title: Accelerated approval of cancer drugs: improved access to therapeutic breakthroughs or early release of unsafe and ineffective drugs?
abstract: OBJECTIVE
  Accelerated approval (AA) was initiated by the US Food and Drug Administration (FDA) to shorten development times of drugs for serious medical illnesses. Sponsors must confirm efficacy in postapproval trials. Confronted with several drugs that received AA on the basis of phase II trials and for which confirmatory trials were incomplete, FDA officials have encouraged sponsors to design AA applications on the basis of interim analyses of phase III trials.
  
  
  METHODS
  We reviewed data on orphan drug status, development time, safety, and status of confirmatory trials of AAs and regular FDA approvals of new molecular entities (NMEs) for oncology indications since 1995.
  
  
  RESULTS
  Median development times for AA NMEs (n = 19 drugs) and regular-approval oncology NMEs (n = 32 drugs) were 7.3 and 7.2 years, respectively. Phase III trials supported efficacy for 75% of regular-approval versus 26% of AA NMEs and for 73% of non-orphan versus 45% of orphan drug approvals. AA accounted for 78% of approvals for oncology NMEs between 2001 and 2003 but accounted for 32% in more recent years. Among AA NMEs, confirmatory trials were nine-fold less likely to be completed for orphan drug versus non-orphan drug indications. Postapproval, black box warnings were added to labels for four oncology NMEs (17%) that had received AA and for two oncology NMEs (9%) that had received regular approval.
  
  
  CONCLUSIONS
  AA oncology NMEs are safe and effective, although development times are not accelerated. A return to endorsing phase II trial designs for AA for oncology NMEs, particularly for orphan drug indications, may facilitate timely FDA approval of novel cancer drugs.
authors.affiliation: Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, 303 E Chicago Ave, Chicago, IL 60611, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Richey
authors.forename: E Alison
authors.initials: EA
authors.lastname: Lyons
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Nebeker
authors.forename: Veena
authors.initials: V
authors.lastname: Shankaran
authors.forename: June M
authors.initials: JM
authors.lastname: McKoy
authors.forename: Thanh Ha
authors.initials: TH
authors.lastname: Luu
authors.forename: Narissa
authors.initials: N
authors.lastname: Nonzee
authors.forename: Steven
authors.initials: S
authors.lastname: Trifilio
authors.forename: Oliver
authors.initials: O
authors.lastname: Sartor
authors.forename: Al B
authors.initials: AB
authors.lastname: Benson
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Carson
authors.forename: Beatrice J
authors.initials: BJ
authors.lastname: Edwards
authors.forename: Douglas
authors.initials: D
authors.lastname: Gilchrist-Scott
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Kuzel
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Raisch
authors.forename: Martin S
authors.initials: MS
authors.lastname: Tallman
authors.forename: Dennis P
authors.initials: DP
authors.lastname: West
authors.forename: Steven
authors.initials: S
authors.lastname: Hirschfeld
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Grillo-Lopez
authors.forename: Charles L
authors.initials: CL
authors.lastname: Bennett
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D017326:Clinical Trials, Phase III as Topic; D017277:Drug Approval / Q000331:legislation & jurisprudence / Q000379:methods*; D006801:Humans; D053208:Kaplan-Meier Estimate; D009369:Neoplasms / Q000188:drug therapy; D009965:Orphan Drug Production / Q000331:legislation & jurisprudence / Q000379:methods* / Q000706:statistics & numerical data; D016016:Proportional Hazards Models; D013997:Time Factors; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000970:Antineoplastic Agents