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• W4379212304 abstract "Drug repurposing involves finding new therapeutic uses for already approved drugs, which can save costs as their pharmacokinetics and pharmacodynamics are already known. Predicting efficacy based on clinical endpoints is valuable for designing phase 3 trials and making Go/No-Go decisions, given the potential for confounding effects in phase 2.This study aims to predict the efficacy of the repurposed Heart Failure (HF) drugs for the Phase 3 Clinical Trial.Our study presents a comprehensive framework for predicting drug efficacy in phase 3 trials, which combines drug-target prediction using biomedical knowledgebases with statistical analysis of real-world data. We developed a novel drug-target prediction model that uses low-dimensional representations of drug chemical structures and gene sequences, and biomedical knowledgebase. Furthermore, we conducted statistical analyses of electronic health records to assess the effectiveness of repurposed drugs in relation to clinical measurements (e.g., NT-proBNP).We identified 24 repurposed drugs (9 with a positive effect and 15 with a non-positive) for heart failure from 266 phase 3 clinical trials. We used 25 genes related to heart failure for drug-target prediction, as well as electronic health records (EHR) from the Mayo Clinic for screening, which contained over 58,000 heart failure patients treated with various drugs and categorized by heart failure subtypes. Our proposed drug-target predictive model performed exceptionally well in all seven tests in the BETA benchmark compared to the six cutting-edge baseline methods (i.e., best performed in 266 out of 404 tasks). For the overall prediction of the 24 drugs, our model achieved an AUCROC of 82.59% and PRAUC (average precision) of 73.39%.The study demonstrated exceptional results in predicting the efficacy of repurposed drugs for phase 3 clinical trials, highlighting the potential of this method to facilitate computational drug repurposing." @default.
• W4379212304 created "2023-06-04" @default.
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• W4379212304 date "2023-06-03" @default.
• W4379212304 modified "2023-10-06" @default.
• W4379212304 title "Artificial Intelligence-based Efficacy Prediction of Phase 3 Clinical Trial for Repurposing Heart Failure Therapies" @default.
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• W4379212304 doi "https://doi.org/10.1101/2023.05.25.23290531" @default.
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