Keyword: Adverse Drug Reactions (ADRs)

ABSTRACT: Adverse drug reactions (ADRs) remain a major global challenge, contributing substantially to patient morbidity, mortality, and healthcare costs. Traditional pharmacovigilance approaches—spontaneous reporting and post-marketing surveillance—are hampered by underreporting, delays, and limited contextual data. The growing availability of electronic health records (EHRs), which capture longitudinal structured and unstructured patient information, presents an unprecedented opportunity to advance ADR prediction. This narrative review synthesizes recent progress in developing and validating predictive models that leverage EHRs, highlighting methodological approaches, challenges, and future directions. Predictive strategies range from traditional regression models to advanced machine learning and deep learning architectures, with multimodal frameworks increasingly integrating structured fields (demographics, labs, prescriptions) and unstructured clinical text through natural language processing. While ensemble and deep learning methods demonstrate superior performance, issues of data quality, missingness, bias, and interpretability persist. Robust validation frameworks—spanning internal cross-validation to multi-center external testing—are critical to ensure generalizability and clinical trustworthiness. Ethical considerations, including fairness, privacy, and transparency, remain central to safe deployment. Looking forward, promising avenues include federated learning across institutions, integration of multi-omics and pharmacogenomic data, explainable AI tailored for clinical use, and real-time monitoring through digital twin frameworks. These trajectories, combined with robust governance and clinician–data scientist collaboration, have the potential to transform ADR detection from a reactive process to proactive, personalized prevention. By synthesizing the existing evidence, this review provides insights into the development of more effective predictive models for ADRs and informs strategies for improving pharmacovigilance. This study will contribute to the ongoing efforts to leverage EHRs and predictive models for improving patient outcomes and reducing the burden of ADRs.