• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

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.

DOI:10.1002/trc2.12280
PMID:35356740
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8943597/
Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e7d/8943597/106c48aaf330/TRC2-8-e12280-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e7d/8943597/045441c989d6/TRC2-8-e12280-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e7d/8943597/e45daa9cf32e/TRC2-8-e12280-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e7d/8943597/442a6aea09e6/TRC2-8-e12280-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e7d/8943597/beec0d88fdc0/TRC2-8-e12280-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e7d/8943597/106c48aaf330/TRC2-8-e12280-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e7d/8943597/045441c989d6/TRC2-8-e12280-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e7d/8943597/e45daa9cf32e/TRC2-8-e12280-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e7d/8943597/442a6aea09e6/TRC2-8-e12280-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e7d/8943597/beec0d88fdc0/TRC2-8-e12280-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e7d/8943597/106c48aaf330/TRC2-8-e12280-g004.jpg

相似文献

1
Impact of non-binding FDA guidances on primary endpoint selection in Alzheimer's disease trials.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
Alzheimers Dement (N Y). 2022 Mar 24;8(1):e12280. doi: 10.1002/trc2.12280. eCollection 2022.
2
Souvenaid for Alzheimer's disease.用于治疗阿尔茨海默病的苏威艾迪。
Cochrane Database Syst Rev. 2020 Dec 15;12(12):CD011679. doi: 10.1002/14651858.CD011679.pub2.
3
Evaluation of the efficacy, safety and tolerability of orally administered BI 409306, a novel phosphodiesterase type 9 inhibitor, in two randomised controlled phase II studies in patients with prodromal and mild Alzheimer's disease.评价新型磷酸二酯酶 9 抑制剂 BI 409306 口服制剂在伴有前驱期和轻度阿尔茨海默病的患者中进行的两项随机对照 2 期研究中的疗效、安全性和耐受性。
Alzheimers Res Ther. 2019 Feb 12;11(1):18. doi: 10.1186/s13195-019-0467-2.
4
Rethinking the Food and Drug Administration's 2013 guidance on developing drugs for early-stage Alzheimer's disease.重新审视美国食品药品监督管理局2013年关于开发早期阿尔茨海默病药物的指南。
Alzheimers Dement. 2014 Mar;10(2):247-50. doi: 10.1016/j.jalz.2013.12.002.
5
Longitudinal Exposure-Response Modeling of Multiple Indicators of Alzheimer's Disease Progression.阿尔茨海默病进展多项指标的纵向暴露-反应建模。
J Prev Alzheimers Dis. 2023;10(2):212-222. doi: 10.14283/jpad.2023.13.
6
Blood biomarkers as surrogate endpoints of treatment responses to aerobic exercise and cognitive training (ACT) in amnestic mild cognitive impairment: the blood biomarkers study protocol of a randomized controlled trial (the ACT Trial).血液生物标志物作为有氧运动和认知训练（ACT）治疗反应的替代终点在遗忘型轻度认知障碍中的应用：一项随机对照试验（ACT 试验）的血液生物标志物研究方案。
Trials. 2020 Jan 6;21(1):19. doi: 10.1186/s13063-019-3798-1.
7
Guidance for industry: patient-reported outcome measures: use in medical product development to support labeling claims: draft guidance.行业指南：患者报告的结局指标：用于医疗产品开发以支持标签声明：指南草案
Health Qual Life Outcomes. 2006 Oct 11;4:79. doi: 10.1186/1477-7525-4-79.
8
9
Minimal clinically important difference in Alzheimer's disease: Rapid review.阿尔茨海默病的最小临床重要差异：快速综述。
Alzheimers Dement. 2024 May;20(5):3352-3363. doi: 10.1002/alz.13770. Epub 2024 Apr 1.
10
The Alzheimer's Prevention Initiative Generation Program: Study design of two randomized controlled trials for individuals at risk for clinical onset of Alzheimer's disease.阿尔茨海默病预防倡议代际项目：针对有阿尔茨海默病临床发病风险个体的两项随机对照试验的研究设计。
Alzheimers Dement (N Y). 2019 Jun 12;5:216-227. doi: 10.1016/j.trci.2019.02.005. eCollection 2019.

