Accelerated approval of cancer drugs: Improved access to therapeutic breakthroughs or early release of unsafe and ineffective drugs?

Elizabeth A. Richey, E. Alison Lyons, Jonathan R. Nebeker, Veena Shankaran, June M. McKoy, Thanh Ha Luu, Narissa Nonzee, Steven Trifilio, Oliver Sartor, Al B. Benson, Kenneth R. Carson, Beatrice J. Edwards, Douglas Gilchrist-Scott, Timothy M. Kuzel, Dennis W. Raisch, Martin S. Tallman, Dennis P. West, Steven Hirschfeld, Antonio J. Grillo-Lopez, Charles L. Bennett

Research output: Contribution to journalArticle

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Abstract

Purpose: 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)4398-4405
Number of pages8
JournalJournal of Clinical Oncology
Volume27
Issue number26
DOIs
StatePublished - Sep 10 2009

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Drug Approval
Orphan Drug Production
United States Food and Drug Administration
Pharmaceutical Preparations
Neoplasms
Drug Labeling
Therapeutics
Safety

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Richey, Elizabeth A. ; Lyons, E. Alison ; Nebeker, Jonathan R. ; Shankaran, Veena ; McKoy, June M. ; Luu, Thanh Ha ; Nonzee, Narissa ; Trifilio, Steven ; Sartor, Oliver ; Benson, Al B. ; Carson, Kenneth R. ; Edwards, Beatrice J. ; Gilchrist-Scott, Douglas ; Kuzel, Timothy M. ; Raisch, Dennis W. ; Tallman, Martin S. ; West, Dennis P. ; Hirschfeld, Steven ; Grillo-Lopez, Antonio J. ; Bennett, Charles L. / Accelerated approval of cancer drugs : Improved access to therapeutic breakthroughs or early release of unsafe and ineffective drugs?. In: Journal of Clinical Oncology. 2009 ; Vol. 27, No. 26. pp. 4398-4405.
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title = "Accelerated approval of cancer drugs: Improved access to therapeutic breakthroughs or early release of unsafe and ineffective drugs?",
abstract = "Purpose: 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. Conclusion: 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.",
author = "Richey, {Elizabeth A.} and Lyons, {E. Alison} and Nebeker, {Jonathan R.} and Veena Shankaran and McKoy, {June M.} and Luu, {Thanh Ha} and Narissa Nonzee and Steven Trifilio and Oliver Sartor and Benson, {Al B.} and Carson, {Kenneth R.} and Edwards, {Beatrice J.} and Douglas Gilchrist-Scott and Kuzel, {Timothy M.} and Raisch, {Dennis W.} and Tallman, {Martin S.} and West, {Dennis P.} and Steven Hirschfeld and Grillo-Lopez, {Antonio J.} and Bennett, {Charles L.}",
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Richey, EA, Lyons, EA, Nebeker, JR, Shankaran, V, McKoy, JM, Luu, TH, Nonzee, N, Trifilio, S, Sartor, O, Benson, AB, Carson, KR, Edwards, BJ, Gilchrist-Scott, D, Kuzel, TM, Raisch, DW, Tallman, MS, West, DP, Hirschfeld, S, Grillo-Lopez, AJ & Bennett, CL 2009, 'Accelerated approval of cancer drugs: Improved access to therapeutic breakthroughs or early release of unsafe and ineffective drugs?', Journal of Clinical Oncology, vol. 27, no. 26, pp. 4398-4405. https://doi.org/10.1200/JCO.2008.21.1961

Accelerated approval of cancer drugs : Improved access to therapeutic breakthroughs or early release of unsafe and ineffective drugs? / Richey, Elizabeth A.; Lyons, E. Alison; Nebeker, Jonathan R.; Shankaran, Veena; McKoy, June M.; Luu, Thanh Ha; Nonzee, Narissa; Trifilio, Steven; Sartor, Oliver; Benson, Al B.; Carson, Kenneth R.; Edwards, Beatrice J.; Gilchrist-Scott, Douglas; Kuzel, Timothy M.; Raisch, Dennis W.; Tallman, Martin S.; West, Dennis P.; Hirschfeld, Steven; Grillo-Lopez, Antonio J.; Bennett, Charles L.

In: Journal of Clinical Oncology, Vol. 27, No. 26, 10.09.2009, p. 4398-4405.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Accelerated approval of cancer drugs

T2 - Improved access to therapeutic breakthroughs or early release of unsafe and ineffective drugs?

AU - Richey, Elizabeth A.

AU - Lyons, E. Alison

AU - Nebeker, Jonathan R.

AU - Shankaran, Veena

AU - McKoy, June M.

AU - Luu, Thanh Ha

AU - Nonzee, Narissa

AU - Trifilio, Steven

AU - Sartor, Oliver

AU - Benson, Al B.

AU - Carson, Kenneth R.

AU - Edwards, Beatrice J.

AU - Gilchrist-Scott, Douglas

AU - Kuzel, Timothy M.

AU - Raisch, Dennis W.

AU - Tallman, Martin S.

AU - West, Dennis P.

AU - Hirschfeld, Steven

AU - Grillo-Lopez, Antonio J.

AU - Bennett, Charles L.

PY - 2009/9/10

Y1 - 2009/9/10

N2 - Purpose: 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. Conclusion: 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.

AB - Purpose: 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. Conclusion: 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.

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