@article{9ec6c445b1ad4a8b82fad0529d57f873,
title = "Machine learning predictive models can improve efficacy of clinical trials for Alzheimer's disease",
abstract = "Background: The ideal participants for Alzheimer's disease (AD) clinical trials would show cognitive decline in the absence of treatment (i.e., placebo arm) and also would be responsive to the therapeutic intervention being studied (i.e., drug arm). One strategy to boost the power of trials is to enroll individuals who are more likely to progress targeted using data-driven predictive models. Objective: To investigate if machine learning (ML) models can effectively predict clinical disease progression (cognitive decline) in mild-to-moderate AD patients during the timeframe of a phase III clinical trial. Methods: Data from 202 participants with a diagnosis of AD at baseline from the Alzheimer's Disease Neuroimaging Initiative (ADNI) was used to train ML classifiers that can differentiate between individuals who had declining cognitive function (DC) and individuals with stable cognitive function (SC). DC was defined as any downward change in the Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog) score over 12 months of follow-up. SC was defined by the absence of decline in ADAS-cog. Trained models were applied to data from 77 participants from the placebo arm of the phase III trial of Semagacestat (LFAN study) to identify subgroups of SC versus DC. Results: Only 74.8% of ADNI participants and 63.6% of LFAN participants had cognitive decline after one year of follow up. K-nearest neighbors (kNN) classifier had an accuracy of 68.3%, sensitivity of 80.1%, and specificity of 33.3% for identifying decliners in ADNI (training sample). In LFAN (validation sample), the model showed an overall accuracy of 61.3%, sensitivity of 65.5%, and specificity of 47.0% in identifying decliners at the 12 months of follow-up. The model had a positive predictive value of 80.8%, which was 17.2% more than the base prevalence of decliners. Conclusions: Machine learning predictive models can be effectively used to boost the power of clinical trials by reducing the sample size.",
keywords = "Alzheimer's disease, clinical trial, cognitive decline, machine learning, predictive analytics",
author = "Ali Ezzati and Lipton, {Richard B.}",
note = "Funding Information: This work was supported by grants from the Alzheimer{\textquoteright}s Association (Ezzati, 2019-AACSF-641329), and the Leonard and Sylvia Marx Foundation (PI: Lipton). Dr. Lipton is also supported by grants from National Institutes of Health NIA 2 P01 AG03949, NIA 1R01AG039409-01, and the Czap Foundation. Funding Information: This work was supported by grants from the Alzheimer's Association (Ezzati, 2019-AACSF-641329), and the Leonard and Sylvia Marx Foundation (PI: Lipton). Dr. Lipton is also supported by grants from National Institutes of Health NIA 2 P01 AG03949, NIA 1R01AG039409-01, and the Czap Foundation. Funding Information: Data collection and sharing for this project was funded by the Alzheimer{\textquoteright}s Disease Neuroimag-ing Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer{\textquoteright}s Association; Alzheimer{\textquoteright}s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujire-bio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; Neu-roRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (http://www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer{\textquoteright}s Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. Publisher Copyright: {\textcopyright} 2020 - IOS Press and the authors. All rights reserved.",
year = "2020",
doi = "10.3233/JAD-190822",
language = "English (US)",
volume = "74",
pages = "55--63",
journal = "Journal of Alzheimer's Disease",
issn = "1387-2877",
publisher = "IOS Press",
number = "1",
}