title: An analysis of protocols and publications suggested that most discontinuations of clinical trials were not based on preplanned interim analyses or stopping rules.
abstract: OBJECTIVE
  To investigate the frequency of interim analyses, stopping rules, and data safety and monitoring boards (DSMBs) in protocols of randomized controlled trials (RCTs); to examine these features across different reasons for trial discontinuation; and to identify discrepancies in reporting between protocols and publications.
  
  
  METHODS
  We used data from a cohort of RCT protocols approved between 2000 and 2003 by six research ethics committees in Switzerland, Germany, and Canada.
  
  
  RESULTS
  Of 894 RCT protocols, 289 prespecified interim analyses (32.3%), 153 stopping rules (17.1%), and 257 DSMBs (28.7%). Overall, 249 of 894 RCTs (27.9%) were prematurely discontinued; mostly due to reasons such as poor recruitment, administrative reasons, or unexpected harm. Forty-six of 249 RCTs (18.4%) were discontinued due to early benefit or futility; of those, 37 (80.4%) were stopped outside a formal interim analysis or stopping rule. Of 515 published RCTs, there were discrepancies between protocols and publications for interim analyses (21.1%), stopping rules (14.4%), and DSMBs (19.6%).
  
  
  CONCLUSIONS
  Two-thirds of RCT protocols did not consider interim analyses, stopping rules, or DSMBs. Most RCTs discontinued for early benefit or futility were stopped without a prespecified mechanism. When assessing trial manuscripts, journals should require access to the protocol.
authors.affiliation: Basel Institute for Clinical Epidemiology and Biostatistics, Department of Clinical Research, University Hospital Basel, Hebelstrasse 10, Basel 4031, Switzerland; Clinic of Internal Medicine, University Hospital Basel, Petersgraben 4, Basel 4031, Switzerland.
authors.forename: Mihaela
authors.initials: M
authors.lastname: Stegert
authors.affiliation: Basel Institute for Clinical Epidemiology and Biostatistics, Department of Clinical Research, University Hospital Basel, Hebelstrasse 10, Basel 4031, Switzerland; Clinic of Medical Oncology, University Hospital Basel, Petersgraben 4, Basel 4031, Switzerland.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Kasenda
authors.affiliation: Cochrane Switzerland, Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital, Route de la Corniche 10, Lausanne 1010, Switzerland.
authors.forename: Erik
authors.initials: E
authors.lastname: von Elm
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, 1280 Main Street West, HSC-2C8, Hamilton, Ontario, Canada L8S 4K1; Department of Medicine, McMaster University, 1280 Main Street West, HSC-2C8, Hamilton, Ontario, Canada L8S 4K1.
authors.forename: John J
authors.initials: JJ
authors.lastname: You
authors.affiliation: German Cochrane Centre, Medical Center, University of Freiburg, Berliner Allee 29, Freiburg 79110, Germany.
authors.forename: Anette
authors.initials: A
authors.lastname: Blümle
authors.affiliation: Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Hirschengraben 84, Zurich 8001, Switzerland.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Tomonaga
authors.affiliation: Basel Institute for Clinical Epidemiology and Biostatistics, Department of Clinical Research, University Hospital Basel, Hebelstrasse 10, Basel 4031, Switzerland.
authors.forename: Ramon
authors.initials: R
authors.lastname: Saccilotto
authors.affiliation: Basel Institute for Clinical Epidemiology and Biostatistics, Department of Clinical Research, University Hospital Basel, Hebelstrasse 10, Basel 4031, Switzerland.
authors.forename: Alain
authors.initials: A
authors.lastname: Amstutz
authors.affiliation: Cochrane Switzerland, Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital, Route de la Corniche 10, Lausanne 1010, Switzerland; Department of Health and Society, Austrian Federal Institute for Health Care, Stubenring 6, Vienna 1010, Austria.
authors.forename: Theresa
authors.initials: T
authors.lastname: Bengough
authors.affiliation: Basel Institute for Clinical Epidemiology and Biostatistics, Department of Clinical Research, University Hospital Basel, Hebelstrasse 10, Basel 4031, Switzerland; Department of Clinical Epidemiology and Biostatistics, McMaster University, 1280 Main Street West, HSC-2C8, Hamilton, Ontario, Canada L8S 4K1. Electronic address: matthias.briel@usb.ch.
authors.forename: Matthias
authors.initials: M
authors.lastname: Briel
mesh_terms: D002985:Clinical Protocols; D026661:Clinical Trials Data Monitoring Committees; D057239:Early Termination of Clinical Trials / Q000592:standards*; D010506:Periodicals as Topic; D016032:Randomized Controlled Trials as Topic / Q000592:standards*
keywords: Data monitoring committees; Early termination of clinical trials; Interim analysis; Protocol; Randomized controlled trials; Stopping Rules