Individual participant data meta-analysis of intervention studies with time-to-event outcomes: A review of the methodology and an applied example



de Jong, Valentijn MT, Moons, Karel GM, Riley, Richard D, Tudur Smith, Catrin ORCID: 0000-0003-3051-1445, Marson, Anthony G ORCID: 0000-0002-6861-8806, Eijkemans, Marinus JC and Debray, Thomas PA
(2020) 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, 11 (2). pp. 148-168.

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Abstract

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
Uncontrolled Keywords: heterogeneity, individual participant data, intervention, meta-analysis, time-to-event
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Population Health
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 17 May 2021 09:03
Last Modified: 18 Jan 2023 22:46
DOI: 10.1002/jrsm.1384
Open Access URL: https://onlinelibrary.wiley.com/doi/full/10.1002/j...
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URI: https://livrepository.liverpool.ac.uk/id/eprint/3123014