title: Trends in utilization of FDA expedited drug development and approval programs, 1987-2014: cohort study.
abstract: OBJECTIVE
  To evaluate the use of special expedited development and review pathways at the US Food and Drug Administration over the past two decades.
  
  
  METHODS
  Cohort study.
  
  
  METHODS
  FDA approved novel therapeutics between 1987 and 2014.
  
  
  METHODS
  Publicly available sources provided each drug's year of approval, their innovativeness (first in class versus not first in class), World Health Organization Anatomic Therapeutic Classification, and which (if any) of the FDA's four primary expedited development and review programs or designations were associated with each drug: orphan drug, fast track, accelerated approval, and priority review.
  
  
  METHODS
  Logistic regression models evaluated trends in the proportion of drugs associated with each of the four expedited development and review programs. To evaluate the number of programs associated with each approved drug over time, Poisson models were employed, with the number of programs as the dependent variable and a linear term for year of approval. The difference in trends was compared between drugs that were first in class and those that were not.
  
  
  RESULTS
  The FDA approved 774 drugs during the study period, with one third representing first in class agents. Priority review (43%) was the most prevalent of the four programs, with accelerated approval (9%) the least common. There was a significant increase of 2.6% per year in the number of expedited review and approval programs granted to each newly approved agent (incidence rate ratio 1.026, 95% confidence interval 1.017 to 1.035, P<0.001), and a 2.4% increase in the proportion of drugs associated with at least one such program (odds ratio 1.024, 95% confidence interval 1.006 to 1.043, P=0.009). Driving this trend was an increase in the proportion of approved, non-first in class drugs associated with at least one program for drugs (P=0.03 for interaction).
  
  
  CONCLUSIONS
  In the past two decades, drugs newly approved by the FDA have been associated with an increasing number of expedited development or review programs. Though expedited programs should be strictly limited to drugs providing noticeable clinical advances, this trend is being driven by drugs that are not first in class and thus potentially less innovative.
authors.affiliation: Program On Regulation, Therapeutics, And Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston 02120, MA, USA akesselheim@partners.org.
authors.forename: Aaron S
authors.initials: AS
authors.lastname: Kesselheim
authors.affiliation: Program On Regulation, Therapeutics, And Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston 02120, MA, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.affiliation: Program On Regulation, Therapeutics, And Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston 02120, MA, USA.
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Franklin
authors.affiliation: Program On Regulation, Therapeutics, And Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston 02120, MA, USA.
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Darrow
mesh_terms: D015331:Cohort Studies; D017277:Drug Approval / Q000706:statistics & numerical data*; D055808:Drug Discovery / Q000639:trends*; D006801:Humans; D013997:Time Factors; D014481:United States; D014486:United States Food and Drug Administration / Q000706:statistics & numerical data / Q000639:trends*