ClinicalTrials.gov and Drugs@FDA: A Comparison of Results Reporting for New Drug Approval Trials.
BACKGROUND
Pharmaceutical companies and other trial sponsors must submit certain trial results to ClinicalTrials.gov. The validity of these results is unclear.


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


METHODS
ClinicalTrials.gov (registry and results database) and Drugs@FDA (medical and statistical reviews).


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


METHODS
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.


CONCLUSIONS
Unknown generalizability to uncontrolled or crossover trial results.


CONCLUSIONS
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.


BACKGROUND
National Library of Medicine.
From The Dartmouth Institute for Health Policy and Clinical Practice, Dartmouth Hitchcock, and Informulary, Lebanon, New Hampshire, and the National Library of Medicine, Bethesda, Maryland.
Lisa M
LM
Schwartz
From The Dartmouth Institute for Health Policy and Clinical Practice, Dartmouth Hitchcock, and Informulary, Lebanon, New Hampshire, and the National Library of Medicine, Bethesda, Maryland.
Steven
S
Woloshin
From The Dartmouth Institute for Health Policy and Clinical Practice, Dartmouth Hitchcock, and Informulary, Lebanon, New Hampshire, and the National Library of Medicine, Bethesda, Maryland.
Eugene
E
Zheng
From The Dartmouth Institute for Health Policy and Clinical Practice, Dartmouth Hitchcock, and Informulary, Lebanon, New Hampshire, and the National Library of Medicine, Bethesda, Maryland.
Tony
T
Tse
From The Dartmouth Institute for Health Policy and Clinical Practice, Dartmouth Hitchcock, and Informulary, Lebanon, New Hampshire, and the National Library of Medicine, Bethesda, Maryland.
Deborah A
DA
Zarin
D002986:Clinical Trials as Topic / Q000592:standards*; D016208:Databases, Factual / Q000592:standards*; D017277:Drug Approval; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D009317:National Library of Medicine (U.S.); D014481:United States; D014486:United States Food and Drug Administration