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. Williams; Nicholas Henschke

doi:10.1001/jama.2021.14075

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. Williams

Nicholas Henschke

Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, University of Oxford, Oxford, England,School of Medicine and Public Health, University of Newcastle, Callaghan, Australia
Prince of Wales Clinical School, Faculty of Medicine, University of New South Wales, Sydney, Australia,Neuroscience Research Australia, Sydney
Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, University of Oxford, Oxford, England,College of Medicine and Health, University of Exeter Medical School, Exeter, England
Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, University of Oxford, Oxford, England
Department of Applied Mathematics, Computer Science, and Statistics, Ghent University, Ghent, Belgium,Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, England
Departments of Epidemiology and Biostatistics, T. H. Chan School of Public Health, Harvard University, Boston, Massachusetts
Department of Psychology, Arizona State University, Phoenix
Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, University of Oxford, Oxford, England,NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, England
JAMA Editorial Office, Chicago, Illinois,Division of General Internal Medicine and Geriatrics, Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
Neuroscience Research Australia, Sydney,School of Health Sciences, Faculty of Medicine, University of New South Wales, Sydney, Australia
Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia,Associate Editor, Annals of Internal Medicine
Faculty of Health, Medicine, and Life Sciences, Maastricht University, Maastricht, the Netherlands,Assoicate Editor, Journal of Clinical Epidemiology
Welch Center for Prevention, Epidemiology, and Clinical Research, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland,Deputy Editor, Annals of Internal Medicine
Department of Epidemiology and Data Science, Amsterdam Public Health Research Institute, Amsterdam University Medical Center, Amsterdam, the Netherlands
Institute of Psychiatry, Psychology, and Neuroscience, King’s College London, London, England
Department of Psychology, University of South Carolina, Columbia
Kaiser Permanente Washington Health Research Institute, Seattle
School of Health Sciences, University of Sydney, Sydney, Australia,Nepean Blue Mountains Local Health District, Kingswood, Australia
School of Medicine and Public Health, University of Newcastle, Callaghan, Australia
School of Public Health, University of Sydney, Sydney, Australia

Research output: Contribution to journal › Article › peer-review

386 Citations (SciVal)

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 language	English
Pages (from-to)	1045-1056
Number of pages	12
Journal	JAMA: Journal of the American Medical Association
Volume	326
Issue number	11
DOIs	https://doi.org/10.1001/jama.2021.14075
Publication status	Published - 21 Sept 2021

Bibliographical note

Funding: This work was supported by project funding from the University of California, Berkeley, Initiative for Transparency in the Social Sciences, a program of the Center for Effective Global Action, with support from the Laura and John Arnold Foundation. Dr Lee was supported by the Neil Hamilton Fairley Early Career Fellowship award APP1126767 from the National Health and Medical Research Council. Dr VanderWeele reported receiving grant R01CA222147 from the National Cancer Institute. Dr MacKinnon was supported by grant R37DA09757 from the National Institute on Drug Abuse. Dr Collins was supported by the NIHR Oxford Biomedical Research Centre and programme grant C49297/A27294 from Cancer Research UK.

Keywords

General Medicine

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10.1001/jama.2021.14075

Cite this

Lee, H., Cashin, A. G., Lamb, S. E., Hopewell, S., Vansteelandt, S., VanderWeele, T. J., MacKinnon, D. P., Mansell, G., Collins, G. S., Golub, R. M., McAuley, J. H., Localio, A. R., van Amelsvoort, L., Guallar, E., Rijnhart, J., Goldsmith, K., Fairchild, A. J., Lewis, C. C., Kamper, S. J., ... Henschke, N. (2021). A Guideline for Reporting Mediation Analyses of Randomized Trials and Observational Studies: The AGReMA Statement. JAMA: Journal of the American Medical Association, 326(11), 1045-1056. https://doi.org/10.1001/jama.2021.14075

