Development and Validation of a Machine Learning Model to Estimate Risk of Adverse Outcomes Within 30 Days of Opioid Dispensation

Machine learning approaches can assist opioid stewardship by identifying high-risk opioid prescribing for potential interventions. To develop a machine learning model for deployment that can estimate the risk of adverse outcomes within 30 days of an opioid dispensation as a potential component of prescription drug monitoring programs using access to real-world data. This prognostic study used population-level administrative health data to construct a machine learning model. This study took place in Alberta, Canada (from January 1, 2018, to December 31, 2019), and included all patients 18 years and older who received at least 1 opioid dispensation from a community pharmacy within the province. Each opioid dispensation served as the unit of analysis. Opioid-related adverse outcomes were identified from administrative data sets. An XGBoost model was developed on 2018 data to estimate the risk of hospitalization, an emergency department visit, or mortality within 30 days of an opioid dispensation; validation on 2019 data was done to evaluate model performance. Model discrimination, calibration, and other relevant metrics are reported using daily and weekly predictions on both ranked predictions and predicted probability thresholds using all data from 2019. A total of 853 324 participants represented 6 181 025 opioid dispensations, with 145 016 outcome events reported (2.3%); 46.4% of the participants were men and 53.6% were women, with a mean (SD) age of 49.1 (15.6) years for men and 51.0 (18.0) years for women. Of the outcome events, 77 326 (2.6% pretest probability) occurred within 30 days of a dispensation in the validation set (XGBoost C statistic, 0.82 [95% CI, 0.81-0.82]). The top 0.1 percentile of estimated risk had a positive likelihood ratio (LR) of 28.7, which translated to a posttest probability of 43.1%. In our simulations, the weekly measured predictions had higher positive LRs in both the highest-risk dispensations and percentiles of estimated risk compared with predictions measured daily. Net benefit analysis showed that using machine learning prediction may not add additional benefit over the entire range of probability thresholds. These findings suggest that prescription drug monitoring programs can use machine learning classifiers to identify patients at risk of opioid-related adverse outcomes and intervene on high-risk ranked predictions. Better access to available administrative and clinical data could improve the prediction performance of