加拿大女王大学Bishal Gyawali团队研究了加速批准癌症药物的阴性验证性试验的监管和临床后果。相关论文于2021年9月9日发表在《英国医学杂志》上。
为了调查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癌症药物的监管处理，并评估负面批准后试验在多大程度上改变了治疗指南中的建议，研究组针对FDA和国家综合癌症网络（NCCN）的报告中获得FDA加速批准且批准后试验为阴性的癌症药物进行了一项回顾性观察研究。主要结局为监管结果，包括撤销、转为定期批准和不采取行动。
研究组共确定了10种癌症药物的18个适应症，这些药物获得了加速批准，但在批准后试验中未能改善主要终点。其中11例（61%）由制造商自愿撤回，1例（用于乳腺癌的贝伐单抗）被FDA撤销。
在11次撤回中，仅2021年就有6次。其余6个（33%）的适应症仍保留在标签上。NCCN指南为那些在批准后试验失败的加速批准药物（有时甚至在批准被撤回或撤销后）提供了高水平的认可（第1类认可为1个，第2A类认可为7个）。
研究结果表明，获得加速批准的癌症药物适应症通常保留在FDA批准的正式药物标签上，并且在法定要求的批准后试验显示主要疗效终点未改善后的几年，继续在临床指南中推荐。研究组呼吁临床指南应更好地与获得加速批准的癌症药物的批准后试验结果保持一致。
附：英文原文
Title: Regulatory and clinical consequences of negative confirmatory trials of accelerated approval cancer drugs: retrospective observational study
Author: Bishal Gyawali, Benjamin N Rome, Aaron S Kesselheim
Issue&Volume: 2021/09/09
Abstract:
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 Of these, 11 (61%) were voluntarily withdrawn by the manufacturer and one (bevacizumab for breast cancer) was revoked by the FDA.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seven) for accelerated approval drugs that have failed post-approval trials, sometimes even after the approval has been withdrawn or revoked.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.
DOI: 10.1136/bmj.n1959
Source: https://www.bmj.com/content/374/bmj.n1959
BMJ-British Medical Journal:《英国医学杂志》，创刊于1840年。隶属于BMJ出版集团，最新IF：93.333
官方网址：http://www.bmj.com/
投稿链接：https://mc.manuscriptcentral.com/bmj
本期文章：《英国医学杂志》：Online/在线发表
