title: The Combined Assessment of Function and Survival (CAFS): a new endpoint for ALS clinical trials.
abstract: Our objective was to describe a new endpoint for amyotrophic lateral sclerosis (ALS), the Combined Assessment of Function and Survival (CAFS). CAFS ranks patients' clinical outcomes based on survival time and change in the ALS Functional Rating Scale-Revised (ALSFRS-R) score. Each patient's outcome is compared to every other patient's outcome, assigned a score, and the summed scores are ranked. The mean rank score for each treatment group can then be calculated. A higher mean CAFS score indicates a better group outcome. Historically, ALS clinical trials have assessed survival and function as independent endpoints. Combined endpoints have been used in other diseases to decrease the confounding effect of mortality on analysis of functional outcomes. We explored the application of a similar approach in ALS, the CAFS endpoint, which was used as a pre-specified secondary analysis in a phase II study of dexpramipexole. Those results and some hypothetical examples based on modeling exercises are presented here. CAFS is the primary endpoint of a dexpramipexole phase III study in ALS. In conclusion, the CAFS is a robust statistical tool for ALS clinical trials and appropriately accounts for and weights mortality in the analysis of function.
authors: Massachusetts General Hospital, Neurological Clinical Research Institute, Boston, Massachusetts 02114, USA. jdberry@partners.org
authors: James D
authors: JD
authors: Berry
authors: Robert
authors: R
authors: Miller
authors: Dan H
authors: DH
authors: Moore
authors: Merit E
authors: ME
authors: Cudkowicz
authors: Leonard H
authors: LH
authors: van den Berg
authors: Douglas A
authors: DA
authors: Kerr
authors: Yingwen
authors: Y
authors: Dong
authors: Evan W
authors: EW
authors: Ingersoll
authors: Donald
authors: D
authors: Archibald
mesh_terms: D000203:Activities of Daily Living / Q000523:psychology; D000690:Amyotrophic Lateral Sclerosis / Q000401:mortality / Q000523:psychology / Q000628:therapy*; D002986:Clinical Trials as Topic / Q000379:methods / Q000592:standards; D017322:Clinical Trials, Phase II as Topic / Q000379:methods / Q000592:standards; D017326:Clinical Trials, Phase III as Topic / Q000379:methods / Q000592:standards; D023381:Endpoint Determination / Q000379:methods / Q000592:standards*; D006801:Humans; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000592:standards*; D020127:Recovery of Function / Q000502:physiology; D015996:Survival Rate / Q000639:trends