RAC Premarketing and Clinical Development 3 — Questions and Answers
Question 1: Which element is NOT required in an informed consent document under 21 CFR Part 50?
- A statement that participation is voluntary
- The approximate number of subjects in the study
- Identification of the sponsor's legal counsel (Correct answer)
- A description of foreseeable risks or discomforts
Correct answer: Identification of the sponsor's legal counsel
21 CFR 50.25 lists required elements of informed consent; identifying the sponsor's legal counsel is not among them.
Question 2: Under the Common Rule (45 CFR Part 46), which category of research qualifies for exemption from full IRB review?
- Research involving prisoners as subjects
- Survey research involving adults where responses are recorded anonymously (Correct answer)
- Phase III clinical trials of marketed drugs
- Research involving children in educational settings testing a new vaccine
Correct answer: Survey research involving adults where responses are recorded anonymously
Anonymous survey research involving adults falls under Common Rule Category 2 exemption when disclosure cannot reasonably place subjects at risk.
Question 3: A company plans to use a validated biomarker as a primary endpoint in a Phase II trial to support dose selection. What FDA pathway provides formal endorsement of this biomarker's use?
- Breakthrough Therapy designation
- Biomarker Qualification Program (Correct answer)
- Fast Track designation
- Accelerated Approval pathway
Correct answer: Biomarker Qualification Program
FDA's Biomarker Qualification Program formally evaluates and endorses a biomarker for a specific context of use in drug development.
Question 4: According to ICH E9(R1), what does the estimand framework primarily help clinical trial designers specify?
- Sample size calculations
- The precise clinical question a trial is intended to answer, including how intercurrent events are handled (Correct answer)
- Statistical significance thresholds
- Randomization algorithms
Correct answer: The precise clinical question a trial is intended to answer, including how intercurrent events are handled
ICH E9(R1) introduced the estimand framework to align the trial objective, design, and analysis by explicitly defining the treatment effect of interest and handling of intercurrent events.
Question 5: In a two-period crossover PK study, the primary concern with a short washout period is:
- Sequence imbalance
- Carryover effect from the first treatment period (Correct answer)
- Increased dropout rate
- IRB non-compliance
Correct answer: Carryover effect from the first treatment period
A carryover effect occurs when drug from period 1 is still present during period 2, confounding period 2 PK measurements.
Question 6: Which FDA guidance introduced the concept of 'substantial evidence' and typically requires at least two adequate and well-controlled trials to support efficacy for a New Drug Application?
- 21 CFR 314.126 (Correct answer)
- 21 CFR 312.21
- 21 CFR 50.25
- 21 CFR 56.111
Correct answer: 21 CFR 314.126
21 CFR 314.126 defines 'adequate and well-controlled studies' and the evidentiary standard required to demonstrate efficacy in an NDA.
Question 7: A sponsor seeks to enroll a pregnant woman in a Phase II trial of a new antiviral. Under 21 CFR Part 50 Subpart B, this population is classified as:
- A vulnerable subject requiring additional safeguards (Correct answer)
- An excluded population under all circumstances
- A non-regulated population if the condition is life-threatening
- An exempt population if consent is obtained from the father
Correct answer: A vulnerable subject requiring additional safeguards
Pregnant women are a vulnerable population under 45 CFR Part 46 Subpart B, requiring additional protections and specific risk-benefit criteria.
RAC Premarketing and Clinical Development 3
Which element is NOT required in an informed consent document under 21 CFR Part 50?