title: Traditional and new composite endpoints in heart failure clinical trials: facilitating comprehensive efficacy assessments and improving trial efficiency.
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.
authors.affiliation: Innovative Clinical Trials, Depar tment of Cardiology & Pneumology, University Medical Center Göttingen (UMG), Germany.
authors.forename: Stefan D
authors.initials: SD
authors.lastname: Anker
authors.affiliation: Bayer Pharma AG, Berlin, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schroeder
authors.affiliation: Department of Cardiology B, Oslo University Hospital Ulleval and University of Oslo, Norway.
authors.forename: Dan
authors.initials: D
authors.lastname: Atar
authors.affiliation: Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Jeroen J
authors.initials: JJ
authors.lastname: Bax
authors.affiliation: Unit of Cardiology, Hospital of Desenzano del Garda, Desenzano del Garda, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Ceconi
authors.affiliation: National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Martin R
authors.initials: MR
authors.lastname: Cowie
authors.affiliation: GlaxoSmithKline, Middlesex, UK.
authors.forename: Adam
authors.initials: A
authors.lastname: Crisp
authors.affiliation: Servier International, Paris, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Dominjon
authors.affiliation: Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK.
authors.forename: Ian
authors.initials: I
authors.lastname: Ford
authors.affiliation: University of Giessen and Marburg Lung Center, UGMLC [member of the German Center for Lung Research (DZL)], Giessen, Germany.|Kerckhoff-Klinik Bad Nauheim, Germany.|Imperial College London, UK.
authors.forename: Hossein-Ardeschir
authors.initials: HA
authors.lastname: Ghofrani
authors.affiliation: Boehringer-Ingelheim GmBH & Co. KG, Ingelheim, Germany.
authors.forename: Savion
authors.initials: S
authors.lastname: Gropper
authors.affiliation: Department of Electrophysiology, Heart Center, University of Leipzig, Leipzig, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Hindricks
authors.affiliation: Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Hlatky
authors.affiliation: Independent Biostatistician, Minneapolis, MN, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Holcomb
authors.affiliation: Amgen, Inc., Thousand Oaks, CA, USA.
authors.forename: Narimon
authors.initials: N
authors.lastname: Honarpour
authors.affiliation: Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: J Wouter
authors.initials: JW
authors.lastname: Jukema
authors.affiliation: Pfizer, Inc., Cambridge, MA, USA.
authors.forename: Albert M
authors.initials: AM
authors.lastname: Kim
authors.affiliation: Bayer Pharma AG, Berlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Kunz
authors.affiliation: Novartis Pharmaceuticals, East Hanover, NJ, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Lefkowitz
authors.affiliation: Servier International, Paris, France.
authors.forename: Chantal
authors.initials: C
authors.lastname: Le Floch
authors.affiliation: Department of Cardiology, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Landmesser
authors.affiliation: King's College Hospital, London, UK.
authors.forename: Theresa A
authors.initials: TA
authors.lastname: McDonagh
authors.affiliation: BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.
authors.forename: John J
authors.initials: JJ
authors.lastname: McMurray
authors.affiliation: Semmelweis University Heart and Vascular Center, Budapest, Hungary.
authors.forename: Bela
authors.initials: B
authors.lastname: Merkely
authors.affiliation: Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Milton
authors.initials: M
authors.lastname: Packer
authors.affiliation: United Kingdom Medicines and Healthcare Products Regulatory Agency, London, UK.
authors.forename: Krishna
authors.initials: K
authors.lastname: Prasad
authors.affiliation: Pfizer, Inc., Cambridge, MA, USA.
authors.forename: James
authors.initials: J
authors.lastname: Revkin
authors.affiliation: IRCCS San Raffaele Hospital Roma, Rome, Italy.|Cardiovascular and Cell Sciences Institute, St. George's University of London, London, UK.
authors.forename: Giuseppe M C
authors.initials: GM
authors.lastname: Rosano
authors.affiliation: Amgen, Inc., Thousand Oaks, CA, USA.
authors.forename: Ransi
authors.initials: R
authors.lastname: Somaratne
authors.affiliation: Campbell University College of Pharmacy and Health Sciences, NC, USA.
authors.forename: Wendy Gattis
authors.initials: WG
authors.lastname: Stough
authors.affiliation: University of Groningen, Groningen, The Netherlands.
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Voors
authors.affiliation: Department of Cardiology, Heart Failure Clinic and Transplantation, University Heart Center Zurich, Zurich, Switzerland.
authors.forename: Frank
authors.initials: F
authors.lastname: Ruschitzka
mesh_terms: D000203:Activities of Daily Living; D002423:Cause of Death; D002986:Clinical Trials as Topic; D006333:Heart Failure / Q000628:therapy*; D006760:Hospitalization; D006801:Humans; D009026:Mortality; D017063:Outcome Assessment, Health Care; D011788:Quality of Life; D016896:Treatment Outcome
keywords: Clinical trial; Endpoint determination; Heart failure; Surrogate endpoints