Indirect comparisons of competing interventions


The randomised controlled trial (RCT) is the most valid design for evaluating the relative efficacy of healthcare technology. However, many competing interventions have not been directly compared in RCTs and indirect methods have been commonly used in meta-analyses. Such indirect comparisons are subject to greater bias (especially selection bias) than head-to-head randomised comparisons, as the benefit of randomisation does not hold across trials. Therefore, it is essential to evaluate such bias that may lead to inaccuracies in the estimates of treatment effects and result in inappropriate policy decisions. The objectives of this study were to survey the frequency of use of indirect comparisons in systematic reviews and evaluate the methods used in their analysis and interpretation; to identify alternative statistical approaches for the analysis of indirect comparisons; and to assess the properties of different statistical methods used for performing indirect comparisons.


When conducting systematic reviews to evaluate the effectiveness of interventions, direct evidence from good-quality RCTs should be used wherever possible. If little or no such evidence exists, it may be necessary to look for indirect comparisons from RCTs. The reviewer needs, however, to be aware that the results may be susceptible to bias.

When making indirect comparisons within a systematic review, an adjusted indirect comparison method should ideally be used using the random effects model. If both direct and indirect comparisons are possible within a review, it is recommended that these be done separately before considering whether to pool data.

Conducted by: AM Glenny1, DG Altman2, F Song3, C Sakarovitch2, JJ Deeks2, R D'Amico2, M Bradburn2, AJ Eastwood4

in collaboration with the International Stroke Trial Collaborative Group

1. Cochrane Oral Health Group, Dental School, University of Manchester; 2. Cancer Research UK, Centre for Statistics in Medicine, Wolfson College Annexe, Oxford; 3. School of Medicine Health Policy and Practice, University of East Anglia; 4. Centre for Reviews and Dissemination

Further details

Project page on HTA Programme website


Glenny AM, Altman DG, Song F, Sakarovitch C, Deeks JJ, D'Amico R, Bradburn M, Eastwood AJ. Indirect comparisons of competing interventions. Health Technol Assess. 2005;9(26):1-148

Song F, Altman DG, Glenny AM, Deeks JJ. Validity of indirect comparison for estimating efficacy of competing interventions: empirical evidence from published meta-analyses. BMJ. 2003;326(7387):472-5


Commissioned by the HTA Programme