Statistical Methods in Medical Research 4ed

18.10 Meta-analysis
Glass (1976) defined meta-analysis as `the statistical analysis of a large collection
of analysis results from individual studies for the purpose of integrating
the findings'. The etymology of the term can be criticized, but it is used
more widely than competitors, such as overviews. To most scientists it would
seem self-evident that all the available evidence on a particular question should
be combined; any failure to do so runs the risk of imprecision and selection bias.
Meta-analyses of clinical trial results were rare before about 1980, and there are
various reasons for their late appearance. There has often been a paucity of
precisely replicated trials, in contrast to the general scientific dictum that results
are to be treated with scepticism unless they can be repeated. Repetition of trials
with positive outcomes has often been regarded as involving unethical randomization,
whilst repetition of negative studies has been rejected as not worthwhile.
These objections gradually became less persuasive. Replication of trials with
positive results was often regarded as ethically permissible, on the grounds that
minor differences in protocol or in patient characteristics might affect the outcome;
and replication of negative trials (for which there was no objection on
medical ethical grounds) became more feasible as resources increased, making it
possible to build a more precise picture of treatment efficacy.
We are concerned here primarily with meta-analysis of clinical trials, but it
may be noted that the integration of study results is an active feature of other
branches of medical research, such as epidemiological surveys (§19.4), diagnostic
tests (§19.9) and bioassay (§20.1), none of which present the ethical features
of clinical trials. Non-medical areas of scientific research in which methods
of meta-analysis are used include agricultural field trials and educational
research.
The present account is necessarily brief. More extensive accounts are given in
the special journal issues edited by Yusuf et al. (1987) and Spitzer (1995), that of
Statistical Methods in Medical Research (1993, Volume 2, No. 2), the booklet
edited by Chalmers and Altman (1995) (who use the term systematic review in a
rather more general sense), and many review articles, such as Jones (1995) and
Thompson (1998).
Planning
18.10 Meta-analysis 641
The planning of a meta-analysis needs almost as much thought as that of a single
trial, and the rules of procedure should be formalized in a protocol. There are
differences in practice between different practitioners, but there would be fairly
wide agreement on the following general principles.
1 The data from different trials should be kept separate, so that treatment
contrasts derived from individual trials are pooled, rather than the