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Publication Information

DOI
PubMed ID
Public Release Type
Journal
Publication Year
2024
Affiliation
1Department of Statistics and Data Sciences, University of Texas at Austin 2Department of Biomedical Data Science, Stanford University 3Department of Biostatistics, Harvard University 1
Authors
Cai T, Parast L, Tian L
Studies

Abstract

Determining whether a surrogate marker can be used to replace a primary outcome in a clinical study is complex. While many statistical methods have been developed to formally evaluate a surrogate marker, they generally do not provide a way to examine potential heterogeneity in the utility of a surrogate marker. Similar to treatment e ect heterogeneity, where the e ect of a treatment varies based on a patient characteristic, heterogeneity in surrogacy means that the strength or utility of the surrogate marker varies based on a patient characteristic. The small number of methods that have been recently developed to examine such heterogeneity cannot accommodate censored time- to-event outcomes. Studies with a censored time-to-event outcome are typically the studies that could most bene t from a surrogate marker because the follow-up time is often quite long. Thus, the development of methods for this setting is essential. In this paper, we develop a robust nonparametric approach to assess heterogeneity in the utility of a surrogate marker with respect to a baseline variable in a censored time-to- event outcome setting. In addition, we propose and evaluate a testing procedure to formally test for heterogeneity. The proposed approach can be used to examine and test for heterogeneity at a single time point or across multiple time points simultane- ously. Finite sample performance of our estimation and testing procedure are examined in a simulation study. We use our proposed method to provide new insight into the complex relationship between change in fasting plasma glucose, diabetes, and sex hor- mones using data from the Diabetes Prevention Program (DPP) study. Speci cally, we examine the heterogeneity of fasting plasma glucose as a surrogate for time to diabetes with respect to sex hormone binding globulin (SHBG). 2