title: Current challenges for clinical trials of cardiovascular medical devices.
abstract: Several features of cardiovascular devices raise considerations for clinical trial conduct. Prospective, randomized, controlled trials remain the highest quality evidence for safety and effectiveness assessments, but, for instance, blinding may be challenging. In order to avoid bias and not confound data interpretation, the use of objective endpoints and blinding patients, study staff, core labs, and clinical endpoint committees to treatment assignment are helpful approaches. Anticipation of potential bias should be considered and planned for prospectively in a cardiovascular device trial. Prospective, single-arm studies (often referred to as registry studies) can provide additional data in some cases. They are subject to selection bias even when carefully designed; thus, they are generally not acceptable as the sole basis for pre-market approval of high risk cardiovascular devices. However, they complement the evidence base and fill the gaps unanswered by randomized trials. Registry studies present device safety and effectiveness in day-to-day clinical practice settings and detect rare adverse events in the post-market period. No single research design will be appropriate for every cardiovascular device or target patient population. The type of trial, appropriate control group, and optimal length of follow-up will depend on the specific device, its potential clinical benefits, the target patient population and the existence (or lack) of effective therapies, and its anticipated risks. Continued efforts on the part of investigators, the device industry, and government regulators are needed to reach the optimal approach for evaluating the safety and performance of innovative devices for the treatment of cardiovascular disease.
authors.affiliation: INSERM, Centre d'Investigation Clinique 9501 Unité 1116, Centre Hospitalier Universitaire, France; Department of Cardiology, Université de Lorraine, Nancy, France. Electronic address: f.zannad@chu-nancy.fr.
authors.forename: Faiez
authors.initials: F
authors.lastname: Zannad
authors.affiliation: Campbell University College of Pharmacy and Health Sciences, Buies Creek, NC, USA.
authors.forename: Wendy Gattis
authors.initials: WG
authors.lastname: Stough
authors.affiliation: Department of Medicine, Division of Cardiology, Montefiore Medical Center, Bronx, NY, USA.
authors.forename: Ileana L
authors.initials: IL
authors.lastname: Piña
authors.affiliation: Cardiovascular Research Foundation, New York, NY, USA; Mount Sinai Medical Center, New York, NY, USA.
authors.forename: Roxana
authors.initials: R
authors.lastname: Mehran
authors.affiliation: Division of Cardiovascular Medicine, The Ohio State University, Columbus, OH, USA.
authors.forename: William T
authors.initials: WT
authors.lastname: Abraham
authors.affiliation: Applied Cachexia Research, Department of Cardiology, Charité Medical School, Campus Virchow-Klinikum, Berlin, Germany.
authors.forename: Stefan D
authors.initials: SD
authors.lastname: Anker
authors.affiliation: Department of Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Gaetano M
authors.initials: GM
authors.lastname: De Ferrari
authors.affiliation: U.S. Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Farb
authors.affiliation: National Heart Lung and Blood Institute, Bethesda, MD, USA.
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Geller
authors.affiliation: CVRx, Inc., Minneapolis, MN, USA.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Kieval
authors.affiliation: Department of Cardiology, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Linde
authors.affiliation: University of California, San Francisco, CA, USA.
authors.forename: Rita F
authors.initials: RF
authors.lastname: Redberg
authors.affiliation: Boston Scientific Corporation, St. Paul, MN, USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Stein
authors.affiliation: Medtronic, Tolochenaz, Switzerland.
authors.forename: Alphons
authors.initials: A
authors.lastname: Vincent
authors.affiliation: ResMed Science Center, ResMed, Martinsried, Germany; Sleep and Ventilation Center Blaubeuren/Lung Center, Ulm, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Woehrle
authors.affiliation: Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Pocock
mesh_terms: D035843:Biomedical Research / Q000592:standards / Q000639:trends; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000628:therapy*; D018795:Device Approval / Q000592:standards; D004867:Equipment Design / Q000592:standards / Q000639:trends; D006801:Humans; D062307:Medical Device Legislation / Q000639:trends*; D011358:Product Surveillance, Postmarketing / Q000592:standards / Q000639:trends*; D016032:Randomized Controlled Trials as Topic
keywords: Cardiovascular devices; Clinical trial; Device approval; Research design