SOCRA Protocol Deviations and Violations 5 — Questions and Answers
Question 1: In a Clinical Study Report structured per ICH E3, where are important protocol deviations described?
- Section 16, Appendices only
- Section 10.2, Protocol Deviations (Correct answer)
- Section 9.4, Treatments
- Section 12, Safety Evaluation
Correct answer: Section 10.2, Protocol Deviations
ICH E3 Section 10.2 describes important protocol deviations related to inclusion/exclusion criteria, trial conduct, patient management, or assessment.
Question 2: Per ICH E6, who is responsible for documenting and explaining any deviation from the approved protocol at the site?
- The sponsor's medical monitor
- The IRB chairperson
- The investigator or a person designated by the investigator (Correct answer)
- The study subject
Correct answer: The investigator or a person designated by the investigator
ICH E6 4.5.3 states that the investigator, or a person the investigator designates, should document and explain any deviation from the approved protocol.
Question 3: In a device study under 21 CFR 812.150, how soon must an investigator report an emergency deviation made to protect a subject's life or physical well-being?
- Within 24 hours
- At the next annual progress report
- Within 15 calendar days
- No later than 5 working days after the emergency occurred (Correct answer)
Correct answer: No later than 5 working days after the emergency occurred
21 CFR 812.150(a)(4) requires notifying the sponsor and IRB within 5 working days of such an emergency deviation.
Question 4: How do major protocol deviations usually affect a subject's inclusion in statistical analysis populations?
- The deviation has no effect on any analysis population
- The subject may be excluded from the per-protocol population but stays in the intent-to-treat population (Correct answer)
- The subject is removed from every analysis population
- The subject's data are deleted from the database
Correct answer: The subject may be excluded from the per-protocol population but stays in the intent-to-treat population
Important deviations often exclude subjects from the per-protocol set, while ITT keeps all randomized subjects.
Question 5: A subject takes a medication the protocol prohibits, on their own and without telling the site. How should this be handled?
- Ignored unless the subject has a serious adverse event
- Not recorded, because the site did not cause it
- Recorded only as an adverse event
- Documented as a protocol deviation and assessed for safety and data impact, even though the subject caused it (Correct answer)
Correct answer: Documented as a protocol deviation and assessed for safety and data impact, even though the subject caused it
Deviations are documented no matter who caused them, and their impact on safety and data integrity must be assessed.
Question 6: A PK blood sample is processed after the protocol-specified stability window. What is the best action?
- Draw a replacement sample without consulting the protocol or sponsor
- Throw the sample away without recording it
- Document the deviation, notify the sponsor, and record the sample's handling accurately (Correct answer)
- Relabel the sample with an earlier processing time
Correct answer: Document the deviation, notify the sponsor, and record the sample's handling accurately
Sample-handling deviations must be documented truthfully and reported so the sponsor can assess data validity.
Question 7: Which FDA regulation requires an investigator to conduct a drug study according to the signed investigator statement, the investigational plan, and applicable regulations?
- 21 CFR 50.25
- 21 CFR 314.80
- 21 CFR 312.60 (Correct answer)
- 21 CFR 56.111
Correct answer: 21 CFR 312.60
21 CFR 312.60 sets out the investigator's general responsibility to conduct the study per the investigational plan and is often cited on Form 483s.
