which resolves not to act on the information

d) The sponsor reports it to the FDA which then imposes a black box warning on the product label

A study may be approved for an IND exemption for all of the following except a) The study will not pursue a new indication b) The study will not pursue a change in the labeling or advertising c) The study will not involve a new population d) The study will not adhere to an approved route of administration or dosage level.

d) The study will not adhere to an approved route of administration or dosage level.

Patients who enroll in clinical trials on the assumption that they will be cured are subject to a) Self-deception b) Misinterpretation c) Optimism d) Therapeutic misconception

d) Therapeutic misconception

A subject on a clinical trial for GI reflux disease experiences several bowel movements and is hospitalized for dehydration. He has been on the test drug for three weeks and the event is thought by the Pl to be related to the test drug. The event should be reported in all of the following ways except a) As a serious adverse event to the IRB b) To the sponsor on the appropriate CRF c) By the sponsor to the regulatory agency d) To the family physician for symptom management

d) To the family physician for symptom management

Individuals utilized by the sponsor for all stages of the clinical trial process may include all of the following except a) Biostatisticians b) Clinical pharmacologists c) Physicians d) Trial subjects where appropriate

d) Trial subjects where appropriate

Which of the following is cited in the principle of justice as exemplifying an injustice? a) The Willowbrook study b) The San Antonio Contraception study c) The Radiation experiments d) Tuskegee study

d) Tuskegee study

According to OHRP an adverse event represents and unanticipated problem if it is a) Unexpected, possibly related to participation b) Unexpected and meets the REGULATORY AGENCY definition of serious c) Possibly related to participation even if expected d) Unexpected, possibly related to participation and places the subject or others at a greater risk of harm than previously recognized.

d) Unexpected, possibly related to participation and places the subject or others at a greater risk of harm than previously recognized.

New safety information regarding a study drug should be updated by the sponsor by a) Notifying the IRB b) Notifying the investigator c) Updating the protocol d) Updating the Investigator's Brochure

d) Updating the Investigator's Brochure

d) Verifying that the investigator follows the approved protocol and all approved amendment(s), if any e) Verifying that written informed consent as obtained before each subject's participation in the trial f) Ensuring that the investigator receives the current Investigator's Brochure, all documents, and all trial supplies needed to conduct the trial properly and to comply with the applicable regulatory requirement(s) g) Ensuring that the investigator and the investigator's trial staff are adequately informed about the trial

With regard to the role of medical care in medical research the Declaration of Helsinki notes: a) Consent for the medical care is not separately required b) Medical care and medical research should be kept separable as much as possible c) Procedures for medical research but not medical care should be described in the informed consent d) When medical research is combined with medical care, additional standards apply to protect the research subjects.

d) When medical research is combined with medical care, additional standards apply to protect the research subjects.

A 51Ok premarket notification is submitted a) When the device is a Class I device only b) Before the initiation of a clinical trail c) When the device is intended for population of less than 4000 d) When the device to be marketed is substantially equivalent to the current approved device.

d) When the device to be marketed is substantially equivalent to the current approved device.

A sponsor may charge a subject for an investigational drug a) If the sponsor's budget needs it b) If the drug is expensive c) If the institution agrees d) With written permission from the FDA.

d) With written permission from the FDA.

The Declaration of Helsinki was formulated by the a) National commission for the protection of human subject b) Council for the international organization of medical sciences c) The War Crimes Tribunal d) World Medical Association

d) World Medical Association

According to ICH, the sponsor may request the following from the IRB a) A copy of the minutes of an IRB meeting b) IRB correspondence with OHRP c) Rationale for IRB disapproval d) Written procedures and membership lists

d) Written procedures and membership lists

The best way for a Pl to inform a subject about a placebo in a double-blind trial includes all of the following except a) There is a fifty percent chance that you may be in a group that does not receive the investigational drug b) Because of the restrictions of the study I cannot tell you if you are in the group receiving drug or a sugar pill c) You will receive the same attention regardless of whether you are in the group receiving a drug or a sugar pill d) You need not concern yourself about whether you are receiving the drug or a sugar pill as we cannot tell you if the clinical trial has had any beneficial effect.

d) You need not concern yourself about whether you are receiving the drug or a sugar pill as we cannot tell you if the clinical trial has had any beneficial effect.

An equivalence or non-inferiority trial is one in which a) Efficacy of a test drug is no worse than an active comparator b) Multiple doses of a test drug are compared to multiple doses of as standard drug c) a only d) a and b

d) a and b a) Efficacy of a test drug is no worse than an active comparator b) Multiple doses of a test drug are compared to multiple doses of as standard drug

The informed consent should adhere to a) GCP b) Declaration of Helsinki c) a only d) a and b

d) a and b a) GCP b) Declaration of Helsinki

An adverse event is one which a) Is an unfavorable and unintended sign, symptom or disease b) Is one that is temporally associated with drug regardless of whether it is related or not c) a only d) a and b

d) a and b a) Is an unfavorable and unintended sign, symptom or disease b) Is one that is temporally associated with drug regardless of whether it is related or not

