Meta‐analysis of time‐to‐event outcomes from randomized trials using restricted mean survival time: application to individual participant data |
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| Authors: | Yinghui Wei Patrick Royston Jayne F Tierney Mahesh K B Parmar |
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| Institution: | 1. MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, London, U.K.;2. Centre for Mathematical Sciences, School of Computing and Mathematics, University of Plymouth, U.K. |
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| 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. Copyright © 2015 John Wiley & Sons, Ltd. |
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| Keywords: | meta‐analysis time‐to‐event outcomes non‐proportional hazards restricted mean survival time |
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