Enriching the design of Alzheimer's disease clinical trials: Application of the polygenic hazard score and composite outcome measures.
Enriching the design of Alzheimer's disease clinical trials: Application of the polygenic hazard score and composite outcome measures.
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DOI：
10.1002/trc2.12071
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Alzheimer's Disease Neuroimaging Initiative
中科院分区：
文献类型：
--
作者：
Banks SJ;Qiu Y;Fan CC;Dale AM;Zou J;Askew B;Feldman HH;Alzheimer's Disease Neuroimaging Initiative
选择阿尔茨海默病（AD）痴呆高风险个体并使用最敏感的结局指标是试验设计的重要方面。我们将来自阿尔茨海默病神经影像学倡议的参与者分为多基因危险评分（PHS）预测绝对风险的第50百分位数。结果指标为阿尔茨海默病评估量表-认知子量表（ADAS-Cog）、ADNI-Mem、临床痴呆评定-方框总和（CDR SB）和认知功能复合2（CFC 2）。除了建模之外，我们还使用功效分析来比较每种技术所需的数量。分析了188名认知正常和319名轻度认知受损（MCI）参与者的数据。使用ADAS-Cog估计样本量，不分层超过24个月，将需要930名MCI受试者，而使用CFC 2并将受试者限制在第50百分位数以上的受试者将只需要284名受试者。在MCI患者队列中结合PHS分层和选择敏感的综合结局指标，可以实现更有效的试验设计，对参与者的负担可能更小，更具成本效益。
Selecting individuals at high risk of Alzheimer's disease (AD) dementia and using the most sensitive outcome measures are important aspects of trial design. We divided participants from Alzheimer's Disease Neuroimaging Initiative at the 50th percentile of the predicted absolute risk of the polygenic hazard score (PHS). Outcome measures were the Alzheimer's Disease Assessment Schedule‐Cognitive Subscale (ADAS‐Cog), ADNI‐Mem, Clinical Dementia Rating‐Sum of Boxes (CDR SB), and Cognitive Function Composite 2 (CFC2). In addition to modeling, we use a power analysis compare numbers needed with each technique. Data from 188 cognitively normal and 319 mild cognitively impaired (MCI) participants were analyzed. Using the ADAS‐Cog to estimate sample sizes, without stratification over 24 months, would require 930 participants with MCI, while using the CFC2 and restricting participants to those in the upper 50th percentile would require only 284 participants. Combining stratification by PHS and selection of a sensitive combined outcome measure in a cohort of patients with MCI can allow trial design that is more efficient, potentially less burdensome on participants, and more cost effective.
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影响因子：
2.1
作者：
Sano M;Raman R;Emond J;Thomas RG;Petersen R;Schneider LS;Aisen PS
通讯作者：
Aisen PS
影响因子：
3.2
作者：
Crane, Paul K.;Carle, Adam;Gibbons, Laura E.;Insel, Philip;Mackin, R. Scott;Gross, Alden;Jones, Richard N.;Mukherjee, Shubhabrata;Curtis, S. McKay;Harvey, Danielle;Weiner, Michael;Mungas, Dan
通讯作者：
Mungas, Dan
影响因子：
158.5
作者：
Green, Robert C.;Roberts, J. Scott;Farrer, Lindsay A.
通讯作者：
Farrer, Lindsay A.
DOI：
10.1186/s13195-017-0300-8
发表时间：
2017-09-12
期刊：
Alzheimer's research & therapy
影响因子：
--
作者：
Caldwell JZK;Berg JL;Cummings JL;Banks SJ;Alzheimer’s Disease Neuroimaging Initiative
通讯作者：
Alzheimer’s Disease Neuroimaging Initiative
DOI：
10.1016/j.trci.2018.11.004
发表时间：
2019-01-01
影响因子：
4.8
作者：
Sabbagh, Marwan N.;Hendrix, Suzanne;Harrison, John E.
通讯作者：
Harrison, John E.