Development and evaluation of machine learning algorithms for the prediction of opioid-related deaths among UK patients with non-cancer pain

The global rise in prescription opioid use has contributed to an opioid epidemic, associated harms, and unintentional deaths in several western countries. Opioids however continue to be regularly prescribed for acute pain and in the chronic pain context due to limited treatment options. Currently there are no accurate tools that help predict which patients prescribed opioids may be at risk of death, which depends on the cultural context and varies across countries. Existing models do not account for statistical considerations such as censoring and competing risks. Using nationally representative data from the United Kingdom from 1,026,139 patients newly prescribed an opioid, we developed three competing risk time-to-event models: a regression model, a random forest, and a deep neural network to predict opioid-related deaths using UK primary care records. The models were externally validated in an external cohort of 337,015 patients. The models exhibited good discrimination and positive predictive value during internal validation (C-statistic for the regression model, random forest, and neural network: 84.3%, 84.4% and 82.1% respectively), and external validation (C-statistic for the regression model, random forest, and neural network: 81.8%, 81.5% and 81.5% respectively). Prior substance abuse, lung and liver comorbidities, morphine, fentanyl, or oxycodone at initiation and co-prescription of gabapentinoids were some of candidate predictors associated with a higher risk of opioid-related mortality within the models. These results demonstrate how routinely collected data from a nationally representative dataset may be used to develop and validate opioids risk algorithms to better help clinicians and patients predict risk to this serious adverse outcome.