arXiv subjects

Alex Luedtke

Publications and source records attributed to Alex Luedtke.

At least 19 recordsLinked to original sources

arXiv2026

Simple Covariate Adjustment for Many Estimands Using Stable Balancing Weights

Covariate adjustment can improve precision in estimating treatment effects in clinical trials, and regulatory guidance increasingly encourages its implementation. Despite its benefits, covariate adjustment can require advanced statistical techniques or tailored approaches for different estimands, which can deter its use in practice. To address this issue, we introduce a simplified approach to covariate adjustment using stable balancing weights that applies directly across many clinical trial estimands, including the average treatment effect, relative risk, Mann-Whitney estimand, and survival ratio. More precisely, our results cover any estimand that is a Hadamard differentiable functional of the arm-specific distributions. Once the weights are obtained, our adjusted estimator can be implemented with the same software used for an unadjusted analysis, provided that software can take observation weights. This construction improves asymptotic efficiency relative to unadjusted estimation and preserves the plug-in relationship between arm-specific marginal and subgroup-specific summaries.

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arXiv2026

Sinkhorn Treatment Effects: A Causal Optimal Transport Measure

We introduce the Sinkhorn treatment effect, an entropic optimal transport measure of divergence between counterfactual distributions. Unlike classical quantities such as the average treatment effect, this measure captures differences across entire distributions. We analyze this divergence as a statistical functional and show it can be written as a smooth transformation of counterfactual mean embeddings with an appropriate kernel. This characterization allows us to establish first-order pathwise differentiability in general, and second-order pathwise differentiability under the null hypothesis of equal counterfactual distributions. Leveraging this smoothness, we construct debiased estimators and use them to obtain asymptotically valid tests for distributional treatment effects with a fixed entropic regularization parameter. Because the power of the test depends on this unknown parameter, we further propose an aggregated test that combines evidence across a grid of regularization choices. Experiments on simulated and image data demonstrate the practical advantages of our estimator and testing procedure.

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arXiv2026

Conditional Distributional Treatment Effects: Doubly Robust Estimation and Testing

Beyond conditional average treatment effects, treatments may impact the entire outcome distribution in covariate-dependent ways, for example, by altering the variance or tail risks for specific subpopulations. We propose a novel estimand to capture such conditional distributional treatment effects, and develop a doubly robust estimator that is minimax optimal in the local asymptotic sense. Using this, we develop a test for the global homogeneity of conditional potential outcome distributions that accommodates discrepancies beyond the maximum mean discrepancy (MMD), has provably valid type 1 error, and is consistent against fixed alternatives -- the first test, to our knowledge, with such guarantees in this setting. Furthermore, we derive exact closed-form expressions for two natural discrepancies (including the MMD), and provide a computationally efficient, permutation-free algorithm for our test.

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arXiv2025

Transforming Conditional Density Estimation Into a Single Nonparametric Regression Task

We propose a way of transforming the problem of conditional density estimation into a single nonparametric regression task via the introduction of auxiliary samples. This allows leveraging regression methods that work well in high dimensions, such as neural networks and decision trees. Our main theoretical result characterizes and establishes the convergence of our estimator to the true conditional density in the data limit. We develop condensit\'e, a method that implements this approach. We demonstrate the benefit of the auxiliary samples on synthetic data and showcase that condensit\'e can achieve good out-of-the-box results. We evaluate our method on a large population survey dataset and on a satellite imaging dataset. In both cases, we find that condensit\'e matches or outperforms the state of the art and yields conditional densities in line with established findings in the literature on each dataset. Our contribution opens up new possibilities for regression-based conditional density estimation and the empirical results indicate strong promise for applied research.

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arXiv2025

Inference on Variable Importance for Treatment Effect Heterogeneity: Shapley Values and Beyond

We provide an inferential framework to assess variable importance for heterogeneous treatment effects. This assessment is especially useful in high-risk domains such as medicine, where decision makers hesitate to rely on black-box treatment recommendation algorithms. The variable importance measures we consider are local in that they may differ across individuals, while the inference is global in that it tests whether a given variable is important for any individual. Our approach builds on recent developments in semiparametric theory for function-valued parameters, and is valid even when statistical machine learning algorithms are employed to quantify treatment effect heterogeneity. We demonstrate the applicability of our method to infectious disease prevention strategies.

