Contrasting Global and Patient-Specific Regression Models via a Neural Network Representation

When developing clinical prediction models, it can be challenging to balance between global models that are valid for all patients and personalized models tailored to individuals or potentially unknown subgroups. To aid such decisions, we propose a diagnostic tool for contrasting global regression models and patient-specific (local) regression models. The core utility of this tool is to identify where and for whom a global model may be inadequate. We focus on regression models and specifically suggest a localized regression approach that identifies regions in the predictor space where patients are not well represented by the global model. As localization becomes challenging when dealing with many predictors, we propose modeling in a dimension-reduced latent representation obtained from an autoencoder. Using such a neural network architecture for dimension reduction enables learning a latent representation simultaneously optimized for both good data reconstruction and for revealing local outcome-related associations suitable for robust localized regression. We illustrate the proposed approach with a clinical study involving patients with chronic obstructive pulmonary disease. Our findings indicate that the global model is adequate for most patients but that indeed specific subgroups benefit from personalized models. We also demonstrate how to map these subgroup models back to the original predictors, providing insight into why the global model falls short for these groups. Thus, the principal application and diagnostic yield of our tool is the identification and characterization of patients or subgroups whose outcome associations deviate from the global model. Introduction In clinical research, conclusions about potential relationships between patient characteristics and outcomes often are based on regression models. More specifically, there might not be just some random variability across the parameters of patients, e.g. as considered in regression modeling with random effects (Pinheiro and Bates, 2000), but different regions in the space spanned by the patient characteristics might require different parameters. For example, the relation of some patient characteristics to the outcome might be more pronounced for older patients with high body weight, without having a corresponding pre-defined subgroup indicator. While sticking to a global model keeps interpretation simple and is beneficial in terms of statistical stability, it would at least be useful to have some diagnostic tool for judging the potential extent of deviations from the global model.