Background:
While there is some consensus on methods for investigating statistical and methodologicalheterogeneity, little attention has been paid to clinical aspects of heterogeneity. The objectiveof this study is to summarize and collate suggested methods for investigating clinicalheterogeneity in systematic reviews.
Methods:
We searched databases (Medline, EMBASE, CINAHL, Cochrane Library, and CONSORT,to December 2010) and reference lists and contacted experts to identify resources providingsuggestions for investigating clinical heterogeneity between controlled clinical trials includedin systematic reviews. We extracted recommendations, assessed resources for risk of bias,and collated the recommendations.
Results:
One hundred and one resources were collected, including narrative reviews, methodologicalreviews, statistical methods papers, and textbooks. These resources generally had a low riskof bias, but there was minimal consensus among them. Resources suggested that plannedinvestigations of clinical heterogeneity should be made explicit in the protocol of the review;clinical experts should be included on the review team; a set of clinical covariates should bechosen considering variables from the participant level, intervention level, outcome level,research setting, or others unique to the research question; covariates should have a clearscientific rationale; there should be a sufficient number of trials per covariate; and results ofany such investigations should be interpreted with caution.
Conclusions:
Though the consensus was minimal, there were many recommendations in the literature forinvestigating clinical heterogeneity in systematic reviews. Formal recommendations forinvestigating clinical heterogeneity in systematic reviews of controlled trials are required.