Trust but Verify: Trial Registration and Determining Fidelity to the Protocol
Authors: Deborah A. Zarin, Tony Tse
Journal: Annals of Internal Medicine (2013)

Editorials2 July 2013Trust but Verify: Trial Registration and Determining Fidelity to the ProtocolDeborah A. Zarin, MD and Tony Tse, PhDDeborah A. Zarin, MDFrom National Library of Medicine, Bethesda, Maryland.Search for more papers by this author and Tony Tse, PhDFrom National Library of Medicine, Bethesda, Maryland.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-159-1-201307020-00011 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail 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 ...References1. Laine C, De Angelis C, Delamothe T, Drazen JM, Frizelle FA, Haug C, et al. Clinical trial registration: looking back and moving ahead [Editorial]. Ann Intern Med. 2007;147:275-7 LinkGoogle Scholar2. Landman GW. Escitalopram for the prevention of peginterferon-α2a-associated depression [Letter]. Ann Intern Med. 2013;158:139-40 LinkGoogle Scholar3. Prasad V. Treatment of moderate to severe hidradenitis suppurativa [Letter]. Ann Intern Med. 2013;159:72. LinkGoogle Scholar4. Schaefer M, Berg T, Sarkar S, and Neumann K. Escitalopram for the prevention of peginterferon-α2a-associated depression [Letter]. Ann Intern Med. 2013;158:140 LinkGoogle Scholar5. Kimball AB, Gu Y, and Okun M. Treatment of moderate to severe hidradenitis suppurativa [Letter]. Ann Intern Med. 2013;159:72-3. LinkGoogle Scholar6. Hannink G, Gooszen HG, and Rovers MM. Comparison of registered and published primary outcomes in randomized clinical trials of surgical interventions. Ann Surg. 2013;257:818-23. [PMID: 23407296] CrossrefMedlineGoogle Scholar7. Zarin DA, Tse T, Williams RJ, Califf RM, and Ide NC. The ClinicalTrials.gov results database—update and key issues. N Engl J Med. 2011;364:852-60. [PMID: 21366476] CrossrefMedlineGoogle Scholar8. Jüni P, Rutjes AW, and Dieppe PA. Are selective COX 2 inhibitors superior to traditional non steroidal anti-inflammatory drugs? [Editorial]. BMJ. 2002;324:1287-8. [PMID: 12039807] CrossrefMedlineGoogle Scholar9. Hughes S. US House Committee raises concerns over ezetimibe trial. 13 December 2007. Accessed at www.theheart.org/article/833387.do on 26 April 2013. Google Scholar10. Drazen JM and Zarin DA. Salvation by registration [Editorial]. N Engl J Med. 2007;356:184-5. [PMID: 17215537] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAuthors: Deborah A. Zarin, MD; Tony Tse, PhDAffiliations: From National Library of Medicine, Bethesda, Maryland.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.Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M13-1109.Corresponding Author: 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, [email protected].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. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoTreatment of Moderate to Severe Hidradenitis Suppurativa Vinay Prasad Metrics 2 July 2013Volume 159, Issue 1Page: 65-67KeywordsArthritisAtherosclerosisCarotid arteriesClinical trialsDisclosureDrug policyPublic policySafety studiesSpecificityStatistical dataStatistical distributionsToxicity ePublished: 2 July 2013 Issue Published: 2 July 2013 Copyright & PermissionsCopyright © 2013 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...