Precision medicine is a medical paradigm that focuses on finding the most effective treatment decision based on individual patient information. For many complex diseases, such as cancer, treatment decisions need to be tailored over time according to patients' responses to previous treatments. Such an adaptive strategy is referred as a dynamic treatment regime. A major challenge in deriving an optimal dynamic treatment regime arises when an extraordinary large number of prognostic factors, such as patient's genetic information, demographic characteristics, medical history and clinical measurements over time are available, but not all of them are necessary for making treatment decision. This makes variable selection an emerging need in precision medicine. In this paper, we propose a penalized multi-stage A-learning for deriving the optimal dynamic treatment regime when the number of covariates is of the non-polynomial (NP) order of the sample size. To preserve the double robustness property of the A-learning method, we adopt the Dantzig selector which directly penalizes the A-leaning estimating equations. Oracle inequalities of the proposed estimators for the parameters in the optimal dynamic treatment regime and error bounds on the difference between the value functions of the estimated optimal dynamic treatment regime and the true optimal dynamic treatment regime are established. Empirical performance of the proposed approach is evaluated by simulations and illustrated with an application to data from the STAR*D study.

The divide and conquer method is a common strategy for handling massive data. In this article, we study the divide and conquer method for cubic-rate estimators under the massive data framework. We develop a general theory for establishing the asymptotic distribution of the aggregated M-estimators using a simple average. Under certain condition on the growing rate of the number of subgroups, the resulting aggregated estimators are shown to have faster convergence rate and asymptotic normal distribution, which are more tractable in both computation and inference than the original M-estimators based on pooled data. Our theory applies to a wide class of M-estimators with cube root convergence rate, including the location estimator, maximum score estimator and value search estimator. Empirical performance via simulations also validate our theoretical findings.

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This paper is concerned with testing linear hypotheses in highdimensional generalized linear models. To deal with linear hypotheses, we first propose constrained partial regularization method and study its statistical properties. We further introduce an algorithm for solving regularization problems with folded-concave penalty functions and linear constraints. To test linear hypotheses, we propose a partial penalized likelihood ratio test, a partial penalized score test and a partial penalized Wald test. We show that the limiting null distributions of these three test statistics are χ 2 distribution with the same degrees of freedom, and under local alternatives, they asymptotically follow non-central χ 2 distributions with the same degrees of freedom and noncentral parameter, provided the number of parameters involved in the test hypothesis grows to ∞ at a certain rate. Simulation studies are conducted to examine the finite sample performance of the proposed tests. Empirical analysis of a real data example is used to illustrate the proposed testing procedures.

In order to identify important variables that are involved in making optimal treatment decision, Lu, Zhang and Zeng (2013) proposed a penalized least squared regression framework for a fixed number of predictors, which is robust against the misspecification of the conditional mean model. Two problems arise: (i) in a world of explosively big data, effective methods are needed to handle ultra-high dimensional data set, for example, with the dimension of predictors is of the non-polynomial (NP) order of the sample size; (ii) both the propensity score and conditional mean models need to be estimated from data under NP dimensionality. In this paper, we propose a robust procedure for estimating the optimal treatment regime under NP dimensionality. In both steps, penalized regressions are employed with the non-concave penalty function, where the conditional mean model of the response given predictors may be misspecified. The asymptotic properties, such as weak oracle properties, selection consistency and oracle distributions, of the proposed estimators are investigated. In addition, we study the limiting distribution of the estimated value function for the obtained optimal treatment regime. The empirical performance of the proposed estimation method is evaluated by simulations and an application to a depression dataset from the STAR*D study.

Reinforcement learning is a general technique that allows an agent to learn an optimal policy and interact with an environment in sequential decision making problems. The goodness of a policy is measured by its value function starting from some initial state. The focus of this paper is to construct confidence intervals (CIs) for a policy's value in infinite horizon settings where the number of decision points diverges to infinity. We propose to model the action-value state function (Q-function) associated with a policy based on series/sieve method to derive its confidence interval. When the target policy depends on the observed data as well, we propose a SequentiAl Value Evaluation (SAVE) method to recursively update the estimated policy and its value estimator. As long as either the number of trajectories or the number of decision points diverges to infinity, we show that the proposed CI achieves nominal coverage even in cases where the optimal policy is not unique. Simulation studies are conducted to back up our theoretical findings. We apply the proposed method to a dataset from mobile health studies and find that reinforcement learning algorithms could help improve patient's health status.

Outcomes of continuous proportions arise in many applied areas. Such data are typically measured as percentages, rates or proportions confined in the unitary interval. In this paper, the R package simplexreg which provides dispersion model fitting of the simplex distribution is introduced to model such proportional outcomes. The maximum likelihood method and generalized estimating equations techniques are available for parameter estimation in cross-sectional and longitudinal studies, respectively. This paper presents methods and algorithms implemented in the package, including parameter estimation, model checking as well as density, cumulative distribution, quantile and random number generating functions of the simplex distribution. The package is applied to real data sets for illustration.

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