van der Laan, Lars
Generalized Venn and Venn-Abers Calibration with Applications in Conformal Prediction
van der Laan, Lars, Alaa, Ahmed
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.
Automatic Debiased Machine Learning for Smooth Functionals of Nonparametric M-Estimands
van der Laan, Lars, Bibaut, Aurelien, Kallus, Nathan, Luedtke, Alex
We propose a unified framework for automatic debiased machine learning (autoDML) to perform inference on smooth functionals of infinite-dimensional M-estimands, defined as population risk minimizers over Hilbert spaces. By automating debiased estimation and inference procedures in causal inference and semiparametric statistics, our framework enables practitioners to construct valid estimators for complex parameters without requiring specialized expertise. The framework supports Neyman-orthogonal loss functions with unknown nuisance parameters requiring data-driven estimation, as well as vector-valued M-estimands involving simultaneous loss minimization across multiple Hilbert space models. We formalize the class of parameters efficiently estimable by autoDML as a novel class of nonparametric projection parameters, defined via orthogonal minimum loss objectives. We introduce three autoDML estimators based on one-step estimation, targeted minimum loss-based estimation, and the method of sieves. For data-driven model selection, we derive a novel decomposition of model approximation error for smooth functionals of M-estimands and propose adaptive debiased machine learning estimators that are superefficient and adaptive to the functional form of the M-estimand. Finally, we illustrate the flexibility of our framework by constructing autoDML estimators for the long-term survival under a beta-geometric model.
Automatic Double Reinforcement Learning in Semiparametric Markov Decision Processes with Applications to Long-Term Causal Inference
van der Laan, Lars, Hubbard, David, Tran, Allen, Kallus, Nathan, Bibaut, Aurรฉlien
Double reinforcement learning (DRL) enables statistically efficient inference on the value of a policy in a nonparametric Markov Decision Process (MDP) given trajectories generated by another policy. However, this approach necessarily requires stringent overlap between the state distributions, which is often violated in practice. To relax this requirement and extend DRL, we study efficient inference on linear functionals of the $Q$-function (of which policy value is a special case) in infinite-horizon, time-invariant MDPs under semiparametric restrictions on the $Q$-function. These restrictions can reduce the overlap requirement and lower the efficiency bound, yielding more precise estimates. As an important example, we study the evaluation of long-term value under domain adaptation, given a few short trajectories from the new domain and restrictions on the difference between the domains. This can be used for long-term causal inference. Our method combines flexible estimates of the $Q$-function and the Riesz representer of the functional of interest (e.g., the stationary state density ratio for policy value) and is automatic in that we do not need to know the form of the latter - only the functional we care about. To address potential model misspecification bias, we extend the adaptive debiased machine learning (ADML) framework of \citet{van2023adaptive} to construct nonparametrically valid and superefficient estimators that adapt to the functional form of the $Q$-function. As a special case, we propose a novel adaptive debiased plug-in estimator that uses isotonic-calibrated fitted $Q$-iteration - a new calibration algorithm for MDPs - to circumvent the computational challenges of estimating debiasing nuisances from min-max objectives.
Stabilized Inverse Probability Weighting via Isotonic Calibration
van der Laan, Lars, Lin, Ziming, Carone, Marco, Luedtke, Alex
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.
Automatic doubly robust inference for linear functionals via calibrated debiased machine learning
van der Laan, Lars, Luedtke, Alex, Carone, Marco
In causal inference, many estimands of interest can be expressed as a linear functional of the outcome regression function; this includes, for example, average causal effects of static, dynamic and stochastic interventions. For learning such estimands, in this work, we propose novel debiased machine learning estimators that are doubly robust asymptotically linear, thus providing not only doubly robust consistency but also facilitating doubly robust inference (e.g., confidence intervals and hypothesis tests). To do so, we first establish a key link between calibration, a machine learning technique typically used in prediction and classification tasks, and the conditions needed to achieve doubly robust asymptotic linearity. We then introduce calibrated debiased machine learning (C-DML), a unified framework for doubly robust inference, and propose a specific C-DML estimator that integrates cross-fitting, isotonic calibration, and debiased machine learning estimation. A C-DML estimator maintains asymptotic linearity when either the outcome regression or the Riesz representer of the linear functional is estimated sufficiently well, allowing the other to be estimated at arbitrarily slow rates or even inconsistently. We propose a simple bootstrap-assisted approach for constructing doubly robust confidence intervals. Our theoretical and empirical results support the use of C-DML to mitigate bias arising from the inconsistent or slow estimation of nuisance functions.
