title: Participation of the elderly, women, and minorities in pivotal trials supporting 2011-2013 U.S. Food and Drug Administration approvals.
abstract: BACKGROUND
  Pivotal trials, the clinical studies that inform U.S. Food and Drug Administration (FDA) approval decisions, provide the foundational evidence supporting the safety and efficacy of novel therapeutics. We determined the representation of the elderly, women, and patients from racial and ethnic minorities in pivotal trials and whether the FDA is making subgroup efficacy analyses among these subpopulations available to the public.
  
  
  METHODS
  We conducted a cross-sectional study of novel therapeutics approved by the FDA between 2011 and 2013. Using publicly available FDA documents, we collected information on the demographic characteristics of pivotal trial participants (age ≥65 years, sex [male, female], race [white, black, Asian, other], and ethnicity [Hispanic, non-Hispanic]) and determined the availability of subgroup analyses by age, sex, race, and ethnicity.
  
  
  RESULTS
  We identified 86 novel therapeutic that were approved by the FDA between 2011 and 2013 for 92 indications on the basis of 206 pivotal trials. The median age of pivotal trial patients was 53.1 years (interquartile range 40.6-60.6), and the mean proportion of patients ≥65 years of age was 28.9 % (95 % CI 23.5-34.4 %). Similar proportions of pivotal trial participants were male (mean 50.3 %, 95 % CI 45.3-55.2 %) and female (mean 49.7 %, 95 % CI 44.7-54.7 %). Most participants were white (mean 79.2 %, 95 % CI 75.9-82.6 %), while the mean proportion of black patients was 7.4 % (95 % CI 5.5-9.3 %), that of Asian patients was 7.4 % (95 % CI 5.2-9.7 %), and that of patients of other races was 5.9 % (95 % CI 4.4-7.5 %). Information about ethnicity was available for only 59.8 % of indications, and where such data were available, the mean proportion of Hispanic participants was 13.3 % (95 % CI 10.3-16.3 %). FDA reviewers performed and made available subgroup efficacy analyses by age, sex, and race for at least one of the pivotal trials used as the basis of approval for over 80 % of indications.
  
  
  CONCLUSIONS
  Although women are equally represented in pivotal trials supporting recent novel therapeutic approvals by the FDA, elderly patients and those from racial and ethnic minorities are underrepresented. FDA reviewers generally perform subgroup efficacy analyses by age, sex, and race and make these subgroup analyses available to the public.
authors.affiliation: Center for Outcomes Research and Evaluation, Yale-New Haven Hospital, New Haven, CT, USA.
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Downing
authors.affiliation: Division of Health Care Policy and Research, Mayo Clinic, Rochester, MN, USA.
authors.forename: Nilay D
authors.initials: ND
authors.lastname: Shah
authors.affiliation: University of Nevada School of Medicine, Reno, NV, USA.
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Neiman
authors.affiliation: Section of General Internal Medicine and the Robert Wood Johnson Foundation Clinical Scholars Program, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Jenerius A
authors.initials: JA
authors.lastname: Aminawung
authors.affiliation: Center for Outcomes Research and Evaluation, Yale-New Haven Hospital, New Haven, CT, USA.|Section of Cardiovascular Medicine and the Robert Wood Johnson Foundation Clinical Scholars Program, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA.|Department of Health Policy and Management, Yale University School of Public Health, New Haven, CT, USA.
authors.forename: Harlan M
authors.initials: HM
authors.lastname: Krumholz
authors.affiliation: Center for Outcomes Research and Evaluation, Yale-New Haven Hospital, New Haven, CT, USA. joseph.ross@yale.edu.|Department of Health Policy and Management, Yale University School of Public Health, New Haven, CT, USA. joseph.ross@yale.edu.|Section of General Internal Medicine and the Robert Wood Johnson Foundation Clinical Scholars Program, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA. joseph.ross@yale.edu.
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Ross
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D002986:Clinical Trials as Topic / Q000379:methods*; D003430:Cross-Sectional Studies; D016208:Databases, Factual; D017277:Drug Approval; D005006:Ethnicity; D005260:Female; D054624:Health Status Disparities; D054625:Healthcare Disparities; D006801:Humans; D008297:Male; D008875:Middle Aged; D008913:Minority Groups; D018579:Patient Selection; D012737:Sex Factors; D013997:Time Factors; D014481:United States; D014486:United States Food and Drug Administration