A Guideline for Reporting Mediation Analyses of Randomized Trials and Observational Studies: The AGReMA Statement

Hopin Lee*, Aidan G Cashin, Sarah E Lamb, Sally Hopewell, Stijn Vansteelandt, Tyler J VanderWeele, David P MacKinnon, Gemma Mansell, Gary S Collins, Robert M Golub, James H McAuley, A Russell Localio, Ludo van Amelsvoort, Eliseo Guallar, Judith Rijnhart, Kimberley Goldsmith, Amanda J Fairchild, Cara C Lewis, Steven J Kamper, Christopher M WilliamsNicholas Henschke, AGReMA group

*Corresponding author for this work

Research output: Contribution to journal(Systematic) Review article peer-review

Abstract

Importance: Mediation analyses of randomized trials and observational studies can generate evidence about the mechanisms by which interventions and exposures may influence health outcomes. Publications of mediation analyses are increasing, but the quality of their reporting is suboptimal.

Objective: To develop international, consensus-based guidance for the reporting of mediation analyses of randomized trials and observational studies (A Guideline for Reporting Mediation Analyses; AGReMA).

Design, Setting, and Participants: The AGReMA statement was developed using the Enhancing Quality and Transparency of Health Research (EQUATOR) methodological framework for developing reporting guidelines. The guideline development process included (1) an overview of systematic reviews to assess the need for a reporting guideline; (2) review of systematic reviews of relevant evidence on reporting mediation analyses; (3) conducting a Delphi survey with panel members that included methodologists, statisticians, clinical trialists, epidemiologists, psychologists, applied clinical researchers, clinicians, implementation scientists, evidence synthesis experts, representatives from the EQUATOR Network, and journal editors (n = 19; June-November 2019); (4) having a consensus meeting (n = 15; April 28-29, 2020); and (5) conducting a 4-week external review and pilot test that included methodologists and potential users of AGReMA (n = 21; November 2020).

Results: A previously reported overview of 54 systematic reviews of mediation studies demonstrated the need for a reporting guideline. Thirty-three potential reporting items were identified from 3 systematic reviews of mediation studies. Over 3 rounds, the Delphi panelists ranked the importance of these items, provided 60 qualitative comments for item refinement and prioritization, and suggested new items for consideration. All items were reviewed during a 2-day consensus meeting and participants agreed on a 25-item AGReMA statement for studies in which mediation analyses are the primary focus and a 9-item short-form AGReMA statement for studies in which mediation analyses are a secondary focus. These checklists were externally reviewed and pilot tested by 21 expert methodologists and potential users, which led to minor adjustments and consolidation of the checklists.

Conclusions and Relevance: The AGReMA statement provides recommendations for reporting primary and secondary mediation analyses of randomized trials and observational studies. Improved reporting of studies that use mediation analyses could facilitate peer review and help produce publications that are complete, accurate, transparent, and reproducible.

Original languageEnglish
Pages (from-to)1045-1056
Number of pages12
JournalJAMA-Journal of the American Medical Association
Volume326
Issue number11
DOIs
Publication statusPublished - 21 Sept 2021

Keywords

  • Checklist
  • Delphi Technique
  • Guidelines as Topic
  • Humans
  • Mediation Analysis
  • Observational Studies as Topic
  • Peer Review
  • Randomized Controlled Trials as Topic
  • Systematic Reviews as Topic
  • CAUSAL
  • IDENTIFIABILITY

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