Treatment Planning & Protocols Flashcards

A protocol specifies that subjects must undergo a 'sentinel dosing' approach for the first cohort. This means:

Answer: One or two subjects are dosed first and observed for safety before dosing the remaining cohort

Sentinel dosing exposes one or two subjects first to identify early safety signals before the remaining cohort is dosed.

A subject enrolled in a pain management study begins taking an over-the-counter NSAID without telling the investigator. This is discovered at the next visit. Under GCP, the investigator should:

Answer: Document the concomitant medication use, assess protocol compliance impact, and report per protocol requirements

Undisclosed concomitant medication use must be documented, evaluated for protocol impact, and reported as required by the protocol and SOPs.

The protocol requires 'blinded independent central review' (BICR) for tumor response assessment. The primary purpose of BICR is to:

Answer: Minimize assessment bias by having blinded reviewers evaluate endpoints centrally

BICR reduces investigator bias in endpoint assessment by using blinded, independent reviewers to evaluate outcomes centrally.

In a protocol, the 'estimand' framework (ICH E9(R1)) defines which of the following?

Answer: The precise treatment effect to be estimated, including the target population, endpoint, and intercurrent event handling

The estimand framework defines exactly what treatment effect is being estimated, including the population, endpoint, and how intercurrent events (like discontinuation) are handled.

A protocol requires a 'mandatory biopsy' as part of the study procedures. A subject refuses the biopsy but wishes to continue in the trial. The correct action is:

Answer: Document the refusal and discontinue the subject per protocol, as mandatory procedures are required for valid data

Mandatory protocol procedures are required for subject eligibility and data validity; refusal of a mandatory procedure typically requires discontinuation per protocol.

A clinical trial protocol uses an 'adaptive design' with response-adaptive randomization. What is a key regulatory concern with this approach?

Answer: Potential for operational bias if allocation changes are not properly blinded and controlled

Adaptive randomization can introduce operational bias if the changing allocation ratios are not masked from site staff or properly controlled.

According to GCP, when an investigator delegates a protocol-specified procedure to a sub-investigator, the investigator must:

Answer: Ensure the delegation is documented and the sub-investigator is adequately trained and qualified

GCP requires that task delegation be formally documented (e.g., on a delegation log) and that delegated individuals are trained and qualified for the tasks assigned.