Global Alzheimer's Platform Trial-Ready Cohort for Preclinical/Prodromal Alzheimer's Disease

全球阿尔茨海默病平台 临床前/前驱阿尔茨海默病试验就绪队列（GAP TRC-PAD） 学术PI：Paul Aisen，Reisa Sperling，Jeff Cummings 总结 越来越多的人认识到阿尔茨海默病（AD）的痴呆前阶段很长， 最佳干预时间旨在改变疾病的神经生物学，最新的药物开发 该项目招募处于临床前/无症状和前驱/轻度认知障碍阶段的参与者。 然而，招聘过程和网站激活的时间表，复杂性和费用， 二级预防试验极具挑战性，实际上，一般来说， 是AD药物开发的最大瓶颈。因此，在我们的领域中，越来越多的人一致认为， 我们必须从根本上彻底改革目前的临床试验招募和评估过程， 干预试验。该提案的总体目标是加快当前和未来的二级预防 通过创新、高效的方法进行试验入组，以识别、评估和入组适当的 临床前和前驱试验候选人，由新的研究中心网络提供支持，该网络具有更强的能力， 高效和有效地进行AD临床试验。我们认为，这只能通过一个 这个项目和差距基金会之间的公私合作伙伴关系，GAP伙伴关系。年开始 2014年初，全球阿尔茨海默病平台（GAP）汇集了学术，工业，宣传和其他 阿尔茨海默氏症的领导者，以确定必要的组成部分，以建立大型的“试验就绪队列”（TRC）， 临床前/前驱AD（PAD）试验（TRC-PAD），并支持预先合格的“试验就绪”网络（GAP-Net） 临床和生物标志物评估所需的特定专业知识和统一流程， 预防试验。本项目的具体目标是建立一个大型TRC-PAD（n=2000; 1000 临床前/1000例前驱AD），以便于使用GAP-Net框架纳入正在进行的PAD试验。 本申请描述了将现有“支线”登记研究和研究连接到GAP登记研究的过程， 获取老年人、非痴呆患者的人口统计学、遗传学和纵向临床和认知信息， 对审判感兴趣的人。登记数据生成AD病理学的风险评分（最初升高 脑中的淀粉样蛋白，但采用适用于tau病理学和其他生物标志物的方法）， 选择候选人进行现场生物标志物（最初是淀粉样蛋白PET扫描）和临床评估。的 这些评估的结果，反过来，允许自适应的统计算法，以改善选择过程 向前看PET扫描显示大脑中淀粉样蛋白积聚（或替代生物标志物）的个体 确认）被邀请加入差距队列，并在GAP网络内进行半年一次的亲自随访 通过资格预审的临床研究中心网络，他们可以被邀请参加早期试验。总体看 这一过程将大大缩短临床前/前驱试验的时间轴，并将解决一系列科学问题。 假设，以指导该领域的进一步发展。

Global Alzheimer's Platform Trial-Ready Cohort for Preclinical/Prodromal Alzheimer's Disease (GAP TRC-PAD) Academic PIs: Paul Aisen, Reisa Sperling, Jeff Cummings SUMMARY Based on growing recognition that the long pre-dementia stages of Alzheimer's disease (AD) represent the optimal time for interventions aimed at modifying the neurobiology of the disease, most recent drug development programs enroll participants at the preclinical/asymptomatic and prodromal/mild cognitive impairment stages. However, the timeframe, complexity and expense of the recruitment process and site activation for these secondary prevention trials are extremely challenging, and indeed site start-up and trial enrollment, in general, represent the greatest bottleneck for drug development for AD. Thus, there is growing consensus in our field that we must fundamentally overhaul the current clinical trial recruitment and assessment process for these early intervention trials. The overarching goal of this proposal is to accelerate current and future secondary prevention trial enrollment through an innovative, highly efficient approach to identify, evaluate, and enroll appropriate preclinical and prodromal trial candidates, supported by a new site network with enhanced capacities for more efficient and effective conduct of AD clinical trials. It is our view that this can be accomplished only through a public-private partnership, the GAP Partnership, between this project and the GAP Foundation. Beginning in early 2014, the Global Alzheimer Platform (GAP) brought together academic, industry, advocacy and other Alzheimer's leaders to identify the necessary components to build large “trial-ready cohorts” (TRC) for preclinical/prodromal AD (PAD) trials (TRC-PAD) and to support a network (GAP-Net) of pre-qualified “trial-ready sites” with specific expertise in and uniform processes for the clinical and biomarker assessments required for prevention trials. The specific goal of the current project is to build a large TRC-PAD (n=2000; 1000 preclinical/1000 prodromal AD), to facilitate enrollment into ongoing PAD trials using the GAP-Net framework. This application describes a process of connecting existing “feeder” registries and studies to a GAP Registry to capture demographic, genetic and longitudinal clinical and cognitive information on older, non-demented individuals interested in trials. The Registry data generates risk scores for AD pathology (initially elevated amyloid in brain, but with methods adaptable to tau pathology and other biomarkers), that allows efficient selection of candidates for in-person biomarker (initially amyloid PET scans) and clinical assessment. The results of these assessments, in turn, allow an adaptive statistical algorithm to improve the selection process moving forward. Individuals with PET scans showing amyloid accumulation in brain (or alternative biomarker confirmation) are invited to join the GAP Cohort, with semi-annual in-person follow-up within the GAP-Net network of pre-qualified clinical sites, from which they can be invited to enroll in early stage trials. Overall, the process will dramatically shorten the timeline for preclinical/prodromal trials, and will address a series of scientific hypotheses to guide further development in the field.