title: Prevalence, characteristics, and publication of discontinued randomized trials.
abstract: OBJECTIVE
  The discontinuation of randomized clinical trials (RCTs) raises ethical concerns and often wastes scarce research resources. The epidemiology of discontinued RCTs, however, remains unclear.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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 Discontinued trials were more likely to remain unpublished than completed trials (55.1% vs 33.6%; OR, 3.19 [95% CI, 2.29-4.43]; P 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
  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.
authors.affiliation: Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital of Basel, Basel, Switzerland.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Kasenda
authors.affiliation: Cochrane Switzerland, Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: Erik
authors.initials: E
authors.lastname: von Elm
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada14Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: John
authors.initials: J
authors.lastname: You
authors.affiliation: German Cochrane Centre, Institute of Medical Biometry and Medical Informatics, Freiburg University Medical Center, Freiburg, Germany.
authors.forename: Anette
authors.initials: A
authors.lastname: Blümle
authors.affiliation: Institute of Social and Preventive Medicine, University of Zurich, Zurich, Switzerland.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Tomonaga
authors.affiliation: Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital of Basel, Basel, Switzerland.
authors.forename: Ramon
authors.initials: R
authors.lastname: Saccilotto
authors.affiliation: Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital of Basel, Basel, Switzerland.
authors.forename: Alain
authors.initials: A
authors.lastname: Amstutz
authors.affiliation: Cochrane Switzerland, Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: Theresa
authors.initials: T
authors.lastname: Bengough
authors.affiliation: German Cochrane Centre, Institute of Medical Biometry and Medical Informatics, Freiburg University Medical Center, Freiburg, Germany.
authors.forename: Joerg J
authors.initials: JJ
authors.lastname: Meerpohl
authors.affiliation: Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital of Basel, Basel, Switzerland.
authors.forename: Mihaela
authors.initials: M
authors.lastname: Stegert
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada15Department of Urology, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland.
authors.forename: Kari A O
authors.initials: KA
authors.lastname: Tikkinen
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada16Department of Internal Medicine, Pontificia Universidad Catolica de Chile, Santiago.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Neumann
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada25Evidence-Based Dentistry Unit, Faculty of Dentistry, Universidad de Chile, Santiago.
authors.forename: Alonso
authors.initials: A
authors.lastname: Carrasco-Labra
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada17Department of Family Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Markus
authors.initials: M
authors.lastname: Faulhaber
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Sohail M
authors.initials: SM
authors.lastname: Mulla
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada26Michael G. DeGroote Institute for Infectious Diseases Research, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Dominik
authors.initials: D
authors.lastname: Mertz
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada18Department of Internal Medicine, American University of Beirut, Beirut, Lebanon19Department of Medicine, State University of New York at Buffalo, Buffal.
authors.forename: Elie A
authors.initials: EA
authors.lastname: Akl
authors.affiliation: Center for Pediatric Clinical Studies, Department of Neonatology, University Children's Hospital, Tuebingen, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Bassler
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada20Department of Anesthesia, McMaster University, Hamilton, Ontario, Canada27Michael G. DeGroote Institute for Pain Research and Care, McMaster University.
authors.forename: Jason W
authors.initials: JW
authors.lastname: Busse
authors.affiliation: Epidemiology Unit, Department of Cardiology, Vall d'Hebron Hospital and CIBER de Epidemiología y Salud Publica (CIBERESP), Barcelona, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Ferreira-González
authors.affiliation: Centre de Recherche Clinique Étienne-Le Bel and Department of Medicine, Université de Sherbrooke, Sherbrooke, Canada.
authors.forename: Francois
authors.initials: F
authors.lastname: Lamontagne
authors.affiliation: Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital of Basel, Basel, Switzerland.
authors.forename: Alain
authors.initials: A
authors.lastname: Nordmann
authors.affiliation: Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital of Basel, Basel, Switzerland13Institute of Nuclear Medicine, University Hospital Bern, Bern, Switzerland.
authors.forename: Viktoria
authors.initials: V
authors.lastname: Gloy
authors.affiliation: Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital of Basel, Basel, Switzerland.
authors.forename: Heike
authors.initials: H
authors.lastname: Raatz
authors.affiliation: IRCCS Orthopedic Institute Galeazzi, Milano, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moja
authors.affiliation: Department of Surgery, University Hospital Basel, Basel, Switzerland.
authors.forename: Rachel
authors.initials: R
authors.lastname: Rosenthal
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada20Department of Anesthesia, McMaster University, Hamilton, Ontario, Canada21Stanford Prevention Research Center, Stanford University, Stanford, California.
authors.forename: Shanil
authors.initials: S
authors.lastname: Ebrahim
authors.affiliation: Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital of Basel, Basel, Switzerland22Academy of Swiss Insurance Medicine, University Hospital of Basel, Basel, Switzerland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schandelmaier
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada23Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Sun
authors.initials: S
authors.lastname: Xin
authors.affiliation: Department of Medicine, Innlandet Hospital Trust-Division Gjøvik, Oppland, Norway.
authors.forename: Per O
authors.initials: PO
authors.lastname: Vandvik
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada12Department of Anesthesia and Pain Medicine, Hospital for Sick Children, Toronto, Ontario, Canada24Institute of Health Policy, Management and Evaluation.
authors.forename: Bradley C
authors.initials: BC
authors.lastname: Johnston
authors.affiliation: Institute of Nuclear Medicine, University Hospital Bern, Bern, Switzerland.
authors.forename: Martin A
authors.initials: MA
authors.lastname: Walter
authors.affiliation: Cochrane Switzerland, Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: Bernard
authors.initials: B
authors.lastname: Burnand
authors.affiliation: Institute of Social and Preventive Medicine, University of Zurich, Zurich, Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Schwenkglenks
authors.affiliation: Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital of Basel, Basel, Switzerland.
authors.forename: Lars G
authors.initials: LG
authors.lastname: Hemkens
authors.affiliation: Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital of Basel, Basel, Switzerland.
authors.forename: Heiner C
authors.initials: HC
authors.lastname: Bucher
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Gordon H
authors.initials: GH
authors.lastname: Guyatt
authors.affiliation: Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital of Basel, Basel, Switzerland3Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Matthias
authors.initials: M
authors.lastname: Briel
mesh_terms: D002170:Canada; D015331:Cohort Studies; D028744:Ethics Committees, Research; D005858:Germany; D006801:Humans; D016017:Odds Ratio; D018579:Patient Selection; D017594:Publication Bias; D016032:Randomized Controlled Trials as Topic / Q000941:ethics / Q000706:statistics & numerical data; D012189:Retrospective Studies; D013557:Switzerland