Estimation of Optimal Dynamic Treatment Regimes using Gaussian Process Emulation

Abstract

In precision medicine, identifying optimal sequences of decision rules, termed dynamic treatment regimes (DTRs), is an important undertaking. One approach investigators may take to infer about optimal DTRs is via Bayesian dynamic Marginal Structural Models (MSMs). These models represent the expected outcome under adherence to a DTR for DTRs in a family indexed by a parameter $ \psi $; the function mapping regimes in the family to the expected outcome under adherence to a DTR is known as the value function. Models that allow for the straightforward identification of an optimal DTR may lead to biased estimates. If such a model is computationally tractable, common wisdom says that a grid-search for the optimal DTR may obviate this difficulty. In a Bayesian context, computational difficulties may be compounded if a posterior mean must be calculated at each grid point. We seek to alleviate these inferential challenges by implementing Gaussian Process ($ \mathcal{GP} $) optimization methods for estimators for the causal effect of adherence to a specified DTR. We examine how to identify optimal DTRs in settings where the value function is multi-modal, which are often not addressed in the DTR literature. We conclude that a $ \mathcal{GP} $ modeling approach that acknowledges noise in the estimated response surface leads to improved results. Additionally, we find that a grid-search may not always yield a robust solution and that it is often less efficient than a $ \mathcal{GP} $ approach. We illustrate the use of the proposed methods by analyzing a clinical dataset with the aim of quantifying the effect of different patterns of HIV therapy.