Good Clinical Practice

Under which circumstance does the FDA allow verbal consent prior to participation in a research study? A) The subject is illiterate. B) The study is minimal risk. C) The subject has a legally authorized representative (LAR). D) The study is greater than minimal risk.

B

Who is ultimately responsible for product accountability at the study site? A) Pharmacist B) Investigator C) Subject D) Clinical research coordinator

B

Class __________________devices are the highest risk devices. General controls and special controls alone are not adequate to ensure their safety and effectiveness.

III

The ICH E6 topic falls under the__________category in the ICH guidelines and pertains specifically to the conduct of clinical research to support marketing applications for drugs. It is one of over two hundred (200) guidance documents issued in this process. ICH E6 provides a unified standard for designing, conducting, recording, and reporting research involving human subjects.

"Efficacy"

In limited circumstances, the FDA allows for an investigator to obtain consent verbally without obtaining a signature on the consent form. The IRB must approve this consent process which is referred to as a ________________________________. The IRB can approve this type of waiver only when study participation presents minimal risk to the subject and the research involves no procedures requiring consent outside the context of participation in a research study.

"waiver of documentation of consent."

An investigator conducting a study of a medical device under an IDE is required to complete and sign which of the following? A) An investigator's agreement B) A memorandum of understanding C) An interagency personnel agreement D) A data use agreement

A

Sponsors must notify regulatory authorities and all participating investigators in writing of events that are both unexpected and serious, and associated with the use of the investigational drug no later than: 48 hours A) 3 calendar days B) 7 calendar days C) 15 calendar days

15

A __________ Premarket Notification is submitted when a manufacturer wishes to market a qualified medical device in the U.S. without conducting clinical trials. To do so, the manufacturer must demonstrate to FDA that the device is equivalent to one already marketed.

510(k)

All unused investigational agents are expected to be returned to the sponsor at the: A) Termination site visit B) Prestudy site visit C) Site initiation visit D) Periodic site visit

A

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: A) 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 B) Obtain a non-disclosure form before notifying the subject's primary physician C) Include a statement in the consent form that confidentiality of trial data cannot be guaranteed because of foreign involvement and the possibility of hacking D) Provide a separate form that notes the possibility that the FDA may inspect the records

A

Identify which party is responsible for reporting directly to the FDA the investigator's financial interests with the sponsor: A) The sponsor B) The IRB C) The investigator's institution D) The investigator

A

In terms of explaining the probability of assignment to trial arms in consent forms, which is true? A) ICH notes that it should be included, but does not specify how the information should be presented. B) FDA requires the probability to be expressed as a percentage chance. C) Neither FDA nor ICH require statements about the probability for random assignment to each treatment arm or the use of a placebo arm. D) The probability of assignment should always be stated as being "like the flip of a coin" because subjects can understand that example.

A

Investigational product dispensing or administration information for the sponsor is recorded on the: A) Case report form B) Form FDA 1572 C) Insurance claim form D) Informed consent form

A

Regarding subject receipt of a signed and dated copy of the consent forms, which is true about FDA regulations? A) The FDA regulations allow subjects or the legally acceptable representatives (LARs) to receive either a signed or unsigned copy. B)The FDA regulations do not specify if the subject or the legally acceptable representative (LAR) must receive a signed and dated copy of the consent forms C) The FDA regulations require that the subject or the legally acceptable representative (LAR) receive a copy of the signed and dated written informed consent form D)The FDA regulations require a witness to document that the subject or the legally acceptable representative (LAR) received the signed and dated copy of the consent forms.

A

When evaluating the causality of an adverse event, which of the following should be a consideration? A) The timing of the event in relation to administration of the investigational agent B) The method used to randomize subjects C) The number of planned interventions in the protocol D) Whether or not the adverse event qualifies as a serious adverse event.

