Dealing with clinical heterogeneity in meta-analysis. Assumptions, methods, interpretation

Objective: There is an ongoing debate how to interpret findings of meta-analyses when substantial clinical heterogeneity is present among included trials. The aim of the present study was to demonstrate various ways of dealing with clinical heterogeneity along with underlying assumptions and interpretation. A recent meta-analysis on long-term psychodynamic psychotherapy (LTPP) was used as an illustrative example.

Method: Re-analysis of published data including calculation of a prediction interval, heterogeneity tests, Bayesian meta-analysis, meta-regression, and subgroup analysis to explore and interpret summary estimates in clinically heterogeneous studies.

Results: Meta-analytic results and their implications varied considerably depending on whether and how clinical heterogeneity was addressed.

Conclusions: Whether or not to trust summary estimates in meta-analysis depends largely on the subjective relevance of clinical heterogeneity present. No single analysis and interpretation strategy can be valid in every context or paradigm, thus, reflection of own beliefs on the role of heterogeneity is needed.