Endpoints for assessing drug activity in clinical trials
1Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Rockville, Maryland 20825, USA. pazdurr@cder.fda.gov
The Oncologist
|June 17, 2008
Summary
Overall survival is the best measure of clinical benefit but requires large trials. Time to progression and response rates offer faster assessments, with symptom improvement also considered clinical benefit.
Area of Science:
- Clinical trial design
- Oncology endpoints
- Drug development
Background:
- Overall survival (OS) is the gold standard for demonstrating clinical benefit in cancer trials.
- OS analysis necessitates large patient cohorts and extended follow-up, and can be confounded by subsequent therapies.
- Alternative endpoints like time to progression (TTP) and response rates (RR) offer more rapid assessments.
Purpose of the Study:
- To compare the utility of different clinical trial endpoints for assessing drug efficacy.
- To highlight the strengths and limitations of overall survival, time to progression, and response rates.
- To discuss the role of symptom improvement as a clinical benefit endpoint.
Main Methods:
- Comparative analysis of established clinical trial endpoints.
- Review of methodologies for assessing overall survival, time to progression, and response rates.
- Discussion of confounding factors and best practices for endpoint evaluation.
Main Results:
- Overall survival provides direct patient benefit but requires extensive resources.
- Time to progression is less resource-intensive and not confounded by post-trial therapies, but requires standardized evaluation.
- Response rates can be assessed in single-arm trials, excluding stable disease, and benefit from blinded review.
Conclusions:
- Each endpoint (OS, TTP, RR) has unique advantages and limitations for evaluating cancer drug efficacy.
- Standardized methodologies and blinded reviews are crucial for reliable assessment of TTP and RR.
- Disease-related symptom improvement is a valid clinical benefit and potential endpoint for drug approval.
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