Meta-analysis: Unresolved issues and future developments

doi:10.1136/bmj.316.7126.221

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George Davey Smith, professor of clinical epidemiology (zetkin@bristol.ac.uk)a,
Matthias Egger, reader in social medicine and epidemiologya

^aDepartment of Social Medicine, University of Bristol, Bristol BS8 2PR

Correspondence to: Professor Davey Smith

Introduction

Since its recent introduction into clinical epidemiology, meta-analysis has established itself as an influential branch of biostatistics. Several books have focused mainly or entirely on meta-analysis in medicine,1 2 3 4 5 and the latest editions of relevant textbooks generally include a section on meta-analysis.6 7 8 9 Computer software entirely devoted to meta-analysis has been developed, and meta-analytic procedures have been introduced in general statistical software packages. We will soon be providing an overview of software packages on the BMJ's website.10 Several unresolved issues concerning meta-analysis remain, and in this final article of our series we address some of the topics that are likely to feature in future discussions of the appropriate practice and domain of meta-analysis.

Should unpublished data be included in meta-analyses?

Publication bias, discussed in detail in a previous article,11 is a major threat to the validity of meta-analysis. Obtaining and including data from unpublished studies seems to be the obvious way of avoiding this problem. Including data from unpublished studies can itself introduce bias, however. Even after extensive consultation with the research community, unpublished studies may remain hidden. The unpublished studies that can be located may thus be an unrepresentative sample of unpublished studies. Whether bias is reduced or increased by including unpublished studies cannot formally be assessed as it is impossible to be certain that all unpublished studies have been located. A further problem relates to the willingness of investigators of located unpublished studies to provide data. This may depend on the findings of the study, more favourable results being provided more readily. This could again bias the findings of a meta-analysis.