Accelerated approval of cancer drugs: improved access to therapeutic breakthroughs or early release of unsafe and ineffective drugs?
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.
Richey
Elizabeth A
EA
Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, 303 E Chicago Ave, Chicago, IL 60611, USA.
Lyons
E Alison
EA
Nebeker
Jonathan R
JR
Shankaran
Veena
V
McKoy
June M
JM
Luu
Thanh Ha
TH
Nonzee
Narissa
N
Trifilio
Steven
S
Sartor
Oliver
O
Benson
Al B
AB
Carson
Kenneth R
KR
Edwards
Beatrice J
BJ
Gilchrist-Scott
Douglas
D
Kuzel
Timothy M
TM
Raisch
Dennis W
DW
Tallman
Martin S
MS
West
Dennis P
DP
Hirschfeld
Steven
S
Grillo-Lopez
Antonio J
AJ
Bennett
Charles L
CL
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
D000970:Antineoplastic Agents