@article{30214c55863544da9f18479a00879cbd,

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

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.",

keywords = "General Medicine",

author = "Hopin Lee and Cashin, \{Aidan G.\} and Lamb, \{Sarah E.\} and Sally Hopewell and Stijn Vansteelandt and VanderWeele, \{Tyler J.\} and MacKinnon, \{David P.\} and Gemma Mansell and Collins, \{Gary S.\} and Golub, \{Robert M.\} and McAuley, \{James H.\} and Localio, \{A. Russell\} and \{van Amelsvoort\}, Ludo and Eliseo Guallar and Judith Rijnhart and Kimberley Goldsmith and Fairchild, \{Amanda J.\} and Lewis, \{Cara C.\} and Kamper, \{Steven J.\} and Williams, \{Christopher M.\} and Nicholas Henschke",

note = "Funding: This work was supported by project funding from the University of California, Berkeley, Initiative for Transparency in the Social Sciences, a program of the Center for Effective Global Action, with support from the Laura and John Arnold Foundation. Dr Lee was supported by the Neil Hamilton Fairley Early Career Fellowship award APP1126767 from the National Health and Medical Research Council. Dr VanderWeele reported receiving grant R01CA222147 from the National Cancer Institute. Dr MacKinnon was supported by grant R37DA09757 from the National Institute on Drug Abuse. Dr Collins was supported by the NIHR Oxford Biomedical Research Centre and programme grant C49297/A27294 from Cancer Research UK.",

year = "2021",

month = sep,

day = "21",

doi = "10.1001/jama.2021.14075",

language = "English",

volume = "326",

pages = "1045--1056",

journal = "JAMA: Journal of the American Medical Association",

issn = "0098-7484",

publisher = "American Medical Association",

number = "11",

}

Lee, H, Cashin, AG, Lamb, SE, Hopewell, S, Vansteelandt, S, VanderWeele, TJ, MacKinnon, DP, Mansell, G, Collins, GS, Golub, RM, McAuley, JH, Localio, AR, van Amelsvoort, L, Guallar, E, Rijnhart, J, Goldsmith, K, Fairchild, AJ, Lewis, CC, Kamper, SJ, Williams, CM & Henschke, N 2021, 'A Guideline for Reporting Mediation Analyses of Randomized Trials and Observational Studies: The AGReMA Statement', JAMA: Journal of the American Medical Association, vol. 326, no. 11, pp. 1045-1056. https://doi.org/10.1001/jama.2021.14075

TY - JOUR

T1 - A Guideline for Reporting Mediation Analyses of Randomized Trials and Observational Studies

T2 - The AGReMA Statement

AU - Lee, Hopin

AU - Cashin, Aidan G.

AU - Lamb, Sarah E.

AU - Hopewell, Sally

AU - Vansteelandt, Stijn

AU - VanderWeele, Tyler J.

AU - MacKinnon, David P.

AU - Mansell, Gemma

AU - Collins, Gary S.

AU - Golub, Robert M.

AU - McAuley, James H.

AU - Localio, A. Russell

AU - van Amelsvoort, Ludo

AU - Guallar, Eliseo

AU - Rijnhart, Judith

AU - Goldsmith, Kimberley

AU - Fairchild, Amanda J.

AU - Lewis, Cara C.

AU - Kamper, Steven J.

AU - Williams, Christopher M.

AU - Henschke, Nicholas

N1 - Funding: This work was supported by project funding from the University of California, Berkeley, Initiative for Transparency in the Social Sciences, a program of the Center for Effective Global Action, with support from the Laura and John Arnold Foundation. Dr Lee was supported by the Neil Hamilton Fairley Early Career Fellowship award APP1126767 from the National Health and Medical Research Council. Dr VanderWeele reported receiving grant R01CA222147 from the National Cancer Institute. Dr MacKinnon was supported by grant R37DA09757 from the National Institute on Drug Abuse. Dr Collins was supported by the NIHR Oxford Biomedical Research Centre and programme grant C49297/A27294 from Cancer Research UK.

PY - 2021/9/21

Y1 - 2021/9/21

N2 - 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.

AB - 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.

KW - General Medicine

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DO - 10.1001/jama.2021.14075

M3 - Article

SN - 0098-7484

VL - 326

SP - 1045

EP - 1056

JO - JAMA: Journal of the American Medical Association

JF - JAMA: Journal of the American Medical Association

IS - 11

ER -

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

Abstract

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Keywords

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