Estimating heterogeneous treatment effects with right-censored data via causal survival forests

There is fast-growing literature on estimating heterogeneous treatment effects via random forests in observational studies. However, there are few approaches available for right-censored survival data. In clinical trials, right-censored survival data are frequently encountered. Quantifying the causal relationship between a treatment and the survival outcome is of great interest. Random forests provide a robust, nonparametric approach to statistical estimation. In addition, recent developments allow forest-based methods to quantify the uncertainty of the estimated heterogeneous treatment effects. We propose causal survival forests that directly target on estimating the treatment effect from an observational study. We establish consistency and asymptotic normality of the proposed estimators and provide an estimator of the asymptotic variance that enables valid confidence intervals of the estimated treatment effect. The performance of our approach is demonstrated via extensive simulations and data from an HIV study

BENK: The Beran Estimator with Neural Kernels for Estimating the Heterogeneous Treatment Effect

A method for estimating the conditional average treatment effect under condition of censored time-to-event data called BENK (the Beran Estimator with Neural Kernels) is proposed. The main idea behind the method is to apply the Beran estimator for estimating the survival functions of controls and treatments. Instead of typical kernel functions in the Beran estimator, it is proposed to implement kernels in the form of neural networks of a specific form called the neural kernels. The conditional average treatment effect is estimated by using the survival functions as outcomes of the control and treatment neural networks which consists of a set of neural kernels with shared parameters. The neural kernels are more flexible and can accurately model a complex location structure of feature vectors. Various numerical simulation experiments illustrate BENK and compare it with the well-known T-learner, S-learner and X-learner for several types of the control and treatment outcome functions based on the Cox models, the random survival forest and the Nadaraya-Watson regression with Gaussian kernels. The code of proposed algorithms implementing BENK is available in https://github.com/Stasychbr/BENK

A nonparametric framework for treatment effect modifier discovery in high dimensions

Heterogeneous treatment effects are driven by treatment effect modifiers, pre-treatment covariates that modify the effect of a treatment on an outcome. Current approaches for uncovering these variables are limited to low-dimensional data, data with weakly correlated covariates, or data generated according to parametric processes. We resolve these issues by developing a framework for defining model-agnostic treatment effect modifier variable importance parameters applicable to high-dimensional data with arbitrary correlation structure, deriving one-step, estimating equation and targeted maximum likelihood estimators of these parameters, and establishing these estimators' asymptotic properties. This framework is showcased by defining variable importance parameters for data-generating processes with continuous, binary, and time-to-event outcomes with binary treatments, and deriving accompanying multiply-robust and asymptotically linear estimators. Simulation experiments demonstrate that these estimators' asymptotic guarantees are approximately achieved in realistic sample sizes for observational and randomized studies alike. This framework is applied to gene expression data collected for a clinical trial assessing the effect of a monoclonal antibody therapy on disease-free survival in breast cancer patients. Genes predicted to have the greatest potential for treatment effect modification have previously been linked to breast cancer. An open-source R package implementing this methodology, unihtee, is made available on GitHub at https://github.com/insightsengineering/unihtee

Multi-stage optimal dynamic treatment regimes for survival outcomes with dependent censoring

We propose a reinforcement learning method for estimating an optimal dynamic treatment regime for survival outcomes with dependent censoring. The estimator allows the treatment decision times to be dependent on the failure time and conditionally independent of censoring, supports a flexible number of treatment arms and treatment stages, and can maximize either the mean survival time or the survival probability at a certain time point. The estimator is constructed using generalized random survival forests, and its consistency is shown using empirical process theory. Simulations and leukemia data analysis results suggest that the new estimator brings higher expected outcomes than existing methods in various settings. An R package dtrSurv is available on CRAN

Estimating Trustworthy and Safe Optimal Treatment Regimes

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