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arXiv2025

Estimation of causal dose-response functions under data fusion

Estimating the causal dose-response function is challenging, particularly when data from a single source are insufficient to estimate responses precisely across all exposure levels. To overcome this limitation, we propose a data fusion framework that leverages multiple data sources that are partially aligned with the target distribution. Specifically, we derive a Neyman-orthogonal loss function tailored for estimating the dose-response function within data fusion settings. To improve computational efficiency, we propose a stochastic approximation that retains orthogonality. We apply kernel ridge regression with this approximation, which provides closed-form estimators. Our theoretical analysis demonstrates that incorporating additional data sources yields tighter finite-sample regret bounds and improved worst-case performance, as confirmed via minimax lower bound comparison. Simulation studies validate the practical advantages of our approach, showing improved estimation accuracy when employing data fusion. This study highlights the potential of data fusion for estimating non-smooth parameters such as causal dose-response functions.

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arXiv2025

Sequentially Doubly Robust Estimation of Conditional Survival Probability with Time-Varying Covariates

It is often of interest to study the association between covariates and the cumulative incidence of a right-censored time-to-event outcome. When time-varying covariates are measured on a fixed discrete time scale, it is desirable to account for these more up-to-date covariates when addressing censoring. For example, in vaccine trials, it is of interest to study the association between immune response levels after administering the vaccine and the cumulative incidence of the endpoint, while accounting for loss to follow-up explained by immune response levels measured at multiple post-vaccination visits. Existing methods rely on stringent parametric assumptions, do not account for informative censoring due to time-varying covariates when time is continuous, only estimate a marginal survival probability, or do not fully use the discrete-time structure of post-treatment covariates. We propose a nonparametric estimator of the continuous-time survival probability conditional on covariates, accounting for censoring due to time-varying covariates measured on a fixed discrete time scale. We show that the estimator is sequentially doubly robust: it is consistent if, within each time window between adjacent visits, the censoring distribution is consistently estimated, or both the time-to-event distribution and a conditional mean probability are consistently estimated. We also show that, in the special case of estimating the marginal survival probability, our estimator is asymptotically efficient. We demonstrate the superior performance of our estimator in a simulation experiment, and apply the method to a COVID-19 vaccine efficacy trial.

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arXiv2025

DoubleGen: Debiased Generative Modeling of Counterfactuals

Generative models for counterfactual outcomes face two key sources of bias. Confounding bias arises when approaches fail to account for systematic differences between those who receive the intervention and those who do not. Misspecification bias arises when methods attempt to address confounding through estimation of an auxiliary model, but specify it incorrectly. We introduce DoubleGen, a doubly robust framework that modifies generative modeling training objectives to mitigate these biases. The new objectives rely on two auxiliaries -- a propensity and outcome model -- and successfully address confounding bias even if only one of them is correct. We provide finite-sample guarantees for this robustness property. We further establish conditions under which DoubleGen achieves oracle optimality -- matching the convergence rates standard approaches would enjoy if interventional data were available -- and minimax rate optimality. We illustrate DoubleGen with three examples: diffusion models, flow matching, and autoregressive language models.

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arXiv2025

Stochastic Gradients under Nuisances

Stochastic gradient optimization is the dominant learning paradigm for a variety of scenarios, from classical supervised learning to modern self-supervised learning. We consider stochastic gradient algorithms for learning problems whose objectives rely on unknown nuisance parameters, and establish non-asymptotic convergence guarantees. Our results show that, while the presence of a nuisance can alter the optimum and upset the optimization trajectory, the classical stochastic gradient algorithm may still converge under appropriate conditions, such as Neyman orthogonality. Moreover, even when Neyman orthogonality is not satisfied, we show that an algorithm variant with approximately orthogonalized updates (with an approximately orthogonalized gradient oracle) may achieve similar convergence rates. Examples from orthogonal statistical learning/double machine learning and causal inference are discussed.

