2016 - 19年新抗生素监管批准时的证据及成本：对美国食品药品监督管理局批准药物的队列研究
Evidence at time of regulatory approval and cost of new antibiotics in 2016-19: cohort study of FDA approved drugs.
作者信息
Mitra-Majumdar Mayookha, Powers John H, Brown Beatrice L, Kesselheim Aaron S
机构信息
Program On Regulation, Therapeutics, And Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital/Harvard Medical School, Boston, MA, USA.
Department of Medicine, George Washington University School of Medicine, Rockville, MD, USA.
出版信息
BMJ Med. 2022 Dec 12;1(1):e000227. doi: 10.1136/bmjmed-2022-000227. eCollection 2022.
OBJECTIVE
To review the clinical evidence, regulatory background, and cost of antibiotics approved by the US Food and Drug Administration (FDA), 2016-19.
DESIGN
Cohort study of FDA approved drugs.
DATA SOURCES
FDA databases, ClinicalTrials.gov, and drug labelling. Launch prices were extracted from IBM Micromedex Red Book.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Antibiotics approved by the FDA from October 2016 to December 2019 were identified, and key features of their clinical development were extracted from publicly available FDA databases, ClinicalTrials.gov, and drug labelling. Launch prices were extracted from IBM Micromedex Red Book to evaluate the cost of treatment against comparators.
RESULTS
15 new antibiotics received at least one special regulatory designation and were supported by a median of two pivotal trials. More than half of the pivotal trials used an active control non-inferiority design. All drugs were approved based on surrogate outcome measures. 52 postmarketing requirements and commitments were included across the cohort (median 3 for each drug). From January 2021, 27 postmarketing requirements and commitments were listed as pending, seven as ongoing, three as delayed, one as submitted, eight as released, and four as fulfilled. The most expensive new antibiotic was pretomanid at $36 399 (£29 618; €34 582) for a course of treatment, and the least expensive was rifamycin ($176). Cost ratios between study drugs and comparators ranged from 0.48 to 134.
CONCLUSIONS
New antibiotics have been approved by the FDA in recent years mostly based on fewer, smaller, and non-inferiority pivotal trials that often used surrogate outcome measures but were commonly more costly. Efforts to incentivise the development of antibiotics should balance growing the antibiotic development pipeline with ensuring that clinical trials provide clinically relevant evidence of effectiveness in showing added benefits for the patient.
目的
回顾2016 - 2019年美国食品药品监督管理局（FDA）批准的抗生素的临床证据、监管背景和成本。
设计
对FDA批准药物的队列研究。
数据来源
FDA数据库、ClinicalTrials.gov和药品标签。上市价格从IBM Micromedex Red Book中提取。
选择研究的纳入标准
确定2016年10月至2019年12月期间FDA批准的抗生素，并从公开可用的FDA数据库、ClinicalTrials.gov和药品标签中提取其临床开发的关键特征。从IBM Micromedex Red Book中提取上市价格，以评估与对照药物相比的治疗成本。
结果
15种新型抗生素至少获得一项特殊监管指定，且得到的关键试验中位数为两项。超过半数的关键试验采用活性对照非劣效性设计。所有药物均基于替代结局指标获批。该队列共纳入52项上市后要求和承诺（每种药物中位数为3项）。截至2021年1月，27项上市后要求和承诺列为待办，7项正在进行，3项延迟，1项已提交，8项已发布，4项已完成。最昂贵的新型抗生素pretomanid一个疗程的费用为36399美元（29618英镑；34582欧元），最便宜的是利福霉素（176美元）。研究药物与对照药物之间的成本比在0.48至134之间。
结论
近年来FDA批准的新型抗生素大多基于数量较少、规模较小的非劣效性关键试验，这些试验通常采用替代结局指标，但成本通常更高。激励抗生素研发的努力应在增加抗生素研发渠道与确保临床试验提供临床相关有效性证据以证明对患者有额外益处之间取得平衡。
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