Protocol Deviations and Violations Flashcards

ICH E6(R2) Section 5.20.1 states that a sponsor's Quality Management System should include risk-based approaches. How does this apply to protocol deviation management?

Answer: Sponsors should focus oversight resources on deviations that pose the greatest risk to subject safety and data reliability

ICH E6(R2) emphasizes risk-based quality management, which means sponsors and sites should prioritize resources to address deviations with the greatest potential impact on subject safety and data integrity.

A subject withdraws consent during a study visit but the CRC continues collecting scheduled data before the withdrawal is formally processed. This situation BEST represents:

Answer: A serious protocol violation that also constitutes a breach of ethical principles

Collecting data from a subject after withdrawal of consent violates both the protocol and the fundamental ethical principle of respect for persons, constituting a serious protocol violation.

Which of the following is a key indicator that a site has a systemic protocol compliance problem rather than isolated deviations?

Answer: Recurring deviations of the same type across multiple subjects and multiple monitoring visits

Repeated deviations of the same type across multiple subjects and visits indicate a systemic process failure requiring root cause analysis and systemic corrective action.

A subject was randomized into a study but was later found to have been ineligible due to a prohibited concomitant medication. The data monitor committee (DMC) is evaluating the study. This deviation should PRIMARILY be reported to:

Answer: The IRB, the sponsor, and documented in the regulatory binder

An enrollment eligibility deviation must be reported to the IRB as a protocol deviation and to the sponsor, and fully documented in the site's regulatory files.

Under 21 CFR 312.66, an investigator must promptly report to the IRB any protocol deviations made to:

Answer: Eliminate apparent immediate hazards to human subjects

21 CFR 312.66 specifically requires investigators to report to the IRB any deviations from the approved protocol made to eliminate apparent immediate hazards to the human subjects.

At a clinical site, all protocol deviations are being captured in a deviation log. According to GCP, which of the following is MOST important about this log?

Answer: It should be complete, contemporaneous, and accessible for review by monitors, auditors, and inspectors

GCP requires that deviation logs be complete, maintained in real time, and available for review by all appropriate oversight parties including monitors, auditors, and regulatory inspectors.

A site receives a sponsor letter stating that a protocol deviation involving incorrect IP storage temperatures was identified. The sponsor concludes the IP is still acceptable for use. What should the site do NEXT?

Answer: Document the deviation and the sponsor's assessment in the site's deviation log and regulatory binder

Even when the sponsor approves continued use of IP after a storage deviation, the site must document both the deviation and the sponsor's disposition decision in the deviation log and regulatory binder per GCP requirements.