CIP Continuing Review & Adverse Event Reporting 2 — Questions and Answers
Question 1: According to OHRP guidance, an unanticipated problem involving risks to subjects or others must meet which three criteria?
- Serious, related to funding, and affecting more than one subject
- Unexpected, related or possibly related to participation, and suggesting greater risk than previously known (Correct answer)
- Expected, severe, and reported within 24 hours of occurrence
- Unexpected, unrelated to the research, and involving physical harm only
Correct answer: Unexpected, related or possibly related to participation, and suggesting greater risk than previously known
OHRP's three-part test requires the event to be unexpected, related or possibly related to participation, and to suggest that subjects or others face greater risk than previously recognized.
Question 2: Under FDA regulations at 21 CFR 312.32, within what timeframe must sponsors report an unexpected fatal or life-threatening serious adverse drug reaction to the IND?
- Within 24 hours of initial receipt of information
- Within 7 calendar days of initial receipt of information (Correct answer)
- Within 15 calendar days of initial receipt of information
- Within 30 calendar days of initial receipt of information
Correct answer: Within 7 calendar days of initial receipt of information
21 CFR 312.32(c)(2) requires sponsors to notify FDA within 7 calendar days of any unexpected fatal or life-threatening serious adverse drug reaction.
Question 3: Which of the following best distinguishes a 'protocol deviation' from a 'protocol violation'?
- A deviation is intentional; a violation is accidental
- A deviation is a minor unplanned departure that does not affect safety; a violation affects subject rights, safety, or study integrity (Correct answer)
- A deviation requires IRB report; a violation requires only PI documentation
- A deviation involves FDA-regulated products; a violation involves non-regulated studies
Correct answer: A deviation is a minor unplanned departure that does not affect safety; a violation affects subject rights, safety, or study integrity
Protocol deviations are minor, unplanned departures with no impact on subject safety or data integrity, while violations are departures that affect subject rights, safety, welfare, or study integrity.
Question 4: Under 45 CFR 46.103(b)(5), institutions must have written procedures for which of the following?
- Providing annual reports to Congress on research activities
- Promptly reporting unanticipated problems and serious or continuing noncompliance to OHRP (Correct answer)
- Conducting quarterly audits of all active protocols
- Publishing adverse event summaries in peer-reviewed journals
Correct answer: Promptly reporting unanticipated problems and serious or continuing noncompliance to OHRP
45 CFR 46.103(b)(5) requires institutions to establish written procedures for ensuring prompt reporting of unanticipated problems and serious or continuing noncompliance to the appropriate parties including OHRP.
Question 5: What constitutes 'continuing noncompliance' that must be reported to OHRP?
- A single protocol deviation that did not harm any subject
- A pattern of repeated or ongoing failure to comply with regulations or IRB requirements (Correct answer)
- A one-time failure to obtain a witness signature on a consent form
- An adverse event that was not anticipated in the original protocol
Correct answer: A pattern of repeated or ongoing failure to comply with regulations or IRB requirements
Continuing noncompliance refers to a pattern of repeated failures or an ongoing failure to adhere to applicable regulations or IRB requirements, not isolated minor deviations.
Question 6: During continuing review, the IRB must verify that all original criteria for approval remain satisfied. Which criterion specifically addresses the fairness of subject selection?
- Risks to subjects are minimized through sound research design
- Selection of subjects is equitable given the purposes of the research and the population studied (Correct answer)
- Adequate provisions exist to protect the privacy of subjects
- The research plan makes adequate provisions for monitoring subject safety
Correct answer: Selection of subjects is equitable given the purposes of the research and the population studied
45 CFR 46.111(a)(3) requires the IRB to ensure equitable selection of subjects, considering the purposes of the research and the populations from which subjects will be drawn.
Question 7: A data breach exposes the identity of subjects enrolled in a stigmatized disease study, creating risk of social harm. Is this reportable as an unanticipated problem?
- No, because no physical injury occurred
- Yes, because it is unexpected, related to participation, and poses greater risk of harm to subjects (Correct answer)
- No, because data breaches are regulated only by HIPAA, not the Common Rule
- Yes, but only if more than five subjects are affected
Correct answer: Yes, because it is unexpected, related to participation, and poses greater risk of harm to subjects
Unanticipated problems include non-physical harms; a confidentiality breach that exposes subjects to social, psychological, legal, or economic harm qualifies if it meets all three OHRP criteria.
CIP Continuing Review & Adverse Event Reporting 2
According to OHRP guidance, an unanticipated problem involving risks to subjects or others must meet which three criteria?