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Traditional and new composite endpoints in heart failure clinical trials: facilitating comprehensive efficacy assessments and improving trial efficiency
Authors:Stefan D Anker  Stefan Schroeder  Dan Atar  Jeroen J Bax  Claudio Ceconi  Martin R Cowie  Adam Crisp  Fabienne Dominjon  Ian Ford  Hossein‐Ardeschir Ghofrani  Savion Gropper  Gerhard Hindricks  Mark A Hlatky  Richard Holcomb  Narimon Honarpour  J Wouter Jukema  Albert M Kim  Michael Kunz  Martin Lefkowitz  Chantal Le Floch  Ulf Landmesser  Theresa A McDonagh  John J McMurray  Bela Merkely  Milton Packer  Krishna Prasad  James Revkin  Giuseppe MC Rosano  Ransi Somaratne  Wendy Gattis Stough  Adriaan A Voors  Frank Ruschitzka
Institution:1. Bayer Healthcare, Berlin, Germany;2. Department of Cardiology B, Oslo University Hospital Ulleval and University of Oslo, Norway;3. Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands;4. Unit of Cardiology, Hospital of Desenzano del Garda, Desenzano del Garda, Italy;5. National Heart and Lung Institute, Imperial College London, London, UK;6. GlaxoSmithKline, Middlesex, UK;7. Servier International, Paris, France;8. Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK;9. University of Giessen and Marburg Lung Center, UGMLC [member of the German Center for Lung Research (DZL)], Giessen, Germany;10. Kerckhoff‐Klinik Bad Nauheim, Germany;11. Imperial College London, UK;12. Boehringer‐Ingelheim GmBH & Co. KG, Ingelheim, Germany;13. Department of Electrophysiology, Heart Center, University of Leipzig, Leipzig, Germany;14. Stanford University School of Medicine, Stanford, CA, USA;15. Independent Biostatistician, Minneapolis, MN, USA;16. Amgen, Inc., Thousand Oaks, CA, USA;17. Pfizer, Inc., Cambridge, MA, USA;18. Novartis Pharmaceuticals, East Hanover, NJ, USA;19. Department of Cardiology, Charité Universit?tsmedizin Berlin, Berlin, Germany;20. King's College Hospital, London, UK;21. BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, UK;22. Semmelweis University Heart and Vascular Center, Budapest, Hungary;23. Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA;24. United Kingdom Medicines and Healthcare Products Regulatory Agency, London, UK;25. IRCCS San Raffaele Hospital Roma, Rome, Italy;26. Cardiovascular and Cell Sciences Institute, St. George's University of London, London, UK;27. Campbell University College of Pharmacy and Health Sciences, NC, USA;28. University of Groningen, Groningen, The Netherlands;29. Department of Cardiology, Heart Failure Clinic and Transplantation, University Heart Center Zurich, Zurich, Switzerland
Abstract:Composite endpoints are commonly used as the primary measure of efficacy in heart failure clinical trials to assess the overall treatment effect and to increase the efficiency of trials. Clinical trials still must enrol large numbers of patients to accrue a sufficient number of outcome events and have adequate power to draw conclusions about the efficacy and safety of new treatments for heart failure. Additionally, the societal and health system perspectives on heart failure have raised interest in ascertaining the effects of therapy on outcomes such as repeat hospitalization and the patient's burden of disease. Thus, novel methods for using composite endpoints in clinical trials (e.g. clinical status composite endpoints, recurrent event analyses) are being applied in current and planned trials. Endpoints that measure functional status or reflect the patient experience are important but used cautiously because heart failure treatments may improve function yet have adverse effects on mortality. This paper discusses the use of traditional and new composite endpoints, identifies qualities of robust composites, and outlines opportunities for future research.
Keywords:Heart failure  Clinical trial  Endpoint determination  Surrogate endpoints
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