Premarketing and Clinical Development Flashcards

A sponsor modifies the protocol to add a new secondary endpoint mid-trial without prior IRB approval. This action most directly violates which regulation?

Answer: 21 CFR 56.108

21 CFR 56.108 requires IRB review and approval of protocol amendments before implementation, including changes to study endpoints.

Under GCP (ICH E6(R2)), who holds primary responsibility for the conduct of a clinical trial at an investigational site?

Answer: The principal investigator

ICH E6(R2) assigns primary responsibility for the conduct of the trial at a site to the principal investigator (PI).

A drug receives Accelerated Approval based on a surrogate endpoint. What post-approval obligation is imposed on the sponsor?

Answer: Conducting confirmatory trials to verify clinical benefit

Under 21 CFR 314.510, Accelerated Approval requires sponsors to conduct post-approval confirmatory studies to verify and describe clinical benefit.

Which study design feature best controls for placebo effect and measurement bias simultaneously in a Phase III efficacy trial?

Answer: Double-blind, randomized, placebo-controlled design

A double-blind, randomized, placebo-controlled design prevents both subjects and evaluators from knowing treatment assignment, controlling placebo effect and assessment bias.

Under 21 CFR Part 312, a sponsor who transfers all obligations to a CRO must ensure which of the following?

Answer: A written agreement describing the transfer of responsibilities exists

21 CFR 312.52 requires a written agreement that specifies which sponsor obligations have been transferred to the CRO; the sponsor retains overall responsibility.

In a pharmacokinetics bridging study supporting a new pediatric formulation, which parameter is most critical to demonstrate bioequivalence to the adult reference product?

Answer: AUC and Cmax within the 80–125% confidence interval limits

FDA bioequivalence standards require the 90% CI for AUC and Cmax ratios to fall within 80–125% of the reference product.

What is the purpose of a Data Safety Monitoring Board (DSMB) in a Phase III clinical trial?

Answer: To provide independent interim safety and efficacy reviews and recommend trial continuation, modification, or stopping

A DSMB independently reviews unblinded interim data to protect subject safety, ensure data integrity, and advise the sponsor on trial continuation.