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Regulatory and clinical consequences of negative confirmatory trials of accelerated approval cancer drugs: retrospective observational study
The BMJ ( IF 105.7 ) Pub Date : 2021-09-09 , DOI: 10.1136/bmj.n1959
Bishal Gyawali 1, 2 , Benjamin N Rome 2 , Aaron S Kesselheim 2
Affiliation  

Objectives To investigate the regulatory handling of cancer drugs that were granted accelerated approval by the US Food and Drug Administration (FDA) but failed to improve the primary endpoint in post-approval trials and to evaluate the extent to which negative post-approval trials changed the recommendations in treatment guidelines. Design Retrospective observational study. Setting FDA and National Comprehensive Cancer Network (NCCN) reports. Included drugs Cancer drugs that received accelerated approval from the FDA and had negative post-approval trials. Main outcome measures Regulatory outcomes, including withdrawal, conversion to regular approval, and no action. Results 18 indications for 10 cancer drugs that received accelerated approval but failed to improve the primary endpoint in post-approval trials were identified. Of these, 11 (61%) were voluntarily withdrawn by the manufacturer and one (bevacizumab for breast cancer) was revoked by the FDA. Of the 11 withdrawals, six occurred in 2021 alone. The remaining six (33%) indications remain on the label. The NCCN guidelines provide a high level of endorsement (category 1 endorsement for one and category 2A endorsement for seven) for accelerated approval drugs that have failed post-approval trials, sometimes even after the approval has been withdrawn or revoked. Conclusion Cancer drug indications that received accelerated approval often remained on formal FDA approved drug labelling and continued to be recommended in clinical guidelines several years after statutorily required post-approval trials showed no improvement in the primary efficacy endpoint. Clinical guidelines should better align with the results of post-approval trials of cancer drugs that received accelerated approval. No additional data available.

中文翻译:

加速批准抗癌药物的负面验证性试验的监管和临床后果:回顾性观察研究

目的 调查获得美国食品和药物管理局 (FDA) 加速批准但未能改善批准后试验主要终点的抗癌药物的监管处理,并评估负面批准后试验改变的程度治疗指南中的建议。设计回顾性观察研究。设置 FDA 和国家综合癌症网络 (NCCN) 报告。包括获得 FDA 加速批准且批准后试验为阴性的抗癌药物。主要结果措施 监管结果,包括撤回、转换为常规批准和不采取行动。结果 10 种癌症药物获得加速批准但未能改善批准后试验中的主要终点的 18 种适应症被确定。这些,11 种(61%)被制造商自愿撤回,1 种(用于乳腺癌的贝伐珠单抗)被 FDA 撤销。在 11 次提款中,仅 2021 年就发生了 6 次。其余六个 (33%) 适应症保留在标签上。NCCN 指南为批准后试验失败的加速批准药物提供了高水平的认可(1 类认可,1 类认可,7 类认可),有时甚至在批准已被撤回或撤销之后。结论 获得加速批准的癌症药物适应症通常保留在正式的 FDA 批准的药物标签上,并在法定要求的批准后试验表明主要疗效终点没有改善几年后继续在临床指南中推荐。临床指南应更好地与获得加速批准的抗癌药物的批准后试验结果保持一致。没有可用的额外数据。
更新日期:2021-09-09
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