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arXiv2025

Coreset selection for the Sinkhorn divergence and generic smooth divergences

We introduce CO2, an efficient algorithm to produce convexly-weighted coresets with respect to generic smooth divergences. By employing a functional Taylor expansion, we show a local equivalence between sufficiently regular losses and their second order approximations, reducing the coreset selection problem to maximum mean discrepancy minimization. We apply CO2 to the Sinkhorn divergence, providing a novel sampling procedure that requires poly-logarithmically many data points to match the approximation guarantees of random sampling. To show this, we additionally verify several new regularity properties for entropically regularized optimal transport of independent interest. Our approach leads to a new perspective linking coreset selection and kernel quadrature to classical statistical methods such as moment and score matching. We showcase this method with a practical application of subsampling image data, and highlight key directions to explore for improved algorithmic efficiency and theoretical guarantees.

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arXiv2025

Automatic Debiased Machine Learning for Smooth Functionals of Nonparametric M-Estimands

We develop a unified framework for automatic debiased machine learning (autoDML) for inference on a broad class of statistical parameters. The framework applies to any smooth functional of a nonparametric M-estimand, defined as the minimizer of a population risk over an infinite-dimensional linear space. Examples include counterfactual regression, quantile, and survival functions, as well as conditional average treatment effects. Rather than requiring manual derivation of influence functions, our approach automates the construction of debiased estimators using three ingredients: the gradient and Hessian of the loss function and a linear approximation of the target functional. Estimation reduces to solving two risk minimization problems, one for the M-estimand and one for a Riesz representer. The framework accommodates Neyman-orthogonal loss functions that depend on nuisance parameters and extends to vector-valued M-estimands through joint risk minimization. We characterize the efficient influence function and construct efficient autoDML estimators via one-step correction, targeted minimum loss estimation, and sieve-based plug-in methods. Under quadratic risk, these estimators satisfy double robustness for linear functionals. We further show that they are robust to mild misspecification of the M-estimand model, incurring only second-order bias. We illustrate the method by estimating long-term survival probabilities under a semiparametric two-parameter beta-geometric failure model.

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arXiv2024

Stabilized Inverse Probability Weighting via Isotonic Calibration

Inverse weighting with an estimated propensity score is widely used by estimation methods in causal inference to adjust for confounding bias. However, directly inverting propensity score estimates can lead to instability, bias, and excessive variability due to large inverse weights, especially when treatment overlap is limited. In this work, we propose a post-hoc calibration algorithm for inverse propensity weights that generates well-calibrated, stabilized weights from user-supplied, cross-fitted propensity score estimates. Our approach employs a variant of isotonic regression with a loss function specifically tailored to the inverse propensity weights. Through theoretical analysis and empirical studies, we demonstrate that isotonic calibration improves the performance of doubly robust estimators of the average treatment effect.

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arXiv2024

Doubly robust inference via calibration

Doubly robust estimators are widely used for estimating average treatment effects and other linear summaries of regression functions. While consistency requires only one of two nuisance functions to be estimated consistently, asymptotic normality for linear functionals typically requires sufficiently fast convergence of both. We address this mismatch by showing that calibrating the nuisance estimators within a doubly robust procedure can yield doubly robust asymptotic normality. We introduce the idea of calibrated debiased machine learning (DML) and propose a specific implementation in which standard DML is augmented with a simple isotonic regression adjustment. We show that, under a partial orthogonality condition, a calibrated DML estimator remains asymptotically normal if either the regression function or Riesz representer of the functional is estimated sufficiently well, allowing the other to converge arbitrarily slowly or even inconsistently. We also propose a bootstrap-assisted method for constructing confidence intervals, enabling doubly robust inference without additional nuisance estimation. In a range of semi-synthetic benchmark datasets, calibrated DML reduces bias and improves coverage relative to standard DML. Our method can be integrated into existing DML pipelines by adding just a few lines of code to calibrate cross-fitted estimates via isotonic regression.

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arXiv2024

Comparing HIV Vaccine Immunogenicity across Trials with Different Populations and Study Designs

Safe and effective preventive vaccines have the potential to help stem the HIV epidemic. The efficacy of such vaccines is typically measured in randomized, double-blind phase IIb/III trials and described as a reduction in newly acquired HIV infections. However, such trials are often expensive, time-consuming, and/or logistically challenging. These challenges lead to a great interest in immune responses induced by vaccination, and in identifying which immune responses predict vaccine efficacy. These responses are termed vaccine correlates of protection. Studies of vaccine-induced immunogenicity vary in size and design, ranging from small, early phase trials, to case-control studies nested in a broader late-phase randomized trial. Moreover, trials can be conducted in geographically diverse study populations across the world. Such diversity presents a challenge for objectively comparing vaccine-induced immunogenicity. To address these practical challenges, we propose a framework that is capable of identifying appropriate causal estimands and estimators, which can be used to provide standardized comparisons of vaccine-induced immunogenicity across trials. We evaluate the performance of the proposed estimands via extensive simulation studies. Our estimators are well-behaved and enjoy robustness properties. The proposed technique is applied to compare vaccine immunogenicity using data from three recent HIV vaccine trials.

