A Doubly Robust Machine Learning Approach for Disentangling Treatment Effect Heterogeneity with Functional Outcomes

Causal inference is paramount for understanding the effects of interventions, yet extracting personalized insights from increasingly complex data remains a significant challenge for modern machine learning. This is the case, in particular, when considering functional outcomes observed over a continuous domain (e.g., time, or space). Estimation of heterogeneous treatment effects, known as CATE, has emerged as a crucial tool for personalized decision-making, but existing meta-learning frameworks are largely limited to scalar outcomes, failing to provide satisfying results in scientific applications that leverage the rich, continuous information encoded in functional data. Here, we introduce FOCaL (Functional Outcome Causal Learning), a novel, doubly robust meta-learner specifically engineered to estimate a functional heterogeneous treatment effect (F-CATE). FOCaL integrates advanced functional regression techniques for both outcome modeling and functional pseudo-outcome reconstruction, thereby enabling the direct and robust estimation of F-CATE. We provide a rigorous theoretical derivation of FOCaL, demonstrate its performance and robustness compared to existing non-robust functional methods through comprehensive simulation studies, and illustrate its practical utility on diverse real-world functional datasets. FOCaL advances the capabilities of machine intelligence to infer nuanced, individualized causal effects from complex data, paving the way for more precise and trustworthy AI systems in personalized medicine, adaptive policy design, and fundamental scientific discovery.

Rescuing double robustness: safe estimation under complete misspecification

Double robustness is a major selling point of semiparametric and missing data methodology. Its virtues lie in protection against partial nuisance misspecification and asymptotic semiparametric efficiency under correct nuisance specification. However, in many applications, complete nuisance misspecification should be regarded as the norm (or at the very least the expected default), and thus doubly robust estimators may behave fragilely. In fact, it has been amply verified empirically that these estimators can perform poorly when all nuisance functions are misspecified. Here, we first characterize this phenomenon of double fragility, and then propose a solution based on adaptive correction clipping (ACC). We argue that our ACC proposal is safe, in that it inherits the favorable properties of doubly robust estimators under correct nuisance specification, but its error is guaranteed to be bounded by a convex combination of the individual nuisance model errors, which prevents the instability caused by the compounding product of errors of doubly robust estimators. We also show that our proposal provides valid inference through the parametric bootstrap when nuisances are well-specified. We showcase the efficacy of our ACC estimator both through extensive simulations and by applying it to the analysis of Alzheimer's disease proteomics data.

FAStEN: an efficient adaptive method for feature selection and estimation in high-dimensional functional regressions

Functional regression analysis is an established tool for many contemporary scientific applications. Regression problems involving large and complex data sets are ubiquitous, and feature selection is crucial for avoiding overfitting and achieving accurate predictions. We propose a new, flexible, and ultra-efficient approach to perform feature selection in a sparse high dimensional function-on-function regression problem, and we show how to extend it to the scalar-on-function framework. Our method combines functional data, optimization, and machine learning techniques to perform feature selection and parameter estimation simultaneously. We exploit the properties of Functional Principal Components, and the sparsity inherent to the Dual Augmented Lagrangian problem to significantly reduce computational cost, and we introduce an adaptive scheme to improve selection accuracy. Through an extensive simulation study, we benchmark our approach to the best existing competitors and demonstrate a massive gain in terms of CPU time and selection performance without sacrificing the quality of the coefficients' estimation. Finally, we present an application to brain fMRI data from the AOMIC PIOP1 study.