SOCRA Protocol Deviations and Violations 2 — Questions and Answers
Question 1: Which of the following is an example of a PROSPECTIVE protocol deviation?
- Discovering after the fact that a subject's baseline labs were not collected
- Obtaining IRB approval to temporarily waive a procedure before it is missed (Correct answer)
- Realizing an ineligible subject was enrolled 3 weeks after randomization
- Documenting a missed visit in the source documents after the window has passed
Correct answer: Obtaining IRB approval to temporarily waive a procedure before it is missed
A prospective deviation occurs when the site identifies a potential departure in advance and obtains appropriate approvals or waivers before the scheduled procedure.
Question 2: A subject on a clinical trial inadvertently received a double dose of the investigational product. What is the MOST appropriate immediate action?
- Document only in the source records and continue the study without notification
- Assess subject safety, report as an adverse event if applicable, and document as a protocol deviation (Correct answer)
- Withdraw the subject immediately and close the case without an IRB report
- Administer the corrective dose and update the protocol amendment
Correct answer: Assess subject safety, report as an adverse event if applicable, and document as a protocol deviation
A dosing error must trigger immediate safety assessment, adverse event reporting if warranted, and documentation as a protocol deviation, with notification to the PI, sponsor, and IRB per their requirements.
Question 3: Under 21 CFR Part 312, which of the following protocol deviations requires prompt reporting to the FDA?
- Any deviation from the protocol, regardless of severity
- Deviations that are not covered by the existing IND application
- Changes to eliminate immediate hazards to subjects, reported as soon as possible (Correct answer)
- Minor administrative deviations that do not affect subject safety
Correct answer: Changes to eliminate immediate hazards to subjects, reported as soon as possible
21 CFR 312.62 and ICH E6 both require that protocol changes implemented to eliminate immediate hazards be reported to the FDA and IRB as soon as possible after the changes are made.
Question 4: Which element is MOST important to include in a protocol deviation report submitted to the IRB?
- The investigator's personal opinion about whether the deviation was avoidable
- A description of the deviation, the impact on subject safety/data integrity, and corrective actions taken (Correct answer)
- The financial cost of the deviation to the sponsor
- A request for additional funding to prevent future deviations
Correct answer: A description of the deviation, the impact on subject safety/data integrity, and corrective actions taken
IRB deviation reports must describe what occurred, assess the impact on subject safety and data integrity, and outline corrective/preventive actions to be taken.
Question 5: A CAPA (Corrective and Preventive Action) plan is developed in response to a protocol deviation. What is the PRIMARY purpose of the 'preventive' component?
- To discipline the staff member who caused the deviation
- To identify and address root causes to prevent recurrence of similar deviations (Correct answer)
- To submit a protocol amendment to the FDA
- To remove the affected subjects from the study analysis
Correct answer: To identify and address root causes to prevent recurrence of similar deviations
The preventive component of a CAPA focuses on identifying the root cause of the deviation and implementing systemic changes to prevent similar events from recurring.
Question 6: During an FDA inspection, an investigator is found to have multiple unreported protocol deviations. What is the MOST likely consequence?
- A routine warning letter with no further action required
- Automatic approval of a protocol amendment
- An FDA Form 483 observation, a Warning Letter, or potential disqualification of the investigator (Correct answer)
- Immediate suspension of the IND by the sponsor
Correct answer: An FDA Form 483 observation, a Warning Letter, or potential disqualification of the investigator
Failure to report protocol deviations can result in FDA 483 inspectional observations, Warning Letters, or investigator disqualification proceedings under 21 CFR Part 312.
Question 7: Which of the following BEST describes a 'waiver' in the context of protocol deviations?
- A post-hoc justification for a deviation already committed
- Sponsor permission granted after the fact to excuse a missed procedure
- Prior written approval from the IRB or sponsor to deviate from a specific protocol requirement (Correct answer)
- An FDA exemption from IND requirements for a specific site
Correct answer: Prior written approval from the IRB or sponsor to deviate from a specific protocol requirement
A protocol waiver is prospective written authorization from the sponsor and/or IRB to deviate from a specific protocol requirement under defined circumstances, obtained before the deviation occurs.
SOCRA Protocol Deviations and Violations 2
Which of the following is an example of a PROSPECTIVE protocol deviation?