A

When must the investigator update the IRB about the progress of a trial? A) During the conduct of the study and at termination B) At study termination only C) Never D) During the conduct of the study only

A

When should the sponsor-monitor conduct the most detailed review of the study protocol with the site's study staff? A) Site initiation visit B) Termination site visit C) Prestudy site visit D) Periodic site visit

A

Which party submits the completed, signed Form FDA 1572 to the FDA? A) Sponsor B) Study monitor C) IRB D) Investigator

A

________ might be submitted for the FDA to evaluate the results of a completed clinical trial of a Class III device.

A Premarket Approval (PMA)

An investigator who applies for an IND for a study and is acting as the study sponsor must comply with the requirements of which of the following: A) Both the sponsor's and investigator's responsibilities B) The sponsor's responsibilities only C) The investigator's responsibilities only

A. In this circumstance, the investigator also has the responsibilities of a sponsor.

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? A) Tell the subject about the new drug but discourage him from switching treatments until the study is completed B) 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. C) Do not tell the subject about the new drug since physicians have the right to try out new treatments with their patients D) Withhold this new information to avoid confusing the subject with other treatment options or alternatives

B

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? A) Study Coordinator B) Principal Investigator C) ED nurse D) Pharmacist

B

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? A) Phase II B) Phase III C) Pre-clinical D) Phase I

B

At which study visits can the site expect the sponsor to review subjects' signed informed consent forms? A) Site initiation and termination visits B) Periodic and termination site visits C) Prestudy and periodic site visits D) Periodic and site initiation visits

B

Evaluation of Unanticipated Adverse Device Effects (UADEs) must be reported to the FDA by the: A) IRB only B) Sponsor C) Investigator only D) IRB and investigator

B

In completing Form FDA 1572, Statement of Investigator, the investigator agrees to A) Report to the FDA any adverse events that occur B) Conduct or supervise the investigation personally C) Maintain a contract with the sponsor D) Maintain records indefinitely

B

Long-term toxicology of an experimental drug in animals most likely refers to which part of drug development? A) Phase II B)Pre-clinical C) Phase I D) Phase III

B

The investigator must report adverse events to the: A) FDA B) Sponsor C) IRB only D) Subject

B

The overall goal of monitoring, audits, and inspection activities is to: A) Review research related publications. B) Ensure the protection of human research subjects and data integrity. C) Manage conflict of interest. D) Resolve disputes between the sponsor and the investigators

B

The packaging of investigational drugs should ideally: A) Look like a marketed product B) Be designed to help with subject compliance C) Be attractive so the study coordinators will use it D) Allow subjects to identify placebo pills

B

Which of the following statements in a consent form is an example of exculpatory language? A) Your participation in this research is voluntary. If you choose not to participate, or change your mind later, your decision will not affect your relationship with your doctor or your right to health care or other services that you may be eligible for. B) I waive any possibility of compensation for injuries that I may receive as a result of participation in this research. C) In the event of any injury related to this research, you will be given medical treatment. d) The investigator may stop you from participating in this research without your consent if you experience side effects that make your condition worse. If you become ill during the research, you may have to drop out.

B "I waive any possibility of compensation for injuries that I may receive as a result of participation in this research." is exculpatory language. Exculpatory language is 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. Such language is specifically prohibited. The other choices provide information without asking the subject to waive any of their rights.

________________is the degree to which, or the rate at which, a medication or other substance is absorbed or becomes available at the targeted place in the body.

Bioavailability

Examples of __________ devices are surgical gloves and tongue depressors.

Class I

510(k) Premarket Notification is submitted: A) When no alternative treatment exists for a life-threatening condition B) Before any clinical trials of an investigational device can begin C) When the new device to be marketed is substantially similar (equivalent) to one already on the market D) When clinical trials of a Class III device are completed

C

Form FDA 1572, Statement of Investigator, is legally binding between the investigator and the: A) IRB B) Subjects C) FDA D) Sponsor

C

ICH E6 describes standards that apply to: A) Research sponsors B) only Investigators C) only Investigators, sponsors, and IRBs D) IRBs only

C

Pharmacokinetics and pharmacodynamics of a new formulation of an investigational drug most likely refers to which clinical phase of a study in humans? A) Phase II B) Pre-clinical C) Phase I D) Phase III

C

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? A) Use of the PDA cycle (Plan, Do, Act) during the annual continuing review. B) Mandatory use of ICH E6 template Case Report Forms for all drug studies to be submitted to regulatory authorities C) Identification of study risks to determine which may safely be omitted from continual monitoring D)Complete on-site documentation audits every 3-6 months.

