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In health and social sciences, it is critically important to identify subgroups of the study population where there is notable heterogeneity of treatment effects (HTE) with respect to the population average. Decision trees have been proposed and commonly adopted for data-driven discovery of HTE due to their high level of interpretability. However, single-tree discovery of HTE can be unstable and oversimplified. This paper introduces Causal Rule Ensemble (CRE), a new method for HTE discovery and estimation through an ensemble-of-trees approach. CRE offers several key features, including 1) an interpretable representation of the HTE; 2) the ability to explore complex heterogeneity patterns; and 3) high stability in subgroups discovery. The discovered subgroups are defined in terms of interpretable decision rules. Estimation of subgroup-specific causal effects is performed via a two-stage approach for which we provide theoretical guarantees. Via simulations, we show that the CRE method is highly competitive when compared to state-of-the-art techniques. Finally, we apply CRE to discover the heterogeneous health effects of exposure to air pollution on mortality for 35.3 million Medicare beneficiaries across the contiguous U.S.

Robust feature selection is vital for creating reliable and interpretable Machine Learning (ML) models. When designing statistical prediction models in cases where domain knowledge is limited and underlying interactions are unknown, choosing the optimal set of features is often difficult. To mitigate this issue, we introduce a Multidata (M) causal feature selection approach that simultaneously processes an ensemble of time series datasets and produces a single set of causal drivers. This approach uses the causal discovery algorithms PC1 or PCMCI that are implemented in the Tigramite Python package. These algorithms utilize conditional independence tests to infer parts of the causal graph. Our causal feature selection approach filters out causally-spurious links before passing the remaining causal features as inputs to ML models (Multiple linear regression, Random Forest) that predict the targets. We apply our framework to the statistical intensity prediction of Western Pacific Tropical Cyclones (TC), for which it is often difficult to accurately choose drivers and their dimensionality reduction (time lags, vertical levels, and area-averaging). Using more stringent significance thresholds in the conditional independence tests helps eliminate spurious causal relationships, thus helping the ML model generalize better to unseen TC cases. M-PC1 with a reduced number of features outperforms M-PCMCI, non-causal ML, and other feature selection methods (lagged correlation, random), even slightly outperforming feature selection based on eXplainable Artificial Intelligence. The optimal causal drivers obtained from our causal feature selection help improve our understanding of underlying relationships and suggest new potential drivers of TC intensification.

We address the computational efficiency in solving the A-optimal Bayesian design of experiments problems for which the observational model is based on partial differential equations and, consequently, is computationally expensive to evaluate. A-optimality is a widely used and easy-to-interpret criterion for the Bayesian design of experiments. The criterion seeks the optimal experiment design by minimizing the expected conditional variance, also known as the expected posterior variance. This work presents a novel likelihood-free method for seeking the A-optimal design of experiments without sampling or integrating the Bayesian posterior distribution. In our approach, the expected conditional variance is obtained via the variance of the conditional expectation using the law of total variance, while we take advantage of the orthogonal projection property to approximate the conditional expectation. Through an asymptotic error estimation, we show that the intractability of the posterior does not affect the performance of our approach. We use an artificial neural network (ANN) to approximate the nonlinear conditional expectation to implement our method. For dealing with continuous experimental design parameters, we integrate the training process of the ANN into minimizing the expected conditional variance. Specifically, we propose a non-local approximation of the conditional expectation and apply transfer learning to reduce the number of evaluations of the observation model. Through numerical experiments, we demonstrate that our method significantly reduces the number of observational model evaluations compared with common importance sampling-based approaches. This reduction is crucial, considering the computationally expensive nature of these models.

This paper considers a joint survival and mixed-effects model to explain the survival time from longitudinal data and high-dimensional covariates. The longitudinal data is modeled using a nonlinear effects model, where the regression function serves as a link function incorporated into a Cox model as a covariate. In that way, the longitudinal data is related to the survival time at a given time. Additionally, the Cox model takes into account the inclusion of high-dimensional covariates. The main objectives of this research are two-fold: first, to identify the relevant covariates that contribute to explaining survival time, and second, to estimate all unknown parameters of the joint model. For that purpose, we consider the maximization of a Lasso penalized likelihood. To tackle the optimization problem, we implement a pre-conditioned stochastic gradient to handle the latent variables of the nonlinear mixed-effects model associated with a proximal operator to manage the non-differentiability of the penalty. We provide relevant simulations that showcase the performance of the proposed variable selection and parameters' estimation method in the joint modeling of a Cox and logistic model.

We study causal inference and efficient estimation for the expected number of recurrent events in the presence of a terminal event. We define our estimand as the vector comprising both the expected number of recurrent events and the failure survival function evaluated along a sequence of landmark times. We identify the estimand in the presence of right-censoring and causal selection as an observed data functional under coarsening at random, derive the nonparametric efficiency bound, and propose a multiply-robust estimator that achieves the bound and permits nonparametric estimation of nuisance parameters. Throughout, no absolute continuity assumption is made on the underlying probability distributions of failure, censoring, or the observed data. Additionally, we derive the class of influence functions when the coarsening distribution is known and review how published estimators may belong to the class. Along the way, we highlight some interesting inconsistencies in the causal lifetime analysis literature.

