Association of the FDA Amendment Act With Trial Registration, Publication, and Outcome Reporting

Trials. 2017 Jul 18;18(1):333. doi: 10.1186/s13063-017-2068-3.

Abstract

Background: Selective clinical trial publication and outcome reporting has the potential to bias the medical literature. The 2007 Food and Drug Administration (FDA) Amendment Act (FDAAA) mandated clinical trial registration and outcome reporting on ClinicalTrials.gov, a publicly accessible trial registry.

Methods: Using publicly available data from ClinicalTrials.gov, FDA documents, and PubMed, we determined registration, publication, and reporting of findings for all efficacy trials supporting FDA approval of new drugs for cardiovascular disease and diabetes between 2005 and 2014, before and after the FDAAA. For published trials, we compared the published interpretation of the findings (positive, equivocal, or negative) with the FDA reviewer's interpretation.

Results: Between 2005 and 2014, the FDA approved 30 drugs for 32 indications of cardiovascular disease (n = 17) and diabetes (n = 15) on the basis of 183 trials (median per indication 5.7 (IQR, 3-8)). Compared with pre FDAAA, post-FDAAA studies were more likely to be registered (78 of 78 (100%) vs 73 of 105 (70%); p < 0.001), to be published (76 of 78 (97%) vs 93 of 105 (89%); p = 0.03), and to present findings concordant with the FDA reviewer's interpretation (74 of 76 (97%) vs 78 of 93 (84%); p = 0.004). Pre FDAAA, the FDA reviewer interpreted 80 (76%) trials as positive and 91 (98%) were published as positive. Post FDAAA, the FDA reviewer interpreted 71 (91%) trials as positive and 71 (93%) were published as positive.

Conclusions: FDAAA was associated with increased registration, publication, and FDA-concordant outcome reporting for trials supporting FDA approval of new drugs for cardiovascular disease and diabetes.

Keywords: Clinical trials; Drug approval; Publications; United States Food and Drug Administration.

Publication types

  • Review

MeSH terms

  • Access to Information / legislation & jurisprudence*
  • Cardiovascular Agents / adverse effects
  • Cardiovascular Agents / therapeutic use*
  • Clinical Trials as Topic / legislation & jurisprudence*
  • Clinical Trials as Topic / standards
  • Drug Approval / legislation & jurisprudence*
  • Government Regulation
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Outcome Assessment, Health Care / legislation & jurisprudence*
  • Outcome Assessment, Health Care / standards
  • Registries
  • Research Design / legislation & jurisprudence*
  • Research Design / standards
  • Treatment Outcome
  • United States
  • United States Food and Drug Administration / legislation & jurisprudence*
  • United States Food and Drug Administration / standards

Substances

  • Cardiovascular Agents
  • Hypoglycemic Agents