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Meta‐analysis of time‐to‐event outcomes from randomized trials using restricted mean survival time: application to individual participant data
Author(s) -
Wei Yinghui,
Royston Patrick,
Tierney Jayne F.,
Parmar Mahesh K. B.
Publication year - 2015
Publication title -
statistics in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.996
H-Index - 183
eISSN - 1097-0258
pISSN - 0277-6715
DOI - 10.1002/sim.6556
Subject(s) - proportional hazards model , meta analysis , survival analysis , statistics , hazard ratio , event (particle physics) , accelerated failure time model , hazard , measure (data warehouse) , estimation , econometrics , computer science , confidence interval , mathematics , medicine , data mining , physics , chemistry , organic chemistry , quantum mechanics , management , economics
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. Copyright © 2015 John Wiley & Sons, Ltd.