For a drug that is in a Phase IV trial and adverse drug reaction is one which a) Is noxious and unintended b) Occurs at normal doses used for prophylaxis c) a only d) a and b

d) a and b a) Is noxious and unintended b) Occurs at normal doses used for prophylaxis

An event may be classified as serious if it a) Not immediately life threatening, but may jeopardize the patient b) Not immediately life threatening but may require and intervention to prevent hospitalization c) a only d) a and b

d) a and b a) Not immediately life threatening, but may jeopardize the patient b) Not immediately life threatening but may require and intervention to prevent hospitalization

The type of monitoring in a confirmatory clinical trial may include a) Oversight of the quality of the clinical trial b) Breaking the blind for treatment comparison and interim analysis c) a only d) a and b

d) a and b a) Oversight of the quality of the clinical trial b) Breaking the blind for treatment comparison and interim analysis

In a clinical trial regarding the statement of benefits a) Reasonably foreseeable benefits should be stated b) Explicitly indicate that there are no benefits if none are expected c) a only d) a and b

d) a and b a) Reasonably foreseeable benefits should be stated b) Explicitly indicate that there are no benefits if none are expected

Toxicology studies in animal models a) Should be reviewed by qualified experts b) Assessed for their implications of subject safety c) a only d) a and b

d) a and b a) Should be reviewed by qualified experts b) Assessed for their implications of subject safety

Adverse drug reactions in the control group should be reported to a) The other manufacturer b) Appropriate regulatory agency c) a only d) a and b

d) a and b a) The other manufacturer b) Appropriate regulatory agency

In order to increase the enrollment number of sites in a clinical trial was doubled. The Pl when notified should a) Share the information with the research team b) File and amendment with the IRB c) Update the consent form and ask the sponsor, if reconsent of enrolled subjects is required d) band C

d) b and c b) File and amendment with the IRB c) Update the consent form and ask the sponsor, if reconsent of enrolled subjects is required

Studies which provide the most information for confirmatory study design are part of a) Phase I studies b) Phase II studies c) a only d) b only

d) b only b) Phase II studies

The drug concentration used in preclinical studies is likely to higher than in human studies by a. 5 fold b. 10 fold c. 100fold d. 1000 fold

d. 1000 fold The way I remembered this one is phase II studies are testing the maximium doseage amount.

A patient in a rheumatoid arthritis clinical trial is required to keep a pain and symptom diary. Which of the following measures would be considered objective in evaluating the trial's efficacy variable a. Number of sleepless nights due to joint pain b. Ability to go for a run c. Number of days off work d. Measures using tape of swelling size in key joints

d. Measures using tape of swelling size in key joints

Which of the following is a renal function test? a. AST b. ALT c. ALP d. Serum creatinine

d. Serum creatinine

an independent group of experts who monitor patient safety and treatment efficacy data while a clinical trial is ongoing

data monitoring committee - sometimes called a data and safety monitoring board (DSMB)

Standard Operation Manual (SOPs)

detailed, written instructions to achieve uniformity of the performance of a specific function

Pre-Award Process

developing the grant or contract proposal and budget, negotiating any sub-awards, signing and submitting proposal, providing required certifications and essential documents to the relevant local review committees before the proposal is submitted to sponsor for review

Audit Plans

differ based upon study design, complexity, number of subjects on trial, etc

Audit Trial

documentation that allows reconstruction of the course of events

Essential Documents

documents which individually and collectively permit evaluation of the conduct of a study and the quality of the data produced

an experimental procedure in which neither the subjects of the experiment nor the persons administering the experiment know the critical aspects of the experiment; "a procedure is used to guard against both experimenter bias and placebo effects"

double-blind study

An IND is not needed for all of the following except a) An application not intended for human use b) In vitro testing c) Laboratory animal studies d) Use of a drug on label e) A contemplated new marketing application

e) A contemplated new marketing application

Regarding the termination or withdrawal of a subject from a research study the consent form should a) Advise that termination may occur without the subject's consent b) Advise regarding the consequences of the subject's decision to withdraw c) Describe the circumstances in which such termination might occur d) Provide procedures for orderly termination e) All of the above

e) All of the above a) Advise that termination may occur without the subject's consent b) Advise regarding the consequences of the subject's decision to withdraw c) Describe the circumstances in which such termination might occur d) Provide procedures for orderly termination

The sponsor changes the eligibility criteria for an IRB approved protocol and adds a QOL questionnaire . The Pl should submit the following to the IRB a) An amendment application b) The modified protocol c) The altered investigator's brochure that triggered the change d) A revised consent form e) All of the above

e) All of the above a) An amendment application b) The modified protocol c) The altered investigator's brochure that triggered the change d) A revised consent form

Toxicological effects in the investigator's brochure should include a) Carcinogenicity b) Irritancy c) Reproductive toxicity d) Genotoxicity and mutagenicity e) All of the above

e) All of the above a) Carcinogenicity b) Irritancy c) Reproductive toxicity d) Genotoxicity and mutagenicity

