Bench-to-bedside review: Avoiding pitfalls in critical care meta-analysis – funnel plots, risk estimates, types of heterogeneity, baseline risk and the ecologic fallacy
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* Corresponding author: Michael C Reade mreade@doctors.net.uk
1 CRISMA Laboratory, Department of Critical Care Medicine, University of Pittsburgh, 3550 Terrace Street, Pittsburgh, PA, 15261, USA
2 Austin Hospital, University of Melbourne, 145 Studley Road, Heidelberg 3084, Australia
3 Royal North Shore Hospital and Northern Clinical School, University of Sydney, Pacific Highway, St Leonards, NSW, 2065, Australia
4 Australian and New Zealand Intensive Care Research Centre, Department of Epidemiology and Preventive Medicine, Monash University, The Alfred Hospital, Commercial Road, Melbourne 3004, Australia
Critical Care 2008, 12:220 doi:10.1186/cc6941
Published: 25 July 2008Abstract
Meta-analysis can be a powerful tool for demonstrating the applicability of a concept beyond the context of individual clinical trials and observational studies, including exploration of effects across different subgroups. Meta-analysis avoids Simpson's paradox, in which a consistent effect in constituent trials is reversed when results are simply pooled. Meta-analysis in critical care medicine is made more complicated, however, by the heterogeneous nature of critically ill patients and the contexts within which they are treated. Failure to properly adjust for this heterogeneity risks missing important subgroup effects in, for example, the interaction of treatment with varying levels of baseline risk. When subgroups are defined by characteristics that vary within constituent trials (such as age) rather than features constant within each trial (such as drug dose), there is the additional risk of incorrect conclusions due to the ecological fallacy. The present review explains these problems and the strategies by which they are overcome.