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Education And Debate

Simultaneous comparison of multiple treatments: combining direct and indirect evidence

BMJ 2005; 331 doi: (Published 13 October 2005) Cite this as: BMJ 2005;331:897
  1. Deborah M Caldwell (, research associate1,
  2. A E Ades, professor of public health science1,
  3. J P T Higgins, senior research associate2
  1. 1 Medical Research Council Health Services Research Collaboration, Department of Social Medicine, University of Bristol, Bristol BS8 2PR
  2. 2 Medical Research Council Biostatistics Unit, Institute of Public Health, Cambridge CB2 2SR
  1. Correspondence to: D M Caldwell
  • Accepted 29 June 2005

How can policy makers decide which of five treatments is the best? Standard meta-analysis provides little help but evidence based decisions are possible


Several possible treatments are often available to treat patients with the same condition. Decisions about optimal care, and the clinical practice guidelines that inform these decisions, rely on evidence based evaluation of the different treatment options.1 2 Systematic reviews and meta-analyses of randomised controlled trials are the main sources of evidence. However, most systematic reviews focus on pair-wise, direct comparisons of treatments (often with the comparator being a placebo or control group), which can make it difficult to determine the best treatment. In the absence of a collection of large, high quality, randomised trials comparing all eligible treatments (which is invariably the situation), we have to rely on indirect comparisons of multiple treatments. For example, an indirect estimate of the benefit of A over B can be obtained by comparing trials of A v C with trials of B v C,35 even though indirect comparisons produce relatively imprecise estimates.6 We describe comparisons of three or more treatments, based on pair-wise or multi-arm comparative studies, as a multiple treatment comparison evidence structure.

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Angioplasty balloon device used to unblock and widen arteries


The need to combine direct and indirect evidence

Concerns have been expressed over the use of indirect comparisons of treatments.4 5 The Cochrane Collaboration's guidance to authors states that indirect comparisons are not randomised, but are “observational studies across trials, and may suffer the biases of observational studies, for example confounding.”7 Some investigators believe that indirect comparisons may systematically overestimate the effects of treatments.3 When both indirect and direct comparisons are available, it has been recommended that the two approaches be considered separately and that direct comparisons should take precedence as a …

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