title: Clinical trial registration, reporting, publication and FDAAA compliance: a cross-sectional analysis and ranking of new drugs approved by the FDA in 2012.
abstract: OBJECTIVE
  To evaluate clinical trial registration, reporting and publication rates for new drugs by: (1) legal requirements and (2) the ethical standard that all human subjects research should be publicly accessible to contribute to generalisable knowledge.
  
  
  METHODS
  Cross-sectional analysis of all clinical trials submitted to the Food and Drug Administration (FDA) for drugs approved in 2012, sponsored by large biopharmaceutical companies.
  
  
  METHODS
  Information from Drugs@FDA, ClinicalTrials.gov, MEDLINE-indexed journals and drug company communications.
  
  
  METHODS
  Clinical trial registration and results reporting in ClinicalTrials.gov, publication in the medical literature, and compliance with the 2007 FDA Amendments Acts (FDAAA), analysed on the drug level.
  
  
  RESULTS
  The FDA approved 15 drugs sponsored by 10 large companies in 2012. We identified 318 relevant trials involving 99 599 research participants. Per drug, a median of 57% (IQR 32-83%) of trials were registered, 20% (IQR 12-28%) reported results in ClinicalTrials.gov, 56% (IQR 41-83%) were published, and 65% (IQR 41-83%) were either published or reported results. Almost half of all reviewed drugs had at least one undisclosed phase II or III trial. Per drug, a median of 17% (IQR 8-20%) of trials supporting FDA approvals were subject to FDAAA mandated public disclosure; of these, a median of 67% (IQR 0-100%) were FDAAA-compliant. 68% of research participants (67,629 of 99,599) participated in FDAAA-subject trials, with 51% (33,405 of 67,629) enrolled in non-compliant trials. Transparency varied widely among companies.
  
  
  CONCLUSIONS
  Trial disclosures for new drugs remain below legal and ethics standards, with wide variation in practices among drugs and their sponsors. Best practices are emerging. 2 of our 10 reviewed companies disclosed all trials and complied with legal disclosure requirements for their 2012 approved drugs. Ranking new drugs on transparency criteria may improve compliance with legal and ethics standards and the quality of medical knowledge.
authors.affiliation: NYU Langone Medical Center, NYU School of Medicine, Bioethics International, New York, New York, USA.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Miller
authors.affiliation: Edmond J. Safra Center for Ethics, Harvard University, Massachusetts General Hospital, Harvard Medical School, Cambridge, Massachusetts, USA.
authors.forename: David
authors.initials: D
authors.lastname: Korn
authors.affiliation: Section of General Internal Medicine and the Robert Wood Johnson Clinical Scholars Program, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA Department of Health Policy and Management, Yale School of Public Health, New Haven, Connecticut, USA Center for Outcomes Research and Evaluation, Yale-New Haven Hospital, New Haven, Connecticut, USA.
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Ross
mesh_terms: D002986:Clinical Trials as Topic / Q000706:statistics & numerical data*; D003430:Cross-Sectional Studies; D016208:Databases, Factual; D030881:Disclosure / Q000941:ethics* / Q000331:legislation & jurisprudence*; D017277:Drug Approval / Q000331:legislation & jurisprudence*; D006801:Humans; D011634:Public Health; D011642:Publications; D058028:Research Report / Q000592:standards; D014481:United States; D014486:United States Food and Drug Administration
keywords: GENERAL MEDICINE (see Internal Medicine); MEDICAL ETHICS; PUBLIC HEALTH