A deep learning framework for drug repurposing via emulating clinical trials on real-world patient data

• Published in: Nature machine intelligence Vol. 3; no. 1; pp. 68 - 75
• Main Authors: Liu, Ruoqi, Wei, Lai, Zhang, Ping
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.01.2021; Nature Publishing Group
• Subjects: 631/114/1305; 631/114/2164; 631/114/2397; 692/308/153; Cardiovascular disease; Clinical trials; Codes; Coronary artery disease; Datasets; Deep learning; Demographics; Drugs; Electronic health records; Engineering; Ingredients; Medical research; Patients; Prescription drugs; Subject specialists
• ISSN: 2522-5839; 2522-5839
• DOI: 10.1038/s42256-020-00276-w

Drug repurposing is an effective strategy to identify new uses for existing drugs, providing the quickest possible transition from bench to bedside. Real-world data, such as electronic health records and insurance claims, provide information on large cohorts of users for many drugs. Here we present an efficient and easily customized framework for generating and testing multiple candidates for drug repurposing using a retrospective analysis of real-world data. Building upon well-established causal inference and deep learning methods, our framework emulates randomized clinical trials for drugs present in a large-scale medical claims database. We demonstrate our framework on a coronary artery disease cohort of millions of patients. We successfully identify drugs and drug combinations that substantially improve the coronary artery disease outcomes but haven’t been indicated for treating coronary artery disease, paving the way for drug repurposing. Many approved drugs can be used to treat diseases other than the one they were developed for, which has the added benefit that the safety of the drug has already been tested. To identify possible candidates for re-purposing trials, Liu et al. have developed a method to use existing electronic patient data to simulate clinical trials and identify drugs that influence the progression of diseases with which they were not previously associated.