A Bayesian Critique of Rank-Based Methods for Surrogate Marker Evaluation

Abstract

Surrogate markers are often employed in clinical trials to replace primary outcomes that may be difficult, expensive, or time-consuming to measure directly. These markers can accelerate the evaluation of new treatments, provided they reliably capture the causal relationship between treatment and true clinical benefit. Parast et al. (2024) recently proposed a rank-based approach for evaluating surrogate markers, characterized by its nonparametric nature and minimal assumptions. While this method is useful in small-sample model-agnostic settings, it has several limitations, including a lack of clear causal interpretation, low statistical power, and insufficient robustness to different data-generating mechanisms. In this paper, we propose a Bayesian approach that addresses these shortcomings by focusing on causal treatment effect estimands and, in doing so, improves power through covariate adjustment. We demonstrate the advantages of our proposed method through a simulation study designed to highlight gains in both accuracy and power.