Identifying, documenting, and examining heterogeneity in systematic reviews of complex interventions

This article describes approaches for planning, dealing, and analyzing heterogeneity in a systematic review of complex interventions. Approaches aim to generate a priori hypotheses of the mechanism of action of a complex intervention to identify the key variables that might contribute to variation among studies and guide statistical analysis. In addition to characteristics related to the population, intervention, and outcomes, we describe study-related variables, such as the way the interventions have been implemented and the context and conduct of studies. These approaches will guide reviewers planning a meta-analysis and provide a rationale for not meta-analyzing data if there is too much variability. Potential difficulties in applying meta-analytical techniques to examine statistical association among study results and sources of potential heterogeneity are described; these include the selection of a fixed or random-effects model, the risk of multiple testing and confounding when studies include different aspects of a complex intervention or different subsamples of the intended participant pool.