Mechanisms Matter: A Demonstration of the Importance of Mechanistic Analysis for Evidence Synthesis Using Two Case Studies

ABSTRACT Rationale Despite a growing recognition of the importance of mechanisms, driven largely by the EBM+ movement, there appears to be little understanding of how to include mechanistic analysis in evidence synthesis. Aims and Objectives To demonstrate the importance of mechanistic analysis for the appraisal of study quality and evidence review. Method Two case studies – masking to prevent the spread of respiratory illnesses and talking therapy for treatment resistant depression – are used to illustrate the issues arising from appraising outcome research without considering mechanisms. Results Mechanistic analysis is important for: designing high‐quality RCTs, appraising their quality (with Risk of Bias tools, GRADE analyses and more broadly) as well as other areas of evidence synthesis.