美国食品药品监督管理局非约束性指南对阿尔茨海默病试验中主要终点选择的影响
Impact of non-binding FDA guidances on primary endpoint selection in Alzheimer's disease trials.
作者信息
Yu Jeffrey C, Hlávka Jakub P, Joe Elizabeth, Richmond Frances J, Lakdawalla Darius N
机构信息
School of Pharmacy University of Southern California Los Angeles California USA.
Leonard D. Schaeffer Center for Health Policy & Economics Los Angeles California USA.
出版信息
Alzheimers Dement (N Y). 2022 Mar 24;8(1):e12280. doi: 10.1002/trc2.12280. eCollection 2022.
INTRODUCTION
The U.S. Food and Drug Administration (FDA)'s guidances help describe the agency's current thinking on regulatory issues and serve as a means of informal policymaking that is non-binding. This study examines the impact of two guidance documents for Alzheimer's disease (AD) trials. The first guidance in 2013 encouraged the use of cognitive/functional endpoints, while the second in 2018 modified such recommendation.
METHODS
Using pivotal trial data, we applied a regression discontinuity in time (RDiT) framework to examine trialist response to these guidance documents. Results were stratified by disease-modifying therapy (DMT) status, and controlled for disease staging, FDA registration status, and trial phase.
RESULTS
Among AD DMT trials, annual use of cognitive/functional composite endpoints significantly increased after the 2013 guidance (+12.9%, < .001), and significantly decreased after the 2018 guidance (-19.9%, = .022).
DISCUSSION
Although guidance documents do not set new legal standards or impose binding requirements, our findings indicate they are broadly followed by AD trialists.
引言
美国食品药品监督管理局（FDA）的指南有助于阐述该机构目前对监管问题的看法，并作为一种不具约束力的非正式政策制定方式。本研究考察了两份针对阿尔茨海默病（AD）试验的指南文件的影响。2013年的第一份指南鼓励使用认知/功能终点指标，而2018年的第二份指南对该建议进行了修改。
方法
利用关键试验数据，我们应用时间回归断点（RDiT）框架来考察试验者对这些指南文件的反应。结果按疾病修饰疗法（DMT）状态进行分层，并对疾病分期、FDA注册状态和试验阶段进行了控制。
结果
在AD DMT试验中，2013年指南发布后，认知/功能复合终点指标的年度使用显著增加（+12.9%，<0.001），而在2018年指南发布后显著下降（-19.9%，=0.022）。
讨论
尽管指南文件没有设定新的法律标准或施加具有约束力的要求，但我们的研究结果表明，AD试验者广泛遵循这些指南。
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