Accelerated approval of cancer drugs: improved access to therapeutic breakthroughs or early release of unsafe and ineffective drugs? Academic Article uri icon

Overview

MeSH

  • Antineoplastic Agents
  • Clinical Trials, Phase III as Topic
  • Humans
  • Kaplan-Meier Estimate
  • Neoplasms
  • Proportional Hazards Models
  • Time Factors
  • United States

MeSH Major

  • Drug Approval
  • Orphan Drug Production
  • United States Food and Drug Administration

abstract

  • 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. 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. 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. 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.

publication date

  • September 10, 2009

has subject area

  • Antineoplastic Agents
  • Clinical Trials, Phase III as Topic
  • Drug Approval
  • Humans
  • Kaplan-Meier Estimate
  • Neoplasms
  • Orphan Drug Production
  • Proportional Hazards Models
  • Time Factors
  • United States
  • United States Food and Drug Administration

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2744277

Digital Object Identifier (DOI)

  • 10.1200/JCO.2008.21.1961

PubMed ID

  • 19636013

Additional Document Info

start page

  • 4398

end page

  • 4405

volume

  • 27

number

  • 26