Originally published as JCO Early Release 10.1200/JCO.2008.21.1961 on July 27 2009

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Accelerated Approval of Cancer Drugs: Improved Access to Therapeutic Breakthroughs or Early Release of Unsafe and Ineffective Drugs?

From the Divisions of Hematology/Oncology and Geriatric Medicine; and Department of Dermatology, Feinberg School of Medicine; and The Robert H. Lurie Comprehensive Cancer Center, Northwestern University; Pharmacy Department, Northwestern Memorial Hospital; and Veterans Affairs Center for Management of Complex Chronic Care, Jesse Brown Veterans Affairs Medical Center, Chicago, IL; Veterans Affairs Salt Lake City Geriatrics, Research, Education, and Clinical Center, Salt Lake City, UT; Tulane Medical School, New Orleans, LA; Siteman Comprehensive Cancer Center, Washington University School of Medicine, St Louis, MO; Veterans Affairs Cooperative Studies Program, Clinical Research Pharmacy Coordinating Center, Albuquerque, NM; National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD; and Neoplastic and Autoimmune Diseases Research Institute, Rancho Santa Fe, CA.

Corresponding author: Charles L. Bennett, MD, PhD, MPP, Northwestern University Feinberg School of Medicine, 303 E Chicago Ave, Olson Pavilion Ste 8250, Chicago, IL 60611; e-mail: cbenne{at}northwestern.edu.

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.

Supported in part by Grants No. 1R01CA 102713-01 and P 30 CA60553 from the National Cancer Institute (C.L.B. and J.M.M.).

Presented in part at the 2008 Annual Meeting of the American Society of Hematology, December 6-9, 2008, San Francisco, CA; and at the Oncology Drug Development Conference at the American Enterprise Institute, March 13-14, 2008, Washington, DC.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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