ClinicalTrials.gov and DrugsFDA: 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. Purpose: To validate results posted on ClinicalTrials.gov against publicly available U.S. Food and Drug Administration (FDA) reviews on DrugsFDA. 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. doi: 10.7326/M15-2658.

Medienart:	Artikel

Erscheinungsjahr:	2016
Erschienen:	2016

Enthalten in:	Zur Gesamtaufnahme - volume:165
Enthalten in:	Annals of internal medicine - 165(2016), 6, Seite 421

Sprache:	Englisch

Beteiligte Personen:	Schwartz, Lisa M [VerfasserIn] Woloshin, Steven [Sonstige Person] Zheng, Eugene [Sonstige Person] Tse, Tony [Sonstige Person] Zarin, Deborah A [Sonstige Person]

Links:	Volltext search.proquest.com

BKL:	44.61 / Innere Medizin / Innere Medizin 44.00 / Medizin: Allgemeines / Medizin: Allgemeines
Themen:	Clinical trials Comparative analysis Drugs FDA approval Pharmaceutical industry Pharmaceuticals Validity

RVK:	RVK Klassifikation XA 23600 XA 10000

doi:	10.7326/M15-2658

funding:
Förderinstitution / Projekttitel:

PPN (Katalog-ID):	OLC1983742120