Uncovering causal mediation effects is of significant value to practitioners seeking to isolate the direct treatment effect from the potential mediated effect. We propose a double machine learning (DML) algorithm for mediation analysis that supports continuous treatments. To estimate the target mediated response curve, our method uses a kernel-based doubly robust moment function for which we prove asymptotic Neyman orthogonality. This allows us to obtain asymptotic normality with nonparametric convergence rate while allowing for nonparametric or parametric estimation of the nuisance parameters. We then derive an optimal bandwidth strategy along with a procedure for estimating asymptotic confidence intervals. Finally, to illustrate the benefits of our method, we provide a numerical evaluation of our approach on a simulation along with an application to real-world medical data to analyze the effect of glycemic control on cognitive functions.

Inherently interpretable machine learning (IML) models provide valuable insights for clinical decision-making but face challenges when features have missing values. Classical solutions like imputation or excluding incomplete records are often unsuitable in applications where values are missing at test time. In this work, we conducted a survey with 71 clinicians from 29 trauma centers across France, including 20 complete responses to study the interaction between medical professionals and IML applied to data with missing values. This provided valuable insights into how missing data is interpreted in clinical machine learning. We used the prediction of hemorrhagic shock as a concrete example to gauge the willingness and readiness of the participants to adopt IML models from three classes of methods. Our findings show that, while clinicians value interpretability and are familiar with common IML methods, classical imputation techniques often misalign with their intuition, and that models that natively handle missing values are preferred. These results emphasize the need to integrate clinical intuition into future IML models for better human-computer interaction.

We study Federated Causal Inference, an approach to estimate treatment effects from decentralized data across centers. We compare three classes of Average Treatment Effect (ATE) estimators derived from the Plug-in G-Formula, ranging from simple meta-analysis to one-shot and multi-shot federated learning, the latter leveraging the full data to learn the outcome model (albeit requiring more communication). Focusing on Randomized Controlled Trials (RCTs), we derive the asymptotic variance of these estimators for linear models. Our results provide practical guidance on selecting the appropriate estimator for various scenarios, including heterogeneity in sample sizes, covariate distributions, treatment assignment schemes, and center effects. We validate these findings with a simulation study.

Distributional Random Forest (DRF) is a flexible forest-based method to estimate the full conditional distribution of a multivariate output of interest given input variables. In this article, we introduce a variable importance algorithm for DRFs, based on the well-established drop and relearn principle and MMD distance. While traditional importance measures only detect variables with an influence on the output mean, our algorithm detects variables impacting the output distribution more generally. We show that the introduced importance measure is consistent, exhibits high empirical performance on both real and simulated data, and outperforms competitors. In particular, our algorithm is highly efficient to select variables through recursive feature elimination, and can therefore provide small sets of variables to build accurate estimates of conditional output distributions.

Policy learning utilizing observational data is pivotal across various domains, with the objective of learning the optimal treatment assignment policy while adhering to specific constraints such as fairness, budget, and simplicity. This study introduces a novel positivity-free (stochastic) policy learning framework designed to address the challenges posed by the impracticality of the positivity assumption in real-world scenarios. This framework leverages incremental propensity score policies to adjust propensity score values instead of assigning fixed values to treatments. We characterize these incremental propensity score policies and establish identification conditions, employing semiparametric efficiency theory to propose efficient estimators capable of achieving rapid convergence rates, even when integrated with advanced machine learning algorithms. This paper provides a thorough exploration of the theoretical guarantees associated with policy learning and validates the proposed framework's finite-sample performance through comprehensive numerical experiments, ensuring the identification of causal effects from observational data is both robust and reliable.

Causal random forests provide efficient estimates of heterogeneous treatment effects. However, forest algorithms are also well-known for their black-box nature, and therefore, do not characterize how input variables are involved in treatment effect heterogeneity, which is a strong practical limitation. In this article, we develop a new importance variable algorithm for causal forests, to quantify the impact of each input on the heterogeneity of treatment effects. The proposed approach is inspired from the drop and relearn principle, widely used for regression problems. Importantly, we show how to handle the forest retrain without a confounding variable. If the confounder is not involved in the treatment effect heterogeneity, the local centering step enforces consistency of the importance measure. Otherwise, when a confounder also impacts heterogeneity, we introduce a corrective term in the retrained causal forest to recover consistency. Additionally, experiments on simulated, semi-synthetic, and real data show the good performance of our importance measure, which outperforms competitors on several test cases. Experiments also show that our approach can be efficiently extended to groups of variables, providing key insights in practice.

