Department of Innovative Research and Education for Clinicians and Trainees, Fukushima Medical University Hospital, Fukushima, Japan.
Center for Innovative Research for Communities and Clinical Excellence, Fukushima Medical University, Fukushima, Japan.
JAMA Netw Open. 2022 Sep 1;5(9):e2230973. doi: 10.1001/jamanetworkopen.2022.30973.
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.
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.
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.
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 Nine trials (10%) failed to verify clinical efficacy, but only 1 of 8 indications assessed (2%) was withdrawn owing to the failed confirmatory trial, which was 136 months after approval.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.
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.
美国食品和药物管理局（FDA）根据许多严重或危及生命的疾病（如传染病和癌症）的替代指标，加速批准了许多药物适应症。包括 FDA 在内的研究人员已经评估了该计划在肿瘤学领域的监管和临床后果，但对非肿瘤学药物的评估却有所欠缺。
评估 26 年来非肿瘤学药物适应症的加速审批计划。
设计、地点和参与者：本回顾性队列研究使用了 FDA 1992 年 6 月至 2018 年 5 月期间批准的非肿瘤学药物适应症的公开可用数据，这些数据涉及获得批准的药物的预批准和确认性试验。数据分析于 2022 年 2 月至 4 月进行。
该研究估计了从加速批准到出现监管结果（如常规批准转换、批准后加框警告标签变化、确认性试验完成和确认性试验结果公布）的中位时间。
FDA 为 57 种非肿瘤学适应症中的 48 种药物授予了加速批准，其中包括 23 种（40%）HIV 治疗药物，这些药物得到了 93 项预批准试验的支持。43 种适应症（75%）在加速批准后中位时间为 53.1（95%CI，38.7 至 70.2）个月后转换为常规批准。在 27 种适应症（47%）中，批准后加框警告标签发生了修改，中位时间为 248.6（95%CI，51.8 至不可估计）个月。在 86 项要求的确认性试验中，有 17 项（20%）未达到批准后的要求。确认性试验完成的中位时间为 39.4（95%CI，30.7 至 47.9）个月。有 9 项试验（10%）未能验证临床疗效，但仅有 1 项（2%）评估的适应症因确认性试验失败而被撤回，这是在批准后 136 个月发生的，该试验失败导致了适应症的撤回。56 项完成的确认性试验（65%）的结果公布，从加速批准到公布结果的中位时间为 52.5（95%CI，35.6 至 82.2）个月。
尽管该计划将非肿瘤学药物适应症的批准时间平均（IQR）缩短了 53.1（26.8-133.2）个月，但批准后通常会在加框警告中添加与安全性相关的标签修改，并且有时无法确认临床疗效。该研究结果和长期随访表明，对这些药物的全面评估可能需要超过十年的时间。
