REACT (Real-world Emulated Clinical Trials): A Framework for Drug Repurposing Applied to Osteoporotic Fractures

Area of Science:

• Pharmacology
• Epidemiology
• Computational Biology

Background:

• Osteoporotic fractures are a significant health concern, with existing treatments having limitations.
• Advances in real-world data and causal inference facilitate drug repurposing for disease prevention.
• Existing frameworks lack large-scale application for systematic drug repurposing in osteoporotic fracture prevention.

Purpose of the Study:

• To develop and validate a scalable framework for real-world emulated clinical trials (REACT) for high-throughput drug screening.
• To apply REACT to identify drugs for preventing osteoporotic fractures in older adults.
• To assess the potential of REACT for accelerating drug discovery and safety surveillance.

Main Methods:

• Developed REACT, a framework operationalizing target trial principles into an automated pipeline.
• Applied REACT to screen 1,222 drugs for associations with osteoporotic fracture prevention.
• Utilized real-world data and causal inference for target trial emulation.

Main Results:

• Identified 18 drugs with statistically significant associations with osteoporotic fracture risk.
• Found 11 drugs with protective effects and 7 drugs with risk-increasing effects.
• Demonstrated convergence of findings with existing biological and observational evidence.

Conclusions:

• REACT is a scalable and robust framework for systematic drug repurposing and safety surveillance.
• The framework successfully identified potential therapeutic agents for osteoporotic fracture prevention.
• REACT shows promise as a generalizable platform for accelerating real-world drug discovery.