Adaptive-TMLE for the Average Treatment Effect based on Randomized Controlled Trial Augmented with Real-World Data
van der Laan, Mark, Qiu, Sky, van der Laan, Lars
We consider the problem of estimating the average treatment effect (ATE) when both randomized control trial (RCT) data and real-world data (RWD) are available. We decompose the ATE estimand as the difference between a pooled-ATE estimand that integrates RCT and RWD and a bias estimand that captures the conditional effect of RCT enrollment on the outcome. We introduce an adaptive targeted minimum loss-based estimation (A-TMLE) framework to estimate them. We prove that the A-TMLE estimator is root-n-consistent and asymptotically normal. Moreover, in finite sample, it achieves the super-efficiency one would obtain had one known the oracle model for the conditional effect of the RCT enrollment on the outcome. Consequently, the smaller the working model of the bias induced by the RWD is, the greater our estimator's efficiency, while our estimator will always be at least as efficient as an efficient estimator that uses the RCT data only. A-TMLE outperforms existing methods in simulations by having smaller mean-squared-error and 95% confidence intervals. A-TMLE could help utilize RWD to improve the efficiency of randomized trial results without biasing the estimates of intervention effects. This approach could allow for smaller, faster trials, decreasing the time until patients can receive effective treatments.
Self-Consistent Conformal Prediction
van der Laan, Lars, Alaa, Ahmed M.
However, a decision-makers often take identical actions in limitation of CP is that the prediction intervals provide valid contexts with identical predicted outcomes. Conformal coverage only marginally, averaged across all possible contexts prediction helps decision-makers quantify - where'context' refers to the information available for outcome uncertainty for actions, allowing for better decision-making. Thus, for a specific context, CP intervals risk management. Inspired by this perspective, may not accurately capture the true outcome variability, leading we introduce self-consistent conformal prediction, to unreliable and potentially harmful decision-making which yields both Venn-Abers calibrated predictions (van Calster et al., 2019; Lloyd-Jones et al., 2019).
Combining T-learning and DR-learning: a framework for oracle-efficient estimation of causal contrasts
van der Laan, Lars, Carone, Marco, Luedtke, Alex
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, including that (i) their practical applicability can be hindered by loss function non-convexity; and (ii) they may suffer from poor performance and instability due to inverse probability weighting and pseudo-outcomes that violate bounds. To avoid these drawbacks, EP-learner constructs an efficient plug-in estimator of the population risk function for the causal contrast, thereby inheriting the stability and robustness properties of plug-in estimation strategies like T-learning. 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 illustrate that EP-learners of the conditional average treatment effect and conditional relative risk outperform state-of-the-art competitors, including T-learner, R-learner, and DR-learner. Open-source implementations of the proposed methods are available in our R package hte3.
Estimating Uncertainty in Multimodal Foundation Models using Public Internet Data
Dutta, Shiladitya, Wei, Hongbo, van der Laan, Lars, Alaa, Ahmed M.
Foundation models are trained on vast amounts of data at scale using self-supervised learning, enabling adaptation to a wide range of downstream tasks. At test time, these models exhibit zero-shot capabilities through which they can classify previously unseen (user-specified) categories. In this paper, we address the problem of quantifying uncertainty in these zero-shot predictions. We propose a heuristic approach for uncertainty estimation in zero-shot settings using conformal prediction with web data. Given a set of classes at test time, we conduct zero-shot classification with CLIP-style models using a prompt template, e.g., "an image of a
Adaptive debiased machine learning using data-driven model selection techniques
van der Laan, Lars, Carone, Marco, Luedtke, Alex, van der Laan, Mark
Debiased machine learning estimators for nonparametric inference of smooth functionals of the data-generating distribution can suffer from excessive variability and instability. For this reason, practitioners may resort to simpler models based on parametric or semiparametric assumptions. However, such simplifying assumptions may fail to hold, and estimates may then be biased due to model misspecification. To address this problem, we propose Adaptive Debiased Machine Learning (ADML), a nonparametric framework that combines data-driven model selection and debiased machine learning techniques to construct asymptotically linear, adaptive, and superefficient estimators for pathwise differentiable functionals. By learning model structure directly from data, ADML avoids the bias introduced by model misspecification and remains free from the restrictions of parametric and semiparametric models. While they may exhibit irregular behavior for the target parameter in a nonparametric statistical model, we demonstrate that ADML estimators provides regular and locally uniformly valid inference for a projection-based oracle parameter. Importantly, this oracle parameter agrees with the original target parameter for distributions within an unknown but correctly specified oracle statistical submodel that is learned from the data. This finding implies that there is no penalty, in a local asymptotic sense, for conducting data-driven model selection compared to having prior knowledge of the oracle submodel and oracle parameter. To demonstrate the practical applicability of our theory, we provide a broad class of ADML estimators for estimating the average treatment effect in adaptive partially linear regression models.