Alzheimer's Clinical Trial InnOvatioN (ACTION) Initiative

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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.