title: Premature Discontinuation of Randomized Trials in Critical and Emergency Care: A Retrospective Cohort Study.
abstract: OBJECTIVE
  Randomized clinical trials that enroll patients in critical or emergency care (acute care) setting are challenging because of narrow time windows for recruitment and the inability of many patients to provide informed consent. To assess the extent that recruitment challenges lead to randomized clinical trial discontinuation, we compared the discontinuation of acute care and nonacute care randomized clinical trials.
  
  
  METHODS
  Retrospective cohort of 894 randomized clinical trials approved by six institutional review boards in Switzerland, Germany, and Canada between 2000 and 2003.
  
  
  METHODS
  Randomized clinical trials involving patients in an acute or nonacute care setting.
  
  
  METHODS
  We recorded trial characteristics, self-reported trial discontinuation, and self-reported reasons for discontinuation from protocols, corresponding publications, institutional review board files, and a survey of investigators.
  
  
  RESULTS
  Of 894 randomized clinical trials, 64 (7%) were acute care randomized clinical trials (29 critical care and 35 emergency care). Compared with the 830 nonacute care randomized clinical trials, acute care randomized clinical trials were more frequently discontinued (28 of 64, 44% vs 221 of 830, 27%; p = 0.004). Slow recruitment was the most frequent reason for discontinuation, both in acute care (13 of 64, 20%) and in nonacute care randomized clinical trials (7 of 64, 11%). Logistic regression analyses suggested the acute care setting as an independent risk factor for randomized clinical trial discontinuation specifically as a result of slow recruitment (odds ratio, 4.00; 95% CI, 1.72-9.31) after adjusting for other established risk factors, including nonindustry sponsorship and small sample size.
  
  
  CONCLUSIONS
  Acute care randomized clinical trials are more vulnerable to premature discontinuation than nonacute care randomized clinical trials and have an approximately four-fold higher risk of discontinuation due to slow recruitment. These results highlight the need for strategies to reliably prevent and resolve slow patient recruitment in randomized clinical trials conducted in the critical and emergency care setting.
authors.affiliation: 1Department of Clinical Research, Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland.2Department of Medicine, Academy of Swiss Insurance Medicine, University Hospital Basel, Basel, Switzerland.3Cochrane Switzerland, Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital, Lausanne, Switzerland.4Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.5Department of Medicine, McMaster University, Hamilton, Ontario, Canada.6German Cochrane Centre, Medical Center-University of Freiburg, Freiburg, Germany.7Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland.8Centre de Recherche Clinique du Centre Hospitalier Universitaire de Sherbrooke, Université de Sherbrooke, Sherbrooke, Canada.9Department of Health and Society, Austrian Federal Institute for Health Care, Vienna, Austria.10Departments of Urology and Public Health, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.11Department of Internal Medicine, Pontificia Universidad Catolica de Chile, Santiago, Chile.12Evidence-Based Dentistry Unit, Faculty of Dentistry, Universidad de Chile, Santiago, Chile.13Michael G. DeGroote Institute for Infectious Diseases Research, McMaster University, Hamilton, Ontario, Canada.14Department of Internal Medicine, American University of Beirut, Beirut, Lebanon.15Department of Medicine, State University of New York at Buffalo, Buffalo, NY.16Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, Chengdu, China.17Department of Neonatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.18Department of Anesthesia, McMaster University, Hamilton, Ontario, Canada.19Michael G. DeGroote Institute for Pain Research and Care, McMaster University, Hamilton, Ontario, Canada.20Epidemiology Unit, Department of Cardiology, Vall d'Hebron Hospital and CIBER de Epidem
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mesh_terms: D002170:Canada; D015331:Cohort Studies; D057239:Early Termination of Clinical Trials / Q000639:trends*; D004638:Emergency Treatment; D005858:Germany; D006801:Humans; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*; D012189:Retrospective Studies; D013557:Switzerland