The conduct and reporting of mediation analysis in recently published randomized controlled trials: results from a methodological systematic review

Objectives: To describe the methodological characteristics of mediation analyses (MAs) reported in recent randomized controlled trials (RCTs) and to propose recommendations on the planning, conduct, and reporting of MAs in practice. Study Design and Setting: We conducted a systematic review by searching MEDLINE (January 1, 2017, to December 1, 2018) for all reports of RCTs or secondary analyses of previously published RCTs that reported a MA. Two reviewers independently screened the title, abstracts, and full texts of the identified reports and extracted the data from the 98 eligible studies. Results: MAs were nearly always (96%) based on a traditional mediation approach. Most studies did not report a sample size calculation for the MA (96%) or assess potential treatment-by-mediator interactions (96%). In 53% of studies, mediators and outcomes were simultaneously measured. In 57% of studies, mediator-mediator and mediator-outcome confounders were adjusted for in the analysis, although adjustment was often limited to few potential confounders. About 30% of studies discussed the assumptions underlying the MA. Conclusion: The conduct and reporting of MAs remained quite heterogeneous in practice. Future MAs could benefit from a consensusbased planning, conduct, and reporting guideline for MA.