Conformal prediction is a theoretically grounded framework for constructing predictive intervals. We study conformal prediction with missing values in the covariates -- a setting that brings new challenges to uncertainty quantification. We first show that the marginal coverage guarantee of conformal prediction holds on imputed data for any missingness distribution and almost all imputation functions. However, we emphasize that the average coverage varies depending on the pattern of missing values: conformal methods tend to construct prediction intervals that under-cover the response conditionally to some missing patterns. This motivates our novel generalized conformalized quantile regression framework, missing data augmentation, which yields prediction intervals that are valid conditionally to the patterns of missing values, despite their exponential number. We then show that a universally consistent quantile regression algorithm trained on the imputed data is Bayes optimal for the pinball risk, thus achieving valid coverage conditionally to any given data point. Moreover, we examine the case of a linear model, which demonstrates the importance of our proposal in overcoming the heteroskedasticity induced by missing values. Using synthetic and data from critical care, we corroborate our theory and report improved performance of our methods.

An individualized treatment regime (ITR) is a decision rule that assigns treatments based on patients' characteristics. The value function of an ITR is the expected outcome in a counterfactual world had this ITR been implemented. Recently, there has been increasing interest in combining heterogeneous data sources, such as leveraging the complementary features of randomized controlled trial (RCT) data and a large observational study (OS). Usually, a covariate shift exists between the source and target population, rendering the source-optimal ITR unnecessarily optimal for the target population. We present an efficient and robust transfer learning framework for estimating the optimal ITR with right-censored survival data that generalizes well to the target population. The value function accommodates a broad class of functionals of survival distributions, including survival probabilities and restrictive mean survival times (RMSTs). We propose a doubly robust estimator of the value function, and the optimal ITR is learned by maximizing the value function within a pre-specified class of ITRs. We establish the $N^{-1/3}$ rate of convergence for the estimated parameter indexing the optimal ITR, and show that the proposed optimal value estimator is consistent and asymptotically normal even with flexible machine learning methods for nuisance parameter estimation. We evaluate the empirical performance of the proposed method by simulation studies and a real data application of sodium bicarbonate therapy for patients with severe metabolic acidaemia in the intensive care unit (ICU), combining a RCT and an observational study with heterogeneity.

In recent decades, technological advances have made it possible to collect large data sets. In this context, the model-based clustering is a very popular, flexible and interpretable methodology for data exploration in a well-defined statistical framework. One of the ironies of the increase of large datasets is that missing values are more frequent. However, traditional ways (as discarding observations with missing values or imputation methods) are not designed for the clustering purpose. In addition, they rarely apply to the general case, though frequent in practice, of Missing Not At Random (MNAR) values, i.e. when the missingness depends on the unobserved data values and possibly on the observed data values. The goal of this paper is to propose a novel approach by embedding MNAR data directly within model-based clustering algorithms. We introduce a selection model for the joint distribution of data and missing-data indicator. It corresponds to a mixture model for the data distribution and a general MNAR model for the missing-data mechanism, which may depend on the underlying classes (unknown) and/or the values of the missing variables themselves. A large set of meaningful MNAR sub-models is derived and the identifiability of the parameters is studied for each of the sub-models, which is usually a key issue for any MNAR proposals. The EM and Stochastic EM algorithms are considered for estimation. Finally, we perform empirical evaluations for the proposed submodels on synthetic data and we illustrate the relevance of our method on a medical register, the TraumaBase (R) dataset.

How to learn a good predictor on data with missing values? Most efforts focus on first imputing as well as possible and second learning on the completed data to predict the outcome. Yet, this widespread practice has no theoretical grounding. Here we show that for almost all imputation functions, an impute-then-regress procedure with a powerful learner is Bayes optimal. This result holds for all missing-values mechanisms, in contrast with the classic statistical results that require missing-at-random settings to use imputation in probabilistic modeling. Moreover, it implies that perfect conditional imputation may not be needed for good prediction asymptotically. In fact, we show that on perfectly imputed data the best regression function will generally be discontinuous, which makes it hard to learn. Crafting instead the imputation so as to leave the regression function unchanged simply shifts the problem to learning discontinuous imputations. Rather, we suggest that it is easier to learn imputation and regression jointly. We propose such a procedure, adapting NeuMiss, a neural network capturing the conditional links across observed and unobserved variables whatever the missing-value pattern. Experiments confirm that joint imputation and regression through NeuMiss is better than various two step procedures in our experiments with finite number of samples.