Synthesising quantitative evidence in systematic reviews of complex health interventions.

Public health and health service interventions are typically complex: they are multifaceted, with impacts at multiple levels and on multiple stakeholders. Systematic reviews evaluating the effects of complex health interventions can be challenging to conduct. This paper is part of a special series of papers considering these challenges particularly in the context of WHO guideline development. We outline established and innovative methods for synthesising quantitative evidence within a systematic review of a complex intervention, including considerations of the complexity of the system into which the intervention is introduced. We describe methods in three broad areas: non-quantitative approaches, including tabulation, narrative and graphical approaches; standard meta-analysis methods, including meta-regression to investigate study-level moderators of effect; and advanced synthesis methods, in which models allow exploration of intervention components, investigation of both moderators and mediators, examination of mechanisms, and exploration of complexities of the system. We offer guidance on the choice of approach that might be taken by people collating evidence in support of guideline development, and emphasise that the appropriate methods will depend on the purpose of the synthesis, the similarity of the studies included in the review, the level of detail available from the studies, the nature of the results reported in the studies, the expertise of the synthesis team and the resources available.