Integrating complex selection rules into the latent overlapping group Lasso for constructing coherent prediction models

The construction of coherent prediction models holds great importance in medical research as such models enable health researchers to gain deeper insights into disease epidemiology and clinicians to identify patients at higher risk of adverse outcomes. One commonly employed approach to developing prediction models is variable selection through penalized regression techniques. Integrating natural variable structures into this process not only enhances model interpretability but can also %increase the likelihood of recovering the true underlying model and boost prediction accuracy. However, a challenge lies in determining how to effectively integrate potentially complex selection dependencies into the penalized regression. In this work, we demonstrate how to represent selection dependencies mathematically, provide algorithms for deriving the complete set of potential models, and offer a structured approach for integrating complex rules into variable selection through the latent overlapping group Lasso. To illustrate our methodology, we applied these techniques to construct a coherent prediction model for major bleeding in hypertensive patients recently hospitalized for atrial fibrillation and subsequently prescribed oral anticoagulants. In this application, we account for a proxy of anticoagulant adherence and its interaction with dosage and the type of oral anticoagulants in addition to drug-drug interactions.