CRA IRB & Informed Consent 3 — Questions and Answers
Question 1: A clinical trial sponsor asks the PI to omit the cost of an experimental drug from the consent form to avoid discouraging enrollment. The PI should:
- Refuse, because subjects must be informed of any additional costs they may incur as a result of participation (Correct answer)
- Comply, because cost disclosure is optional under 45 CFR 46
- Include cost information only in the HIPAA authorization, not the consent form
- Agree if the IRB grants a waiver based on minimal financial risk to subjects
Correct answer: Refuse, because subjects must be informed of any additional costs they may incur as a result of participation
45 CFR 46.116(b)(9) requires disclosure of any additional costs to subjects that may result from participating in the research.
Question 2: Which of the following best describes the concept of 'therapeutic misconception' in the context of informed consent?
- A subject's erroneous belief that research procedures are tailored to their personal medical benefit rather than to test a hypothesis (Correct answer)
- A researcher's false assumption that all subjects have understood and agreed to all study procedures
- An IRB's incorrect conclusion that a study poses minimal risk when it does not
- A sponsor's mistaken belief that FDA approval eliminates the need for IRB review
Correct answer: A subject's erroneous belief that research procedures are tailored to their personal medical benefit rather than to test a hypothesis
Therapeutic misconception occurs when subjects conflate research participation with individualized clinical care, undermining truly voluntary, informed consent.
Question 3: An IRB is reviewing a study that will enroll prisoners. Under Subpart C of 45 CFR 46, which of the following is NOT an allowable category of research involving prisoners?
- Research on conditions affecting the general population for which prisoners are not at greater risk
- Research studying causes, effects, and processes of incarceration
- Research on practices intended to improve prisoner health or well-being
- Research on pharmaceutical products for enhancement of cognitive performance unrelated to prisoner conditions (Correct answer)
Correct answer: Research on pharmaceutical products for enhancement of cognitive performance unrelated to prisoner conditions
Subpart C limits permissible prisoner research to specific categories; cognitive enhancement pharmaceuticals unrelated to prisoner-specific conditions do not qualify.
Question 4: When must an IRB's approval of research expire according to 45 CFR 46.109(e)?
- No later than one year after the date of approval unless the IRB determines a shorter period is appropriate (Correct answer)
- Two years after initial approval for minimal-risk studies
- At the completion of subject enrollment regardless of the calendar date
- Upon submission of the final study report to the sponsor
Correct answer: No later than one year after the date of approval unless the IRB determines a shorter period is appropriate
The Common Rule requires that IRB approval expire no later than one year from the date of approval, with the option for a shorter period.
Question 5: A prospective subject is a ward of the state. Under 45 CFR 46 Subpart D, who may provide permission for the child's enrollment in research that presents greater than minimal risk with no direct benefit?
- An IRB-appointed advocate who has no conflicting interest and is acting in the child's best interest, along with assent from the child (Correct answer)
- The state social worker assigned to the child's case, if they have legal guardianship
- Any adult family member, since parental permission requirements are waived for wards of the state
- The child alone, provided they are at least 7 years old and demonstrate understanding
Correct answer: An IRB-appointed advocate who has no conflicting interest and is acting in the child's best interest, along with assent from the child
For wards of the state in research not otherwise approvable under Subpart D, an IRB-appointed advocate must substitute for the parent or guardian, and the child's assent is still required.
Question 6: A PI proposes collecting biospecimens from adults under a waiver of informed consent, arguing the samples are de-identified. Under the 2018 Common Rule, this is permissible only if:
- The IRB finds the criteria for waiver of consent are satisfied, including that the research could not practicably be carried out without the waiver (Correct answer)
- The PI certifies in writing that re-identification is technically impossible
- The sponsor provides indemnification for any privacy breach resulting from re-identification
- Subjects are provided an opt-out mechanism within 30 days of sample collection
Correct answer: The IRB finds the criteria for waiver of consent are satisfied, including that the research could not practicably be carried out without the waiver
Waivers of informed consent for biospecimen research require the IRB to make specific findings under 45 CFR 46.116(f), including that the research could not practicably be conducted without the waiver.
Question 7: During an IRB audit, it is found that a PI obtained verbal consent but failed to document it in any subject file. Under GCP ICH E6(R2), this represents a deficiency in:
- Essential documents that must be on file to demonstrate that the trial was conducted in compliance with GCP (Correct answer)
- Protocol deviation reporting requirements only
- IRB composition requirements under 21 CFR 56.107
- The sponsor's monitoring obligations rather than the investigator's obligations
Correct answer: Essential documents that must be on file to demonstrate that the trial was conducted in compliance with GCP
ICH E6(R2) Section 8 requires that signed informed consent forms be retained as essential documents; failure to document consent is a GCP compliance deficiency.
CRA IRB & Informed Consent 3
A clinical trial sponsor asks the PI to omit the cost of an experimental drug from the consent form to avoid discouraging enrollment.
The PI should: