Sample size estimates for biomarker-based outcome measures in clinical trials in autosomal dominant Alzheimer's disease.

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The Journal of Prevention of Alzheimer's Disease Pub Date : 2025-03-20 DOI:10.1016/j.tjpad.2025.100133

David M Cash, Katy E Morgan, Antoinette O'Connor, Thomas D Veale, Ian B Malone, Teresa Poole, Tammie Ls Benzinger, Brian A Gordon, Laura Ibanez, Yan Li, Jorge J Llibre-Guerra, Eric McDade, Guoqiao Wang, Jasmeer P Chhatwal, Gregory S Day, Edward Huey, Mathias Jucker, Johannes Levin, Yoshiki Niimi, James M Noble, Jee Hoon Roh, Racquel Sánchez-Valle, Peter R Schofield, Randall J Bateman, Chris Frost, Nick C Fox

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引用次数: 0

Abstract

Introduction: Alzheimer disease (AD)-modifying therapies are approved for treatment of early-symptomatic AD. Autosomal dominant AD (ADAD) provides a unique opportunity to test therapies in presymptomatic individuals.

Methods: Using data from the Dominantly Inherited Alzheimer Network (DIAN), sample sizes for clinical trials were estimated for various cognitive, imaging, and CSF outcomes. Sample sizes were computed for detecting a reduction of either absolute levels of AD-related pathology (amyloid, tau) or change over time in neurodegeneration (atrophy, hypometabolism, cognitive change).

Results: Biomarkers measuring amyloid and tau pathology had required sample sizes below 200 participants per arm (examples CSF Aβ42/40: 47[95 %CI 25,104], cortical PIB 49[28,99], CSF p-tau181 74[48,125]) for a four-year trial in presymptomatic individuals (CDR=0) to have 80 % power (5 % statistical significance) to detect a 25 % reduction in absolute levels of pathology, allowing 40 % dropout. For cognitive, MRI, and FDG, it was more appropriate to detect a 50 % reduction in rate of change. Sample sizes ranged from 250 to 900 (examples hippocampal volume: 338[131,2096], cognitive composite: 326[157,1074]). MRI, FDG and cognitive outcomes had lower sample sizes when including indivduals with mild impairment (CDR=0.5 and 1) as well as presymptomatic individuals (CDR=0).

Discussion: Despite the rarity of ADAD, presymptomatic clinical trials with feasible sample sizes given the number of cases appear possible.

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常染色体显性阿尔茨海默病临床试验中基于生物标志物的结果测量的样本量估计。

导言：阿尔茨海默病（AD）改良疗法已被批准用于治疗早期症状性AD。常染色体显性遗传性阿尔茨海默病（ADAD）为在无症状个体中测试疗法提供了一个独特的机会：方法：利用常染色体显性遗传阿尔茨海默病网络（DIAN）的数据，估算了各种认知、影像和脑脊液结果的临床试验样本量。计算样本量的目的是检测AD相关病理（淀粉样蛋白、tau）绝对水平的降低或神经退行性变（萎缩、代谢低下、认知变化）随时间的变化：测量淀粉样蛋白和tau病理学的生物标志物要求每组样本量低于200人（例如，CSF Aβ42/40：47[95 %CI 25,104]，皮质PIB 49[28,99]，CSF p-tau181 74[48,125]），对无症状者（CDR=0）进行为期四年的试验，在允许40%辍学的情况下，80%的功率（5%统计显著性）可检测到病理学绝对水平降低25%。对于认知、核磁共振成像和 FDG，检测变化率减少 50% 更为合适。样本量从 250 到 900 不等（海马体积示例：338[131,2096]，认知综合：326[157,1074]）：326[157,1074]).MRI、FDG和认知结果的样本量在包括轻度受损者（CDR=0.5和1）以及无症状者（CDR=0）时较低：讨论：尽管ADAD非常罕见，但考虑到病例数量，无症状临床试验的样本量似乎是可行的。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

The Journal of Prevention of Alzheimer's Disease Medicine-Psychiatry and Mental Health

CiteScore

9.20

自引率

0.00%

发文量

期刊介绍： The JPAD Journal of Prevention of Alzheimer’Disease will publish reviews, original research articles and short reports to improve our knowledge in the field of Alzheimer prevention including: neurosciences, biomarkers, imaging, epidemiology, public health, physical cognitive exercise, nutrition, risk and protective factors, drug development, trials design, and heath economic outcomes.JPAD will publish also the meeting abstracts from Clinical Trial on Alzheimer Disease (CTAD) and will be distributed both in paper and online version worldwide.We hope that JPAD with your contribution will play a role in the development of Alzheimer prevention.