title: Meta-analysis of time-to-event outcomes from randomized trials using restricted mean survival time: application to individual participant data.
abstract: Meta-analysis of time-to-event outcomes using the hazard ratio as a treatment effect measure has an underlying assumption that hazards are proportional. The between-arm difference in the restricted mean survival time is a measure that avoids this assumption and allows the treatment effect to vary with time. We describe and evaluate meta-analysis based on the restricted mean survival time for dealing with non-proportional hazards and present a diagnostic method for the overall proportional hazards assumption. The methods are illustrated with the application to two individual participant meta-analyses in cancer. The examples were chosen because they differ in disease severity and the patterns of follow-up, in order to understand the potential impacts on the hazards and the overall effect estimates. We further investigate the estimation methods for restricted mean survival time by a simulation study.
authors.affiliation: MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, London, U.K.|Centre for Mathematical Sciences, School of Computing and Mathematics, University of Plymouth, U.K.
authors.forename: Yinghui
authors.initials: Y
authors.lastname: Wei
authors.affiliation: MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, London, U.K.
authors.forename: Patrick
authors.initials: P
authors.lastname: Royston
authors.affiliation: MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, London, U.K.
authors.forename: Jayne F
authors.initials: JF
authors.lastname: Tierney
authors.affiliation: MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, London, U.K.
authors.forename: Mahesh K B
authors.initials: MK
authors.lastname: Parmar
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D003198:Computer Simulation; D004812:Epidemiologic Methods; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D015201:Meta-Analysis as Topic; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy
keywords: meta-analysis; non-proportional hazards; restricted mean survival time; time-to-event outcomes