• Mihaela Stegert, Benjamin Kasenda, Erik von Elm, John J You, Anette Blümle, Yuki Tomonaga, Ramon Saccilotto, Alain Amstutz, Theresa Bengough, Matthias Briel, and DISCO study group.
• Basel Institute for Clinical Epidemiology and Biostatistics, Department of Clinical Research, University Hospital Basel, Hebelstrasse 10, Basel 4031, Switzerland; Clinic of Internal Medicine, University Ho... more spital Basel, Petersgraben 4, Basel 4031, Switzerland. less
• J Clin Epidemiol. 2016 Jan 1; 69: 152-60.

ObjectivesTo 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.Study Design And SettingWe used data from a cohort of RCT protocols approved between 2000 and 2003 by six research ethics committees in Switzerland, Germany, and Canada.ResultsOf 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%).ConclusionTwo-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.Copyright © 2016 Elsevier Inc. All rights reserved.

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