Does the protocol specify whether and how replacement of withdrawn subjects may occur?

• A. The protocol may specify whether replacement occurs
• B. Replacement is always mandatory
• C. The protocol specifies whether and how replacement may occur
• D. Replacement decisions are made after data lock

Answer: (C)

In GCP, the protocol governs how the trial is run, including how to handle subject withdrawals and whether replacements are allowed. The best answer reflects that the protocol specifies both whether replacement may occur and the procedure for it. This planning ensures the trial can meet its planned sample size and maintains the integrity of the data and the analysis, by predefining who can be replaced, when replacement is allowed, how many additional subjects are needed, how data from replaced subjects will be treated, and how consent and eligibility requirements will be handled.

Why the other ideas don’t fit as well: replacement isn’t always mandatory—some trials are designed without replacement, so it’s not automatic. Decisions about replacement aren’t made after data lock, because such changes would threaten the validity and integrity of the trial; all replacement rules should be set and documented before or during the protocol, not after data collection is complete.