Learning plug-in surrogate endpoints for randomized experiments

We establish a formal connection between the decades-old surrogate outcome model in biostatistics and economics and the emerging field of prediction-powered inference (PPI). The connection treats predictions from pre-trained models, prevalent in the age of AI, as cost-effective surrogates for expensive outcomes. Building on the surrogate outcomes literature, we develop recalibrated prediction-powered inference, a more efficient approach to statistical inference than existing PPI proposals. Our method departs from the existing proposals by using flexible machine learning techniques to learn the optimal ``imputed loss'' through a step we call recalibration. Importantly, the method always improves upon the estimator that relies solely on the data with available true outcomes, even when the optimal imputed loss is estimated imperfectly, and it achieves the smallest asymptotic variance among PPI estimators if the estimate is consistent. Computationally, our optimization objective is convex whenever the loss function that defines the target parameter is convex. We further analyze the benefits of recalibration, both theoretically and numerically, in several common scenarios where machine learning predictions systematically deviate from the outcome of interest. We demonstrate significant gains in effective sample size over existing PPI proposals via three applications leveraging state-of-the-art machine learning/AI models.

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.

Organizations and researchers show increasing interest in using large language models (LLMs) in place of human participants in A/B tests, in the hope of experimenting faster and at lower cost. We study when a treatment effect estimated on LLM outcomes can recover the effect for the human population of interest. Distributional equivalence between LLM and human outcomes would make any standard estimator valid but is unrealistic. We therefore develop a statistical framework that adapts surrogate endpoint theory to LLMs, showing that calibrating LLM outcomes to human outcomes identifies the average treatment effect under surrogacy and comparability conditions that are jointly weaker than distributional equivalence. We present a falsification test for surrogacy and a bound on the worst-case bias from limited overlap between the LLM and human samples. We further show that the stochasticity inherent to LLMs can weaken surrogacy for identification while also introducing bias and variance during estimation, but that using an average over multiple LLM draws per unit as the surrogate mitigates these issues. Simulations validate the results, and an empirical application to the Upworthy Research Archive dataset shows that raw LLM outputs recover only 39% of the human treatment effect while nonparametric calibration closes the gap. A central takeaway is that A/B testing on LLM responses is correct only by assumption, whereas A/B testing on humans is correct by design, and that the required assumptions are hardest to justify precisely where LLMs promise the greatest benefit. We discuss the choice of LLM, prompting, and temperature as design variables, the compounded challenge posed by long-term outcomes, and how to size human pilot studies for validation.