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Comparative Study
. 2016 Sep 20;165(6):421-30.
doi: 10.7326/M15-2658. Epub 2016 Jun 14.

ClinicalTrials.gov and Drugs@FDA: A Comparison of Results Reporting for New Drug Approval Trials

Lisa M Schwartz  1 , Steven Woloshin  1 , Eugene Zheng  1 , Tony Tse  1 , Deborah A Zarin  1
Affiliations
Comparative Study

ClinicalTrials.gov and Drugs@FDA: A Comparison of Results Reporting for New Drug Approval Trials

Lisa M Schwartz et al. Ann Intern Med. .

Abstract

Background: Pharmaceutical companies and other trial sponsors must submit certain trial results to ClinicalTrials.gov. The validity of these results is unclear.

Purpose: To validate results posted on ClinicalTrials.gov against publicly available U.S. Food and Drug Administration (FDA) reviews on Drugs@FDA.

Data sources: ClinicalTrials.gov (registry and results database) and Drugs@FDA (medical and statistical reviews).

Study selection: 100 parallel-group, randomized trials for new drug approvals (January 2013 to July 2014) with results posted on ClinicalTrials.gov (15 March 2015).

Data extraction: 2 assessors extracted, and another verified, the trial design, primary and secondary outcomes, adverse events, and deaths.

Results: 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.

Limitation: Unknown generalizability to uncontrolled or crossover trial results.

Conclusion: 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.

Primary funding source: National Library of Medicine.

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Conflict of interest statement

Statement Drs. Schwartz and Woloshin are co-founders and shareholders in Informulary, Inc., a company that provides data about the benefits, harms and uncertainties of prescription drugs. EZ was paid by Informulary for work on this study. Drs. Zarin and Tse are Director and Program Analyst, respectively, at ClinicalTrials.gov.

Figures

Figure
Figure
Trial search and selection. *The 20 unmatched trials were from 8 new drug reviews: 4 had other matched trials, 4 did not. The 50 trials without results in both sources were from 21 new drug reviews: 12 had other matched trials, 9 did not.
See this image and copyright information in PMC

References

    1. Food and Drug Administration Amendments Act of 2007: Public Law 110–85.

    1. ClinicalTrials.gov. [Accessed February 24, 2016];“Basic Results” Data Element Definitions (DRAFT) 2015 Apr; Available at: https://prsinfo.clinicaltrials.gov/results_definitions.html.

    1. §402(j)(a)(5)(C) of the Public Health Service Act, as amended by FDAAA.

    1. Zarin D, Tse T, Williams R, Califf R, Ide N. The ClinicalTrials.gov results database - update and key issues. N Engl J Med. 2011;364:852–60. - PMC - PubMed
    1. Becker J, Krumholz H, Ben-Josef G, Ross J. Reporting of results in ClinicalTrials.gov and high-impact journals. JAMA. 2014;311:1063–65. - PMC - PubMed

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