A serious adverse event is on which results in a) Death or life threatening event b) A hospitalization or prolongation of hospitalization c) Persistent or significant disability d) Congenital anomaly or birth defect e) All of the above

e) All of the above a) Death or life threatening event b) A hospitalization or prolongation of hospitalization c) Persistent or significant disability d) Congenital anomaly or birth defect

According to ICH the investigator should promptly report the following to the IRB: a) Deviations from protocol to eliminate immediate hazards b) Changes in risk in protocol c) Serious and unexpected adverse drug reactions d) New information that may affect the safety of subjects e) All of the above

e) All of the above a) Deviations from protocol to eliminate immediate hazards b) Changes in risk in protocol c) Serious and unexpected adverse drug reactions d) New information that may affect the safety of subjects

According to ICH the additional documents to be placed on file during a clinical trial include a) Enrollment and screening logs b) Annual reports to the IRB c) Signature sheet/delegation log d) Drug accountability records e) All of the above

e) All of the above a) Enrollment and screening logs b) Annual reports to the IRB c) Signature sheet/delegation log d) Drug accountability records

In doing a note to the informed consent the CRC should record a) If an interpreter was present and information about the interpreter b) The date, time ,place and duration of the consent process c) The use of a witness or legal guardian d) The fact that all queries were answered and no procedures initiated prior to the conference e) All of the above

e) All of the above a) If an interpreter was present and information about the interpreter b) The date, time ,place and duration of the consent process c) The use of a witness or legal guardian d) The fact that all queries were answered and no procedures initiated prior to the conference

According to ICH the statistical analysis section of the protocol should include a) Sample size and power calculations b) Description of the statistical methods to be used c) Level of significance for hypothesis testing d) Criteria for termination of the trial e) All of the above

e) All of the above a) Sample size and power calculations b) Description of the statistical methods to be used c) Level of significance for hypothesis testing d) Criteria for termination of the trial

With regard to drug accountability the monitor should a) Verify storage items and adequacy of supplies b) Verify whether eligible patients are getting the drug at the right doses c) Verify whether subjects are informed and trained about drug use and storage d) Verify the receipt, use, return and disposition of unused drug e) All of the above

e) All of the above a) Verify storage items and adequacy of supplies b) Verify whether eligible patients are getting the drug at the right doses c) Verify whether subjects are informed and trained about drug use and storage d) Verify the receipt, use, return and disposition of unused drug

Actions that the IRB can take when reviewing a study are a) Approve b) Approve with conditions c) Defer pending major modifications d) Disapprove e) All of the above may apply

e) All of the above may apply a) Approve b) Approve with conditions c) Defer pending major modifications d) Disapprove

A regulatory path to market for a device may include a) An IDE b) APMA c) A 510K application d) An HOE e) All of the above.

e) All of the above. a) An IDE b) APMA c) A 510K application d) An HOE

A significant risk device is a) Implantable b) Poses a serious risk to health c) Mitigates a serious risk to subject d) Essential for diagnosis , treatment or cure e) All of the above.

e) All of the above. a) Implantable b) Poses a serious risk to health c) Mitigates a serious risk to subject d) Essential for diagnosis , treatment or cure e) All of the above.

The FDA guidance on an independent DSMB states that the sponsor should consider one for a clinical trial if the trial is a) Multisite and phase 3 b) Involves a vulnerable population c) Has a complex design d) Is pivotal for study outcome e) All of the above.

e) All of the above. a) Multisite and phase 3 b) Involves a vulnerable population c) Has a complex design d) Is pivotal for study outcome

According to ICH statistical analysis section of the protocol should specify whether the following subjects will be included in the analysis except a) All randomized subjects b) All dosed subjects c) All evaluable subjects d) All eligible subjects e) All screened subjects

e) All screened subjects

An adverse event is defined as serious if it is a) Death or life threatening event b) Results in hospitalization or prolongation of a hospitalization c) Results in a persistent or significant disability d) Results in a congenital anomaly or birth defect e) Any of the above

e) Any of the above a) Death or life threatening event b) Results in hospitalization or prolongation of a hospitalization c) Results in a persistent or significant disability d) Results in a congenital anomaly or birth defect

Laboratory related protocol deviations can include a) Improper lab sample collection b) Improper shipment of a lab sample which results in a non-evaluable sample. c) Improper storage of the sample prior to shipment d) Shipment of the sample by non-certified personnel e) Any of the above.

e) Any of the above. a) Improper lab sample collection b) Improper shipment of a lab sample which results in a non-evaluable sample. c) Improper storage of the sample prior to shipment d) Shipment of the sample by non-certified personnel

A Form 1571 includes all of the following items except a) The protocol b) The investigator's brochure c) A chemistry manufacturing and controls section d) Pharmacology and toxicology data e) Financial disclosure of the sponsor

e) Financial disclosure of the sponsor

1.1 All of the following items are required on a Form 1572 except a) The principal investigator's CV b) Information on sub investigators c) Laboratory facilities utilized d) IRB information e) Financial disclosures of the principal investigator

e) Financial disclosures of the principal investigator

Under ICH a vulnerable subject may include all of the following except (choose all that apply) a) Medical pharmacy, dental or nursing students b) Members of the armed forces c) Subordinate hospital or laboratory personnel d) Persons kept in detention e) Pregnant women f) Fetuses and neonates g) Children h) Unemployed, impoverished or homeless persons i) Nomads, refugees j) The elderly k) Ethnic minority groups I) Uneducated or illiterate individuals

e) Pregnant women f) Fetuses and neonates j) The elderly I) Uneducated or illiterate individuals

