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Validity of indirect comparison for estimating efficacy of competing interventions: empirical evidence from published meta-analyses

BMJ 2003; 326 doi: (Published 01 March 2003) Cite this as: BMJ 2003;326:472
  1. Fujian Song, senior research fellow ({at},
  2. Douglas G Altman, professor of statistics in medicineb,
  3. Anne-Marie Glenny, lecturer in evidence based oral health carec,
  4. Jonathan J Deeks, senior medical statisticianb
  1. a Department of Public Health and Epidemiology, University of Birmingham, Birmingham B15 2TT
  2. b Centre for Statistics in Medicine, Institute of Health Sciences, Oxford OX3 7LF
  3. c Cochrane Oral Health Group, University Dental Hospital of Manchester, Manchester M15 6FH
  1. Correspondence to: F Song
  • Accepted 16 January 2003


Objective: To determine the validity of adjusted indirect comparisons by using data from published meta-analyses of randomised trials.

Design: Direct comparison of different interventions in randomised trials and adjusted indirect comparison in which two interventions were compared through their relative effect versus a common comparator. The discrepancy between the direct and adjusted indirect comparison was measured by the difference between the two estimates.

Data sources: Database of abstracts of reviews of effectiveness (1994-8), the Cochrane database of systematic reviews, Medline, and references of retrieved articles.

Results: 44 published meta-analyses (from 28 systematic reviews) provided sufficient data. In most cases, results of adjusted indirect comparisons were not significantly different from those of direct comparisons. A significant discrepancy (P<0.05) was observed in three of the 44 comparisons between the direct and the adjusted indirect estimates. There was a moderate agreement between the statistical conclusions from the direct and adjusted indirect comparisons (κ 0.51). The direction of discrepancy between the two estimates was inconsistent.

Conclusions: Adjusted indirect comparisons usually but not always agree with the results of head to head randomised trials. When there is no or insufficient direct evidence from randomised trials, the adjusted indirect comparison may provide useful or supplementary information on the relative efficacy of competing interventions. The validity of the adjusted indirect comparisons depends on the internal validity and similarity of the included trials.

What is already known on this topic

What is already known on this topic Many competing interventions have not been compared in randomised trials

Indirect comparison of competing interventions has been carried out in systematic reviews, often implicitly

Indirect comparison adjusted by a common control can partially take account of prognostic characteristics of patients in different trials

What this study adds

What this study adds Results of adjusted indirect comparison usually, but not always, agree with those of head to head randomised trials

The validity of adjusted indirect comparisons depends on the internal validity and similarity of the trials involved


  • Funding This paper is based on a project (96/51/99) funded by the NHS R&D Health Technology Assessment Programme, UK. DGA is supported by Cancer Research UK. The guarantor accepts full responsibility for the conduct of the study, had access to the data, and controlled the decision to publish.

  • Competing interests None declared.

  • Embedded Image Details of methods and a worked example, references for 28 systematic reviews, and three tables are on

  • Accepted 16 January 2003
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