CTA Protocol Development & Review 3 — Questions and Answers
Question 1: In a double-blind randomized controlled trial protocol, what mechanism ensures that neither the investigator nor the subject knows the treatment assignment?
- Stratified randomization
- Blinding and allocation concealment procedures (Correct answer)
- Intent-to-treat analysis
- Placebo washout period
Correct answer: Blinding and allocation concealment procedures
Blinding and allocation concealment procedures are the mechanisms that prevent investigators and subjects from knowing treatment assignments.
Question 2: When reviewing a protocol's eligibility criteria, why is it important to include specific upper and lower age limits?
- To meet FDA administrative requirements only
- To ensure the study population reflects the intended therapeutic indication and safety profile (Correct answer)
- To reduce the number of enrolled subjects
- To satisfy IRB membership requirements
Correct answer: To ensure the study population reflects the intended therapeutic indication and safety profile
Specific age limits define the target population, ensure results are applicable to the intended indication, and address safety considerations for vulnerable populations.
Question 3: What is the role of a Data Safety Monitoring Board (DSMB) in relation to protocol review?
- To approve protocol amendments before IRB submission
- To conduct independent interim analyses and recommend study continuation, modification, or termination (Correct answer)
- To audit source documents at clinical sites
- To manage study randomization codes
Correct answer: To conduct independent interim analyses and recommend study continuation, modification, or termination
A DSMB independently reviews interim safety and efficacy data and recommends whether a study should continue, be modified, or be stopped.
Question 4: A protocol requires fasting blood samples but a site collected samples from non-fasting subjects. This represents which type of protocol issue?
- A major protocol deviation (Correct answer)
- A minor administrative error
- A serious adverse event
- An acceptable protocol adaptation
Correct answer: A major protocol deviation
Collecting blood samples outside protocol-specified conditions (fasting) constitutes a major protocol deviation that can affect data integrity.
Question 5: Which component of a protocol ensures continuity of care if a participant is discontinued from the study?
- Washout period specifications
- Discontinuation and withdrawal criteria section (Correct answer)
- Randomization procedures
- Drug accountability procedures
Correct answer: Discontinuation and withdrawal criteria section
The discontinuation and withdrawal criteria section outlines procedures for safely removing participants and ensuring appropriate follow-up care.
Question 6: What is the primary purpose of including a 'stopping rules' section in a clinical trial protocol?
- To define criteria for pausing or terminating the trial based on safety or efficacy signals (Correct answer)
- To describe administrative procedures for closing a site
- To outline procedures for document archiving
- To specify criteria for replacing withdrawn subjects
Correct answer: To define criteria for pausing or terminating the trial based on safety or efficacy signals
Stopping rules pre-specify the safety or efficacy thresholds that would trigger pausing or terminating the trial to protect participants.
Question 7: Under 21 CFR Part 312, which type of IND is designed for studies to be conducted by investigators who are NOT the IND sponsor?
- Commercial IND
- Investigator IND (Correct answer)
- Emergency IND
- Treatment IND
Correct answer: Investigator IND
An Investigator IND is submitted by a physician-investigator who initiates and conducts a study and is responsible for the IND, distinct from a sponsor-IND.
CTA Protocol Development & Review 3
In a double-blind randomized controlled trial protocol, what mechanism ensures that neither the investigator nor the subject knows the treatment assignment?