C

When evaluating the causality of an adverse event and the investigator determines that there is a likelihood that the investigational product is the cause of the event, but other causes cannot be ruled out, this is called: A) Definitely related B) Unrelated C) Possibly related

C

When the FDA conducts an inspection, the inspectors will: A) Issue a warning letter. B) Recommend protocol changes. C) Review regulatory records. D) Determine if the Assurance should be restricted.

C

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? A) Adverse Event Summary Report, but only from unblinded portions of studies ("open-label IND safety report") B) IND renewal application C) IND report D) Marketing plan (that is, annual updated projection of sales and profits)

C

Where is information on storage requirements for the investigational product usually found? A) On the product code-breaker label B) In the case report form directions C) In the study protocol D) In the drug accountability log

C

Which of the following best describes the principle of Respect for Persons as Described in the Belmont Report? a) Risk/benefit assessment, justification of research, comprehension b) comprehension, conflicts of interest, risk/benefit ration c) information, comprehension, voluntariness d) voluntariness, risk/benefit assessment. selection of subjects.

C

Which of the following is an acceptable criterion for determining that a study of an approved drug does not require an IND? A) The study involves a route of administration that significantly increases the risks to the patient. B) The study intends to invoke an exception from informed consent. C) The study is not intended to be reported to FDA to support a new indication or support a labeling change. D) The study intends to involve more than one hundred (100) patients in a study.

C

Which of the following is an important component of drug accountability? A) Manufacturer's compounding procedures B) Patent expiration date C) Drug shipping and disposition records D) Environmental controls

C

Which of the following is an investigator's commitment to the sponsor? A) Retain study documents for three (3) years after study completion at the site B) Submit documents to sponsor for yearly approval to continue the study C) Submit a new Form FDA 1572 to the sponsor as needed D) Provide the financial disclosure document directly to FDA

C

An inspection is conducted by: A) Sponsor B) CRO C) Regulatory agency D) Monitor

C A regulatory agency (such as the FDA) conducts an inspection. The sponsor, CRO, and monitor perform monitoring and audits.

Examples of_____________devices are flexible laryngoscopes and surgical drills.

Class II

___________ devices are moderate risk devices and are subject to both general controls and special controls such as specific FDA performance standards, post-market surveillance, or special control guidance to ensure their safety and effectiveness.

Class II

Examples of _____________ devices are artificial organs, replacement heart valves, and pacemakers.

Class III

ICH E6 also defines what a "____________________" of the original record is. In order for a record to be (this), the paper or electronic copy of the original record must have been verified (for example, by a dated signature) or generated through a validated process to produce an exact copy of the original.

Certified Copy

___________________ means that 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.

Controlled

A primary purpose of the ICH is to: A) Require publication of negative trial results. B) Develop mandatory worldwide regulations for drug development. C) Require FDA registration of worldwide clinical trials. D) Minimize the need for redundant research.

D

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? A) No report is needed because these are not serious adverse events. B) Report only the concussion because it might become serious. C) No report is needed because the subject was a passenger in the vehicle and not driving. D) Report adverse events of both a broken wrist and a mild concussion.

D

According to ICH E6, an "audit" is defined as: A) An official review of documents, facilities, records, and any other resources related to a clinical trial. B) An institutional self-assessment C) The act of overseeing the progress of a clinical trial. D) A systematic and independent examination of trial-related activities and documents.

D

Accurate reporting of adverse events is most important for: A) Updating recruitment materials. B) Ensuring correct site reimbursement for work performed. C) Allowing rechallenge of subjects. D) Ensuring subject safety.

D

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, which of the following describes the best course of action for the investigator: A) Do not use the test article until either the subject or the subject's legally authorized representative can give consent. B) Submit a research protocol to the IRB and justify an expedited review approval of the consent document so the test article can be used immediately. C) Sign the consent form on behalf of the subject and use the test article. D) 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.

