Assessing Surrogate Heterogeneity in Real World Data Using Meta-Learners

• URL: http://arxiv.org/abs/2504.15386v1
• Date: Mon, 21 Apr 2025 18:54:48 GMT
• Title: Assessing Surrogate Heterogeneity in Real World Data Using Meta-Learners
• Authors: Rebecca Knowlton, Layla Parast,
• Abstract summary: We propose a framework to assess surrogate heterogeneity in real-world, non-randomized, data.<n>Our approach allows us to quantify heterogeneity in surrogate strength with respect to patient characteristics.<n>We use our framework to identify individuals for whom the surrogate is a valid replacement of the primary outcome.
• Score: 0.0
• License: http://arxiv.org/licenses/nonexclusive-distrib/1.0/
• Abstract: Surrogate markers are most commonly studied within the context of randomized clinical trials. However, the need for alternative outcomes extends beyond these settings and may be more pronounced in real-world public health and social science research, where randomized trials are often impractical. Research on identifying surrogates in real-world non-randomized data is scarce, as available statistical approaches for evaluating surrogate markers tend to rely on the assumption that treatment is randomized. While the few methods that allow for non-randomized treatment/exposure appropriately handle confounding individual characteristics, they do not offer a way to examine surrogate heterogeneity with respect to patient characteristics. In this paper, we propose a framework to assess surrogate heterogeneity in real-world, i.e., non-randomized, data and implement this framework using various meta-learners. Our approach allows us to quantify heterogeneity in surrogate strength with respect to patient characteristics while accommodating confounders through the use of flexible, off-the-shelf machine learning methods. In addition, we use our framework to identify individuals for whom the surrogate is a valid replacement of the primary outcome. We examine the performance of our methods via a simulation study and application to examine heterogeneity in the surrogacy of hemoglobin A1c as a surrogate for fasting plasma glucose.

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