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      Competing risks analyses: objectives and approaches

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          Abstract

          Studies in cardiology often record the time to multiple disease events such as death, myocardial infarction, or hospitalization. Competing risks methods allow for the analysis of the time to the first observed event and the type of the first event. They are also relevant if the time to a specific event is of primary interest but competing events may preclude its occurrence or greatly alter the chances to observe it. We give a non-technical overview of competing risks concepts for descriptive and regression analyses. For descriptive statistics, the cumulative incidence function is the most important tool. For regression modelling, we introduce regression models for the cumulative incidence function and the cause-specific hazard function, respectively. We stress the importance of choosing statistical methods that are appropriate if competing risks are present. We also clarify the role of competing risks for the analysis of composite endpoints.

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          Composite outcomes in randomized trials: greater precision but with greater uncertainty?

          Composite outcomes, in which multiple end points are combined, are frequently used as primary outcome measures in randomized trials and are often associated with increased statistical efficiency. However, such measures may prove challenging for the interpretation of results. In this article, we examine the use of composite outcomes in major clinical trials, assess the arguments for and against them, and provide guidance on their application and reporting. To assess incidence and quality of reporting, we systematically reviewed the use of composite end points in clinical trials in Annals of Internal Medicine, BMJ, Circulation, Clinical Infectious Diseases, Journal of the American College of Cardiology, JAMA, Lancet, New England Journal of Medicine, and Stroke from 1997 through 2001 using a sensitive search strategy. We selected for review 167 original reports of randomized trials (with a total of 300 276 patients) that included a composite primary outcome that incorporated all-cause mortality. Sixty-three trials (38%) were neutral both for the primary end point and the mortality component. Sixty trials (36%) reported significant results for the primary outcome measure but not for the mortality component. Only 6 trials (4%) were significant for the mortality component but not for the primary composite outcome, whereas 19 trials (11%) were significant for both. Twenty-two trials (13%) were inadequately reported. Our review suggests that reporting of composite outcomes is generally inadequate, implying that the results apply to the individual components of the composite outcome rather than only to the overall composite. Current guidelines for the undertaking and reporting of clinical trials could be revised to reflect the common use of composite outcomes in clinical trials.
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            Survival probabilities (the Kaplan-Meier method).

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              Competing risks and the clinical community: irrelevance or ignorance?

              Life expectancy has dramatically increased in industrialized nations over the last 200 hundred years. The aging of populations carries over to clinical research and leads to an increasing representation of elderly and multimorbid individuals in study populations. Clinical research in these populations is complicated by the fact that individuals are likely to experience several potential disease endpoints that prevent some disease-specific endpoint of interest from occurrence. Large developments in competing risks methodology have been achieved over the last decades, but we assume that recognition of competing risks in the clinical community is still marginal. It is the aim of this article to address translational aspects of competing risks to the clinical community. We describe clinical populations where competing risks issues may arise. We then discuss the importance of agreement between the competing risks methodology and the study aim, in particular the distinction between etiologic and prognostic research questions. In a review of 50 clinical studies performed in individuals susceptible to competing risks published in high-impact clinical journals, we found competing risks issues in 70% of all articles. Better recognition of issues related to competing risks and of statistical methods that deal with competing risks in accordance with the aim of the study is needed. Copyright © 2011 John Wiley & Sons, Ltd.
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                Author and article information

                Journal
                Eur Heart J
                Eur. Heart J
                eurheartj
                ehj
                European Heart Journal
                Oxford University Press
                0195-668X
                1522-9645
                07 November 2014
                07 April 2014
                07 April 2014
                : 35
                : 42 , Focus Issue on Epidemiology of Cardiovascular Disease
                : 2936-2941
                Affiliations
                [1 ]Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme , Ho Chi Minh City, Vietnam
                [2 ]Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford , Oxford, UK
                [3 ]Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel , Basel, Switzerland
                [4 ]ERA–EDTA Registry, Department of Medical Informatics, Academic Medical Center, University of Amsterdam , Amsterdam, The Netherlands
                [5 ]Department of Cardiology, University Hospital Basel , Basel, Switzerland
                [6 ]Centre INSERM U897 Epidemiology-Biostatistics, ISPED, University of Bordeaux , Bordeaux, France
                [7 ]Section for Clinical Biometrics, Center for Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna , Vienna, Austria
                Author notes
                [* ]Corresponding author. Tel: +84 839237954, Fax: +84 839238904, Email: mwolbers@ 123456oucru.org
                Article
                ehu131
                10.1093/eurheartj/ehu131
                4223609
                24711436
                332219b9-4578-455e-9fc5-60502f877d22
                © The Author 2014. Published by Oxford University Press on behalf of the European Society of Cardiology.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 27 January 2014
                : 25 February 2014
                : 12 March 2014
                Categories
                Reviews
                Statistical Tutorials

                Cardiovascular Medicine
                multiple failure causes,combined endpoints,cumulative incidence function,cause-specific hazard function,survival analysis

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