A systematic review of machine learning applications in predicting opioid associated adverse events

Machine learning has increasingly been applied to predict opioid-related harms due to its ability to handle complex interactions and generating actionable predictions. This review evaluated the types and quality of ML methods in opioid safety research, identifying 44 studies using supervised ML through searches of Ovid MEDLINE, PubMed and SCOPUS databases. Commonly predicted outcomes included postoperative opioid use (n = 15, 34%) opioid overdose (n = 8, 18%), opioid use disorder (n = 8, 18%) and persistent opioid use (n = 5, 11%) with varying definitions. Most studies (96%) originated from North America, with only 7% reporting external validation. Model performance was moderate to strong, but calibration was often missing (41%). Transparent reporting of model development was often incomplete, with key aspects such as calibration, imbalance correction, and handling of missing data absent. Infrequent external validation limited the generalizability of current models. Addressing these aspects is critical for transparency, interpretability, and future implementation of the results.