Source documents in a clinical trial refer to all except a) Medical notes and pertinent parts of a medical record b) Laboratory and radiology findings c) Pathology reports d) Patient diaries and pharmacy records e) Site monitoring reports

e) Site monitoring reports

Investigator bias in an experimental study is a) An effect caused in a treatment group because of the special attention paid to it by the investigator b) The participants form an interpretation of the experiment's purpose and modify their behavior accordingly c) Occurs in cognitive trial where the perception of one trait is influenced by the perception of another trait. d) An effect ,caused by psychological influence, experienced by the patient when they are unaware that they are not being administered the medication for the clinical trial e) The investigator's paradigm in experimental design and analysis predetermines the interpretation of the results f) Patients in the control group become aware of group membership and turn rebellious and alter behavior to contradict the experiment's purpose

e) The investigator's paradigm in experimental design and analysis predetermines the interpretation of the results

Features of the informed consent in ICH which differ from DHHS guidelines include all of the following except a) The probability of assignments to each treatment group b) The risks and benefits of alternative treatments c) The access to the subject's medical records for the monitor, auditor and IRB d) The anticipated expenses for the subject e) The number of subjects in the trial.

e) The number of subjects in the trial.

Crossover Design

each subject is randomised to a sequence of 2 or more treatments, and acts as its own control for treatment comparisons

A trial that will result in providing an answer to a specific question with a limited human exposure in terms of dose, time and number of participants to the study. Also will have no therapeutic or diagnostic intent.

exploratory trial

During the course of a clinical trial the CRC notices that the Hct values have been consistently low in several subjects. Upon further investigation it was discovered that the lab assistant was storing the samples under his desk and sending the entire batch for analysis once every week. The CRC should a) Immediately inform the Pl b) File a protocol deviation with the IRB c) Inform the sponsor d) Arrange to have the lab assistant retrained or disciplined e) Initiate a CAPA plan f) All of the above

f) All of the above a) Immediately inform the Pl b) File a protocol deviation with the IRB c) Inform the sponsor d) Arrange to have the lab assistant retrained or disciplined e) Initiate a CAPA plan

According to ICH the investigator's brochure should include a) Physical, chemical and pharmaceutical properties and formulations b) Nonclinical studies including nonclinical pharmacology c) Pharmacokinetics and toxicology d) Effects in humans e) Summary of data and guidance for the investigator f) All of the above

f) All of the above a) Physical, chemical and pharmaceutical properties and formulations b) Nonclinical studies including nonclinical pharmacology c) Pharmacokinetics and toxicology d) Effects in humans e) Summary of data and guidance for the investigator

ICH guidelines for trial design in protocol preparation includes all except a) Description of the designs (double-blind, placebo, parallel design) b) Randomization and blinding c) Dosage regimens d) Stopping rules e) Data recorded directly without source documents f) IRB communication guidelines

f) IRB communication guidelines

The monitor should ensure all of the following except (check all that apply) a) Informed consent was obtained before subject participation b) The investigator receives the investigator's brochure c) Protocol procedures are performed is specified in the protocol's schedule of assessments d) Only eligible subjects are enrolled e) CRFs are accurate and supported by sourced documents f) Participate in the meetings between the investigator and staff g) Contribute to the investigator's recruitment efforts h) Failed visits, test and procedures not performed are reported on CRFs i) Adverse events are reported to the IRB and sponsor in timely fashion

f) Participate in the meetings between the investigator and staff g) Contribute to the investigator's recruitment efforts h) Failed visits, test and procedures not performed are reported on CRFs

The John Henry effect in an experimental study is a) An effect caused in a treatment group because of the special attention paid to it by the investigator b) The participants form an interpretation of the experiment's purpose and modify their behavior accordingly c) Occurs in cognitive trials where the perception of one trait is influenced by the perception of another trait d) An effect ,caused by psychological influence, experienced by the patient when they are unaware that they are not being administered the medication for the clinical trial e) The investigator's paradigm in experimental design and analysis predetermines the interpretation of the results. f) Patients in the control group become aware of group membership and turn rebellious and alter behavior to contradict the experiment's purpose

f) Patients in the control group become aware of group membership and turn rebellious and alter behavior to contradict the experiment's purpose

