美国食品和药物管理局监管审查员对新疗法的分歧和上市后安全措施。

US Food and Drug Administration regulatory reviewer disagreements and postmarket safety actions among new therapeutics.

机构信息

Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada

Dalhousie University, Halifax, Nova Scotia, Canada.

出版信息

BMJ Evid Based Med. 2023 Jun;28(3):151-156. doi: 10.1136/bmjebm-2022-112005. Epub 2023 Mar 21.

DOI:10.1136/bmjebm-2022-112005

PMID:36944478

Abstract

OBJECTIVES

To examine the association between regulatory reviewer disagreements and postmarket safety actions among novel therapeutics approved by the US Food and Drug Administration (FDA) between 2011 and 2015. Disagreements among FDA reviewers regarding the recommendation for a novel therapeutic's approval, its safety, the indicated patient population and/or other parameters of the drug's approval are common. However, the implications of such disagreements-particularly with respect to postmarket safety actions-are poorly understood.

DESIGN

Cross-sectional study.

SETTING

All novel therapeutics approved by the FDA between January 2011 and December 2015.

PARTICIPANTS

None.

MAIN OUTCOME MEASURES

Postmarket safety actions defined as new label warnings/increased warning severity, FDA safety communications and safety-related therapeutic withdrawals after the original regulatory approval.

RESULTS

Among 174 novel therapeutics approved by the FDA between 2011 and 2015, 42 (24%) had at least one regulatory reviewer disagreement. Altogether, 156 instances of disagreement were observed. Following market approval, a total of 253 postmarket safety actions were taken by the FDA among all new therapeutics, with at least one postmarket safety action identified for 98 (56.3%) of the 174 novel therapeutic approvals. Overall, therapeutics that were the subject of disagreement during the FDA's review had fewer safety actions following approval compared with therapeutics in which no disagreement was observed (38.1% vs 62.1%; RR 0.61, 95% CI 0.41 to 0.92; p=0.006). Therapeutic approvals containing at least one reviewer disagreement also more often carried a black box warning at the point of approval (47.7% vs 31.1%; RR 1.53, 95% CI 1.02 to 2.30; p=0.05).

CONCLUSIONS

This investigation of regulatory reviewer disagreements and postmarket safety actions among new therapeutics suggests that disagreements among regulatory reviewers may lead to important pre-emptive actions, potentially mitigating the need for postmarket safety actions to be taken.

摘要

目的

考察 2011 年至 2015 年间美国食品和药物管理局（FDA）批准的新型治疗药物中监管审查员意见分歧与上市后安全措施之间的关系。FDA 审查员在推荐新型治疗药物的批准、其安全性、适用患者人群和/或药物批准的其他参数方面存在分歧是很常见的。然而，对于这些分歧的影响，尤其是对于上市后安全措施的影响，了解甚少。

设计

横断面研究。

设置

2011 年 1 月至 2015 年 12 月期间 FDA 批准的所有新型治疗药物。

参与者

无。

主要观察指标

上市后安全措施定义为原始监管批准后出现新的标签警示/警示严重程度增加、FDA 安全通讯和与安全相关的药物撤市。

结果

在 2011 年至 2015 年间 FDA 批准的 174 种新型治疗药物中，有 42 种（24%）至少存在一次监管审查员意见分歧。总共观察到 156 次分歧。在市场批准后，FDA 对所有新型治疗药物共采取了 253 项上市后安全措施，在 174 种新型治疗药物批准中，至少有 1 种批准后出现安全措施的药物占 98 种（56.3%）。总体而言，在 FDA 审查过程中存在分歧的治疗药物在批准后采取的安全措施较少，而在没有观察到分歧的治疗药物中则较多（38.1%比 62.1%；RR 0.61，95%CI 0.41 至 0.92；p=0.006）。含有至少一名审查员意见分歧的治疗药物在批准时更常带有黑框警告（47.7%比 31.1%；RR 1.53，95%CI 1.02 至 2.30；p=0.05）。