AOCNP Clinical Trials and Evidence-Based Oncology Practice 5 — Questions and Answers
Question 1: Which endpoint is considered most rigorous for demonstrating clinical benefit in oncology trials submitted for FDA approval?
- Objective response rate (ORR)
- Disease-free survival (DFS)
- Overall survival (OS) (Correct answer)
- Time to response (TTR)
Correct answer: Overall survival (OS)
Overall survival is the gold-standard endpoint because it directly measures patient longevity and is unambiguous.
Question 2: A phase I dose-escalation trial uses a 3+3 design. A dose level has 1 DLT in the first 3 patients. What happens next?
- The dose is immediately declared the MTD
- Three additional patients are enrolled at the same dose level (Correct answer)
- Dose escalation proceeds to the next level automatically
- The trial is halted for a safety review
Correct answer: Three additional patients are enrolled at the same dose level
In the 3+3 design, one DLT in the first cohort triggers enrollment of 3 more patients at the same dose before escalation decisions are made.
Question 3: Which regulatory pathway allows the FDA to approve a cancer drug based on a surrogate endpoint reasonably likely to predict clinical benefit?
- Regular approval
- Accelerated approval (Correct answer)
- Priority review designation
- Orphan drug designation
Correct answer: Accelerated approval
Accelerated approval allows use of surrogate or intermediate endpoints (e.g., ORR, PFS) when likely to predict clinical benefit, with confirmatory trials required.
Question 4: An NP notes that a published RCT has a high attrition rate with differential dropout between arms. Which type of bias is most concerning?
- Selection bias
- Performance bias
- Attrition bias (Correct answer)
- Detection bias
Correct answer: Attrition bias
Attrition bias occurs when differential or substantial loss to follow-up between arms distorts the comparison of outcomes.
Question 5: What does the Number Needed to Treat (NNT) represent in oncology evidence appraisal?
- The number of patients who must be screened to find one eligible for a trial
- The number of patients who must be treated to prevent one additional adverse outcome (Correct answer)
- The ratio of responders to non-responders in the treatment arm
- The minimum sample size required for statistical significance
Correct answer: The number of patients who must be treated to prevent one additional adverse outcome
NNT is the inverse of absolute risk reduction and indicates how many patients must receive treatment for one to benefit.
Question 6: A clinical trial stratifies patients by ECOG performance status at randomization. What is the primary purpose of stratification?
- To increase the total sample size needed
- To ensure balance of prognostic factors between treatment arms (Correct answer)
- To allow open-label allocation of treatments
- To eliminate the need for interim analyses
Correct answer: To ensure balance of prognostic factors between treatment arms
Stratified randomization ensures that important prognostic variables are distributed equally between arms, reducing confounding.
Question 7: Which statement best describes the 'intention-to-treat' (ITT) principle in oncology RCT analysis?
- Patients are analyzed only if they complete all planned treatment cycles
- All randomized patients are analyzed in their originally assigned group regardless of protocol adherence (Correct answer)
- Patients who cross over to the other arm are excluded from analysis
- Only patients achieving an objective response are included in survival analysis
Correct answer: All randomized patients are analyzed in their originally assigned group regardless of protocol adherence
ITT analysis includes all randomized participants in their assigned group, preserving the benefits of randomization and minimizing bias.
AOCNP Clinical Trials and Evidence-Based Oncology Practice 5
Which endpoint is considered most rigorous for demonstrating clinical benefit in oncology trials submitted for FDA approval?