It would be usual practice for a CRO to assume all of the responsibilities outlined below except a) Implementation of randomization schema b) Review of all regulatory aspects pertaining to the laboratory c) Review of all regulatory aspects of drug accountability d) Implementing and monitoring payments to subjects. e) Collection of SAE reports and forwarding to sponsor f) Protocol preparation and DSMB management

f) Protocol preparation and DSMB management

Good Clinical Practice represents all of the features below except a) Is a standard for the design conduct performance of a clinical trial b) A standard for auditing, recording, monitoring and reporting of a clinical trial c) Assurance that the d) data are accurate and credible e) Assurance that the rights, integrity and confidentiality of trial subjects is protected f) Represents a mandatory regulatory guidance for clinical trial management

f) Represents a mandatory regulatory guidance for clinical trial management

is one of the many experimental designs used in psychological experiments where two or more independent variables are simultaneously manipulated to observe their effects on the dependent variables

factorial design

Food and Drug Administration (FDA)

federal agency responsible for the regulation and enforcement of drug evaluation and distribution policies

Features pertinent to drug metabolism in a Preterm new born include a) Immaturity of renal and hepatic clearance mechanism b) Drug binding and displacement from proteins c) Penetration into the CNS d) Unique neonatal conditions e) Rapid maturation of physiologic processes that radically influence drug dosing f) Transdermal absorption of drugs g) All of the above

g) All of the above a) Immaturity of renal and hepatic clearance mechanism b) Drug binding and displacement from proteins c) Penetration into the CNS d) Unique neonatal conditions e) Rapid maturation of physiologic processes that radically influence drug dosing f) Transdermal absorption of drugs

The Declaration of Helsinki contains which of the following items: a) In medical research most procedures involve risks and burdens b) The welfare of animals must be respected c) Medical research is justified only if there is likelihood that the research populations stand to benefit from the results of the research d) Medical research should only be carried out if the importance of the objective outweighs the inherent risks to the subjects e) Negative as well as positive results should be published or made publicly available. f) Post-trial provision of a beneficial treatment should be provided with the relevant information to study participants g) All of the above

g) All of the above a) In medical research most procedures involve risks and burdens b) The welfare of animals must be respected c) Medical research is justified only if there is likelihood that the research populations stand to benefit from the results of the research d) Medical research should only be carried out if the importance of the objective outweighs the inherent risks to the subjects e) Negative as well as positive results should be published or made publicly available. f) Post-trial provision of a beneficial treatment should be provided with the relevant information to study participants

Which of the duties listed below are typically carried out by the sponsor and not the CRO? a) Protocol preparation and updates b) Investigator brochure preparation and updates c) Correspondence and interaction with the FDA d) Manufacture and supply of investigational drug e) Preparation of the pharmacy manual f) Management of the DSMB g) All of the above

g) All of the above a) Protocol preparation and updates b) Investigator brochure preparation and updates c) Correspondence and interaction with the FDA d) Manufacture and supply of investigational drug e) Preparation of the pharmacy manual f) Management of the DSMB

ICH guidelines for protocol preparation in clinical trials includes all except: a) Inclusion and exclusion criteria b) Withdrawal and replacement of subjects c) Schedule of assessments d) Assessments of safety and efficacy e) Statistical analysis f) Publication policy g) Conflict of interest disclosure

g) Conflict of interest disclosure

It would be usual practice for a CRO to assume all of the responsibilities outlined below except a) Collection of forms 1572 form the Pl b) Preparation and distribution of the regulatory binder c) Site initiation and site close out visits d) Monitoring data integrity and quality e) Reviewing the delegation of authority log f) Pretrial investigator and facilities assessment g) Preparation of the investigator's brochure and the updates h) Distribution of the protocol and protocol updates.

g) Preparation of the investigator's brochure and the updates

Protocol Deviation (or Violation)

generally an unexplained excursion from the requirements of the protocol that is not implemented or intended as a systematic change

A phase I oncology study for lymphoma in children should enroll e) Healthy adults f) Healthy children g) Children with any known cancer h) Children with lymphoma who have failed standard treatment

h) Children with lymphoma who have failed standard treatment

The study monitor should verify all of the following except a) Informed consents b) Receipt and distribution of current copies of the investigator's brochure c) Delegation of duties to staff d) Eligibility of enrolled subjects e) Recruitment rate f) Case report forms and source documents g) Record of failed visits and tests and procedures not done h) The budget for the site and accuracy of financial disclosures

h) The budget for the site and accuracy of financial disclosures

h) Verifying that the investigator and the investigator's trial staff are performing the specified trial functions, in accordance with the protocol and any other written agreement between the sponsor and the investigator/institution, and have not delegated these functions to unauthorized individuals i) verifying that the investigator is enrolling only eligible subjects j) reporting the subject recruitment rate k) Verifying that source documents and other trial records are accurate, complete, kept up-to-date and maintained l) Verifying that the investigator provides all the required reports, notifications, applications, and submissions, and that these documents are accurate, complete, timely, legible, dated, and identify the trial

E6(R1) 5.18.4 -- Monitor's Responsibilities -- The monitor(s) in accordance with the sponsor's requirements should ensure that the trial is conducted and documented properly by carrying out the following activities when relevant and necessary to the trial and the trial site: c) verifying ,for the investigational product(s): (Part 2)

i) That storage times and conditions are acceptable, and that supplies are sufficient throughout the trial ii) that the investigational product(s) are supplied only to subjects who are eligible to receive it and at the protocol specified dose(s) iii) that subjects are provided with necessary instruction on properly using, handling, storing, and returning the investigational product(s) iv) that the receipt, use, and return of the investigational product(s) at the trial sites are controlled and documented adequately v) that the disposition of unused investigational requirement(s) and is in accordance with the sponsor

