A central goal of modern causal inference is estimating heterogeneous treatment effects to answer questions like "how does an intervention affect each unit," rather than only on average. We study this problem with panel-data where we observe $n$ units across $m$ times under unknown, non-uniform treatment assignments. The data in this setting is naturally represented as a matrix of all unit--time treatment effects. Estimating heterogeneous treatment effects can then be expressed as obtaining a good estimation of each row's average in this matrix. This allows us to formulate the problem as matrix completion, which can be solved under natural low-rankness assumptions. However, existing matrix-completion guarantees are not powerful enough to get meaningful bounds for the per-row guarantee required for estimating the heterogeneous treatment effect; roughly speaking, they are only useful for estimating average treatment effect bounds, as also illustrated in a recent line of work. We give a simple, computationally efficient estimator that, without knowledge of the propensities and under standard low-rankness and regularity assumptions, achieves a row-wise $\ell_2$ error of $\tilde{O}(\sqrt{\frac{1}{n} + \frac{n}{m^2}})$. Technically, our analysis establishes the first sharp row-wise $\ell_2$-perturbation bound for low-rank approximation, complementing existing spectral-, Frobenius-, and entrywise perturbation theory.

Estimating how much an intervention helps a given individual the conditional average treatment effect (CATE) is increasingly central to decision-making in medicine, economics, and policy, where an estimate is most useful when accompanied by a calibrated uncertainty interval. We study the few-placebo regime, in which one treatment arm is much smaller than the other, as arises in unequal-allocation trials and small-holdout $A/B$ tests. The standard estimator in this setting is the X-Learner, and a natural way to obtain credible intervals is to make its second stage Bayesian. We show that these intervals under-cover: they contain the true effect less often than their nominal level. We trace this to a structural cause the X-Learner's regression target inherits the bias of a nuisance model fitted to the small arm, so the posterior is centered away from the true effect and we find that the standard remedy, regressing an orthogonal doubly-robust score, is also unreliable here, since the regime's limited overlap leaves the estimator either highly variable or, once stabilized, biased once more. Both consequences reflect a pattern that extends beyond causal inference: a separately estimated variance is attached to a point estimate of a hard-to-learn quantity, and the point estimate's bias is not captured by that variance. We propose GP-CATE, which models each arm's outcome surface with a Gaussian process, so the scarce arm's uncertainty enters the posterior directly rather than as an unmodelled bias. Across synthetic and semi-synthetic benchmarks, GP-CATE attains calibrated coverage where the estimators we compare against including Causal Forest and BART do not, at the cost of intervals that are appropriately wide when the data are uninformative.

This paper studies adaptive targeting under network interference in a bandit setting, where treatments applied to one individual may affect others through spillover effects. We consider a linear model in a sparse regime, where each individual's outcome can be affected by at most a few others. We first establish a regret lower bound showing that ignoring the network structure and reducing the problem to a standard linear bandit inevitably leads to inefficient learning, particularly in large populations. To understand how structural information can be leveraged, we analyze regimes with varying levels of knowledge of the interference structure: (1) full support knowledge, (2) knowledge of the column support sizes, and (3) no prior knowledge. For each regime, we establish regret lower bounds characterizing the fundamental limits of learning, and develop algorithms that achieve near-optimal regret. Together, our results provide a unified view of how knowledge of the interference structure governs the efficiency of online learning under interference, and offer practical adaptive targeting algorithms in each setting. Numerical experiments on synthetic and real-world data demonstrate the practical benefits of our algorithms.

When treatment effects are naturally expressed as ratios -- as in medicine, pricing, and marketing -- the ratio-based CATE $τ(x) = E[Y|W=1,X=x] / E[Y|W=0,X=x]$ is the appropriate estimand. Yet existing estimators either impose a log-linear parametric structure or apply generic regression without robustness guarantees for this functional. We introduce the Q-Learner, which decomposes $τ(x)$ into a product of two odds ratios, reducing ratio-CATE estimation for binary outcomes to two propensity classification tasks. We further derive doubly robust augmentations for both S/T- and Q-style ratio learners and characterize their distinct robustness properties. In benchmarks on seven RCT datasets, the Q-Learner is the most consistently competitive method in low-conversion regimes, where its propensity-only construction sidesteps the imbalanced regression that hurts outcome-based estimators. On four observational datasets, where propensity must be estimated and confounding cannot be ruled out, the DR learners introduced here decisively come out on top, making them practitioners' natural default for confounded observational data.

Estimating heterogeneous treatment effects with machine learning has attracted substantial attention in both academic research and industrial practice. However, the two communities often evaluate models under markedly different conditions. Methodological work typically relies on semi-simulated benchmarks and metrics that require counterfactual outcomes, whereas real-world applications rely on observable metrics based on ranking or test outcomes. Despite the well-known gap between methodological progress and practical deployment, the relationship between these evaluation regimes has not been examined systematically. We conduct a large-scale empirical study of treatment effect evaluation across standard semi-simulated benchmark families and real-world datasets. Our benchmark covers meta-learners paired with multiple base learners, as well as specialized causal machine learning models. We evaluate these methods using observable metrics common in application-oriented literature, alongside counterfactual metrics commonly used in methods papers. Our results reveal two complementary gaps. First, counterfactual metrics do not reliably recover the estimators preferred by observable metrics, even on the same semi-simulated benchmarks. Second, rankings obtained on semi-simulated benchmarks do not transfer to real datasets. We further find that simple meta-learners with strong base models are consistently competitive, in contrast to specialized causal models. Overall, our findings suggest that progress in treatment effect estimation research should not be assessed solely through counterfactual metrics and semi-simulated benchmarks, but it would benefit from incorporating observable metrics and real-data validation.

