A review of methods for comparing treatments evaluated in studies that form disconnected networks of evidence

A network meta-analysis allows a simultaneous comparison between treatments evaluated in RCTs that share at least one treatment with at least one other study. Estimates of treatment effects may be required for treatments across disconnected networks of evidence, which requires a different statistical approach and modelling assumptions to account for imbalances in prognostic variable and treatment effect modifiers between studies. In this paper, we review and discuss methods for comparing treatments evaluated in studies which form disconnected networks of evidence. Several methods have been proposed but assessing which are appropriate often depends on the clinical context as well as the availability of data. Most methods account for sampling variation but do not always account for others sources of uncertainty. We suggest that further research is required to assess the properties of methods and the use of approaches that allow the incorporation of external information to reflect parameter and structural uncertainty.