Treatment Planning & Protocols Flashcards

In a clinical trial protocol, an 'allowed concomitant medication' list is provided. A subject requires a drug NOT on the list. The investigator should:

Answer: Consult the protocol's prohibited medication section, contact the sponsor, and document the decision

When a concomitant medication is not addressed, the investigator must cross-reference prohibited lists, consult the sponsor, and carefully document the clinical rationale.

A protocol specifies 'stratified randomization' by disease severity. What is the PRIMARY advantage of this approach over simple randomization?

Answer: It ensures balance of key prognostic factors across treatment arms

Stratified randomization ensures that important prognostic variables are balanced between arms, reducing confounding.

A physician investigator receives a protocol that includes a 'run-in period' before randomization. What is the primary purpose of a run-in period?

Answer: To assess subject compliance, tolerability, or to wash out prior treatments before randomization

Run-in periods assess compliance, tolerability to study drug, or eliminate prior treatment effects before subjects are randomized.

Under ICH E6(R2) GCP guidelines, the protocol must include which of the following regarding treatment?

Answer: Description of investigational product, dose, schedule, route, and duration

ICH E6(R2) requires the protocol to specify the investigational product's dose, dosage regimen, route of administration, and treatment duration.

A subject in a double-blind trial develops symptoms suggesting the study drug rather than placebo. The investigator considers unblinding. In what circumstance is emergency unblinding justified?

Answer: When knowledge of treatment assignment is essential for subject safety or medical management

Emergency unblinding is justified only when knowing the treatment assignment is medically necessary for subject safety.

A Phase III protocol uses a 'non-inferiority' design. What does this mean for the treatment planning hypothesis?

Answer: The experimental treatment is hypothesized to be no worse than the active comparator by a pre-specified margin

Non-inferiority trials test whether an experimental treatment is not worse than an active comparator by a clinically acceptable margin (the non-inferiority margin).

When a protocol includes an 'interim analysis,' what is the primary risk that must be managed?

Answer: Inflation of Type I error (false positive) if proper alpha spending is not applied

Interim analyses increase the chance of a false positive finding unless an alpha spending function (e.g., O'Brien-Fleming) is pre-specified to control Type I error.