Mining Real-World Big Data to Characterize Adverse Drug Reaction Quantitatively: Mixed Methods Study

Background Adverse drug reactions (ADRs), which are the phenotypic manifestations of clinical drug toxicity in humans, are a major concern in precision clinical medicine. A comprehensive evaluation of ADRs is helpful for unbiased supervision of marketed drugs and for discovering new drugs with high success rates. Objective In current practice, drug safety evaluation is often oversimplified to the occurrence or nonoccurrence of ADRs. Given the limitations of current qualitative methods, there is an urgent need for a quantitative evaluation model to improve pharmacovigilance and the accurate assessment of drug safety. Methods In this study, we developed a mathematical model, namely the Adverse Drug Reaction Classification System (ADReCS) severity-grading model, for the quantitative characterization of ADR severity, a crucial feature for evaluating the impact of ADRs on human health. The model was constructed by mining millions of real-world historical adverse drug event reports. A new parameter called Severityₛcore was introduced to measure the severity of ADRs, and upper and lower score boundaries were determined for 5 severity grades. Results The ADReCS severity-grading model exhibited excellent consistency (99. 22%) with the expert-grading system, the Common Terminology Criteria for Adverse Events. Hence, we graded the severity of 6277 standard ADRs for 129, 407 drug-ADR pairs. Moreover, we calculated the occurrence rates of 6272 distinct ADRs for 127, 763 drug-ADR pairs in large patient populations by mining real-world medication prescriptions. With the quantitative features, we demonstrated example applications in systematically elucidating ADR mechanisms and thereby discovered a list of drugs with improper dosages. Conclusions In summary, this study represents the first comprehensive determination of both ADR severity grades and ADR frequencies. This endeavor establishes a strong foundation for future artificial intelligence applications in discovering new drugs with high efficacy and low toxicity. It also heralds a paradigm shift in clinical toxicity research, moving from qualitative description to quantitative evaluation.