E6(R1) 4.8.10 Both the informed consent discussion and the written informed consent form and any other written information to be provided to subjects should include explanations of. . .Part 2

i) The alternative procedure(s) or course(s) of treatment that may be available to the subject, and their important potential benefits and risks j) The compensation and/or treatment available to the subject in the event of trial-related injury k) The anticipated prorated payment, if any, to the subject for participating in the trial l) The anticipated expenses, if any, to the subject for participating in the trial m) That the subject's participation in the trial is voluntary and that the subject may refuse to participate or withdraw from the trial, at any time, without penalty or loss of benefits to which the subject is otherwise entitled n) That the monitor(s), the auditor(s), the IRB/IEC, and the regulatory authority(ies) will be granted direct access to the subject's original medical records for verification of clinical trial procedures and/or data, without violating the confidentiality fo the subject, to the extent permitted by applicable laws and regulations and that, by signing a written informed consent form, the subject or the subject's legally acceptable representative is authorizing such access

E6(R1) 5.18.4 -- Monitor's Responsibilities -- The monitor(s) in accordance with the sponsor's requirements should ensure that the trial is conducted and documented properly by carrying out the following activities when relevant and necessary to the trial and the trial site: m) Checking the accuracy and completeness of the CRF entries, source documents and other trial-related records against each other. The monitor specifically should verify that: (Part 5)

i) the data required by the protocol are reported accurately on the CRFs and are consistent with the source documents ii) any dose and/or therapy modifications are well documented for each of the trial subjects iii) aderse events, concomitant medications and intercurrent illnesses are reported in accordance with the protocol on the CRF's iv) visits that the subjects fail to make, tests that are not conducted, and examinations that are reported as such on the CRFs v) All withdrawals and dropouts of enrolled subjects from the trial are reported and explained on the CRFs

compensate (someone) for harm or loss; reimburse secure (someone) against legal responsibility for their actions; insure

idemnify

a thing that persuades or influences someone to do something

inducement

E8 3.1.3.1.a -- Estimation of initial safety and tolerability

intended to determine the tolerability of the dose range expected to be needed for later clinical studies and to determine the nature of adverse reactions that can be expected--typically include both single and multiple dose administration

In clinical trials and other scientific studies, it s an analysis of data that is conducted before data collection has been completed. Clinical trials are unusual in that enrollment of subjects is a continual process staggered in time.

interim analysis

Good Clinical Practice (GCP)

international ethical and scientific quality standard for designing, conducting, recording, and reporting trials that involve the participation of human subjects

International Council for Harmonisation (ICH)

international standard for the design, conduct, monitoring, and reporting of clinical research of investigational drugs.

When evaluating the causality of an adverse event, which of the following should be a consideration? The timing of the event in relation to administration of the

investigational agent

Significant Risk (SR) Device

investigational device that is implanted and presents a potential for serious risk to the health, safety, or welfare of a subject; those that support or sustain human life and present the potential for serious risk to the health, safety, or welfare of a subject; is very important in diagnosing, curing, mitigating, or treating disease or preventing impairment to human health, and presents the potential for serious risk to the health, safety, or welfare of a subject; or otherwise presents a potential for serious risk to the health, safety or welfare of a subject. Examples of SR devices include: sutures, cardiac pacemakers, hydrocephalus shunts, and orthopedic implants.

Who gives IB to IRB?

investigator

1.2 elements of an Investigational Brochure (IB) and/or investigational device use (instructions for use, user manual) ICH 7

is a compilation of the clinical and nonclinical data on the investigational product(s) that are relevant to the study of the product(s) in human subjects.

Consenting illiterate subjects

is okay, but must have impartial witness present

What is 21 CFR Part 11 compliance?

it is compliance that dictates that those companies who use electronic systems for document and signature control must provide assurance that the electronic documents are authentic. The regulations all stipulate the necessity of the confidentiality of electronic records.

According to ICH the essential documents to be placed on file before the start of a clinical trial include all of the following except a) Investigator's brochure b) Protocol and other sponsor/ CRO agreements c) Informed consents d) Recruiting and advertising information e) Financial aspects and insurance information f) IRB approvals g) CV for investigator and sub investigator h) Randomization and decoding information i) Site initiation report and pre-trial site suitability assessments j) Forms 1571 and 1572

j) Forms 1571 and 1572

Surrogate variable

kind of fill in for other variables and are pretty general

Exculpatory Language

language in the consent document through which the subject is made to waive or appear to waive any of his/her legal rights, or releases or appears to release the investigator, the sponsor, the institution, or its agents from liability for negligence

Independent Data-Monitoring Committee (IDMC)

may be established by the sponsor to assess at intervals the progress of a clinical trial, the safety data, and the critical efficiency endpoints, and to recommend to the sponsor whether to continue, modify, or stop a trial

Who acts as main point of contact b/w the PI & sponsor?

monitor

Audits differ from monitoring visits because

monitoring visits assess safety of subjects and day to day data collection & source documents. audits look for compliance with approved protocols

