Yu Jeffrey C, Hlávka Jakub P, Joe Elizabeth, Richmond Frances J, Lakdawalla Darius N
School of Pharmacy University of Southern California Los Angeles California USA.
Leonard D. Schaeffer Center for Health Policy & Economics Los Angeles California USA.
Alzheimers Dement (N Y). 2022 Mar 24;8(1):e12280. doi: 10.1002/trc2.12280. eCollection 2022.
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.
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.
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).
Although guidance documents do not set new legal standards or impose binding requirements, our findings indicate they are broadly followed by AD trialists.
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。
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。
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）。
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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