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Annual Review of Statistics and Its Application

Volume 10, 2023

Surrogate Endpoints in Clinical Trials

Abstract

Surrogate markers are often used in clinical trials settings when obtaining a final outcome to evaluate the effectiveness of a treatment requires a long wait, is expensive to obtain, or both. Formal definitions of surrogate marker quality resulting from a large variety of estimation approaches have been proposed over the years. I review this work, with a particular focus on approaches that use the causal inference paradigm, as these conceptualize a good marker as one in the causal pathway between the treatment and outcome. I also focus on efforts to evaluate the risk of a surrogate paradox, a damaging situation where the surrogate is positively associated with the outcome, and the causal effect of the treatment on the surrogate is in a helpful direction, but the ultimate causal effect of the treatment on the outcome is harmful. I then review some recent work in robust surrogate marker estimation and conclude with a discussion and suggestions for future research.

Keyword(s): causal association, causal effectiveness, causal inference, Prentice criteria, principal stratification, surrogate marker, surrogate paradox
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2023-03-09
2024-04-30
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/content/journals/10.1146/annurev-statistics-032921-035359
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Surrogate Endpoints in Clinical Trials
Annual Review of Statistics and Its Application 10, 75 (2023); https://doi.org/10.1146/annurev-statistics-032921-035359
/content/journals/10.1146/annurev-statistics-032921-035359
/content/journals/10.1146/annurev-statistics-032921-035359
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