Composite Outcomes Can Distort the Nature and Magnitude of Treatment Benefits in Clinical Trials
Authors: Ignacio Ferreira-Gonzalez
Journal: Annals of Internal Medicine (2009)

Letters21 April 2009Composite Outcomes Can Distort the Nature and Magnitude of Treatment Benefits in Clinical TrialsIgnacio Ferreira-Gonzalez, MD, PhD, Gaieta Permanyer-Miralda, MD, PhD, Jason W. Busse, MSc, P. J. Devereaux, MD, BSc, PhD, Gordon H. Guyatt, MD, MSc, Pablo Alonso-Coello, MD, and Victor M. Montori, MD, MScIgnacio Ferreira-Gonzalez, MD, PhDFrom Vall d'Hebron Hospital, CIBER de Epidemiología y Salud Pública, 08035 Barcelona, Spain; McMaster University, Hamilton, Ontario L8N 3Z5, Canada; Iberoamerican Cochrane Center, Hospital de la Santa Creu i Sant Pau, CIBER de Epidemiología y Salud Pública, 08025 Barcelona, Spain; and Mayo Clinic, Rochester, MN 55905., Gaieta Permanyer-Miralda, MD, PhDFrom Vall d'Hebron Hospital, CIBER de Epidemiología y Salud Pública, 08035 Barcelona, Spain; McMaster University, Hamilton, Ontario L8N 3Z5, Canada; Iberoamerican Cochrane Center, Hospital de la Santa Creu i Sant Pau, CIBER de Epidemiología y Salud Pública, 08025 Barcelona, Spain; and Mayo Clinic, Rochester, MN 55905., Jason W. Busse, MScFrom Vall d'Hebron Hospital, CIBER de Epidemiología y Salud Pública, 08035 Barcelona, Spain; McMaster University, Hamilton, Ontario L8N 3Z5, Canada; Iberoamerican Cochrane Center, Hospital de la Santa Creu i Sant Pau, CIBER de Epidemiología y Salud Pública, 08025 Barcelona, Spain; and Mayo Clinic, Rochester, MN 55905., P. J. Devereaux, MD, BSc, PhDFrom Vall d'Hebron Hospital, CIBER de Epidemiología y Salud Pública, 08035 Barcelona, Spain; McMaster University, Hamilton, Ontario L8N 3Z5, Canada; Iberoamerican Cochrane Center, Hospital de la Santa Creu i Sant Pau, CIBER de Epidemiología y Salud Pública, 08025 Barcelona, Spain; and Mayo Clinic, Rochester, MN 55905., Gordon H. Guyatt, MD, MScFrom Vall d'Hebron Hospital, CIBER de Epidemiología y Salud Pública, 08035 Barcelona, Spain; McMaster University, Hamilton, Ontario L8N 3Z5, Canada; Iberoamerican Cochrane Center, Hospital de la Santa Creu i Sant Pau, CIBER de Epidemiología y Salud Pública, 08025 Barcelona, Spain; and Mayo Clinic, Rochester, MN 55905., Pablo Alonso-Coello, MDFrom Vall d'Hebron Hospital, CIBER de Epidemiología y Salud Pública, 08035 Barcelona, Spain; McMaster University, Hamilton, Ontario L8N 3Z5, Canada; Iberoamerican Cochrane Center, Hospital de la Santa Creu i Sant Pau, CIBER de Epidemiología y Salud Pública, 08025 Barcelona, Spain; and Mayo Clinic, Rochester, MN 55905., and Victor M. Montori, MD, MScFrom Vall d'Hebron Hospital, CIBER de Epidemiología y Salud Pública, 08035 Barcelona, Spain; McMaster University, Hamilton, Ontario L8N 3Z5, Canada; Iberoamerican Cochrane Center, Hospital de la Santa Creu i Sant Pau, CIBER de Epidemiología y Salud Pública, 08025 Barcelona, Spain; and Mayo Clinic, Rochester, MN 55905.