Assessing opioid overdose risk: a review of clinical prediction models utilizing patient-level data

Drug, and specifically opioid-related, overdoses remain a major public health problem in the United States. Multiple studies have examined individual risk factors associated with overdose risk, but research developing clinical risk prediction tools for overdose has only emerged in the last few years. We conducted a comprehensive review of the literature on patient-level factors associated with opioid-related overdose risk, with an emphasis on clinical risk prediction models for opioid-related overdose in the United States. Studies that developed and/or validated clinical prediction models were closely reviewed and evaluated to determine the state of the field. We identified 12 studies that reported risk prediction models for opioid-related overdose risk. Published models were developed from a variety of data sources, including Veterans Health Administration data, Medicare data, commercial insurance data, and statewide linked datasets. Studies reported model performance using measures of discrimination, usually at good-to-excellent levels, though they did not always assess calibration. C-statistics were better for models that included clinical predictors (c-statistics: 0.75-0.95) compared to models without them (c-statistics: 0.69-0.82). External validation of models was rare, and we found no studies evaluating implementation of models or risk prediction tools into clinical practice. A common feature of these models was a high rate of false positives, largely because opioid-related overdose is rare in the general population. Thus, efforts to implement prediction models into practice should take into account that published models overestimate overdose risk for many low-risk patients. Future prediction models assessing overdose risk should employ external validation and address model calibration. In order to translate findings from prediction models into clinical public health benefit, future studies should focus on developing clinical prediction tools based on prediction models, implementing these tools into clinical practice, and evaluating the impact of these models on treatment decisions, patient outcomes, and, ultimately, opioid overdose rates.