A competing risks regression model for the association between time-varying opioid exposure and risk of overdose

In the opioid research, predicting the risk of overdose or other adverse outcomes from opioid prescription patterns can help health professionals identify high-risk individuals. Challenges may arise in modeling the exposure-time-response association if the intensity, duration, and timing of exposure vary among subjects, and if exposures have a cumulative or latency effect on the risk. Further challenges may arise when the data involve competing risks, where subjects may fail from one of multiple events and failure from one precludes the risk of experiencing others. In this study, we proposed a competing risks regression model via subdistribution hazards to directly estimate the association between longitudinal patterns of opioid exposure and cumulative incidence of opioid overdose. The model incorporated weighted cumulative effects of the exposure and used penalized splines in the partial likelihood equation to estimate the weights flexibly. The proposed model is able to distinguish different opioid prescription patterns even though these patterns have the same overall intensity during the study period. Performance of the model was evaluated through simulation.