Lisa M. Schwartz, MD, MS; Steven Woloshin, MD, MS; Eugene Zheng, BA; Tony Tse, PhD; Deborah A. Zarin, MD
Disclosures: Drs. Schwartz and Woloshin report personal fees from the National Library of Medicine during the conduct of the study and are cofounders of and shareholders in Informulary, a company that provides data about the benefits, harms, and uncertainties of prescription drugs. Mr. Zheng was paid by Informulary while conducting the work. Dr. Tse is employed as an analyst at ClinicalTrials.gov. Dr. Zarin is the director of ClinicalTrials.gov. Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M15-2658.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer.
Requests for Single Reprints: Steven Woloshin, MD, The Dartmouth Institute, Level 5, WTRB, 1 Medical Center Drive, Lebanon, NH 03756; e-mail, firstname.lastname@example.org.
Current Author Addresses: Drs. Schwartz and Woloshin: The Dartmouth Institute, Level 5, WTRB, 1 Medical Center Drive, Lebanon, NH 03756.
Mr. Zheng: 2900 University Avenue Southeast, Apartment 306, Minneapolis, MN 55414.
Drs. Tse and Zarin: National Library of Medicine, 8600 Rockville Pike, Bethesda, MD 20894.
Author Contributions: Conception and design: L.M. Schwartz, S. Woloshin, E. Zheng, T. Tse, D.A. Zarin.
Analysis and interpretation of the data: L.M. Schwartz, S. Woloshin, E. Zheng, T. Tse, D.A. Zarin.
Drafting of the article: L.M. Schwartz, S. Woloshin, T. Tse, D.A. Zarin.
Critical revision for important intellectual content: L.M. Schwartz, S. Woloshin, T. Tse, D.A. Zarin.
Final approval of the article: L.M. Schwartz, S. Woloshin, E. Zheng, T. Tse, D.A. Zarin.
Administrative, technical, or logistic support: E. Zheng, T. Tse, D.A. Zarin.
Collection and assembly of data: L.M. Schwartz, S. Woloshin, E. Zheng.
Pharmaceutical companies and other trial sponsors must submit certain trial results to ClinicalTrials.gov. The validity of these results is unclear.
To validate results posted on ClinicalTrials.gov against publicly available U.S. Food and Drug Administration (FDA) reviews on Drugs@FDA.
ClinicalTrials.gov (registry and results database) and Drugs@FDA (medical and statistical reviews).
100 parallel-group, randomized trials for new drug approvals (January 2013 to July 2014) with results posted on ClinicalTrials.gov (15 March 2015).
2 assessors extracted, and another verified, the trial design, primary and secondary outcomes, adverse events, and deaths.
Most trials were phase 3 (90%), double-blind (92%), and placebo-controlled (73%) and involved 32 drugs from 24 companies. Of 137 primary outcomes identified from ClinicalTrials.gov, 134 (98%) had corresponding data at Drugs@FDA, 130 (95%) had concordant definitions, and 107 (78%) had concordant results. Most differences were nominal (that is, relative difference <10%). Primary outcome results in 14 trials could not be validated. Of 1927 secondary outcomes from ClinicalTrials.gov, Drugs@FDA mentioned 1061 (55%) and included results data for 367 (19%). Of 96 trials with 1 or more serious adverse events in either source, 14 could be compared and 7 had discordant numbers of persons experiencing the adverse events. Of 62 trials with 1 or more deaths in either source, 25 could be compared and 17 were discordant.
Unknown generalizability to uncontrolled or crossover trial results.
Primary outcome definitions and results were largely concordant between ClinicalTrials.gov and Drugs@FDA. Half the secondary outcomes, as well as serious events and deaths, could not be validated because Drugs@FDA includes only “key outcomes” for regulatory decision making and frequently includes only adverse event results aggregated across multiple trials.
National Library of Medicine.
Lisa M. Schwartz, Steven Woloshin, Eugene Zheng, Tony Tse, Deborah A. Zarin. ClinicalTrials.gov and Drugs@FDA: A Comparison of Results Reporting for New Drug Approval Trials. Ann Intern Med. 2016;165:421–430. doi: 10.7326/M15-2658
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Published: Ann Intern Med. 2016;165(6):421-430.
Published at www.annals.org on 14 June 2016
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