title: Designing effective drug and device development programs for hospitalized heart failure: a proposal for pretrial registries.
abstract: Recent international phase III clinical trials of novel therapies for hospitalized heart failure (HHF) have failed to improve the unacceptably high postdischarge event rate. These large studies have demonstrated notable geographic and site-specific variation in patient profiles and enrollment. Possible contributors to the lack of success in HHF outcome trials include challenges in selecting clinical sites capable of (1) providing adequate numbers of appropriately selected patients and (2) properly executing the study protocol. We propose a "pretrial registry" as a novel tool for improving the efficiency and quality of international HHF trials by focusing on the selection and cultivation of high-quality sites. A pretrial registry may help assess a site's ability to achieve adequate enrollment of the target patient population, integrate protocol requirements into clinical workflow, and accomplish appropriate follow-up. Although such a process would be associated with additional upfront resource investment, this appropriation may be modest in comparison with the downstream costs associated with maintenance of poorly performing sites, failed clinical trials, and the global health and economic burden of HHF. This review is based on discussions between scientists, clinical trialists, and regulatory representatives regarding methods for improving international HHF trials that took place at the United States Food and Drug Administration on January 12th, 2012.
authors: Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, IL.
authors: Stephen J
authors: SJ
authors: Greene
authors: Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, IL.
authors: Ami N
authors: AN
authors: Shah
authors: Division of Cardiology, Emory University, Atlanta, GA.
authors: Javed
authors: J
authors: Butler
authors: Department of Medicine, Stanford University School of Medicine, Stanford, CA.
authors: Andrew P
authors: AP
authors: Ambrosy
authors: Department of Innovative Clinical Trials, University Medical Centre Göttingen, Göttingen, Germany.
authors: Stefan D
authors: SD
authors: Anker
authors: Institute of Emergency for Cardiovascular Diseases Prof. C.C.Iliescu, University of Medicine Carol Davila, Bucuresti, Romania.
authors: Ovidiu
authors: O
authors: Chioncel
authors: Department of Emergency Medicine, Vanderbilt University, Nashville, TN.
authors: Sean P
authors: SP
authors: Collins
authors: Department of Cardiology, Witten University, Witten, Germany; Global Drug Discovery, Clinical Sciences, Bayer Pharma AG, Berlin, Germany.
authors: Wilfried
authors: W
authors: Dinh
authors: Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD.
authors: Preston M
authors: PM
authors: Dunnmon
authors: Ahmanson-UCLA Cardiomyopathy Center, Los Angeles, CA.
authors: Gregg C
authors: GC
authors: Fonarow
authors: National University Health System, Singapore.
authors: Carolyn S P
authors: CS
authors: Lam
authors: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC.
authors: Robert J
authors: RJ
authors: Mentz
authors: Department of Cardiology, Graz, Austria.
authors: Burkert
authors: B
authors: Pieske
authors: Global Clinical Development, Bayer Pharma AG, Berlin, Germany.
authors: Lothar
authors: L
authors: Roessig
authors: Division of Cardiology, IRCC San Raffaele, Rome, Italy.
authors: Giuseppe M C
authors: GM
authors: Rosano
authors: Internal Medicine, Cardiology, and Intensive Care Medicine, Nippon Medical School Musashi-Kosugi Hospital, Kanagawa, Japan.
authors: Naoki
authors: N
authors: Sato
authors: Department of Medicine, Massachusetts General Hospital, Boston, MA.
authors: Muthiah
authors: M
authors: Vaduganathan
authors: Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, IL. Electronic address: m-gheorghiade@northwestern.edu.
authors: Mihai
authors: M
authors: Gheorghiade
mesh_terms: D002985:Clinical Protocols; D017322:Clinical Trials, Phase II as Topic / Q000592:standards / Q000706:statistics & numerical data; D017326:Clinical Trials, Phase III as Topic; D014943:Global Health; D019983:Guideline Adherence; D006333:Heart Failure / Q000188:drug therapy / Q000401:mortality / Q000628:therapy*; D006760:Hospitalization; D006801:Humans; D015337:Multicenter Studies as Topic; D012042:Registries; D035703:Therapies, Investigational; D016896:Treatment Outcome