Targeted maximum likelihood estimation of vaccine effectiveness and immune correlates in test-negative design studies with missing data

The test-negative design (TND) is a resource-efficient observational study design that can assess vaccine effectiveness and exposure-proximal immune correlates of disease. The TND enrolls symptomatic individuals seeking diagnostic testing and compares case status by an exposure variable, such as vaccination status or immune marker level, that is measured at testing. While the TND reduces confounding by healthcare-seeking behavior, other sources of confounding may remain. TND studies may also have missing data in the exposure variable due to incomplete records or two-phase sampling designs. We present a targeted maximum likelihood estimation approach involving a semiparametric logistic regression model that targets a causal conditional risk ratio of symptomatic disease in the healthcare-seeking population. Under causal and missing at random assumptions, our method produces an efficient, asymptotically linear estimator that provides flexible, data-driven confounding control and valid causal inference when analyzing TND studies with missing exposure variable data. We evaluate our method's finite sample properties using plasmode simulations of a two-phase TND immune correlates study. We also apply our method to assess COVID-19 vaccine effectiveness and antibody marker correlates of COVID-19 from TND study cohorts derived from the Moderna Coronavirus Efficacy phase 3 trial.

Calibeating Prediction-Powered Inference

We study semisupervised mean estimation with a small labeled sample, a large unlabeled sample, and a black-box prediction model whose output may be miscalibrated. A standard approach in this setting is augmented inverse-probability weighting (AIPW) [Robins et al., 1994], which protects against prediction-model misspecification but can be inefficient when the prediction score is poorly aligned with the outcome scale. We introduce Calibrated Prediction-Powered Inference, which post-hoc calibrates the prediction score on the labeled sample before using it for semisupervised estimation. This simple step requires no retraining and can improve the original score both as a predictor of the outcome and as a regression adjustment for semisupervised inference. We study both linear and isotonic calibration. For isotonic calibration, we establish first-order optimality guarantees: isotonic post-processing can improve predictive accuracy and estimator efficiency relative to the original score and simpler post-processing rules, while no further post-processing of the fitted isotonic score yields additional first-order gains. For linear calibration, we show first-order equivalence to PPI++. We also clarify the relationship among existing estimators, showing that the original PPI estimator is a special case of AIPW and can be inefficient when the prediction model is accurate, while PPI++ is AIPW with empirical efficiency maximization [Rubin et al., 2008]. In simulations and real-data experiments, our calibrated estimators often outperform PPI and are competitive with, or outperform, AIPW and PPI++. We provide an accompanying Python package, ppi_aipw, at https://larsvanderlaan.github.io/ppi-aipw/.

A Researcher's Guide to Empirical Risk Minimization

This guide develops high-probability regret bounds for empirical risk minimization (ERM). The presentation is modular: we state broadly applicable guarantees under high-level conditions and give tools for verifying them for specific losses and function classes. We emphasize that many ERM rate derivations can be organized around a three-step recipe -- a basic inequality, a uniform local concentration bound, and a fixed-point argument -- which yields regret bounds in terms of a critical radius, defined via localized Rademacher complexity, under a mild Bernstein-type variance--risk condition. To make these bounds concrete, we upper bound the critical radius using local maximal inequalities and metric-entropy integrals, recovering familiar rates for VC-subgraph, Sobolev/Hölder, and bounded-variation classes. We also review ERM with nuisance components -- including weighted ERM and Neyman-orthogonal losses -- as they arise in causal inference, missing data, and domain adaptation. Following the orthogonal learning framework, we highlight that these problems often admit regret-transfer bounds linking regret under an estimated loss to population regret under the target loss. These bounds typically decompose regret into (i) statistical error under the estimated (optimized) loss and (ii) approximation error due to nuisance estimation. Under sample splitting or cross-fitting, the first term can be controlled using standard fixed-loss ERM regret bounds, while the second term depends only on nuisance-estimation accuracy. We also treat the in-sample regime, where nuisances and the ERM are fit on the same data, deriving regret bounds and giving sufficient conditions for fast rates.

Stationary Reweighting Yields Local Convergence of Soft Fitted Q-Iteration

Fitted Q-iteration (FQI) and its entropy-regularized variant, soft FQI, are central tools for value-based model-free offline reinforcement learning, but can behave poorly under function approximation and distribution shift. In the entropy-regularized setting, we show that the soft Bellman operator is locally contractive in the stationary norm of the soft-optimal policy, rather than in the behavior norm used by standard FQI. This geometric mismatch explains the instability of soft Q-iteration with function approximation in the absence of Bellman completeness. To restore contraction, we introduce stationary-reweighted soft FQI, which reweights each regression update using the stationary distribution of the current policy. We prove local linear convergence under function approximation with geometrically damped weight-estimation errors, assuming approximate realizability. Our analysis further suggests that global convergence may be recovered by gradually reducing the softmax temperature, and that this continuation approach can extend to the hardmax limit under a mild margin condition.

Efficient Inference for Inverse Reinforcement Learning and Dynamic Discrete Choice Models

Inverse reinforcement learning (IRL) and dynamic discrete choice (DDC) models explain sequential decision-making by recovering reward functions that rationalize observed behavior. Flexible IRL methods typically rely on machine learning but provide no guarantees for valid inference, while classical DDC approaches impose restrictive parametric specifications and often require repeated dynamic programming. We develop a semiparametric framework for debiased inverse reinforcement learning that yields statistically efficient inference for a broad class of reward-dependent functionals in maximum entropy IRL and Gumbel-shock DDC models. We show that the log-behavior policy acts as a pseudo-reward that point-identifies policy value differences and, under a simple normalization, the reward itself. We then formalize these targets, including policy values under known and counterfactual softmax policies and functionals of the normalized reward, as smooth functionals of the behavior policy and transition kernel, establish pathwise differentiability, and derive their efficient influence functions. Building on this characterization, we construct automatic debiased machine-learning estimators that allow flexible nonparametric estimation of nuisance components while achieving $\sqrt{n}$-consistency, asymptotic normality, and semiparametric efficiency. Our framework extends classical inference for DDC models to nonparametric rewards and modern machine-learning tools, providing a unified and computationally tractable approach to statistical inference in IRL.

