de Jong, VMT, Moons, KGM, Riley, RD ORCID:, Smith, CT, Marson, AG, Eijkemans, MJC and Debray, TPA (2019) Individual participant data meta-analysis of intervention studies with time-to-event outcomes: A review of the methodology and an applied example. Research Synthesis Methods.

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Many randomized trials evaluate an intervention effect on time-to-event outcomes. Individual participant data (IPD) from such trials can be obtained and combined in a so-called IPD meta-analysis (IPD-MA), to summarize the overall intervention effect. We performed a narrative literature review to provide an overview of methods for conducting an IPD-MA of randomized intervention studies with a time-to-event outcome. We focused on identifying good methodological practice for modeling frailty of trial participants across trials, modeling heterogeneity of intervention effects, choosing appropriate association measures, dealing with (trial differences in) censoring and follow-up times, and addressing time-varying intervention effects and effect modification (interactions). We discuss how to achieve this using parametric and semi-parametric methods, and describe how to implement these in a one-stage or two-stage IPD-MA framework. We recommend exploring heterogeneity of the effect(s) through interaction and non-linear effects. Random effects should be applied to account for residual heterogeneity of the intervention effect. We provide further recommendations, many of which specific to IPD-MA of time-to-event data from randomized trials examining an intervention effect. We illustrate several key methods in a real IPD-MA, where IPD of 1225 participants from 5 randomized clinical trials were combined to compare the effects of Carbamazepine and Valproate on the incidence of epileptic seizures.

Item Type: Article
Additional Information: This is the accepted author manuscript (AAM). The final published version (version of record) is available online via Wiley at - please refer to any applicable terms of use of the publisher.
Uncontrolled Keywords: heterogeneity, individual participant data, intervention, meta‐analysis, time‐to‐event
Subjects: R Medicine > R Medicine (General) > R735 Medical education. Medical schools. Research
Divisions: Faculty of Medicine and Health Sciences > Primary Care Health Sciences
Related URLs:
Depositing User: Symplectic
Date Deposited: 13 Dec 2019 14:02
Last Modified: 23 Mar 2021 09:58

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