University of North Carolina at Chapel Hill Graduate School
Doi
Abstract
Precision medicine aims to deliver optimal, individualized treatments for patients by accounting for their unique characteristics. With a foundation in reinforcement learning, decision theory, and causal inference, the field of precision medicine has seen many advancements in recent years. Significant focus has been placed on creating algorithms to estimate individualized treatment rules (ITRs), which map from patient covariates to the space of available treatments with the goal of maximizing patient outcome. In Chapter 1, we extend ITR estimation methodology in the scenario where variance of the outcome is heterogeneous with respect to treatment and covariates. Accordingly, we propose Stabilized Direct Learning (SD-Learning), which utilizes heteroscedasticity in the error term through a residual reweighting framework that models residual variance via flexible machine learning algorithms such as XGBoost and random forests. We also develop an internal cross-validation scheme which determines the best residual model among competing models. Further, we extend this methodology to multi-arm treatment scenarios. In Chapter 2, we develop ITR estimation methodology for situations where clinical decision-making involves balancing multiple outcomes of interest. Our proposed framework estimates an ITR which maximizes a combination of the multiple clinical outcomes, accounting for the fact that patients may ascribe importance to outcomes differently (utility heterogeneity). This approach employs inverse reinforcement learning (IRL) techniques through an expert-augmentation solution, whereby physicians provide input to guide the utility estimation and ITR learning processes. In Chapter 3, we apply an end-to-end precision medicine workflow to novel data from older adults with Type 1 Diabetes in order to understand the heterogeneous treatment effects of continuous glucose monitoring (CGM) and develop an interpretable ITR to reveal patients for which CGM confers a major safety benefit. The results from this analysis elucidate the demographic and clinical markers which moderate CGM's success, provide the basis for using diagnostic CGM to inform therapeutic CGM decisions, and serve to augment clinical decision-making. Finally, in Chapter 4, as a future research direction, we propose a deep autoencoder framework which simultaneously performs feature selection and ITR optimization, contributing to methodology built for direct consumption of unstructured, high-dimensional data in the precision medicine pipeline.Doctor of Philosoph
