title: Endpoints for assessing drug activity in clinical trials.
abstract: 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.
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Rockville, Maryland 20825, USA. pazdurr@cder.fda.gov
authors.forename: Richard
authors.initials: R
authors.lastname: Pazdur
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D018450:Disease Progression; D023381:Endpoint Determination; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents