An analysis of protocols and publications suggested that most discontinuations of clinical trials were not based on preplanned interim analyses or stopping rules

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• 作者：Mihaela Stegert^a ; ^b ; Benjamin Kasenda^a ; ^c ; Erik von Elm^d ; John J. You^e ; ^f ; Anette Blü ; mle^g ; Yuki Tomonaga^h ; Ramon Saccilotto^a ; Alain Amstutz^a ; Theresa Bengough^d ; ⁱ ; Matthias Briel^a ; ^e ; ^{matthias.briel@usb.ch" class="auth_mail" title="E-mail the corresponding author} ; ; the DISCO study groupMihaela Stegert ; Benjamin Kasenda ; Erik von Elm ; John J. You ; Anette Blü ; mle ; Yuki Tomonaga ; Ramon Saccilotto ; Alain Amstutz ; Theresa Bengough ; Joerg J. Meerpohl ; Kari A.O. Tikkinen ; Ignacio Neumann ; Alonso Carrasco-Labra ; Markus Faulhaber ; Sohail Mulla ; Dominik Mertz ; Elie A. Akl ; Dirk Bassler ; Jason W. Busse ; Ignacio Ferreira-Gonzá ; lez ; Francois Lamontagne ; Alain Nordmann ; Viktoria Gloy ; Kelechi Kalu Olu ; Heike Raatz ; Lorenzo Moja ; Rachel Rosenthal ; Shanil Ebrahim ; Stefan Schandelmaier ; Xin Sun ; Per O. Vandvik ; Bradley C. Johnston ; Martin A. Walter ; Bernard Burnand ; Matthias Schwenkglenks ; Lars G. Hemkens ; Heiner C. Bucher ; Gordon H. Guyatt ; Matthias Briel
• 关键词：Randomized controlled trials ; Protocol ; Early termination of clinical trials ; Data monitoring committees ; Interim analysis ; Stopping Rules
• 刊名：Journal of Clinical Epidemiology
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：69
• 期：Complete
• 页码：152-160
• 全文大小：262 K

文摘

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.

Study Design and Setting

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%).

Conclusion

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.