RAC Clinical Trials and GCP 3 — Questions and Answers
Question 1: Which ICH E6(R2) addendum requirement was specifically added to strengthen sponsor oversight of clinical trial quality?
- Increased IRB meeting frequency
- Risk-based monitoring (RBM) and Quality Management Systems (QMS) (Correct answer)
- Mandatory site audits every 6 months
- Real-time electronic CRF submission to FDA
Correct answer: Risk-based monitoring (RBM) and Quality Management Systems (QMS)
ICH E6(R2) introduced requirements for risk-based monitoring and a quality management system approach to identify and address critical data and process risks.
Question 2: A subject enrolled in a Phase II oncology trial dies unexpectedly. The investigator believes the death is unrelated to the study drug. Which action is required first?
- Notify the IRB within 24 hours and the sponsor immediately (Correct answer)
- Close the site pending investigation
- Amend the informed consent form
- File a MedWatch report directly to FDA
Correct answer: Notify the IRB within 24 hours and the sponsor immediately
Any unexpected subject death must be reported to the IRB promptly (typically within 24 hours) and to the sponsor immediately per GCP and protocol requirements.
Question 3: Under 21 CFR 50.25, which element of informed consent addresses what happens if a subject is injured during research?
- Purpose of research
- Compensation and treatment available for injury (Correct answer)
- Anticipated duration of participation
- Confidentiality procedures
Correct answer: Compensation and treatment available for injury
21 CFR 50.25(a)(6) requires that consent explain whether compensation or medical treatment is available if injury occurs.
Question 4: The 'intention-to-treat' (ITT) population in a clinical trial refers to:
- Only subjects who completed all protocol visits
- All randomized subjects analyzed in the group to which they were assigned (Correct answer)
- Subjects who met all inclusion/exclusion criteria
- Subjects with no major protocol deviations
Correct answer: All randomized subjects analyzed in the group to which they were assigned
ITT analysis includes all randomized subjects analyzed according to their original treatment assignment, regardless of protocol adherence.
Question 5: A Data Safety Monitoring Board (DSMB) is MOST commonly used in clinical trials to:
- Audit CRF data for accuracy
- Provide independent interim review of accumulating safety and efficacy data (Correct answer)
- Approve protocol amendments
- Certify investigator qualifications
Correct answer: Provide independent interim review of accumulating safety and efficacy data
A DSMB independently reviews unblinded interim data to recommend continuation, modification, or early stopping of a trial based on safety or efficacy.
Question 6: Under ICH E6, which party is ultimately responsible for the conduct of a clinical trial?
- The IRB/IEC
- The principal investigator
- The sponsor (Correct answer)
- The regulatory authority
Correct answer: The sponsor
The sponsor bears ultimate responsibility for implementing and maintaining quality systems and for the overall conduct of the clinical trial per ICH E6.
Question 7: Which FDA phase typically involves the LARGEST number of human subjects to establish efficacy and monitor adverse reactions in a general population?
- Phase I
- Phase II
- Phase III (Correct answer)
- Phase IV
Correct answer: Phase III
Phase III trials are large-scale studies (typically hundreds to thousands of subjects) designed to confirm efficacy and detect adverse reactions at a population level.
RAC Clinical Trials and GCP 3
Which ICH E6(R2) addendum requirement was specifically added to strengthen sponsor oversight of clinical trial quality?