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arXiv2024

Propensity Score Augmentation in Matching-based Estimation of Causal Effects

When assessing the causal effect of a binary exposure using observational data, confounder imbalance across exposure arms must be addressed. Matching methods, including propensity score-based matching, can be used to deconfound the causal relationship of interest. They have been particularly popular in practice, at least in part due to their simplicity and interpretability. However, these methods can suffer from low statistical efficiency compared to many competing methods. In this work, we propose a novel matching-based estimator of the average treatment effect based on a suitably-augmented propensity score model. Our procedure can be shown to have greater statistical efficiency than traditional matching estimators whenever prognostic variables are available, and in some cases, can nearly reach the nonparametric efficiency bound. In addition to a theoretical study, we provide numerical results to illustrate our findings. Finally, we use our novel procedure to estimate the effect of circumcision on risk of HIV-1 infection using vaccine efficacy trial data.

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arXiv2024

Simplifying debiased inference via automatic differentiation and probabilistic programming

We introduce an algorithm that simplifies the construction of efficient estimators, making them accessible to a broader audience. 'Dimple' takes as input computer code representing a parameter of interest and outputs an efficient estimator. Unlike standard approaches, it does not require users to derive a functional derivative known as the efficient influence function. Dimple avoids this task by applying automatic differentiation to the statistical functional of interest. Doing so requires expressing this functional as a composition of primitives satisfying a novel differentiability condition. Dimple also uses this composition to determine the nuisances it must estimate. In software, primitives can be implemented independently of one another and reused across different estimation problems. We provide a proof-of-concept Python implementation and showcase through examples how it allows users to go from parameter specification to efficient estimation with just a few lines of code.

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arXiv2024

Combining T-learning and DR-learning: a framework for oracle-efficient estimation of causal contrasts

We introduce efficient plug-in (EP) learning, a novel framework for the estimation of heterogeneous causal contrasts, such as the conditional average treatment effect and conditional relative risk. The EP-learning framework enjoys the same oracle efficiency as Neyman-orthogonal learning strategies, such as DR-learning and R-learning, while addressing some of their primary drawbacks: (i) their practical applicability can be hindered by non-convex loss functions; and (ii) they may suffer from poor performance and instability due to inverse probability weighting and pseudo-outcomes that violate bounds. To overcome these issues, the EP-learner leverages an efficient plug-in estimator of the population risk function for the causal contrast. In doing so, it inherits the stability of plug-in strategies such as T-learning, while improving on their efficiency. Under reasonable conditions, EP-learners based on empirical risk minimization are oracle-efficient, exhibiting asymptotic equivalence to the minimizer of an oracle-efficient one-step debiased estimator of the population risk function. In simulation experiments, we show that EP-learners of the conditional average treatment effect and conditional relative risk outperform state-of-the-art competitors, including the T-learner, R-learner, and DR-learner. Open-source implementations of the proposed methods are available in our \texttt{R} package \texttt{hte3}.

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arXiv2024

Estimation of subsidiary performance metrics under optimal policies

In policy learning, the goal is typically to optimize a primary performance metric, but other subsidiary metrics often also warrant attention. This paper presents two strategies for evaluating these subsidiary metrics under a policy that is optimal for the primary one. The first relies on a novel margin condition that facilitates Wald-type inference. Under this and other regularity conditions, we show that the one-step corrected estimator is efficient. Despite the utility of this margin condition, it places strong restrictions on how the subsidiary metric behaves for nearly optimal policies, which may not hold in practice. We therefore introduce alternative, two-stage strategies that do not require a margin condition. The first stage constructs a set of candidate policies and the second builds a uniform confidence interval over this set. We provide numerical simulations to evaluate the performance of these methods in different scenarios.

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