Wolz Robin, Schwarz Adam J, Gray Katherine R, Yu Peng, Hill Derek L G
From IXICO Plc (R.W., K.R.G., D.L.G.H.), London, UK; Department of Computing (R.W., K.R.G.,), Imperial College London, UK; Eli Lilly and Company (A.J.S., P.Y.), Indianapolis, IN; Department of Psychology and Brain Sciences (A.J.S.), Indiana University, Bloomington; and Department of Radiology and Imaging Sciences (A.J.S.), Indiana University School of Medicine, Indianapolis.
Neurology. 2016 Sep 20;87(12):1235-41. doi: 10.1212/WNL.0000000000003126. Epub 2016 Aug 24.
To investigate the effect of enriching mild cognitive impairment (MCI) clinical trials using combined markers of amyloid pathology and neurodegeneration.
We evaluate an implementation of the recent National Institute for Aging-Alzheimer's Association (NIA-AA) diagnostic criteria for MCI due to Alzheimer disease (AD) as inclusion criteria in clinical trials and assess the effect of enrichment with amyloid (A+), neurodegeneration (N+), and their combination (A+N+) on the rate of clinical progression, required sample sizes, and estimates of trial time and cost.
Enrichment based on an individual marker (A+ or N+) substantially improves all assessed trial characteristics. Combined enrichment (A+N+) further improves these results with a reduction in required sample sizes by 45% to 60%, depending on the endpoint.
Operationalizing the NIA-AA diagnostic criteria for clinical trial screening has the potential to substantially improve the statistical power of trials in MCI due to AD by identifying a more rapidly progressing patient population.
探讨使用淀粉样蛋白病理学和神经退行性变的联合标志物丰富轻度认知障碍（MCI）临床试验的效果。
我们评估了将近期美国国立衰老研究所-阿尔茨海默病协会（NIA-AA）针对阿尔茨海默病（AD）所致MCI的诊断标准作为临床试验纳入标准的实施情况，并评估了用淀粉样蛋白（A+）、神经退行性变（N+）及其组合（A+N+）进行富集对临床进展率、所需样本量以及试验时间和成本估计的影响。
基于单个标志物（A+或N+）的富集显著改善了所有评估的试验特征。联合富集（A+N+）进一步改善了这些结果，所需样本量减少了45%至60%，具体取决于终点指标。
将NIA-AA诊断标准用于临床试验筛查，通过识别进展更快的患者群体，有可能显著提高AD所致MCI试验的统计效力。
