REACT (Real-world Emulated Clinical Trials): A Framework for Drug Repurposing Applied to Osteoporotic Fractures
Jianing Liu1, Seungyeon Lee1,2, Xianhui Chen1,2
1Department of Biomedical Informatics, The Ohio State University, Columbus, Ohio, USA.
Abstract:
Osteoporotic fractures remain common despite available therapies, highlighting the need for new, safe, and affordable treatment options. Advances in real-world data and causal inference have enabled target trial emulation, with prior frameworks demonstrating drug repurposing using observational data. However, no large-scale trial emulation framework has been applied to systematic drug repurposing for osteoporotic fracture prevention. To address this gap, we developed REACT (Real-world Emulated Clinical Trials), a scalable framework that operationalizes established target trial principles into an automated, comparator-robust pipeline for high-throughput drug screening. Applied to fracture prevention in older adults with osteoporosis, REACT screened 1,222 drugs and identified 18 with statistically significant associations, including 11 with protective effects and 7 with risk-increasing effects. The convergence of these findings with biological and prior observational evidence underscores REACT's ability to surface clinically meaningful patterns and its potential as a generalizable platform for accelerating real-world drug discovery and safety surveillance.
Insights
A new framework called REACT (Real-world Emulated Clinical Trials) screened 1,222 drugs to find new treatments for preventing osteoporotic fractures. It identified 18 drugs with significant associations, aiding drug discovery.
Area of Science:
- Pharmacology
- Epidemiology
- Computational Biology
Background:
- Osteoporotic fractures are a significant health issue, with current treatments being insufficient.
- Existing drug repurposing methods using observational data lack large-scale trial emulation.
- There is a critical need for novel, safe, and cost-effective therapies for osteoporosis.
Purpose of the Study:
- To develop and validate a scalable framework for systematic drug repurposing for osteoporotic fracture prevention.
- To apply target trial emulation principles to real-world data for high-throughput drug screening.
- To identify potential drug candidates for preventing fractures in older adults with osteoporosis.
Main Methods:
- Developed REACT (Real-world Emulated Clinical Trials), an automated pipeline operationalizing target trial principles.
- Applied REACT to a large dataset of older adults with osteoporosis to screen 1,222 drugs.
- Utilized causal inference and comparator-robust methods for drug screening and association analysis.
Main Results:
- Identified 18 drugs with statistically significant associations for osteoporotic fracture prevention.
- Found 11 drugs demonstrating protective effects and 7 drugs showing risk-increasing effects.
- Demonstrated convergence of findings with existing biological and observational evidence.
Conclusions:
- REACT is a generalizable platform for accelerating real-world drug discovery and safety surveillance.
- The framework effectively surfaces clinically meaningful patterns from real-world data.
- Identified drug candidates warrant further investigation for osteoporotic fracture prevention.
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