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The Dangers of Stopping a Trial Too Early
Matthias Briel, MD, MSc1; Dirk Bassler, MD, MSc2; Amy T. Wang, MD3; Gordon H. Guyatt, MD, MSc4; Victor M. Montori, MD, MSc3
1 Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Helbelstrasse 10, 4031, Basel, Switzerland
2 Department of Neonatology, Center for Pediatric Clinical Studies, University Children’s Hospital Tuebingen, Cawler Strasse 7, 72076 Tuebingen, Germany
3 Knowledge and Evaluation Research Unit, Mayo Clinic, Plummer 3-35, 200 First Street S.W., Rochester, MN 55905. Email address for V.M. Montori: kerunit@mayo.edu
4 Department of Clinical Epidemiology and Biostatistics, McMaster University, HSC 2C, 1200 Main Street West, Hamilton, ON L8L 2X2, Canada
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Disclosure: None of the authors received payments or services, either directly or indirectly (i.e., via his or her institution), from a third party in support of any aspect of this work. None of the authors, or their institution(s), have had any financial relationship, in the thirty-six months prior to submission of this work, with any entity in the biomedical arena that could be perceived to influence or have the potential to influence what is written in this work. Also, no author has had any other relationships, or has engaged in any other activities, that could be perceived to influence or have the potential to influence what is written in this work. The complete Disclosures of Potential Conflicts of Interest submitted by authors are always provided with the online version of the article.

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Investigation performed at the Mayo Clinic, Rochester, Minnesota, and McMaster University, Hamilton, Ontario, Canada

Copyright © 2012 by The Journal of Bone and Joint Surgery, Inc.
J Bone Joint Surg Am, 2012 Jul 18;94(Suppl 1(E)):56-60. doi: 10.2106/JBJS.K.01412
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To ensure that participants in randomized controlled trials are protected from harm, interim analyses and review of results by an independent data monitoring committee have become standard practice. If an analysis of accumulating data partway through a trial reveals an unanticipated degree of benefit or toxicity, or differences in outcomes between the intervention and control groups are so unimpressive that any prospect of a positive result with the planned sample size is extremely unlikely, investigators may stop the trial earlier than originally scheduled. The practice of stopping randomized controlled trials early is, however, problematic, especially if the trial is stopped for apparent benefit. Concerns in trials stopped early for apparent benefit include appropriate interpretation of results and ethical problems concerning trial participants, clinicians, and society as a whole. In this article, we review the epidemiology of trials stopped early and illustrate some of the problems and controversies associated with stopping randomized controlled trials early for apparent benefit. Finally, we offer guidance for clinicians, those running clinical trials, and authors of systematic reviews.

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