Finding the Pathway: Mediation Analyses in Randomized Controlled Trials
Authors: A. Russell Localio, Anne R. Meibohm, Eliseo Guallar
Journal: Annals of Internal Medicine (2020)

Understanding Clinical Research21 April 2020Finding the Pathway: Mediation Analyses in Randomized Controlled TrialsA. Russell Localio, PhD, Anne R. Meibohm, PhD, and Eliseo Guallar, MD, DrPHA. Russell Localio, PhDUniversity of Pennsylvania, Philadelphia, Pennsylvania (A.R.L.)Search for more papers by this author, Anne R. Meibohm, PhDAmerican College of Physicians, Philadelphia, Pennsylvania (A.R.M.)Search for more papers by this author, and Eliseo Guallar, MD, DrPHJohns Hopkins Bloomberg School of Public Health, Baltimore, Maryland (E.G.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M20-0887 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail The goal of clinical investigation often lies not only in estimating the effects of treatment or exposure but also in understanding their mechanisms. Identifying the pathways from treatment to outcome and explaining potential causes of the outcome—those are the specific domain of “mediation analysis” (1). In their report in Annals, Vallurupalli and colleagues (2) used the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS) to ask whether canakinumab reduced the incidence of anemia of chronic inflammation in patients with a history of myocardial infarction and high levels of high-sensitivity C-reactive protein (hsCRP) and whether reductions in hsCRP mediated this effect.CANTOS participants ...References1. VanderWeele TJ. Explanation in Causal Inference. Methods for Mediation and Interaction. Oxford Univ Pr; 2015. Google Scholar2. Vallurupalli M, MacFadyen JG, Glynn RJ, et al. Effects of interleukin-1β inhibition on incident anemia. Exploratory analyses from a randomized trial. Ann Intern Med. 2020;172:523-32. doi:10.7326/M19-2945 LinkGoogle Scholar3. Valeri L, Vanderweele TJ. 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[PMID: 25418811] doi:10.1007/s11121-014-0528-5 CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: University of Pennsylvania, Philadelphia, Pennsylvania (A.R.L.)American College of Physicians, Philadelphia, Pennsylvania (A.R.M.)Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland (E.G.)Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M20-0887.Corresponding Author: A. Russell Localio, PhD, Division of Biostatistics, Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, 617 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104; e-mail, [email protected]upenn.edu.Current Author Addresses: Dr. Localio: Division of Biostatistics, Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, 617 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104.Dr. Meibohm: American College of Physicians, 190 N. Independence Mall West, Philadelphia, PA 19106.Dr. Guallar: Departments of Epidemiology and Medicine, Johns Hopkins Bloomberg School of Public Health, 2024 East Monument Street, Room 2-645, Baltimore, MD 21205.Author Contributions: Conception and design: A.R. Localio.Analysis and interpretation of the data: A.R. Localio.Drafting of the article: A.R. Localio, A.R. Meibohm.Critical revision for important intellectual content: A.R. Localio, E. Guallar.Final approval of the article: A.R. Localio, A.R. Meibohm, E. Guallar.Statistical expertise: A.R. Localio, E. Guallar.Administrative, technical, or logistic support: A.R. Localio.This article was published at Annals.org on 24 March 2020. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoEffects of Interleukin-1β Inhibition on Incident Anemia Mounica Vallurupalli , Jean G. MacFadyen , Robert J. Glynn , Tom Thuren , Peter Libby , Nancy Berliner , and Paul M Ridker Metrics Cited byImproved Relationship Quality, Equitable Gender Attitudes, and Reduced Alcohol Abuse as Key Mechanisms to Reduce Intimate Partner Violence in the Bandebereho Couples’ Randomized Trial in Rwanda 21 April 2020Volume 172, Issue 8Page: 553-557KeywordsAnemiaBiostatisticsDrugsEpidemiologyHealth statisticsHigh sensitivity c reactive proteinObservational studiesPrevention, policy, and public healthRandomized trialsThrombosis ePublished: 24 March 2020 Issue Published: 21 April 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...