Recent statistical and reinforcement learning methods have significantly advanced patient care strategies. However, these approaches face substantial challenges in high-stakes contexts, including missing data, inherent stochasticity, and the critical requirements for interpretability and patient safety. Our work operationalizes a safe and interpretable framework to identify optimal treatment regimes. This approach involves matching patients with similar medical and pharmacological characteristics, allowing us to construct an optimal policy via interpolation. We perform a comprehensive simulation study to demonstrate the framework's ability to identify optimal policies even in complex settings. Ultimately, we operationalize our approach to study regimes for treating seizures in critically ill patients. Our findings strongly support personalized treatment strategies based on a patient's medical history and pharmacological features. Notably, we identify that reducing medication doses for patients with mild and brief seizure episodes while adopting aggressive treatment for patients in intensive care unit experiencing intense seizures leads to more favorable outcomes.

Sparse decision trees are one of the most common forms of interpretable models. While recent advances have produced algorithms that fully optimize sparse decision trees for prediction, that work does not address policy design, because the algorithms cannot handle weighted data samples. Specifically, they rely on the discreteness of the loss function, which means that real-valued weights cannot be directly used. For example, none of the existing techniques produce policies that incorporate inverse propensity weighting on individual data points. We present three algorithms for efficient sparse weighted decision tree optimization. The first approach directly optimizes the weighted loss function; however, it tends to be computationally inefficient for large datasets. Our second approach, which scales more efficiently, transforms weights to integer values and uses data duplication to transform the weighted decision tree optimization problem into an unweighted (but larger) counterpart. Our third algorithm, which scales to much larger datasets, uses a randomized procedure that samples each data point with a probability proportional to its weight. We present theoretical bounds on the error of the two fast methods and show experimentally that these methods can be two orders of magnitude faster than the direct optimization of the weighted loss, without losing significant accuracy.

A treatment regime is a rule that assigns a treatment to patients based on their covariate information. Recently, estimation of the optimal treatment regime that yields the greatest overall expected clinical outcome of interest has attracted a lot of attention. In this work, we consider estimation of the optimal treatment regime with electronic medical record data under a semi-supervised setting. Here, data consist of two parts: a set of `labeled' patients for whom we have the covariate, treatment and outcome information, and a much larger set of `unlabeled' patients for whom we only have the covariate information. We proposes an imputation-based semi-supervised method, utilizing `unlabeled' individuals to obtain a more efficient estimator of the optimal treatment regime. The asymptotic properties of the proposed estimators and their associated inference procedure are provided. Simulation studies are conducted to assess the empirical performance of the proposed method and to compare with a fully supervised method using only the labeled data. An application to an electronic medical record data set on the treatment of hypotensive episodes during intensive care unit (ICU) stays is also given for further illustration.

Recently, there has been growing interest in estimating optimal treatment regimes which are individualized decision rules that can achieve maximal average outcomes. This paper considers the problem of inference for optimal treatment regimes in the model-free setting, where the specification of an outcome regression model is not needed. Existing model-free estimators are usually not suitable for the purpose of inference because they either have nonstandard asymptotic distributions, or are designed to achieve fisher-consistent classification performance. This paper first studies a smoothed robust estimator that directly targets estimating the parameters corresponding to the Bayes decision rule for estimating the optimal treatment regime. This estimator is shown to have an asymptotic normal distribution. Furthermore, it is proved that a resampling procedure provides asymptotically accurate inference for both the parameters indexing the optimal treatment regime and the optimal value function. A new algorithm is developed to calculate the proposed estimator with substantially improved speed and stability. Numerical results demonstrate the satisfactory performance of the new methods.

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 provide sufficient conditions for the identification of both value function $E[Y_{\cD(L)}]$ for a given regime $\cD$ and optimal regime $\arg \max_{\cD} E[Y_{\cD(L)}]$ with the aid of a binary instrumental variable, when no unmeasured confounding fails to hold. We establish consistency of the proposed weighted estimators. We also extend the proposed method to identify and estimate the optimal treatment regime among those who would comply to the assigned treatment under monotonicity. In this latter case, we establish the somewhat surprising result that the complier optimal regime can be consistently estimated without directly collecting compliance information and therefore without the complier average treatment effect itself being identified. Furthermore, we propose novel semiparametric locally efficient and multiply robust estimators. Our approach is illustrated via extensive simulation studies and a data application on the effect of child rearing on labor participation.

The estimation of optimal treatment regimes is of considerable interest to precision medicine. In this work, we propose a causal $k$-nearest neighbor method to estimate the optimal treatment regime. The method roots in the framework of causal inference, and estimates the causal treatment effects within the nearest neighborhood. Although the method is simple, it possesses nice theoretical properties. We show that the causal $k$-nearest neighbor regime is universally consistent. That is, the causal $k$-nearest neighbor regime will eventually learn the optimal treatment regime as the sample size increases. We also establish its convergence rate. However, the causal $k$-nearest neighbor regime may suffer from the curse of dimensionality, i.e. performance deteriorates as dimensionality increases. To alleviate this problem, we develop an adaptive causal $k$-nearest neighbor method to perform metric selection and variable selection simultaneously. The performance of the proposed methods is illustrated in simulation studies and in an analysis of a chronic depression clinical trial.

In order to identify important variables that are involved in making optimal treatment decision, Lu et al. (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 two-step estimation procedure for deriving 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.

Variable selection for optimal treatment regime in a clinical trial or an observational study is getting more attention. Most existing variable selection techniques focused on selecting variables that are important for prediction, therefore some variables that are poor in prediction but are critical for decision-making may be ignored. A qualitative interaction of a variable with treatment arises when treatment effect changes direction as the value of this variable varies. The qualitative interaction indicates the importance of this variable for decision-making. Gunter et al. (2011) proposed S-score which characterizes the magnitude of qualitative interaction of each variable with treatment individually. In this article, we developed a sequential advantage selection method based on the modified S-score. Our method selects qualitatively interacted variables sequentially, and hence excludes marginally important but jointly unimportant variables {or vice versa}. The optimal treatment regime based on variables selected via joint model is more comprehensive and reliable. With the proposed stopping criteria, our method can handle a large amount of covariates even if sample size is small. Simulation results show our method performs well in practical settings. We further applied our method to data from a clinical trial for depression.