High-throughput target trial emulation for Alzheimer’s disease drug repurposing with real-world data
Year: 2023
Type: article
Study design: Observational Study
Abstract: Target trial emulation is the process of mimicking target randomized trials using real-world data, where effective confounding control for unbiased treatment effect estimation remains a main challenge. Although various approaches have been proposed for this challenge, a systematic evaluation is still lacking. Here we emulated trials for thousands of medications from two large-scale real-world data warehouses, covering over 10 years of clinical records for over 170 million patients, aiming to identify new indications of approved drugs for Alzheimer's disease. We assessed different propensity score models under the inverse probability of treatment weighting framework and suggested a model selection strategy for improved baseline covariate balancing. We also found that the deep learning-based propensity score model did not necessarily outperform logistic regression-based methods in covariate balancing. Finally, we highlighted five top-ranked drugs (pantoprazole, gabapentin, atorvastatin, fluticasone, and omeprazole) originally intended for other indications with potential benefits for Alzheimer's patients.
Source: Nature Communications
Institutions: Weill Cornell Medicine, University of Florida Health, University of Florida, University of Kentucky, Icahn School of Medicine at Mount Sinai, Cleveland Clinic, Cleveland Clinic Lerner College of Medicine, Case Comprehensive Cancer Center, Case Western Reserve University, University of Connecticut, University of Pennsylvania
Language: English
Subfield: Statistics and Probability
Field: Mathematics
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $6,290
Funders: National Science Foundation, International Business Machines Corporation, National Institutes of Health, National Institute on Aging, National Institute of Mental Health, National Institute on Drug Abuse, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Neurological Disorders and Stroke, U.S. National Library of Medicine
Awards: Multimodal single-cell genomic and epigenomic analyses elucidate Alzheimer’s sexual dimorphism in human immune systems aging, G1110151009, G1254130036, Advancing Drug Repositioning for Alzheimer’s Disease using Real-world Data, G1580824251, G1598070753, Developing Suicide Risk Algorithms for Diverse Clinical Settings using Data Fusion, G2091755577, Post-Acute Sequelae of SARS-CoV-2 Infection and Subsequent Disease Progression in Individuals with AD/ADRD: Influence of the Social and Environmental Determinants of Health, G2601383572, G2654747551, G2742075923, G3398941559, G3583581720, CAREER: Interpretable Deep Modeling of Discrete Time Event Sequences, G4696575845, G4713501941, Alzheimer's Disease and Related Dementia-like Sequelae of SARS-CoV-2 Infection: Virus-Host Interactome, Neuropathobiology, and Drug Repurposing, The benefits and harms of lung cancer screening in Florida, G5002870449, G5062585832, Identification of Mild Cognitive Impairment using Machine Learning from Language and Behavior Markers, AI-ADRD: Accelerating interventions of AD/ADRD via Machine learning methods, Using Electronic Health Records from a Large Clinical Data Research Network to Understand Cancer Burden and Cancer Risks Among Transgender and Gender Nonconforming (TGNC) Individuals, SYSTEMATIC DRUG REPURPOSING TARGETING IMMUNE ACTIVATION NETWORKS IN ALZHEIMER'S DISEASE (AD), G5648657692, Optimizing the Population Representativeness of Older Adults in Alzheimer's Disease and Related Dementia Clinical Trials, G6776800937, G756448444, G805756564, nvestigating the role of neuroinflammation in Limbic-predominant age related TDP43 encephalopathy, G9000027382, G9000030512, G9000036590, G9000047826, G9000053926, G9000076811, G9000079008, G9000217025, G9000264030, G9000314582, G9000319873, Renewal of Centers of Biomedical Research Excellence (COBRE) (Phase 2) CNTN - Resubmission, An end-to-end informatics framework to study Multiple Chronic Conditions (MCC)'s impact on Alzheimer's disease using harmonized electronic health records, TRiPOD: Toward Reusable Phenotypes in Observational Data for AD/ADRD - managing definitions and correcting bias, University of Kentucky Alzheimer's Disease Research Center, Alzheimer's MultiOme Data Repurposing: Artificial Intelligence, Network Medicine, and Therapeutics Discovery, G979114264, G982581970
OpenAlex ID: W4389549989