Semiparametric Modeling of Biomarker Trajectory and Variability With Correlated Measurement Errors

Fuente: Wiley Open Access
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Auteurs principaux: Renwen Luo, Chuoxin Ma, Jianxin Pan
Format: Artículo Open Access
Publié: Wiley 2025
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author Renwen Luo
Chuoxin Ma
Jianxin Pan
author_facet Renwen Luo
Chuoxin Ma
Jianxin Pan
Renwen Luo
Chuoxin Ma
Jianxin Pan
collection Wiley Open Access
contents Semiparametric Modeling of Biomarker Trajectory and Variability With Correlated Measurement Errors Renwen Luo Chuoxin Ma Jianxin Pan Statistics in Medicine ABSTRACTThe prognostic significance of biomarker variability in predicting associated disease risk is well‐established. However, prevailing methods that assess the relationship between biomarker variability and time to event often overlook within‐subject correlation in longitudinal measurement errors, resulting in biased parameter estimates and erroneous statistical inference. Additionally, these methods typically assume that biomarker trajectory can be represented as a linear combination of spline basis functions with normally distributed random effects. This not only leads to significant computational demands due to the necessity of high‐dimensional integration over the random effects but also limits the applicability because of the normality restriction imposed on the random effects. This paper addresses these limitations by incorporating correlated longitudinal measurement errors and proposing a novel semiparametric multiplicative random effects model. This model does not assume normality for the random effects and eliminates the need for integration with respect to them. The biomarker variability is incorporated as a covariate within a Cox model for time‐to‐event data, thus facilitating a joint modeling strategy. We demonstrate the asymptotic properties of the proposed estimators and validate their performance through simulation studies. The methodology is applied to assess the impact of systolic blood pressure variability on cardiovascular mortality using data from the Atherosclerosis Risk in Communities study. 10.1002/sim.70028 http://onlinelibrary.wiley.com/termsAndConditions#vor
doi_str_mv 10.1002/sim.70028
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id wiley_oa_10_1002_sim_70028
institution Wiley Open Access
license_str_mv http://onlinelibrary.wiley.com/termsAndConditions#vor
publishDate 2025
publisher Wiley
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spellingShingle Semiparametric Modeling of Biomarker Trajectory and Variability With Correlated Measurement Errors
Renwen Luo
Chuoxin Ma
Jianxin Pan
Statistics in Medicine
Semiparametric Modeling of Biomarker Trajectory and Variability With Correlated Measurement Errors Renwen Luo Chuoxin Ma Jianxin Pan Statistics in Medicine ABSTRACTThe prognostic significance of biomarker variability in predicting associated disease risk is well‐established. However, prevailing methods that assess the relationship between biomarker variability and time to event often overlook within‐subject correlation in longitudinal measurement errors, resulting in biased parameter estimates and erroneous statistical inference. Additionally, these methods typically assume that biomarker trajectory can be represented as a linear combination of spline basis functions with normally distributed random effects. This not only leads to significant computational demands due to the necessity of high‐dimensional integration over the random effects but also limits the applicability because of the normality restriction imposed on the random effects. This paper addresses these limitations by incorporating correlated longitudinal measurement errors and proposing a novel semiparametric multiplicative random effects model. This model does not assume normality for the random effects and eliminates the need for integration with respect to them. The biomarker variability is incorporated as a covariate within a Cox model for time‐to‐event data, thus facilitating a joint modeling strategy. We demonstrate the asymptotic properties of the proposed estimators and validate their performance through simulation studies. The methodology is applied to assess the impact of systolic blood pressure variability on cardiovascular mortality using data from the Atherosclerosis Risk in Communities study. 10.1002/sim.70028 http://onlinelibrary.wiley.com/termsAndConditions#vor
title Semiparametric Modeling of Biomarker Trajectory and Variability With Correlated Measurement Errors
topic Statistics in Medicine
url https://onlinelibrary.wiley.com/doi/10.1002/sim.70028