D

Development of most new drugs, from discovery to marketing approval, usually takes: A) 5 years B) Less than 5 months C) 1-3 years D) 9 years or more

D

For a Phase I new drug study in humans, what is the primary source of the data included in the initial Investigator's Brochure? A) Clinical Trails B) FDA files C) Post-approval Surveillance Studies D) Pre-clinical data.

D

In the United States, following the ICH E6 guideline is: A) Mandatory for studies conducted outside the United States. B) Mandatory for drug studies. C) Mandatory for investigational device studies. D) Voluntary for FDA-regulated drug studies.

D

The ICH GCP guidelines: A) Require certification of clinical research sites and investigators B) Guarantee that a submission in any ICH region will be approved for marketing. C) Replace FDA regulations for internationally conducted studies of drugs that will be marketed in the U.S. D) Set standards for the design, conduct, monitoring and reporting of clinical research.

D

The sponsor must submit an IND Safety Report to the FDA if an adverse event is (1) serious; (2) unexpected; and: A) (3) can reasonably be expected to recur. B) (3) is life-threatening but listed in the Investigator's Brochure. C) (3) resolves quickly. D) (3) there is a reasonable possibility that the drug caused the event.

D

Which monitoring visit would not include an inventory of investigational agents? A) Periodic site visit B) Termination site visit C) Site initiation visit D) Prestudy site visit

D

Which of the following best describes when the majority of case report form (CRF) data are verified against source record information? A) Site initiation visit B) Termination site visit C) Prestudy site visit D) Periodic site visits

D

Which of the following is required at a prestudy site visit? A) Review of regulatory document files B) Review of data from previous studies C) Evaluation of staff performance records D) Evaluation of the site's capacity to conduct the study

D

Which of the following should take place during periodic site visits? A) Analysis of data B) Initial assessment of the site's potential to enroll research subjects C) Determination of adverse event causality D) Identification of protocol violations

D

T/F Physicians are not allowed to use products for an indication not listed in a the approved labeling ("off label").

F; however, the physician has the responsibility to be well informed about the product and to base the proposed use on scientific rationale and medical evidence.

Form _________________ is a contractual agreement between the sponsor and FDA.

FDA 1571

Per federal law, clinical trials may require the submission of an Investigational New Drug (IND) application or Investigational Device Exemption (IDE). The U.S. _______________________________ has regulations in place for determining whether an IND or IDE is required.

Food and Drug Administration (FDA)

An ______ must be submitted when clinical trials of investigational devices are needed to determine the safety and effectiveness of a new device or when studying substantial modifications to or new intended uses for devices already on the market.

IDE

______________ is a standard for the design, conduct, performance, monitoring, auditing, recording, analyses, and reporting of clinical trials.

Good Clinical Practice (GCP)

Class __________ devices are the lowest risk devices and are governed by general controls (that is, Establishment Registration, Device Listing, Compliance with Good Manufacturing Practice [GMP] regulation, labeling, and Medical Device Reporting [MDR] of death or serious injuries).

I

_____________________ is a compilation of the clinical and nonclinical data on the investigational product and serves as a resource for investigators, Institutional Review Boards/Independent Ethics Committees (IRBs/IECs) during the conduct of a clinical trial.

Investigator's Brochure (IB)

_____________________ is 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 procedure(s) involved in the research.

Legally Authorized Representative (LAR)

the PI of a study has a daughter, who is married and lives with her husband, who is a sales representative for the sponsor of that study. His daughter received $132,000 from the sponsor during the past twelve months. Must Dr. Thompson disclose his daughter's income?

No. Investigators must report their own income and financial interests as well as income and financial interests of their spouse and each dependent child. The PI's daughter is not a "dependent child."

If a clinical investigation is not conducted under an IND or is for a medical device, must investigators sign a 1572?

No. Under the regulations, a 1572 is only required for studies of investigational drugs and biologics conducted under an IND. It is not required for studies that are not done under an IND, and is not applicable to investigational device studies.