Public service programs often allocate limited resources under uncertainty about their benefits, creating a need for randomization to support credible evaluation. In practice, however, applicants commonly enter waitlists where resources are prioritized toward individuals judged to have higher need through tiered priority queues, making direct randomization difficult. Motivated by this, we develop an experimental design framework for learning treatment effects while treating those most in need where incoming applicants are randomized into priority queues based on their assessed risk scores. Treatments are then provided across queues in priority order and first-in-first-out within queue as budget becomes available. Our contributions are two-fold. First, we characterize what causal effects are identified under this priority-queue allocation. When arrivals are exogenous, treatments are conditionally randomized, and hence standard estimands are identified; when arrivals are endogenous, queue randomization instead provides an instrument for treatment, identifying local treatment effects induced by the queuing process. Second, we develop optimized queue-assignment designs that trade off statistical efficiency against prioritizing higher-need applicants. We show in the process that, despite dependence in treatment assignments induced by the design, usual iid efficiency bounds remain well-justified design objectives. We illustrate the proposed designs using data from a housing allocation program in a large U.S. county.

Adaptive experimentation enables efficient estimation of causal effects, but existing methods are not designed for survival data with censoring, where event times are only partially observed (e.g., overall survival in cancer trials but with dropout). In this paper, we develop a novel framework for adaptive experimentation to estimate causal effects under right censoring. For this, we derive the semiparametric efficiency bound for the average survival effect curve as a function of the treatment allocation policy and thereby obtain a closed-form efficiency-optimal allocation policy. The policy generalizes classical Neyman allocation to survival settings by prioritizing patient strata where both event and censoring dynamics induce high uncertainty. Building on this, we propose the Adaptive Survival Estimator (ASE), an adaptive framework that learns the allocation policy and estimates the average survival effect curve sequentially. Our framework has three main benefits: (i) it accommodates arbitrary machine learning models for nuisance estimation; (ii) it is guided by a closed-form efficiency-optimal allocation policy; and (iii) it admits strong theoretical guarantees, including asymptotic normality via a martingale central limit theorem. We demonstrate our framework across various numerical experiments to show consistent efficiency gains over uniform randomization and censoring-agnostic baselines.

Subgroup analyses within randomized controlled trials are often underpowered due to limited sample sizes. We address this challenge by leveraging trial participants outside the subgroup of interest to augment estimation within the subgroup. Specifically, we study two Targeted Maximum Likelihood Estimators (TMLEs) that borrow information from non-subgroup participants within the same trial: a TMLE with pooled regression (TMLE-PR) and an Adaptive Targeted Maximum Likelihood Estimator (A-TMLE). Both estimators enable information sharing without relying on any external real-world data, thereby capitalizing on key strengths of the trial: most importantly, the protection against bias afforded by the randomized treatment, but also harmonized data collection, and consistent treatment and outcome definitions. The general strategy proposed here directly advances the priorities of key regulatory agencies, including the FDA, by improving the precision of subgroup-specific treatment effect estimates without introducing external sources of bias, thereby facilitating rigorous inference to support equitable labeling, access, and post-market evaluation. In a case study based on analysis of data from a cardiovascular outcome trial (LEADER, NCT01179048), we estimate the risk reduction of major adverse cardiac events (MACE) under liraglutide treatment among Black and Asian subgroups -- each comprising less than 10\% of the trial population -- using the proposed estimators that borrow information from the remainder of the trial. Using A-TMLE, in particular, we find estimated absolute MACE risk reductions of 1.6, 1.5, and 1.5 percentage points among Asian participants and 2.1, 2.0, and 2.1 percentage points among Black participants at 365, 540, and 730 days, respectively, with 95\% confidence intervals excluding the null at each time point.

Single-arm trials are an important study design for evaluating drug efficacy and safety without enrolling patients into a control arm. Although they do not provide the gold-standard evidence of randomized controlled trials, they are increasingly used in clinical development as they offer an efficient, ethical, and practical alternative. A wide variety of approaches can be used to construct control comparators and estimate treatment effects, from fixed comparators informed by clinical knowledge to data-based and model-based patient-level comparators, also known as synthetic controls. Powerful and flexible machine learning models can allow outcome-model-based synthetic controls to overcome key limitations of direct data-based approaches, yield more robust estimates of treatment effects, and provide a principled way to incorporate corrections or encode additional assumptions when external data are not directly comparable. In this work, we argue that outcome-model-based synthetic control arms are an important tool for single-arm trials. We focus on digital twins, personalized predictions of disease progression generated from machine learning models trained on historical datasets, which naturally leverage these flexible approaches. We review doubly robust estimators, present power and sample size formulas, and discuss trade-offs in selecting historical data for training and analysis. We also outline practical considerations for deploying digital twins within the framework of recent FDA draft guidance on the use of artificial intelligence in drug development. Finally, we reanalyze data from trials in amyotrophic lateral sclerosis and Huntington's disease to demonstrate the proposed methods.

Experimental design has emerged as a powerful approach for improving the sample efficiency of A/B testing, yet existing designs rely critically on correctly specified models. We study robust sequential experimental design under model misspecification and develop a unified framework that covers both contextual bandit and dynamic settings. Theoretically, we prove that our design bounds the worst-case mean squared error of the estimated treatment effect. Empirically, we demonstrate the effectiveness of the proposed approach using synthetic and real-world datasets from a leading technology company.