CCRC terms

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

During the conduct of the study and at termination

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 what?

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

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

Informed Consent

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

It is a FDA guidance

The primary purpose of the ICH is to:

Minimize the need for redundant research

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.

By regulation, investigators are required to make a final study report to:

The sponsor and the IRB

Under which circumstance does the FDA allow verbal consent prior to participation in a research study?

The study is minimal risk.

Contract Research Organization

A person or organization contracted by the sponsor to preform 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. If a trial is conducted by a team of individuals at the site, the investigator is the responsible leader. Also called PI

Impartial Witness

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

Investigational Product

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

Blinding

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

Validation of Computerized Systems

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.

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 the trial subjects are protected.

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 protocol, sponsor standard operating procedures, GCP, and regulatory requirements.

Protocol Amendment

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

Audit Report

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

Source data

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.

Quality Assurance

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.

Legally Acceptable Representative

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.

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.

Serious Adverse Event (SAE)

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

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.

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

Demonstrate efficacy within the established safe dose range

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.

By regulation, an investigator must keep records relating to:

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

Audit Trail

Documentation that allows reconstruction of the course of events

Essential Documents

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

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

FDA

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

GCPs are derived from all the following:

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

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. Examples: patients with incurable diseases, patients in nursing homes, patients in emergency situations, refugees, minors, pregnant women.

The ICH E6 GCP describes standards that apply to:

Investigators, sponsors, and IRBs

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

Just starting to enroll

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.

Any proposed advertising for the study:

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

Financial disclosure applies to:

Only the people listed on the 1572

Source Document

Original documents, data, records

The FDA considers advertising for study subjects to be:

Part of the consent process

Direct Access

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

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

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

Phase III

Phase III Trial

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

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

Confidentiality

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

The purpose of an IRB is to:

Protect the rights and welfare of human subjects of research.

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

Recruiting sufficient subjects

Double Blind

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

What are the three principles of the Belmont Report?

Respect for Persons, Beneficence, Justice

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

The ICH GCP Guidelines are:

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

Case report forms are completed by:

The CRC

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

The CRC or the investigator

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.

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

The sponsor

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

Most sponsors will expect an investigative site to keep all study records for how long?

Until the sponsor says they may be destroyed.

Phase II Trial

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.

A classification of FDA audits that says the deviations found were not serious is:

VAI

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

Protocol

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

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.

Contract

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.

Informed Consent is documented by:

A written, signed, and dated informed consent form

Trial Compliance

Adherence to all trial-related requirements, GCP, and the applicable regulatory requirements.

Study initiation meetings are usually held:

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

Adverse Drug Reaction

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

Independent Ethics Comittee

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.

Institutional Review Board

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.

Comparator

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

Applicable Regulatory Requirements

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

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

Before enrolling any patients in the study

Nonclinical Study

Biomedical studies not performed on human subjects

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

Closed

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

False

Visit Windows

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

What are the two parts under the Principle of Beneficence?

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

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.

Payments to subjects in clinical trials should:

Be done only with prior IRB approval

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

Human subjects

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.

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

Increases the risks to subjects

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

Information, comprehension, and voluntariness

Single Blind

Refers to the subject being unaware of the treatment assignment

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, SOP, GCP, and the applicable regulatory requirements.

IRB Approval

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.

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

The full protocol and the informed consent

In the U.S, following the ICH E6 GCP is:

Voluntary for FDA-regulated drug studies.

The IRB must inform the investigator the study has been approved by:

Written notification saying it has been approved

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

9 or more years

Investigator's Brochure

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.

Certified Copy

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.

Sponsor

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