Fitted Q Evaluation Without Bellman Completeness via Stationary Weighting

Fitted Q-evaluation (FQE) is a central method for off-policy evaluation in reinforcement learning, but it generally requires Bellman completeness: that the hypothesis class is closed under the evaluation Bellman operator. This requirement is challenging because enlarging the hypothesis class can worsen completeness. We show that the need for this assumption stems from a fundamental norm mismatch: the Bellman operator is gamma-contractive under the stationary distribution of the target policy, whereas FQE minimizes Bellman error under the behavior distribution. We propose a simple fix: reweight each regression step using an estimate of the stationary density ratio, thereby aligning FQE with the norm in which the Bellman operator contracts. This enables strong evaluation guarantees in the absence of realizability or Bellman completeness, avoiding the geometric error blow-up of standard FQE in this setting while maintaining the practicality of regression-based evaluation.

Bellman Calibration for V-Learning in Offline Reinforcement Learning

We introduce Iterated Bellman Calibration, a simple, model-agnostic, post-hoc procedure for calibrating off-policy value predictions in infinite-horizon Markov decision processes. Bellman calibration requires that states with similar predicted long-term returns exhibit one-step returns consistent with the Bellman equation under the target policy. We adapt classical histogram and isotonic calibration to the dynamic, counterfactual setting by repeatedly regressing fitted Bellman targets onto a model's predictions, using a doubly robust pseudo-outcome to handle off-policy data. This yields a one-dimensional fitted value iteration scheme that can be applied to any value estimator. Our analysis provides finite-sample guarantees for both calibration and prediction under weak assumptions, and critically, without requiring Bellman completeness or realizability.

Hybrid Meta-learners for Estimating Heterogeneous Treatment Effects

Estimating conditional average treatment effects (CATE) from observational data involves modeling decisions that differ from supervised learning, particularly concerning how to regularize model complexity. Previous approaches can be grouped into two primary "meta-learner" paradigms that impose distinct inductive biases. Indirect meta-learners first fit and regularize separate potential outcome (PO) models and then estimate CATE by taking their difference, whereas direct meta-learners construct and directly regularize estimators for the CATE function itself. Neither approach consistently outperforms the other across all scenarios: indirect learners perform well when the PO functions are simple, while direct learners outperform when the CATE is simpler than individual PO functions. In this paper, we introduce the Hybrid Learner (H-learner), a novel regularization strategy that interpolates between the direct and indirect regularizations depending on the dataset at hand. The H-learner achieves this by learning intermediate functions whose difference closely approximates the CATE without necessarily requiring accurate individual approximations of the POs themselves. We demonstrate empirically that intentionally allowing suboptimal fits to the POs improves the bias-variance tradeoff in estimating CATE. Experiments conducted on semi-synthetic and real-world benchmark datasets illustrate that the H-learner consistently operates at the Pareto frontier, effectively combining the strengths of both direct and indirect meta-learners.

Nonparametric Instrumental Variable Inference with Many Weak Instruments

We study inference on linear functionals in the nonparametric instrumental variable (NPIV) problem with a discretely-valued instrument under a many-weak-instruments asymptotic regime, where the number of instrument values grows with the sample size. A key motivating example is estimating long-term causal effects in a new experiment with only short-term outcomes, using past experiments to instrument for the effect of short- on long-term outcomes. Here, the assignment to a past experiment serves as the instrument: we have many past experiments but only a limited number of units in each. Since the structural function is nonparametric but constrained by only finitely many moment restrictions, point identification typically fails. To address this, we consider linear functionals of the minimum-norm solution to the moment restrictions, which is always well-defined. As the number of instrument levels grows, these functionals define an approximating sequence to a target functional, replacing point identification with a weaker asymptotic notion suited to discrete instruments. Extending the Jackknife Instrumental Variable Estimator (JIVE) beyond the classical parametric setting, we propose npJIVE, a nonparametric estimator for solutions to linear inverse problems with many weak instruments. We construct automatic debiased machine learning estimators for linear functionals of both the structural function and its minimum-norm projection, and establish their efficiency in the many-weak-instruments regime.

Generalized Venn and Venn-Abers Calibration with Applications in Conformal Prediction

Ensuring model calibration is critical for reliable predictions, yet popular distribution-free methods, such as histogram binning and isotonic regression, provide only asymptotic guarantees. We introduce a unified framework for Venn and Venn-Abers calibration, generalizing Vovk's binary classification approach to arbitrary prediction tasks and loss functions. Venn calibration leverages binning calibrators to construct prediction sets that contain at least one marginally perfectly calibrated point prediction in finite samples, capturing epistemic uncertainty in the calibration process. The width of these sets shrinks asymptotically to zero, converging to a conditionally calibrated point prediction. Furthermore, we propose Venn multicalibration, a novel methodology for finite-sample calibration across subpopulations. For quantile loss, group-conditional and multicalibrated conformal prediction arise as special cases of Venn multicalibration, and Venn calibration produces novel conformal prediction intervals that achieve quantile-conditional coverage. As a separate contribution, we extend distribution-free conditional calibration guarantees of histogram binning and isotonic calibration to general losses.