We propose a new nonparametric modeling framework for causal inference when outcomes depend on how agents are linked in a social or economic network. Such network interference describes a large literature on treatment spillovers, social interactions, social learning, information diffusion, disease and financial contagion, social capital formation, and more. Our approach works by first characterizing how an agent is linked in the network using the configuration of other agents and connections nearby as measured by path distance. The impact of a policy or treatment assignment is then learned by pooling outcome data across similarly configured agents. We demonstrate the approach by proposing an asymptotically valid test for the hypothesis of policy irrelevance/no treatment effects and bounding the mean-squared error of a k-nearest-neighbor estimator for the average or distributional policy effect/treatment response.

Statistical machine learning methods often face the challenge of limited data available from the population of interest. One remedy is to leverage data from auxiliary source populations, which share some conditional distributions or are linked in other ways with the target domain. Techniques leveraging such \emph{dataset shift} conditions are known as \emph{domain adaptation} or \emph{transfer learning}. Despite extensive literature on dataset shift, limited works address how to efficiently use the auxiliary populations to improve the accuracy of risk evaluation for a given machine learning task in the target population. In this paper, we study the general problem of efficiently estimating target population risk under various dataset shift conditions, leveraging semiparametric efficiency theory. We consider a general class of dataset shift conditions, which includes three popular conditions -- covariate, label and concept shift -- as special cases. We allow for partially non-overlapping support between the source and target populations. We develop efficient and multiply robust estimators along with a straightforward specification test of these dataset shift conditions. We also derive efficiency bounds for two other dataset shift conditions, posterior drift and location-scale shift. Simulation studies support the efficiency gains due to leveraging plausible dataset shift conditions.

Mobile digital health (mHealth) studies often collect multiple within-day self-reported assessments of participants' behaviour and health. Indexed by time of day, these assessments can be treated as functional observations of continuous, truncated, ordinal, and binary type. We develop covariance estimation and principal component analysis for mixed-type functional data like that. We propose a semiparametric Gaussian copula model that assumes a generalized latent non-paranormal process generating observed mixed-type functional data and defining temporal dependence via a latent covariance. The smooth estimate of latent covariance is constructed via Kendall's Tau bridging method that incorporates smoothness within the bridging step. The approach is then extended with methods for handling both dense and sparse sampling designs, calculating subject-specific latent representations of observed data, latent principal components and principal component scores. Importantly, the proposed framework handles all four mixed types in a unified way. Simulation studies show a competitive performance of the proposed method under both dense and sparse sampling designs. The method is applied to data from 497 participants of National Institute of Mental Health Family Study of the Mood Disorder Spectrum to characterize the differences in within-day temporal patterns of mood in individuals with the major mood disorder subtypes including Major Depressive Disorder, and Type 1 and 2 Bipolar Disorder.

Semi-competing risks refer to the phenomenon where a primary outcome event (such as mortality) can truncate an intermediate event (such as relapse of a disease), but not vice versa. Under the multi-state model, the primary event is decomposed to a direct outcome event and an indirect outcome event through intermediate events. Within this framework, we show that the total treatment effect on the cumulative incidence of the primary event can be decomposed into three separable pathway effects, corresponding to treatment effects on population-level transition rates between states. We next propose estimators for the counterfactual cumulative incidences of the primary event under hypothetical treatments by generalized Nelson-Aalen estimators with inverse probability weighting, and then derive the consistency and asymptotic normality of these estimators. Finally, we propose hypothesis testing procedures on these separable pathway effects based on logrank statistics. We have conducted extensive simulation studies to demonstrate the validity and superior performance of our new method compared with existing methods. As an illustration of its potential usefulness, the proposed method is applied to compare effects of different allogeneic stem cell transplantation types on overall survival after transplantation.

We study universal traits which emerge both in real-world complex datasets, as well as in artificially generated ones. Our approach is to analogize data to a physical system and employ tools from statistical physics and Random Matrix Theory (RMT) to reveal their underlying structure. We focus on the feature-feature covariance matrix, analyzing both its local and global eigenvalue statistics. Our main observations are: (i) The power-law scalings that the bulk of its eigenvalues exhibit are vastly different for uncorrelated random data compared to real-world data, (ii) this scaling behavior can be completely recovered by introducing long range correlations in a simple way to the synthetic data, (iii) both generated and real-world datasets lie in the same universality class from the RMT perspective, as chaotic rather than integrable systems, (iv) the expected RMT statistical behavior already manifests for empirical covariance matrices at dataset sizes significantly smaller than those conventionally used for real-world training, and can be related to the number of samples required to approximate the population power-law scaling behavior, (v) the Shannon entropy is correlated with local RMT structure and eigenvalues scaling, and substantially smaller in strongly correlated datasets compared to uncorrelated synthetic data, and requires fewer samples to reach the distribution entropy. These findings can have numerous implications to the characterization of the complexity of data sets, including differentiating synthetically generated from natural data, quantifying noise, developing better data pruning methods and classifying effective learning models utilizing these scaling laws.