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Register a new userA Bayesian Nonparametric Approach for Estimating Individualized Treatment-Response Curves
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We study the problem of estimating the continuous response over time to interventions using observational time series---a retrospective dataset where the policy by which the data are generated is unknown to the learner. We are motivated by applications where response varies by individuals and therefore, estimating responses at the individual-level is valuable for personalizing decision-making. We refer to this as the problem of estimating individualized treatment response (ITR) curves. In statistics, G-computation formula (Robins, 1986) has been commonly used for estimating treatment responses from observational data containing sequential treatment assignments. However, past studies have focused predominantly on obtaining point-in-time estimates at the population level. We leverage the G-computation formula and develop a novel Bayesian nonparametric (BNP) method that can flexibly model functional data and provide posterior inference over the treatment response curves at both the individual and population level. On a challenging dataset containing time series from patients admitted to a hospital, we estimate responses to treatments used in managing kidney function and show that the resulting fits are more accurate than alternative approaches. Accurate methods for obtaining ITRs from observational data can dramatically accelerate the pace at which personalized treatment plans become possible.
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Precision medicine is an emerging scientific topic for disease treatment and prevention that takes into account individual patient characteristics. It is an important direction for clinical research, and many statistical methods have been recently proposed. One of the primary goals of precision medicine is to obtain an optimal individual treatment rule (ITR), which can help make decisions on treatment selection according to each patients specific characteristics. Recently, outcome weighted learning (OWL) has been proposed to estimate such an optimal ITR in a binary treatment setting by maximizing the expected clinical outcome. However, for ordinal treatment settings, such as individualized dose finding, it is unclear how to use OWL. In this paper, we propose a new technique for estimating ITR with ordinal treatments. In particular, we propose a data duplication technique with a piecewise convex loss function. We establish Fisher consistency for the resulting estimated ITR under certain conditions, and obtain the convergence and risk bound properties. Simulated examples and two applications to datasets from an irritable bowel problem and a type 2 diabetes mellitus observational study demonstrate the highly competitive performance of the proposed method compared to existing alternatives.
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.
Semi-supervised clustering is the task of clustering data points into clusters where only a fraction of the points are labelled. The true number of clusters in the data is often unknown and most models require this parameter as an input. Dirichlet process mixture models are appealing as they can infer the number of clusters from the data. However, these models do not deal with high dimensional data well and can encounter difficulties in inference. We present a novel nonparameteric Bayesian kernel based method to cluster data points without the need to prespecify the number of clusters or to model complicated densities from which data points are assumed to be generated from. The key insight is to use determinants of submatrices of a kernel matrix as a measure of how close together a set of points are. We explore some theoretical properties of the model and derive a natural Gibbs based algorithm with MCMC hyperparameter learning. The model is implemented on a variety of synthetic and real world data sets.
Randomized controlled trials typically analyze the effectiveness of treatments with the goal of making treatment recommendations for patient subgroups. With the advance of electronic health records, a great variety of data has been collected in clinical practice, enabling the evaluation of treatments and treatment policies based on observational data. In this paper, we focus on learning individualized treatment rules (ITRs) to derive a treatment policy that is expected to generate a better outcome for an individual patient. In our framework, we cast ITRs learning as a contextual bandit problem and minimize the expected risk of the treatment policy. We conduct experiments with the proposed framework both in a simulation study and based on a real-world dataset. In the latter case, we apply our proposed method to learn the optimal ITRs for the administration of intravenous (IV) fluids and vasopressors (VP). Based on various offline evaluation methods, we could show that the policy derived in our framework demonstrates better performance compared to both the physicians and other baselines, including a simple treatment prediction approach. As a long-term goal, our derived policy might eventually lead to better clinical guidelines for the administration of IV and VP.
Estimating the Individual Treatment Effect from observational data, defined as the difference between outcomes with and without treatment or intervention, while observing just one of both, is a challenging problems in causal learning. In this paper, we formulate this problem as an inference from hidden variables and enforce causal constraints based on a model of four exclusive causal populations. We propose a new version of the EM algorithm, coined as Expected-Causality-Maximization (ECM) algorithm and provide hints on its convergence under mild conditions. We compare our algorithm to baseline methods on synthetic and real-world data and discuss its performances.
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