Division of Pharmacotherapy & Experimental Therapeutics, UNC Eshelman School of Pharmacy, 301 Pharmacy Lane, Chapel Hill, NC, 27599, USA.
Ther Innov Regul Sci. 2021 Jan;55(1):98-110. doi: 10.1007/s43441-020-00194-4. Epub 2020 Aug 6.
Cases of discordance between the US Food and Drug Administration (FDA) and its advisory committees are uncommon. Due to the importance of oncology therapies, we sought to identify and discuss instances of disagreement between the regulatory decision made by FDA, and the recommendation made by its Oncologic Drugs Advisory Committee (ODAC) via committee vote. Public databases (Oncologic Drugs Advisory Committee Meeting Materials, Drugs@FDA) as well as publicly available documents from ODAC meetings were reviewed to discern cases of disagreement between the two bodies. This review of public data yielded six (6) instances in which FDA's ultimate regulatory decision went against the recommendation of the ODAC. The six cases are briefly discussed and key drivers for or against an approval decision are outlined. In cases where FDA's decision was less conservative than that of the ODAC, the value of therapies with novel mechanisms of action which provide new options for patients, as well as regulatory precedent were observed as key drivers for regulatory decision-making. In cases where FDA took a more conservative approach than the ODAC, the importance of appropriate clinical trial design, clinically relevant trial endpoints, and the integrity of the data collected were stressed as driving the ultimate regulatory decision.
美国食品和药物管理局（FDA）与其顾问委员会之间出现意见不一致的情况并不常见。鉴于肿瘤治疗的重要性，我们试图通过委员会投票来确定并讨论 FDA 做出的监管决定与肿瘤药物顾问委员会（ODAC）提出的建议之间存在分歧的情况。我们查阅了公共数据库（肿瘤药物顾问委员会会议资料、Drugs@FDA）以及 ODAC 会议的公开文件，以辨别这两个机构之间存在分歧的情况。对公共数据的审查共发现 6 例 FDA 的最终监管决定与 ODAC 建议相悖的情况。简要讨论了这 6 个案例，并概述了赞成或反对批准决定的关键驱动因素。在 FDA 的决定比 ODAC 更不保守的情况下，具有新颖作用机制的治疗方法为患者提供了新的选择，以及监管先例被视为监管决策的关键驱动因素。在 FDA 采取比 ODAC 更保守的方法的情况下，适当的临床试验设计、与临床相关的试验终点以及所收集数据的完整性被强调为推动最终监管决策的关键因素。
