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/先兆阿尔茨海默病的试验就绪队列(GAP TRC-PAD) 学术个人资料：保罗·艾森、雷萨·斯珀林、杰夫·卡明斯 摘要 基于越来越多的人认识到阿尔茨海默病(AD)的漫长痴呆前期阶段代表着 旨在修改疾病神经生物学、最新药物开发的干预措施的最佳时间 该计划招收临床前/无症状和前驱/轻度认知障碍阶段的参与者。 然而，招聘过程和现场激活的时间框架、复杂性和费用 二级预防试验极具挑战性，而且确实是现场启动和试验登记，总的来说， 是AD药物开发的最大瓶颈。因此，我们这个领域越来越多的共识是 我们必须从根本上彻底改革目前的临床试验招募和评估程序，以便及早 干预试验。这项提案的首要目标是加速当前和未来的二级预防 通过创新、高效的方法进行试用登记，以确定、评估和登记适当 临床前和先兆试验候选者，由一个新的站点网络支持，该网络增强了对更多 高效、有效地开展AD临床试验。我们认为，这只能通过一个 这个项目和GAP基金会之间的公私伙伴关系，GAP伙伴关系。开始于 2014年初，全球阿尔茨海默病平台(GAP)汇集了学术界、工业界、倡导者和其他 阿尔茨海默氏症的领导者确定必要的组件来为以下患者建立大型“试验就绪队列”(TRC) 临床前/前驱AD(PAD)试验(TRC-PAD)，并支持预先合格的网络(GAP-Net) 具有临床和生物标记物评估所需的特定专业知识和统一流程的站点 预防试验。目前项目的具体目标是建造一个大型TRC-PAD(n=2000；1000 临床前/1000先兆AD)，以促进使用GAP-Net框架参加正在进行的PAD试验。 本申请描述了将现有的“Feeder”注册表和研究连接到GAP注册表的过程，以 获取老年人、非痴呆者的人口统计、遗传和纵向临床及认知信息 对试验感兴趣的个人。注册表数据为AD病理生成风险分数(最初为高 大脑中的淀粉样蛋白，但具有适应tau病理和其他生物标志物的方法)，这使得高效 选择面对面生物标记物(最初是淀粉样蛋白PET扫描)和临床评估的候选者。这个 这些评估的结果反过来又允许自适应统计算法来改进选择过程 继续前进。PET扫描显示淀粉样蛋白在大脑中积聚(或替代生物标记物)的个人 确认)被邀请加入GAP队列，并在GAP-Net内进行半年一次的面对面跟踪 资格预审的临床站点网络，他们可以被邀请参加早期试验。总体而言， 这一过程将大大缩短临床前/前驱试验的时间线，并将解决一系列科学问题 指导该领域进一步发展的假设。

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.