_________(2015) is an oversight agency that protects volunteers in "research that is conducted or supported by the U.S. Department of Health and Human Services (HHS).

Office for Human Research Protections (OHRP)

__________________ describes the effects of the agent while in the body.

Pharmacodynamics

________________is the use of genetic information to predict whether a drug will help make a patient well or ill.

Pharmacogenomics

___________________________describes how the agent moves through and is excreted from the body.

Pharmacokinetics

_______________________is generally an unplanned excursion from the requirements of the protocol that is not implemented or intended as a systematic change.

Protocol Deviation (or Violation)

________________________ means an individual who both initiates and conducts the clinical investigation and under whose immediate direction the investigational drug or device is being administered, used, or dispensed.

Sponsor-Investigator

T/F ICH E6 is not codified in U.S. federal regulation and does not carry the same legally binding weight of the code of federal regulations.

T

T/F the U.S. compliance with ICH E6 is voluntary, but as with any published FDA guidance, compliance is considered part of GCP.

T

_________________ is a compilation of the pre-clinical and clinical data on the investigational product(s) that are relevant to the study of the product(s) in human subjects.

The Investigator's Brochure (IB)

Consider a study conducted a regional hospital where the investigator is one of the on staff physicians. The study focuses on smoking habits among the hospital's nurses and its relationship to lung cancer. Does this research involve subjects potentially vulnerable to coercion or undue influence? Yes or no.

The answer is yes. Because the nurses are members of a hierarchical structure within the study facility, the nurses are considered to be vulnerable to coercion or undue influence.

Must the investigator be a physician

The regulations do not require that the investigator be a physician. Sponsors are required to select only investigators qualified by training and experience as appropriate experts to investigate the drug

The two (2) 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

Who is responsible for making the initial risk determination for a device being used in a study?

The sponsor-investigator.

__________________________ are 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 (ICH [2016] E6 Section 1.61)

Vulnerable Subjects

If an investigator sees study subjects at more than one site, should the investigator list all sites on the 1572?

Yes. The names and addresses of each of the study sites should be identified in Section #3. However, if the protocol specifies that the investigative product can be administered at a subject's home (for example, the protocol allows for daily injections to be administered by a registered nurse in the subject's home), the subjects' home addresses do not have to be listed on the 1572. Study records should reflect that the test article was administered at subjects' homes per the protocol

The FDA requires retention of investigational drug study records for: A) At least one (1) year after the last subject completes all study interventions B) At least two (2) years after the investigational drug's approval by the FDA C) At least three (3) years after the study has ended at the site D) Indefinitely

b

Devices are classed according to the level of control needed to ensure their ________ and ___________

safety and effectiveness

the FDA recommends that _____________________ must be obtained before the subject participates in any procedures that are done solely for research purposes, including determining eligibility for the study and withdrawing medication (wash-out).

informed consent

According to ICH E6 Section 5.18, the purposes of trial_____________ are to verify that: The rights and well-being of human subjects are protected. The reported trial data are accurate, complete and verifiable from source documents. The conduct of the trial is in compliance with the currently approved protocol/amendment(s), with GCP, and with applicable regulatory requirements.

monitoring

The first step in the drug-development process allows investigators to evaluate the drug using tissue cultures and animal models. This research is referred to as ______________.

preclinical studies

The first Investigator's Brochure IB for a proposed clinical trial of a new drug is based primarily on which of the following? a) preclinical trials b) Phase II studies.

preclinical trials

ICH has developed over _______________ guidelines on Quality, Safety, Efficacy and Multidisciplinary topics, in addition to products including Electronic Standards for the Transfer of Regulatory Information (ESTRI), the Common Technical Document (CTD & eCTD), and the Medical Dictionary for Regulatory Activities (MedDRA).

sixty (60)

There are two instances when it is necessary for an investigator to complete and sign a new 1572:

when an investigator is participating in a new protocol that has been added to the IND and when a new investigator is added to the study (21 CFR 312.53(c)).