引用本文的文献

1
A novel longitudinal rank-sum test for multiple primary endpoints in clinical trials: Applications to neurodegenerative disorders.一种用于临床试验中多个主要终点的新型纵向秩和检验：在神经退行性疾病中的应用。
Stat Biopharm Res. 2025 Mar 17. doi: 10.1080/19466315.2025.2458018.
2
Emerging Alzheimer's disease treatment paradigms: A late-stage clinical trial review.新兴的阿尔茨海默病治疗模式：晚期临床试验综述。
Alzheimers Dement (N Y). 2024 Dec 27;10(4):e70022. doi: 10.1002/trc2.70022. eCollection 2024 Oct-Dec.

本文引用的文献

1
Food and Drug Administration Guidance Documents and New Medical Devices: The Case of Breast Prostheses.食品药品监督管理局指导文件与新型医疗器械：以乳房假体为例。
Am J Ther. 2021;28(1):e127-e130. doi: 10.1097/MJT.0000000000000888.
2
Alzheimer's disease drug development pipeline: 2020.2020年阿尔茨海默病药物研发进展
Alzheimers Dement (N Y). 2020 Jul 16;6(1):e12050. doi: 10.1002/trc2.12050. eCollection 2020.
3
Choosing primary endpoints for clinical trials of health care interventions.选择医疗保健干预措施临床试验的主要终点。
Contemp Clin Trials Commun. 2019 Nov 12;16:100486. doi: 10.1016/j.conctc.2019.100486. eCollection 2019 Dec.
4
Alzheimer's disease drug development pipeline: 2019.2019年阿尔茨海默病药物研发进程
Alzheimers Dement (N Y). 2019 Jul 9;5:272-293. doi: 10.1016/j.trci.2019.05.008. eCollection 2019.
5
Primary Endpoints in Current Phase II/III Trials for Alzheimer Disease: A Systematic Survey of Trials Registered at ClinicalTrials.gov.当前阿尔茨海默病 II/III 期临床试验的主要终点：对 ClinicalTrials.gov 注册试验的系统调查。
Alzheimer Dis Assoc Disord. 2020 Jan-Mar;34(1):97-100. doi: 10.1097/WAD.0000000000000297.
6
Understanding the Use of Composite Endpoints in Clinical Trials.理解临床试验中复合终点的应用。
West J Emerg Med. 2018 Jul;19(4):631-634. doi: 10.5811/westjem.2018.4.38383. Epub 2018 Jun 4.
7
Alzheimer's disease drug development pipeline: 2018.2018年阿尔茨海默病药物研发进展
Alzheimers Dement (N Y). 2018 May 3;4:195-214. doi: 10.1016/j.trci.2018.03.009. eCollection 2018.
8
The importance of endpoint selection: How effective does a drug need to be for success in a clinical trial of a possible Alzheimer's disease treatment?终点选择的重要性：在一项可能用于治疗阿尔茨海默病的临床试验中，药物需要达到多高的疗效才能取得成功？
Eur J Epidemiol. 2018 Jul;33(7):635-644. doi: 10.1007/s10654-018-0381-0. Epub 2018 Mar 23.
9
Alzheimer's disease drug development pipeline: 2017.2017年阿尔茨海默病药物研发进展
Alzheimers Dement (N Y). 2017 May 24;3(3):367-384. doi: 10.1016/j.trci.2017.05.002. eCollection 2017 Sep.
10
Alzheimer's drug-development pipeline: 2016.2016年阿尔茨海默病药物研发进展
Alzheimers Dement (N Y). 2016 Aug 17;2(4):222-232. doi: 10.1016/j.trci.2016.07.001. eCollection 2016 Nov.