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. 2022 Sep 1;5(9):e2230973.
doi: 10.1001/jamanetworkopen.2022.30973.

US Food and Drug Administration Accelerated Approval Program for Nononcology Drug Indications Between 1992 and 2018

Kenji Omae  1   2 , Akira Onishi  3 , Ethan Sahker  4   5 , Toshi A Furukawa  4
Affiliations

US Food and Drug Administration Accelerated Approval Program for Nononcology Drug Indications Between 1992 and 2018

Kenji Omae et al. JAMA Netw Open. .

Abstract

Importance: The US Food and Drug Administration (FDA) grants accelerated approval according to surrogate measures of numerous drug indications for serious or life-threatening illnesses such as infectious diseases and cancer. Investigators, including the FDA, have evaluated the program's regulatory and clinical consequences in oncology, but evaluation of nononcology drugs is lacking.

Objective: To evaluate the accelerated approval program for nononcology drug indications over a period of 26 years.

Design, setting, and participants: This retrospective cohort study used publicly available data on FDA nononcology drug indications granted accelerated approval from June 1992 through May 2018, with preapproval and confirmatory trials for approved drugs. Data were analyzed from February to April 2022.

Main outcomes and measures: The study estimated the median time from accelerated approval to occurrence of regulatory outcomes such as regular approval conversion, postapproval boxed warning label changes, confirmatory trial completion, and confirmatory trial results publication.

Results: The FDA granted accelerated approval of 48 drugs for 57 nononcology indications, including 23 (40%) HIV treatments, supported by 93 preapproval trials. Forty-three indications (75%) were converted to regular approval at a median time of 53.1 (95% CI, 38.7 to 70.2) months from accelerated approval. There were postapproval label modifications on boxed warnings in 27 indications (47%) with a median time of 248.6 (95% CI, 51.8 to not estimable) months from accelerated approval. Of the 86 required confirmatory trials, 17 (20%) had not fulfilled the postapproval requirements. The median time to confirmatory trial completion was 39.4 (95% CI, 30.7 to 47.9) months. Nine trials (10%) failed to verify clinical efficacy, but only 1 of 8 indications assessed (2%) was withdrawn owing to the failed confirmatory trial, which was 136 months after approval. Results were published in 56 completed confirmatory trials (65%), with the median time being 52.5 (95% CI, 35.6 to 82.2) months from accelerated approval to publication.

Conclusions and relevance: Although the program expedited the approval of nononcology drug indications by a median (IQR) of 53.1 (26.8-133.2) months, safety-related label modifications were often added in boxed warnings after approval, and clinical efficacy was sometimes not confirmed. The study findings and long follow-up period suggest that comprehensive evaluation of such drugs may take more than a decade.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Omae reported receiving grants from The Health Care Science Institute during the conduct of the study; personal fees from Astellas Pharma, Kyowa Hakko Kirin, Ono Pharmaceutical, and iHope International outside the submitted work. Dr Onishi reported receiving grants from Advantest, Pfizer Inc, and Bristol-Myers Squibb; personal fees from Pfizer Inc, Asahi Kasei Pharma, Chugai Pharmaceutical Co, Eli Lilly Japan K.K, Ono Pharmaceutical Co., Mitsubishi Tanabe Pharma, Takeda Pharmaceutical Company Limited, Daiichi Sankyo Co, and Ayumi, UCB-Japan; Dr Onishi also reported belonging to a department that is financially supported by Nagahama City, Toyooka City, Tanabe-Mitsubishi, Chugai, Ayumi, and Asahi-Kasei. Dr Furukawa reported receiving grants from Mitsubishi-Tanabe and Shionogi and personal fees from Mitsubishi-Tanabe, Shionogi, SONY, and Kyoto University Original outside the submitted work; in addition, Dr Furukawa had a patent pending for 2020-548587, a patent pending for 2022-082495, and a patent for intellectual properties for Kokoro-app licensed to Mitsubishi-Tanabe. No other disclosures were reported.

Figures

Figure.
Figure.. Cumulative Instances of Use of Accelerated Approval Program for Nononcology Drugs, June 1992 to May 2018
See this image and copyright information in PMC

References

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