SOCRA Protocol Deviations and Violations 1 — Questions and Answers
Question 1: Which of the following BEST defines a protocol deviation in a clinical trial?
- Any change to the protocol that is approved by the sponsor in advance
- An unplanned departure from the procedures described in the approved protocol (Correct answer)
- A formal amendment to the protocol submitted to the IRB
- A sponsor-initiated modification to study eligibility criteria
Correct answer: An unplanned departure from the procedures described in the approved protocol
A protocol deviation is an unplanned, unintentional departure from the approved protocol procedures that occurs during the conduct of a study.
Question 2: A subject enrolled in a clinical trial misses a required blood draw by 5 days due to a personal emergency. How should the Clinical Research Coordinator (CRC) handle this?
- Remove the subject from the study immediately
- Document the missed visit as a protocol deviation and notify the PI and sponsor (Correct answer)
- Reschedule the draw without documenting the variance
- Obtain a retroactive protocol amendment from the IRB
Correct answer: Document the missed visit as a protocol deviation and notify the PI and sponsor
Missed assessments outside the protocol-specified window must be documented as protocol deviations and reported per the sponsor's and IRB's procedures.
Question 3: Under ICH E6(R2) Good Clinical Practice, which party bears primary responsibility for ensuring protocol compliance at the investigative site?
- The sponsor's Clinical Research Associate (CRA)
- The Institutional Review Board (IRB)
- The Principal Investigator (PI) (Correct answer)
- The FDA district office
Correct answer: The Principal Investigator (PI)
ICH E6(R2) Section 4.1 states the investigator is responsible for conducting the trial in compliance with the protocol agreed to by the sponsor and approved by the IRB.
Question 4: Which of the following protocol deviations would MOST likely be classified as a major (significant) deviation requiring prompt IRB reporting?
- A subject's study visit occurred 2 days outside the allowed visit window
- A required quality-of-life questionnaire was administered in a different order than specified
- An ineligible subject was enrolled because inclusion criteria were not properly verified (Correct answer)
- A laboratory sample was processed 30 minutes later than the protocol specified
Correct answer: An ineligible subject was enrolled because inclusion criteria were not properly verified
Enrolling an ineligible subject directly violates inclusion/exclusion criteria, potentially affecting subject safety and data integrity, making it a major deviation requiring prompt IRB notification.
Question 5: What is the PRIMARY distinction between a protocol deviation and a protocol violation?
- Violations involve unapproved drug doses; deviations involve missed visits only
- Violations are intentional departures while deviations are unintentional
- A violation is a deviation that significantly affects subject safety or data integrity (Correct answer)
- Deviations require FDA reporting while violations are only reported to the IRB
Correct answer: A violation is a deviation that significantly affects subject safety or data integrity
While usage varies by organization, a protocol violation is generally considered a deviation that significantly affects subject rights, safety, or the integrity of study data.
Question 6: According to FDA regulations at 21 CFR 312.62, how long must an investigator retain records of protocol deviations for drugs studied under an IND?
- 1 year after study completion
- 2 years after the study is completed or discontinued, or 2 years after FDA approval (Correct answer)
- 5 years after the last subject visit
- 7 years after the last enrolled subject completes the study
Correct answer: 2 years after the study is completed or discontinued, or 2 years after FDA approval
21 CFR 312.62(c) requires investigators to retain records for 2 years following the date a marketing application is approved or 2 years after the investigation is discontinued.
Question 7: When a protocol deviation is identified during a monitoring visit, the Clinical Research Associate (CRA) should FIRST:
- Report the deviation directly to the FDA without notifying the site
- Document the finding in the monitoring report and discuss corrective actions with the PI (Correct answer)
- Suspend all study activities at the site until the deviation is resolved
- Immediately notify the IRB before informing the sponsor
Correct answer: Document the finding in the monitoring report and discuss corrective actions with the PI
The CRA should document the finding in the monitoring report and work with the investigator to implement corrective and preventive actions (CAPA), per standard sponsor monitoring procedures.
SOCRA Protocol Deviations and Violations 1
Which of the following BEST defines a protocol deviation in a clinical trial?