Incorporating Covariates into Measures of Surrogate Paradox Risk

Fatema Shafie Khorassani, Jeremy M. G. Taylor, Niko Kaciroti and Michael R. Elliott ()
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Fatema Shafie Khorassani: Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA
Jeremy M. G. Taylor: Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA
Niko Kaciroti: Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA
Michael R. Elliott: Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA

Stats, 2023, vol. 6, issue 1, 1-23

Abstract: Clinical trials often collect intermediate or surrogate endpoints other than their true endpoint of interest. It is important that the treatment effect on the surrogate endpoint accurately predicts the treatment effect on the true endpoint. There are settings in which the proposed surrogate endpoint is positively correlated with the true endpoint, but the treatment has opposite effects on the surrogate and true endpoints, a phenomenon labeled “surrogate paradox”. Covariate information may be useful in predicting an individual’s risk of surrogate paradox. In this work, we propose methods for incorporating covariates into measures of assessing the risk of surrogate paradox using the meta-analytic causal association framework. The measures calculate the probability that a treatment will have opposite effects on the surrogate and true endpoints and determine the size of a positive treatment effect on the surrogate endpoint that would reduce the risk of a negative treatment effect on the true endpoint as a function of covariates, allowing the effects of covariates on the surrogate and true endpoint to vary across trials.

Keywords: surrogate markers; surrogate endpoints; meta-analysis; causal association; covariate information (search for similar items in EconPapers)
JEL-codes: C1 C10 C11 C14 C15 C16 (search for similar items in EconPapers)
Date: 2023
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