IPD meta-analysis of time-to-event data: One-stage versus two-stage approaches to estimating the hazard ratio

Article type
Authors
Bowden J1, Tierney J2, Simmonds M3, Copas A2, Higgins J1
1MRC Biostatistics Unit
2MRC Clinical Trials Unit
3Queen Mary University of London
Abstract
Background: Meta-analyses of individual patient data (IPD) provide a strong and authoritative basis for evidence synthesis. IPD are particularly useful when the outcome of interest is the time to an event. Methodological developments now enable the meta-analysis of time-to-event IPD using a single model, allowing treatment effect and across-trial heterogeneity parameters to be estimated simultaneously. This differs from the standard approaches used with aggregate data, and also predominantly with IPD.

Methods: Facilitated by a simulation study, we investigate what these new 'one-stage’ random-effects models offer over standard 'two-stage’ approaches. Results and Conclusions: We find that two-stage approaches represent a robust, reliable and easily implementable way to estimate treatment effects and account for heterogeneity. Nevertheless, one-stage models can be used to provide a deeper insight into the data. Software for fitting one-stage Cox models with random effects using REML methodology is made available, and its use demonstrated on an IPD meta-analysis assessing post operative radio therapy for patients with non-small cell lung cancer.