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تسجيل مستخدم جديدEstimating Individualized Decision Rules with Tail Controls
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With the emergence of precision medicine, estimating optimal individualized decision rules (IDRs) has attracted tremendous attention in many scientific areas. Most existing literature has focused on finding optimal IDRs that can maximize the expected outcome for each individual. Motivated by complex individualized decision making procedures and popular conditional value at risk (CVaR) measures, we propose a new robust criterion to estimate optimal IDRs in order to control the average lower tail of the subjects outcomes. In addition to improving the individualized expected outcome, our proposed criterion takes risks into consideration, and thus the resulting IDRs can prevent adverse events. The optimal IDR under our criterion can be interpreted as the decision rule that maximizes the ``worst-case scenario of the individualized outcome when the underlying distribution is perturbed within a constrained set. An efficient non-convex optimization algorithm is proposed with convergence guarantees. We investigate theoretical properties for our estimated optimal IDRs under the proposed criterion such as consistency and finite sample error bounds. Simulation studies and a real data application are used to further demonstrate the robust performance of our method.
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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 pr
oposed. 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.
Individualized treatment rules (ITR) can improve health outcomes by recognizing that patients may respond differently to treatment and assigning therapy with the most desirable predicted outcome for each individual. Flexible and efficient prediction
models are desired as a basis for such ITRs to handle potentially complex interactions between patient factors and treatment. Modern Bayesian semiparametric and nonparametric regression models provide an attractive avenue in this regard as these allow natural posterior uncertainty quantification of patient specific treatment decisions as well as the population wide value of the prediction-based ITR. In addition, via the use of such models, inference is also available for the value of the Optimal ITR. We propose such an approach and implement it using Bayesian Additive Regression Trees (BART) as this model has been shown to perform well in fitting nonparametric regression functions to continuous and binary responses, even with many covariates. It is also computationally efficient for use in practice. With BART we investigate a treatment strategy which utilizes individualized predictions of patient outcomes from BART models. Posterior distributions of patient outcomes under each treatment are used to assign the treatment that maximizes the expected posterior utility. We also describe how to approximate such a treatment policy with a clinically interpretable ITR, and quantify its expected outcome. The proposed method performs very well in extensive simulation studies in comparison with several existing methods. We illustrate the usage of the proposed method to identify an individualized choice of conditioning regimen for patients undergoing hematopoietic cell transplantation and quantify the value of this method of choice in relation to the Optimal ITR as well as non-individualized treatment strategies.
With a large number of baseline covariates, we propose a new semi-parametric modeling strategy for heterogeneous treatment effect estimation and individualized treatment selection, which are two major goals in personalized medicine. We achieve the fi
rst goal through estimating a covariate-specific treatment effect (CSTE) curve modeled as an unknown function of a weighted linear combination of all baseline covariates. The weight or the coefficient for each covariate is estimated by fitting a sparse semi-parametric logistic single-index coefficient model. The CSTE curve is estimated by a spline-backfitted kernel procedure, which enables us to further construct a simultaneous confidence band (SCB) for the CSTE curve under a desired confidence level. Based on the SCB, we find the subgroups of patients that benefit from each treatment, so that we can make individualized treatment selection. The innovations of the proposed method are three-fold. First, the proposed method can quantify variability associated with the estimated optimal individualized treatment rule with high-dimensional covariates. Second, the proposed method is very flexible to depict both local and global associations between the treatment and baseline covariates in the presence of high-dimensional covariates, and thus it enjoys flexibility while achieving dimensionality reduction. Third, the SCB achieves the nominal confidence level asymptotically, and it provides a uniform inferential tool in making individualized treatment decisions.
Recent development in data-driven decision science has seen great advances in individualized decision making. Given data with individual covariates, treatment assignments and outcomes, researchers can search for the optimal individualized treatment r
ule (ITR) that maximizes the expected outcome. Existing methods typically require initial estimation of some nuisance models. The double robustness property that can protect from misspecification of either the treatment-free effect or the propensity score has been widely advocated. However, when model misspecification exists, a doubly robust estimate can be consistent but may suffer from downgraded efficiency. Other than potential misspecified nuisance models, most existing methods do not account for the potential problem when the variance of outcome is heterogeneous among covariates and treatment. We observe that such heteroscedasticity can greatly affect the estimation efficiency of the optimal ITR. In this paper, we demonstrate that the consequences of misspecified treatment-free effect and heteroscedasticity can be unified as a covariate-treatment dependent variance of residuals. To improve efficiency of the estimated ITR, we propose an Efficient Learning (E-Learning) framework for finding an optimal ITR in the multi-armed treatment setting. We show that the proposed E-Learning is optimal among a regular class of semiparametric estimates that can allow treatment-free effect misspecification. In our simulation study, E-Learning demonstrates its effectiveness if one of or both misspecified treatment-free effect and heteroscedasticity exist. Our analysis of a Type 2 Diabetes Mellitus (T2DM) observational study also suggests the improved efficiency of E-Learning.
Recent exploration of optimal individualized decision rules (IDRs) for patients in precision medicine has attracted a lot of attention due to the heterogeneous responses of patients to different treatments. In the existing literature of precision med
icine, an optimal IDR is defined as a decision function mapping from the patients covariate space into the treatment space that maximizes the expected outcome of each individual. Motivated by the concept of Optimized Certainty Equivalent (OCE) introduced originally in cite{ben1986expected} that includes the popular conditional-value-of risk (CVaR) cite{rockafellar2000optimization}, we propose a decision-rule based optimized covariates dependent equivalent (CDE) for individualized decision making problems. Our proposed IDR-CDE broadens the existing expected-mean outcome framework in precision medicine and enriches the previous concept of the OCE. Numerical experiments demonstrate that our overall approach outperforms existing methods in estimating optimal IDRs under heavy-tail distributions of the data.
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