Monitors & Auditors differ in what major way?

monitors are supplied by sponsor as part of sponsor team. Auditors are independent.

is a clinical trial conducted at more than one medical center or clinic

multicenter research trial

n) Informing the investigator of any CRF entry error, omission, or illegibility. The monitor should ensure that appropriate corrections, additions, or deletions are made, dated, explained (if necessary), and initialed by the investigator or by a member of the investigator's trial staff who is authorized to initial CRF changes for the investigator. This authorization should be documented o) Determining whether all adverse events (AEs) are appropriately reported within the time periods required by GCP, the protocol, the IRB/IEC, the sponsor, and the applicable regulatory requirement(s) p) determining whether the investigator is maintaining the essential documents q) communicating deviations from the protocol, SOPs, GCP, and the applicable regulatory requirements to the investigator and taking appropriate action designed to prevent recurrence of the detected deviations

The sponsor must also notify FDA of any unexpected fatal or life-threatening suspected adverse reaction as soon as possible but in no case later than how many calendar days after the sponsor's initial receipt of the information

no case later than 7 calendar days after the sponsor's initial receipt of the information.

Serious, unexpected reactions (ADRs) that are not fatal or life-threatening must be filed as soon as possible but no later than how many calendar days after first knowledge by the sponsor that the case meets the minimum criteria for expedited reporting.

no later than 15 calendar days after first knowledge by the sponsor

fatal / life threatening ADRs should be submitted in what time frame?

no later than 7 days, but ASAP

Trials which compare treatments may not be designed to show that one treatment is superior. These trials aim to show that the new drug is no worse than standard treatment.

non-inferiority or equivalence trials

harmful, poisonous, or very unpleasant

noxious

In inferential statistics, it is a default hypothesis that a quantity to be measured is zero

null hypothesis

Date/time on ICF

only date is required; time is generally preferred by PIs

is a type of clinical trial in which information is not withheld from trial participants. In particular, both the researchers and participants know which treatment is being administered

open-label trial, or open trial

Source data

original clinical information from source documents (medical record information)

Source Documents

original documents, data, and records involved in the clinical trial

Is a complete randomized design in which each patient receives one and only one treatment in a random fashion.

parallel group design

Direct Access

permission to examine, analyze, verify, and reproduce any records and reports that are important to evaluation of a clinical trial

Legally acceptable representative

person whom is lawfully able to consent on behalf of another

A standard study that is the conventional method for evaluating the the movement of drugs within the body of a drug in human subjects. In such a study, subjects are given a single dose or repeated doses of an investigational drug. Then, blood and urine samples are collected in compliance with a fixed schedule.

pharmacokinetic study

the branch of pharmacology concerned with the movement of drugs within the body

pharmacokinetics

In a trial that one group of participants (the control arm) receives an inactive drug (or other intervention), called a placebo, while another group of participants (the experimental arm) receives the active drug being tested. The two groups are compared to see if the drug is more effective than the placebo.

placebo-controlled trial

A design is an experiment in which measurements are taken on individuals both before and after they're involved in some treatment. Pretest-posttest designs can be used in both experimental and quasi-experimental research and may or may not include control groups.

pretest-posttest design

Confidentiality

prevention of disclosure, to other than authorized individuals, of a sponsor's proprietary information or of a subject's identity

Clinical Trial

process of studying human subjects to assess the effect of a particular intervention (Drug, biologic, device, procedure or behavior change) on a pre specified set of measurable events.

Payment to subjects must be....

prorated & not contingent on subject completing study

inflicting or intended as punishment; disciplinary, corrective (of a tax or other charge) extremely high.

punitive

an adverse drug reaction requires what level of causality?

reasonable possibility

Is a result measured within an assay that can be influenced by other factors. For example, in a trial you can test whether a new drug is effective in reducing a certain symptom of a heart disease.

response variable

This phrase means that a causal relationship between a medicinal product and an adverse event is at least a reasonable possibility, i.e., the relationship cannot be ruled out.

responses to a medicinal products

In statistics, the term refers to the strength of a statistical model, tests, and procedures according to the specific conditions of the statistical analysis a study hopes to achieve. Given that these conditions of a study are met, the models can be verified to be true through the use of mathematical proofs.

robust or robustness

A term used in clinical trials for the outcome variable specified in the study protocol that is of greatest importance to the trial's primary objective, and usually the one used in the sample size calculation.

secondary variable

in human drug trials it is defined as any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, may have caused a congenital anomaly/birth defect, or requires intervention to prevent permanent impairment or damage

serious adverse event (SAE)

ADRs should be expeditiously reported when what two factors are present?

serious/unexpected

Changes in risk to subjects...

should be included & approved on an updated ICF - patients enrolled should be re-consented

Secondary Variable

should relate to trial primary variable and be limited in number

Financial Conflict of Interest (FCOI)

significant financial interest that could directly and significantly affect the design, conduct, or reporting of research.

