Deborah A. Zarin, MD; Tony Tse, PhD
Disclaimer: The ideas and opinions expressed are the authors. They do not represent any policy position of the National Institutes of Health, Public Health Service, or Department of Health and Human Services.
Potential Conflicts of Interest: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M13-1109.
Requests for Single Reprints: Deborah A. Zarin, MD, Lister Hill National Center for Biomedical Communications, U.S. National Library of Medicine, National Institutes of Health, 8600 Rockville Pike, Bethesda, MD 20894; e-mail, firstname.lastname@example.org.
Current Author Addresses: Drs. Zarin and Tse: Lister Hill National Center for Biomedical Communications, U.S. National Library of Medicine, National Institutes of Health, 8600 Rockville Pike, Bethesda, MD 20894.
Zarin D., Tse T.; Trust but Verify: Trial Registration and Determining Fidelity to the Protocol. Ann Intern Med. 2013;159:65-67. doi: 10.7326/0003-4819-159-1-201307020-00011
Download citation file:
Published: Ann Intern Med. 2013;159(1):65-67.
Clinical trials, like all scientific experiments, are guided by protocols that outline the study design, conduct, and analysis. Deviations from the protocol that cannot be scientifically justified are worrisome because they could undermine the validity of the study or analysis. One type of protocol deviation that generates a great deal of concern involves unacknowledged changes to the primary outcome measure. Assumptions about this measure and its distribution underlie the analyses of power and statistical significance. These assumptions depend on prespecification and could be invalidated if the measure were in fact chosen after examination of trial data.
Before 2005, it was taken on trust that a published “primary outcome measure” referred to the measure specified in the protocol, unless otherwise stated. However, after disclosure of several cases in which published measures represented as “prespecified” were actually established “post hoc,” it became clear that readers of the literature could be misled.
to gain full access to the content and tools.
Learn more about subscription options.
Register Now for a free account.
Cardiology, Emergency Medicine, Rheumatology, Dyslipidemia, Coronary Risk Factors.
Copyright © 2016 American College of Physicians. All Rights Reserved.
Print ISSN: 0003-4819 | Online ISSN: 1539-3704
Conditions of Use
This PDF is available to Subscribers Only