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Original Investigation
March 12, 2014

Prevalence, Characteristics, and Publication of Discontinued Randomized Trials

Author Affiliations
  • 1Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital of Basel, Basel, Switzerland
  • 2Cochrane Switzerland, Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital, Lausanne, Switzerland
  • 3Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada
  • 4German Cochrane Centre, Institute of Medical Biometry and Medical Informatics, Freiburg University Medical Center, Freiburg, Germany
  • 5Institute of Social and Preventive Medicine, University of Zurich, Zurich, Switzerland
  • 6Center for Pediatric Clinical Studies, Department of Neonatology, University Children’s Hospital, Tuebingen, Germany
  • 7Epidemiology Unit, Department of Cardiology, Vall d’Hebron Hospital and CIBER de Epidemiología y Salud Publica (CIBERESP), Barcelona, Spain
  • 8Centre de Recherche Clinique Étienne-Le Bel and Department of Medicine, Université de Sherbrooke, Sherbrooke, Canada
  • 9IRCCS Orthopedic Institute Galeazzi, Milano, Italy
  • 10Department of Surgery, University Hospital Basel, Basel, Switzerland
  • 11Department of Medicine, Innlandet Hospital Trust-Division Gjøvik, Oppland, Norway
  • 12Department of Anesthesia and Pain Medicine, Hospital for Sick Children, Toronto, Ontario, Canada
  • 13Institute of Nuclear Medicine, University Hospital Bern, Bern, Switzerland
  • 14Department of Medicine, McMaster University, Hamilton, Ontario, Canada
  • 15Department of Urology, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland
  • 16Department of Internal Medicine, Pontificia Universidad Catolica de Chile, Santiago
  • 17Department of Family Medicine, McMaster University, Hamilton, Ontario, Canada
  • 18Department of Internal Medicine, American University of Beirut, Beirut, Lebanon
  • 19Department of Medicine, State University of New York at Buffalo, Buffalo, New York
  • 20Department of Anesthesia, McMaster University, Hamilton, Ontario, Canada
  • 21Stanford Prevention Research Center, Stanford University, Stanford, California
  • 22Academy of Swiss Insurance Medicine, University Hospital of Basel, Basel, Switzerland
  • 23Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, Chengdu, China
  • 24Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
  • 25Evidence-Based Dentistry Unit, Faculty of Dentistry, Universidad de Chile, Santiago
  • 26Michael G. DeGroote Institute for Infectious Diseases Research, McMaster University, Hamilton, Ontario, Canada
  • 27Michael G. DeGroote Institute for Pain Research and Care, McMaster University, Hamilton, Ontario, Canada
JAMA. 2014;311(10):1045-1052. doi:10.1001/jama.2014.1361
Abstract

Importance  The discontinuation of randomized clinical trials (RCTs) raises ethical concerns and often wastes scarce research resources. The epidemiology of discontinued RCTs, however, remains unclear.

Objectives  To determine the prevalence, characteristics, and publication history of discontinued RCTs and to investigate factors associated with RCT discontinuation due to poor recruitment and with nonpublication.

Design and Setting  Retrospective cohort of RCTs based on archived protocols approved by 6 research ethics committees in Switzerland, Germany, and Canada between 2000 and 2003. We recorded trial characteristics and planned recruitment from included protocols. Last follow-up of RCTs was April 27, 2013.

Main Outcomes and Measures  Completion status, reported reasons for discontinuation, and publication status of RCTs as determined by correspondence with the research ethics committees, literature searches, and investigator surveys.

Results  After a median follow-up of 11.6 years (range, 8.8-12.6 years), 253 of 1017 included RCTs were discontinued (24.9% [95% CI, 22.3%-27.6%]). Only 96 of 253 discontinuations (37.9% [95% CI, 32.0%-44.3%]) were reported to ethics committees. The most frequent reason for discontinuation was poor recruitment (101/1017; 9.9% [95% CI, 8.2%-12.0%]). In multivariable analysis, industry sponsorship vs investigator sponsorship (8.4% vs 26.5%; odds ratio [OR], 0.25 [95% CI, 0.15-0.43]; P < .001) and a larger planned sample size in increments of 100 (−0.7%; OR, 0.96 [95% CI, 0.92-1.00]; P = .04) were associated with lower rates of discontinuation due to poor recruitment. Discontinued trials were more likely to remain unpublished than completed trials (55.1% vs 33.6%; OR, 3.19 [95% CI, 2.29-4.43]; P < .001).

Conclusions and Relevance  In this sample of trials based on RCT protocols from 6 research ethics committees, discontinuation was common, with poor recruitment being the most frequently reported reason. Greater efforts are needed to ensure the reporting of trial discontinuation to research ethics committees and the publication of results of discontinued trials.

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