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Register a new userProximal Learning for Individualized Treatment Regimes Under Unmeasured Confounding
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Data-driven individualized decision making has recently received increasing research interests. Most existing methods rely on the assumption of no unmeasured confounding, which unfortunately cannot be ensured in practice especially in observational studies. Motivated by the recent proposed proximal causal inference, we develop several proximal learning approaches to estimating optimal individualized treatment regimes (ITRs) in the presence of unmeasured confounding. In particular, we establish several identification results for different classes of ITRs, exhibiting the trade-off between the risk of making untestable assumptions and the value function improvement in decision making. Based on these results, we propose several classification-based approaches to finding a variety of restricted in-class optimal ITRs and develop their theoretical properties. The appealing numerical performance of our proposed methods is demonstrated via an extensive simulation study and one real data application.
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Bayesian causal inference offers a principled approach to policy evaluation of proposed interventions on mediators or time-varying exposures. We outline a general approach to the estimation of causal quantities for settings with time-varying confounding, such as exposure-induced mediator-outcome confounders. We further extend this approach to propose two Bayesian data fusion (BDF) methods for unmeasured confounding. Using informative priors on quantities relating to the confounding bias parameters, our methods incorporate data from an external source where the confounder is measured in order to make inferences about causal estimands in the main study population. We present results from a simulation study comparing our data fusion methods to two common frequentist correction methods for unmeasured confounding bias in the mediation setting. We also demonstrate our method with an investigation of the role of stage at cancer diagnosis in contributing to Black-White colorectal cancer survival disparities.
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.
The data drawn from biological, economic, and social systems are often confounded due to the presence of unmeasured variables. Prior work in causal discovery has focused on discrete search procedures for selecting acyclic directed mixed graphs (ADMGs), specifically ancestral ADMGs, that encode ordinary conditional independence constraints among the observed variables of the system. However, confounded systems also exhibit more general equality restrictions that cannot be represented via these graphs, placing a limit on the kinds of structures that can be learned using ancestral ADMGs. In this work, we derive differentiable algebraic constraints that fully characterize the space of ancestral ADMGs, as well as more general classes of ADMGs, arid ADMGs and bow-free ADMGs, that capture all equality restrictions on the observed variables. We use these constraints to cast causal discovery as a continuous optimization problem and design differentiable procedures to find the best fitting ADMG when the data comes from a confounded linear system of equations with correlated errors. We demonstrate the efficacy of our method through simulations and application to a protein expression dataset. Code implementing our methods is open-source and publicly available at https://gitlab.com/rbhatta8/dcd and will be incorporated into the Ananke package.
There is a fast-growing literature on estimating optimal treatment regimes based on randomized trials or observational studies under a key identifying condition of no unmeasured confounding. Because confounding by unmeasured factors cannot generally be ruled out with certainty in observational studies or randomized trials subject to noncompliance, we propose a general instrumental variable approach to learning optimal treatment regimes under endogeneity. Specifically, we establish identification of both value function $E[Y_{mathcal{D}(L)}]$ for a given regime $mathcal{D}$ and optimal regimes $text{argmax}_{mathcal{D}} E[Y_{mathcal{D}(L)}]$ with the aid of a binary instrumental variable, when no unmeasured confounding fails to hold. We also construct novel multiply robust classification-based estimators. Furthermore, we propose to identify and estimate optimal treatment regimes among those who would comply to the assigned treatment under a standard monotonicity assumption. In this latter case, we establish the somewhat surprising result that complier optimal regimes can be consistently estimated without directly collecting compliance information and therefore without the complier average treatment effect itself being identified. Our approach is illustrated via extensive simulation studies and a data application on the effect of child rearing on labor participation.
Although the exposure can be randomly assigned in studies of mediation effects, any form of direct intervention on the mediator is often infeasible. As a result, unmeasured mediator-outcome confounding can seldom be ruled out. We propose semiparametric identification of natural direct and indirect effects in the presence of unmeasured mediator-outcome confounding by leveraging heteroskedasticity restrictions on the observed data law. For inference, we develop semiparametric estimators that remain consistent under partial misspecifications of the observed data model. We illustrate the proposed estimators through both simulations and an application to evaluate the effect of self-efficacy on fatigue among health care workers during the COVID-19 outbreak.
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