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Meta-analysis of individual patient data from randomized trials: a review of methods used in practice

MRC Biostatistics Unit, Robinson Way, Cambridge, UK

Julian P T Higginsa

MRC Biostatistics Unit, Robinson Way, Cambridge CB2 2SR, UK. julian.higgins{at}mrc-bsu.cam.ac.uk

Lesley A Stewartb

Jayne F Tierneyb

MRC Clinical Trials Unit, London, UK Cochrane Centre, Oxford, UK

Mike J Clarke

UK Cochrane Centre, Oxford, UK

Simon G Thompson

MRC Biostatistics Unit, Robinson Way, Cambridge, UK

Background Meta-analyses based on individual patient data (IPD) are regarded as the gold standard for systematic reviews. However, the methods used for analysing and presenting results from IPD meta-analyses have received little discussion.

Methods We review 44 IPD meta-analyses published during the years 1999–2001. We summarize whether they obtained all the data they sought, what types of approaches were used in the analysis, including assumptions of common or random effects, and how they examined the effects of covariates.

Results Twenty-four out of 44 analyses focused on time-to-event outcomes, and most analyses (28) estimated treatment effects within each trial and then combined the results assuming a common treatment effect across trials. Three analyses failed to stratify by trial, analysing the data is if they came from a single mega-trial. Only nine analyses used random effects methods. Covariate-treatment interactions were generally investigated by subgrouping patients. Seven of the meta-analyses included data from less than 80% of the randomized patients sought, but did not address the resulting potential biases.

Conclusions Although IPD meta-analyses have many advantages in assessing the effects of health care, there are several aspects that could be further developed to make fuller use of the potential of these time-consuming projects. In particular, IPD could be used to more fully investigate the influence of covariates on heterogeneity of treatment effects, both within and between trials. The impact of heterogeneity, or use of random effects, are seldom discussed. There is thus considerable scope for enhancing the methods of analysis and presentation of IPD meta-analysis.

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