Alzheimer's Clinical Trial InnOvatioN (ACTION) Initiative

摘要 国家老年痴呆症和相关痴呆症研究所的研究实施 Mildman阐明了该研究所推进阿尔茨海默病（AD）研究的目标。的 AD和相关疾病领导奖要求申请人解决 对新的和早期的调查人员进行培训和指导。所提出的研究必须 是突破性的和改变模式的。在《执行战略》的八个重点领域中， Milestone的框架是试验创新和翻译以及临床研究-药理学。 这里提出的阿尔茨海默氏症临床试验创新（行动）倡议包括 研究和指导方面的领导奖。行动倡议将包括 开发临床试验观察站（CTO）和嵌入式导师计划。捕捉和模板化寡 建立在主要研究者对clinicaltrials.gov的先前分析的基础上。这个联邦登记处包含了所有 在美国进行的试验和在美国境外进行的许多试验。它包括1期、2期和3期临床试验 临床前、前驱期和AD痴呆试验。PI进行并发表了关于 试验设计、生物标志物和来自登记研究的临床结局数据。2016年，国会通过了一项法律， 要求在试验完成后1年内在网站上公布试验结果。PI建议 建立一个由工程师、计算机科学家、统计学家和生物信息学专家组成的多学科团队 使用人工智能技术询问现在可用的数据范围， 学习和深度学习。一个外部咨询委员会将确保质量和传播。的 阿尔茨海默氏症协会将合作传播结果。一个可访问的门户网站， 数据库将使审查的数据随时可用于分析和预测/建模的计划 临床试验不断增长的真实世界AD试验数据库将允许越来越精确的预测 基于基线特征、下降轨迹、药物治疗、 机制以及AD所有阶段的临床和生物标志物特征。数据使用 由PI、学员、学术试验领导者和行业试验赞助商提供。确定了三名初始学员 从神经心理学，精神病学和工程学;更多的将增加与该计划的增长。的 ACTION Initiative有可能改变临床试验计划和结果， 对NIA实施里程碑的影响，并加速新疗法的开发， AD患者和有风险的患者。学员将为AD药物开发和临床的未来提供动力 审判计划

Abstract The National Institute on Aging Alzheimer's Disease and Related Dementias Research Implementation Milestones articulate the goals of the Institute for advancing Alzheimer's disease (AD) research. The Leadership Award for AD and Related Disorders requires that the applicant address objectives of the Milestones and provide mentorship to new and early stage investigators. The research proposed must be groundbreaking and paradigm changing. Among the eight focus areas within the Implementation Milestones' framework are Trial Innovation and Translation and Clinical Research – Pharmacological. The Alzheimer's Clinical Trial InnOvationN (ACTION) Initiative proposed here embraces both the research and mentoring aspects of the Leadership Award. The ACTION Initiative will include development of a Clinical Trials Observatory (CTO) and an embedded mentorship program. The CTO builds on the principal investigator's prior analyses of clinicaltrials.gov. This federal registry contains all trials conducted in the US and many trials conducted ex-US. It includes Phase 1, 2 and 3 clinical trials of preclinical, prodromal, and AD dementia trials. The PI has conducted and published research on the trial design, biomarker, and clinical outcomes data from the registry. In 2016, Congress passed a law requiring that trial outcomes be posted on the site within 1 year of completion of the trial. The PI proposes to build a multi-disciplinary team of engineers, computer scientists, statisticians, and bioinformatic experts to interrogate the range of data now available using artificial intelligence techniques including machine learning and deep learning. An external advisory committee will ensure quality and dissemination. The Alzheimer's Association will collaborate on results dissemination. An accessible web portal for the database will make reviewed data readily available for analyses and prediction/modeling of planned clinical trials. The growing database of real-world AD trial data will allow increasingly precise prediction of trial outcomes based on complex relationships among baseline features, trajectories of decline, drug mechanisms, and clinical and biomarker characteristics across all stages of AD. The data will be used by the PI, mentees, academic trial leaders, and industry trial sponsors. Three initial mentees are identified from neuropsychology, psychiatry, and engineering; more will be added with growth of the program. The ACTION Initiative has the potential to transform clinical trial planning and outcomes, leading to substantial impact on the Implementation Milestones of the NIA and accelerating development of new therapies for patients with AD and those at risk. Mentees will power the future of AD drug development and clinical trial planning.