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

doi:10.1001/jama.2021.14075

. 2021 Sep 21;326(11):1045-1056.

doi: 10.1001/jama.2021.14075.

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

Hopin Lee^{1

2}, Aidan G Cashin^{3

4}, Sarah E Lamb^{1

5}, Sally Hopewell¹, Stijn Vansteelandt^{6

7}, Tyler J VanderWeele⁸, David P MacKinnon⁹, Gemma Mansell¹⁰, Gary S Collins^{1

11}, Robert M Golub^{12

13}, James H McAuley^{4

14}; AGReMA group; A Russell Localio^{15

16}, Ludo van Amelsvoort^{17

18}, Eliseo Guallar^{19

20}, Judith Rijnhart²¹, Kimberley Goldsmith²², Amanda J Fairchild²³, Cara C Lewis²⁴, Steven J Kamper^{25

26}, Christopher M Williams², Nicholas Henschke²⁷

Affiliations

¹ Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, University of Oxford, Oxford, England.
² School of Medicine and Public Health, University of Newcastle, Callaghan, Australia.
³ Prince of Wales Clinical School, Faculty of Medicine, University of New South Wales, Sydney, Australia.
⁴ Neuroscience Research Australia, Sydney.
⁵ College of Medicine and Health, University of Exeter Medical School, Exeter, England.
⁶ Department of Applied Mathematics, Computer Science, and Statistics, Ghent University, Ghent, Belgium.
⁷ Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, England.
⁸ Departments of Epidemiology and Biostatistics, T. H. Chan School of Public Health, Harvard University, Boston, Massachusetts.
⁹ Department of Psychology, Arizona State University, Phoenix.
¹⁰ College of Health and Life Sciences, Aston University, Birmingham, England.
¹¹ NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, England.
¹² JAMA Editorial Office, Chicago, Illinois.
¹³ Division of General Internal Medicine and Geriatrics, Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
¹⁴ School of Health Sciences, Faculty of Medicine, University of New South Wales, Sydney, Australia.
¹⁵ Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
¹⁶ Associate Editor, Annals of Internal Medicine.
¹⁷ Faculty of Health, Medicine, and Life Sciences, Maastricht University, Maastricht, the Netherlands.
¹⁸ Assoicate Editor, Journal of Clinical Epidemiology.
¹⁹ Welch Center for Prevention, Epidemiology, and Clinical Research, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland.
²⁰ Deputy Editor, Annals of Internal Medicine.
²¹ Department of Epidemiology and Data Science, Amsterdam Public Health Research Institute, Amsterdam University Medical Center, Amsterdam, the Netherlands.
²² Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, England.
²³ Department of Psychology, University of South Carolina, Columbia.
²⁴ Kaiser Permanente Washington Health Research Institute, Seattle.
²⁵ School of Health Sciences, University of Sydney, Sydney, Australia.
²⁶ Nepean Blue Mountains Local Health District, Kingswood, Australia.
²⁷ School of Public Health, University of Sydney, Sydney, Australia.

PMID: 34546296
PMCID: PMC8974292
DOI: 10.1001/jama.2021.14075

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

Hopin Lee et al. JAMA. 2021.

. 2021 Sep 21;326(11):1045-1056.

doi: 10.1001/jama.2021.14075.

Authors

Affiliations

¹ Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, University of Oxford, Oxford, England.
² School of Medicine and Public Health, University of Newcastle, Callaghan, Australia.
³ Prince of Wales Clinical School, Faculty of Medicine, University of New South Wales, Sydney, Australia.
⁴ Neuroscience Research Australia, Sydney.
⁵ College of Medicine and Health, University of Exeter Medical School, Exeter, England.
⁶ Department of Applied Mathematics, Computer Science, and Statistics, Ghent University, Ghent, Belgium.
⁷ Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, England.
⁸ Departments of Epidemiology and Biostatistics, T. H. Chan School of Public Health, Harvard University, Boston, Massachusetts.
⁹ Department of Psychology, Arizona State University, Phoenix.
¹⁰ College of Health and Life Sciences, Aston University, Birmingham, England.
¹¹ NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, England.
¹² JAMA Editorial Office, Chicago, Illinois.
¹³ Division of General Internal Medicine and Geriatrics, Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
¹⁴ School of Health Sciences, Faculty of Medicine, University of New South Wales, Sydney, Australia.
¹⁵ Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
¹⁶ Associate Editor, Annals of Internal Medicine.
¹⁷ Faculty of Health, Medicine, and Life Sciences, Maastricht University, Maastricht, the Netherlands.
¹⁸ Assoicate Editor, Journal of Clinical Epidemiology.
¹⁹ Welch Center for Prevention, Epidemiology, and Clinical Research, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland.
²⁰ Deputy Editor, Annals of Internal Medicine.
²¹ Department of Epidemiology and Data Science, Amsterdam Public Health Research Institute, Amsterdam University Medical Center, Amsterdam, the Netherlands.
²² Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, England.
²³ Department of Psychology, University of South Carolina, Columbia.
²⁴ Kaiser Permanente Washington Health Research Institute, Seattle.
²⁵ School of Health Sciences, University of Sydney, Sydney, Australia.
²⁶ Nepean Blue Mountains Local Health District, Kingswood, Australia.
²⁷ School of Public Health, University of Sydney, Sydney, Australia.

