Learning Optimal Distributionally Robust Individualized Treatment Rules.
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ABSTRACT:
SUBMITTER: Mo W
PROVIDER: S-EPMC8221611 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Precision medicine seeks to provide treatment only if, when, to whom, and at the dose it is needed. Thus, precision medicine is a vehicle by which healthcare can be made both more effective and efficient. Individualized treatment rules operationalize precision medicine as a map from current patient information to a recommended treatment. An optimal individualized treatment rule is defined as maximizing the mean of a pre-specified scalar outcome. However, in settings with multiple outcomes, choosing a scalar composite outcome by which to define optimality is difficult. Furthermore, when there is heterogeneity across patient preferences for these outcomes, it may not be possible to construct a single composite outcome that leads to high-quality treatment recommendations for all patients. We simultaneously estimate the optimal individualized treatment rule for all composite outcomes representable as a convex combination of the (suitably transformed) outcomes. For each patient, we use a preference elicitation questionnaire and item response theory to derive the posterior distribution over preferences for these composite outcomes and subsequently derive an estimator of an optimal individualized treatment rule tailored to patient preferences. We prove that as the number of subjects and items on the questionnaire diverge, our estimator is consistent for an oracle optimal individualized treatment rule wherein each patient's preference is known a priori. We illustrate the proposed method using data from a clinical trial on antipsychotic medications for schizophrenia.
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Project description:Personalized medicine has received increasing attention among statisticians, computer scientists, and clinical practitioners. A major component of personalized medicine is the estimation of individualized treatment rules (ITRs). Recently, Zhao et al. (2012) proposed outcome weighted learning (OWL) to construct ITRs that directly optimize the clinical outcome. Although OWL opens the door to introducing machine learning techniques to optimal treatment regimes, it still has some problems in performance. (1) The estimated ITR of OWL is affected by a simple shift of the outcome. (2) The rule from OWL tries to keep treatment assignments that subjects actually received. (3) There is no variable selection mechanism with OWL. All of them weaken the finite sample performance of OWL. In this article, we propose a general framework, called Residual Weighted Learning (RWL), to alleviate these problems, and hence to improve finite sample performance. Unlike OWL which weights misclassification errors by clinical outcomes, RWL weights these errors by residuals of the outcome from a regression fit on clinical covariates excluding treatment assignment. We utilize the smoothed ramp loss function in RWL, and provide a difference of convex (d.c.) algorithm to solve the corresponding non-convex optimization problem. By estimating residuals with linear models or generalized linear models, RWL can effectively deal with different types of outcomes, such as continuous, binary and count outcomes. We also propose variable selection methods for linear and nonlinear rules, respectively, to further improve the performance. We show that the resulting estimator of the treatment rule is consistent. We further obtain a rate of convergence for the difference between the expected outcome using the estimated ITR and that of the optimal treatment rule. The performance of the proposed RWL methods is illustrated in simulation studies and in an analysis of cystic fibrosis clinical trial data.
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Project description:For many mental disorders, latent mental status from multiple-domain psychological or clinical symptoms may perform as a better characterization of the underlying disorder status than a simple summary score of the symptoms, and they may also serve as more reliable and representative features to differentiate treatment responses. Therefore, in order to address the complexity and heterogeneity of treatment responses for mental disorders, we provide a new paradigm for learning optimal individualized treatment rules (ITRs) by modeling patients' latent mental status. We first learn the multi-domain latent states at baseline from the observed symptoms under a restricted Boltzmann machine (RBM) model, through which patients' heterogeneous symptoms are represented using an economical number of latent variables and yet remains flexible. We then optimize a value function defined by the latent states after treatment by exploiting a transformation of the observed symptoms based on the RBM without modeling the relationship between the latent mental states before and after treatment. The optimal treatment rules are derived using a weighted large margin classifier. We derive the convergence rate of the proposed estimator under the latent models. Simulation studies are conducted to test the performance of the proposed method. Finally, we apply the developed method to real world studies and we demonstrate the utility and advantage of our method in tailoring treatments for patients with major depression, and identify patient subgroups informative for treatment recommendations.
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Project description:There is an extensive literature on the estimation and evaluation of optimal individualized treatment rules in settings where all confounders of the effect of treatment on outcome are observed. We study the development of individualized decision rules in settings where some of these confounders may not have been measured but a valid binary instrument is available for a binary treatment. We first consider individualized treatment rules, which will naturally be most interesting in settings where it is feasible to intervene directly on treatment. We then consider a setting where intervening on treatment is infeasible, but intervening to encourage treatment is feasible. In both of these settings, we also handle the case that the treatment is a limited resource so that optimal interventions focus the available resources on those individuals who will benefit most from treatment. Given a reference rule, we evaluate an optimal individualized rule by its average causal effect relative to a prespecified reference rule. We develop methods to estimate optimal individualized rules and construct asymptotically efficient plug-in estimators of the corresponding average causal effect relative to a prespecified reference rule.
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