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Endpoints for Assessing Drug Activity in Clinical Trials

Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Rockville, Maryland, USA

Key Words. Endpoints • Survival • Time to progression • Response rate

Correspondence: Richard Pazdur, M.D., Food and Drug Administration, 1451 Rockville Pike, Woodmont Office Complex 2, Rockville, Maryland 20825, USA. Telephone: 301-594-2473; Fax: 301-594-0498; e-mail: pazdurr{at}cder.fda.gov

Disclosure: R.P. is director of the Office of Oncology Drug Products within the Center for Drug Evaluation and Research of the U.S. Food and Drug Administration (FDA). However, the views expressed in this manuscript are the results of independent work and do not necessarily represent the views or findings of the FDA or the U.S. government. No potential conflicts of interest were reported by the author, planners, reviewers, or staff managers of this article.

Overall survival remains the gold standard for the demonstration of clinical benefit. An improvement in overall survival is a direct clinical benefit to patients. An analysis of overall survival requires larger patient numbers and longer follow-up than other endpoints. Survival analysis may be confounded by subsequent therapies. Time to progression usually requires smaller clinical trials and may be more rapidly assessed than trials using overall survival as an endpoint. This endpoint is not confounded by subsequent therapies. Time to progression must use the same evaluation techniques and schedules for all therapies being evaluated. Blinding of trials or the use of an external blinded radiographic review committee is recommended in assessing time to progression. Unlike overall survival and time to progression, which must be evaluated in randomized trials, response rates can be accurately assessed using a single-arm trial. Stable disease is not included in a response rate determination and is optimally evaluated by assessing tumor progression in a randomized trial. Improvement in disease-related symptoms is considered clinical benefit and may be an appropriate endpoint for drug approval.

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