PMID: 34546296
PMCID: PMC8974292
DOI: 10.1001/jama.2021.14075

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Lamb reported being a member of boards for the Health Technology Assessment (additional capacity funding board, end of life care and add-on studies board, prioritization group board, and trauma board). Dr VanderWeele reported receiving personal fees from Statistical Horizons. Dr Localio reported receiving grants from the Annals of Internal Medicine. Dr Guallar reported receiving personal fees from the American College of Physicians (Annals of Internal Medicine). Dr Kamper reported receiving grants from the National Health and Medical Research Council of Australia Fellowship. No other disclosures were reported.

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Comment in

Reporting Findings From Mediation Analyses.
Fontanarosa PB. Fontanarosa PB. JAMA. 2021 Sep 21;326(11):1057. doi: 10.1001/jama.2021.15786. JAMA. 2021. PMID: 34546315 No abstract available.
A Reporting Guideline for Mediation Analyses.
Yadav K, Lewis RJ. Yadav K, et al. JAMA. 2021 Sep 21;326(11):1011-1012. doi: 10.1001/jama.2021.15462. JAMA. 2021. PMID: 34546316 No abstract available.

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References

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[1] VanderWeele TJ. Explanation in Causal Inference: Methods for Mediation and Interaction. Oxford University Press; 2015.

[2] VanderWeele TJ. Explanation in Causal Inference: Methods for Mediation and Interaction. Oxford University Press; 2015.

[3] Lee H, Herbert RD, McAuley JH. Mediation analysis. JAMA. 2019;321(7):697–698. doi:10.1001/jama.2018.21973 - DOI - PubMed

[4] Lee H, Herbert RD, McAuley JH. Mediation analysis. JAMA. 2019;321(7):697–698. doi:10.1001/jama.2018.21973 - DOI - PubMed

[5] Nielsen L, Riddle M, King JW, et al.; NIH Science of Behavior Change Implementation Team. The NIH Science of Behavior Change Program: transforming the science through a focus on mechanisms of change. Behav Res Ther. 2018;101:3–11. doi:10.1016/j.brat.2017.07.002 - DOI - PMC - PubMed

[6] Nielsen L, Riddle M, King JW, et al.; NIH Science of Behavior Change Implementation Team. The NIH Science of Behavior Change Program: transforming the science through a focus on mechanisms of change. Behav Res Ther. 2018;101:3–11. doi:10.1016/j.brat.2017.07.002 - DOI - PMC - PubMed

[7] National Institutefor Health Research. Efficacy and mechanism evaluation. Accessed August 28, 2020. https://www.nihr.ac.uk/explore-nihr/funding-programmes/efficacy-and-mech...

[8] National Institutefor Health Research. Efficacy and mechanism evaluation. Accessed August 28, 2020. https://www.nihr.ac.uk/explore-nihr/funding-programmes/efficacy-and-mech...

[9] Nguyen TQ, Schmid I, Stuart EA. Clarifying causal mediation analysis for the applied researcher: defining effects based on what we want to learn. Psychol Methods. 2021;26(2):255–271. doi:10.1037/met0000299 - DOI - PMC - PubMed

[10] Nguyen TQ, Schmid I, Stuart EA. Clarifying causal mediation analysis for the applied researcher: defining effects based on what we want to learn. Psychol Methods. 2021;26(2):255–271. doi:10.1037/met0000299 - DOI - PMC - PubMed

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

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Comment in

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