Estimating Individualized Treatment Regimes from Crossover Designs

The field of precision medicine aims to tailor treatment based on patient-specific factors in a reproducible way. To this end, estimating an optimal individualized treatment regime (ITR) that recommends treatment decisions based on patient characteristics to maximize the mean of a pre-specified outcome is of particular interest. Several methods have been proposed for estimating an optimal ITR from clinical trial data in the parallel group setting where each subject is randomized to a single intervention. However, little work has been done in the area of estimating the optimal ITR from crossover study designs. Such designs naturally lend themselves to precision medicine, because they allow for observing the response to multiple treatments for each patient. In this paper, we introduce a method for estimating the optimal ITR using data from a 2x2 crossover study with or without carryover effects. The proposed method is similar to policy search methods such as outcome weighted learning; however, we take advantage of the crossover design by using the difference in responses under each treatment as the observed reward. We establish Fisher and global consistency, present numerical experiments, and analyze data from a feeding trial to demonstrate the improved performance of the proposed method compared to standard methods for a parallel study design.

Estimating Dynamic Treatment Regimes in Mobile Health Using V-learning

The vision for precision medicine is to use individual patient characteristics to inform a personalized treatment plan that leads to the best healthcare possible for each patient. Mobile technologies have an important role to play in this vision as they offer a means to monitor a patient's health status in real-time and subsequently to deliver interventions if, when, and in the dose that they are needed. Dynamic treatment regimes formalize individualized treatment plans as sequences of decision rules, one per stage of clinical intervention, that map current patient information to a recommended treatment. However, existing methods for estimating optimal dynamic treatment regimes are designed for a small number of fixed decision points occurring on a coarse time-scale. We propose a new reinforcement learning method for estimating an optimal treatment regime that is applicable to data collected using mobile technologies in an outpatient setting. The proposed method accommodates an indefinite time horizon and minute-by-minute decision making that are common in mobile health applications. We show the proposed estimators are consistent and asymptotically normal under mild conditions. The proposed methods are applied to estimate an optimal dynamic treatment regime for controlling blood glucose levels in patients with type 1 diabetes.