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-150-8-200904210-00016 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:In their article, Lim and colleagues (1) contribute important insights into the use of composite outcomes in clinical trials. Their article contributes to a debate initiated a few years ago (2–6). Confirming our earlier work (5), the study by Lim and colleagues shows that composite outcomes in cardiovascular trials are common, components usually vary in importance to patients, events occur more frequently in the less important components than in the most important ones, and less important outcomes (such as angina) usually drive the effect of the therapy on the composite.What new contributions do Lim and colleagues ...References1. Lim E, Brown A, Helmy A, Mussa S, Altman DG. Composite outcomes in cardiovascular research: a survey of randomized trials. Ann Intern Med. 2008;149:612-7. [PMID: 18981486] LinkGoogle Scholar2. Freemantle N, Calvert M, Wood J, Eastaugh J, Griffin C. Composite outcomes in randomized trials: greater precision but with greater uncertainty? JAMA. 2003;289:2554-9. [PMID: 12759327] CrossrefMedlineGoogle Scholar3. Montori VM, Permanyer-Miralda G, Ferreira-González I, Busse JW, Pacheco-Huergo V, Bryant D, et al. Validity of composite end points in clinical trials. BMJ. 2005;330:594-6. [PMID: 15761002] CrossrefMedlineGoogle Scholar4. Ferreira-González I, Permanyer-Miralda G, Busse JW, Bryant DM, Montori VM, Alonso-Coello P, et al. Methodologic discussions for using and interpreting composite endpoints are limited, but still identify major concerns. J Clin Epidemiol. 2007;60:651-7; discussion 658-62. [PMID: 17573977] Google Scholar5. Ferreira-González I, Busse JW, Heels-Ansdell D, Montori VM, Akl EA, Bryant DM, et al. Problems with use of composite end points in cardiovascular trials: systematic review of randomised controlled trials. BMJ. 2007;334:786. [PMID: 17403713] CrossrefMedlineGoogle Scholar6. Guyatt GH, Montori VM, Ferreira-Gonzalez I, Busse JW, Schunemann HJ, Jaeschke R, et al. Composite endpoints.. In: Guyatt GH, Rennie D, Meade MO, Cook DJ, eds. Users' Guides to the Medical Literature. 2nd ed. Columbus, OH: McGraw-Hill; 2008:237-48. Google Scholar Author, Article, and Disclosure InformationAuthors: Ignacio Ferreira-Gonzalez, MD, PhD; Gaieta Permanyer-Miralda, MD, PhD; Jason W. Busse, MSc; P. J. Devereaux, MD, BSc, PhD; Gordon H. Guyatt, MD, MSc; Pablo Alonso-Coello, MD; Victor M. Montori, MD, MScAffiliations: From Vall d'Hebron Hospital, CIBER de Epidemiología y Salud Pública, 08035 Barcelona, Spain; McMaster University, Hamilton, Ontario L8N 3Z5, Canada; Iberoamerican Cochrane Center, Hospital de la Santa Creu i Sant Pau, CIBER de Epidemiología y Salud Pública, 08025 Barcelona, Spain; and Mayo Clinic, Rochester, MN 55905.Disclosures: None disclosed. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoComposite Outcomes in Cardiovascular Research: A Survey of Randomized Trials Eric Lim , Adam Brown , Adel Helmy , Shafi Mussa , and Douglas G. 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Part 1The Need to Standardize Functional Outcome in Randomized Trials of Hip FractureMagnitude of effects in clinical trials published in high-impact general medical journalsDesign and Analysis of Studies with Binary- Event Composite EndpointsDelphi-Consensus Weights for Ischemic and Bleeding Events to Be Included in a Composite Outcome for RCTs in Thrombosis PreventionFactors affecting power of tests for multiple binary outcomesOutcome Measures, Interim Analyses, and Bayesian Approaches to Randomized Trials 21 April 2009Volume 150, Issue 8Page: 566-567KeywordsAnginaCardiovascular therapyClinical trialsConflicts of interestMotivation ePublished: 21 April 2009 Issue Published: 21 April 2009 Copyright & PermissionsCopyright © 2009 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...