A sponsor proposes research to evaluate reengineering a commercially available pacemaker. It is hoped that the new pacemaker will pose fewer risks to individuals when compared to the current commercially available product. How should this device be classified?

significant risk device

In a clinical trial, it is usually in the form of a scale of ordered categorical ratings—that integrates objective variables and the investigator's overall impression about the state or change in state of a subject as a result of the trial's intervention or therapy.

single variable

A CRO has been enlisted to oversee a study, who is primarily responsible for integrity of trial data?

sponsor

Who appoints a monitor?

sponsor

Who creates SOPs

sponsor

Who gives IB to investigator?

sponsor

Who initiates and secures the agreement?

sponsor

Frequentist Methods

statistical methods, such as significance tests and confidence intervals, which can be interpreted in terms of the frequency of certain outcomes occurring in hypothetical repeated realizations of the same experimental situation

demand or specify (a requirement), typically as part of a bargain or agreement

stipulate

studies in support of special populations: geriatrics

Controlled

subjects are split into at least two groups: those receiving the experimental agent and those receiving a standard treatment for the condition (an active control), no treatment, or a placebo. If subjects are assigned randomly into these groups, the study is a randomized controlled trial.

the action or fact of maintaining or supporting oneself at a minimum level

subsistence

A variable in a clinical trial that provides an indirect measure of efficacy in situations where direct measure of a clinical effect is not possible or practical.

surrogate variable

audit

systematic and independent examination of trial-related activities and documents to determine whether the evaluated trial-related activities were conducted, and the data were recorded, analyzed, and accurately reported according to the protocol, sponsor's standard operating procedures (SOPs), Good Clinical Practice (GCP), and the applicable regulatory requirement

Regarding subject receipt of a signed and dated copy of the consent forms, what is different for FDA regulations?

the FDA regulations allow subjects or LARs to receive either a signed or unsigned copy of ICF.

Inspection

the act by a regulatory authority of conducting and official review of documents, facilities, records, and any other resources that re deemed by the authority to be related to the clinical trial an that maybe located at the site of the trial

Monitoring

the act of overseeing the progress of a clinical trial, and of ensuring it is conducted, recorded, and reported in accordance with the protocol, standard operating procedures (SOPs), GCP, and the applicable regulatory requirement

Monitoring

the act of overseeing the progress of a clinical trial, and of ensuring that it is conducted, recorded, and reported in accordance with the protocol, SOPs, and GCP

Content Validity

the extend to which a variable (e.g. a rating scale) measures what it is supposed to measure

Generalisation

the extend to which the findings of a clinical trial can be reliably extrapolated from the subjects who participated in the trial to a broader patient population and a broader range of clinical settings

Meta-Analysis

the formal evaluation of the quantitative evidence from two or more trials bearing on the same qusetion

Trial Site

the location(s) where trial-related activities are actually conducted

According to ICH E6, who must sign the Informed Consent Form or ICF?

the person who conducted the informed consent discussion, the subject or subject's LAR

Well-being (of the trial subjects)

the physical and mental integrity of the subjects participating in a clinical trial

Bioavailability

the rate at and the extent to which a nutrient is absorbed and used

Full Analysis Set

the set of subjects that is as close as possible to the ideal implied by the intention-to-treat principle

E6(R1) 6.6.1

the treatments to be administered, including the names of all the products, the doses, the dosing schedules, the route/modes of administration, and the treatment periods, including the follow-up periods for subjects for each investigational product treatment/trial treatment group/arm of the trial

The sponsor must submit an IND safety report to the FDA if an adverse event is (1) serious; (2) unexpected; AND:

there is a reasonable possibility that the drug caused the event

Non-Significant Risk (NSR) Device studies

those that involve a device that does not pose a significant risk to subjects. Examples of NSR devices include: most daily-wear contact lenses and lens solutions, ultrasonic dental scalers, and temporary urinary catheters.

E6(R1) 8.4.1 -- Investigational Products Accountability at Site

to document that the investigational products have been used according to the protocol. To document the final accounting of investigational products received at the site, dispensed to subjects, returned by the subjects, and returned to sponsor LOCATION: -Investigator/Institution -Sponsor

Primary Variable

typically should only be 1 primary variable safety should be considered & sometimes can be included

Severe

used to describe the intensity of an event

QA/QI

uses retrospective data obtained through chart reviews to evaluate and improve a process, program, or line of service.

Single-blinding

usually refers to the subject(s) being unaware

Double- blinding

usually refers to the subject(s), investigator(s), monitor, and, in some cases, data analyst(s) being unaware of the treatment assignment(s).

Can be defined broadly as the toxicological phenomena studied in nonwhole animal models. This broad connotation includes tissue slices, isolated organs, isolated primary cell cultures, explants cultures, cell lines, and even subcellular fractions like that of mitochondria, microsomes, and even membranes.

vitro toxicology

Composite Variable

when a single primary variable can't be selected from multiple measurements associated with primary variable-a useful strategy is to combine the multiple measuremetns into a single variable

3.4.21 ICH guidelines, ACRP Key Terms for CCRC exam, CCRC Exam, ACRP CCRC EXAM PREP, CCRC Exam Prep, ACRP CCRC, *CCRC Study Set

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