Early-stage Alzheimer disease: getting trial-ready.
Early-stage Alzheimer disease: getting trial-ready.
复制标题
早期阿尔茨海默病：准备好试验。
DOI：
10.1038/s41582-022-00645-6
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发表时间：
2022-07
期刊：
影响因子：
--
通讯作者：
Raman R
中科院分区：
文献类型：
--
作者：
Aisen PS;Jimenez-Maggiora GA;Rafii MS;Walter S;Raman R
减缓阿尔茨海默病（AD）的进展可能是我们这个时代最大的未满足的医疗需求。虽然一种AD治疗药物已获得FDA有争议的加速批准，但迫切需要更有效和更容易获得的治疗方法。越来越多的共识是，对于AD中有意义的疾病改变，治疗干预必须在疾病的非常早期（临床前或前驱）阶段开始。虽然已经开发了用于这种早期临床试验的方法，但是识别和招募所需的无症状或最小症状的研究参与者需要多年时间，并且需要大量资金。例如，在无症状性阿尔茨海默病的抗淀粉样蛋白治疗试验（第一个在临床前AD中进行的III期试验）中，需要3.5年和超过5，900次筛选才能招募和随机分配1，169名参与者。需要新的临床试验基础设施来提高招募效率并加速治疗进展。北美、欧洲和亚洲的合作正在通过建立临床前和前驱AD患者的试验就绪队列来满足这一需求。这些合作正在采用创新方法来吸引目标人群，评估脑淀粉样蛋白积累的风险，选择生物标志物研究的参与者并确定试验的资格。在未来，这些计划可以提供有效的工具，追求初级预防AD。在这里，我们回顾了迄今为止已经建立的AD试验就绪队列的经验教训，目的是为正在进行的和未来的努力提供信息，以实现高效，具有成本效益的试验招募。越来越多的共识是，在阿尔茨海默病的早期阶段进行干预对疾病的改善是必要的。在这里，作者讨论了招募无症状或轻度症状参与者进行临床试验的挑战，重点是“试验就绪”队列作为一种潜在的解决方案。试验就绪队列是识别符合早期阿尔茨海默病（AD）临床试验条件的参与者的有效策略。建立这些队列需要大量的规划和技术基础设施，以便利征聘、远程纵向评估、数据管理和数据储存。对于遗传决定的AD风险人群，如家族性AD和唐氏综合征患者，存在试验就绪队列;来自这些队列的纵向数据正在提高我们对早期疾病进展的理解，为临床试验设计提供信息，并加速干预研究的招募。到目前为止，早期AD的试验就绪队列所面临的挑战包括难以招募具有种族和种族代表性的队列;对于在线队列，难以留住参与者。正在进行的工作的结果将揭示策略的成功，以提高队列的多样性和保留，以及转诊到临床试验的比率。
Slowing the progression of Alzheimer disease (AD) might be the greatest unmet medical need of our time. Although one AD therapeutic has received a controversial accelerated approval from the FDA, more effective and accessible therapies are urgently needed. Consensus is growing that for meaningful disease modification in AD, therapeutic intervention must be initiated at very early (preclinical or prodromal) stages of the disease. Although the methods for such early-stage clinical trials have been developed, identification and recruitment of the required asymptomatic or minimally symptomatic study participants takes many years and requires substantial funds. As an example, in the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease Trial (the first phase III trial to be performed in preclinical AD), 3.5 years and more than 5,900 screens were required to recruit and randomize 1,169 participants. A new clinical trials infrastructure is required to increase the efficiency of recruitment and accelerate therapeutic progress. Collaborations in North America, Europe and Asia are now addressing this need by establishing trial-ready cohorts of individuals with preclinical and prodromal AD. These collaborations are employing innovative methods to engage the target population, assess risk of brain amyloid accumulation, select participants for biomarker studies and determine eligibility for trials. In the future, these programmes could provide effective tools for pursuing the primary prevention of AD. Here, we review the lessons learned from the AD trial-ready cohorts that have been established to date, with the aim of informing ongoing and future efforts towards efficient, cost-effective trial recruitment. Consensus is growing that intervention in the very early stages of Alzheimer disease is necessary for disease modification. Here, the authors discuss the challenges of recruiting asymptomatic or mildly symptomatic participants for clinical trials, focusing on ‘trial-ready’ cohorts as a potential solution. Trial-ready cohorts are an effective strategy for the identification of participants eligible for clinical trials in early-stage Alzheimer disease (AD). Building these cohorts requires considerable planning and technological infrastructure to facilitate recruitment, remote longitudinal assessment, data management and data storage. Trial-ready cohorts exist for genetically determined populations at risk of AD, such as those with familial AD and Down syndrome; the longitudinal data from these cohorts is improving our understanding of the disease progression in early stages, informing clinical trial design and accelerating recruitment to intervention studies. So far, the challenges experienced by trial-ready cohorts for early-stage AD have included difficulties recruiting an ethnically and racially representative cohort; and for online cohorts, difficulty retaining participants. The results of ongoing work will reveal the success of strategies to improve cohort diversity and retention, and the rates of referral to clinical trials.
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影响因子：
3.9
作者：
Cromer, Jason A.;Harel, Brian T.;Maruff, Paul
通讯作者：
Maruff, Paul
影响因子：
2.9
作者：
Brueton, V. C.;Stevenson, F.;Rait, G.
通讯作者：
Rait, G.
DOI：
10.1177/1471301218789307
发表时间：
2018-11-01
影响因子：
2.4
作者：
Gregory, Sarah;Wells, Katie;Milne, Richard
通讯作者：
Milne, Richard
DOI：
10.1002/trc2.12179
发表时间：
2021
期刊：
Alzheimer's & dementia (New York, N. Y.)
影响因子：
--
作者：
Cummings J;Lee G;Zhong K;Fonseca J;Taghva K
通讯作者：
Taghva K
影响因子：
4
作者：
Darby, David G.;Brodtmann, Amy;Rowe, Christopher
通讯作者：
Rowe, Christopher