Jointly Modeling Time‐To‐Event and Longitudinal Data With Individual‐Specific Change Points: A Case Study in Modeling Tumor Burden

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Main Authors: Ethan M. Alt, Yixiang Qu, Emily Meghan Damone, Jing‐ou Liu, Chenguang Wang, Joseph G. Ibrahim
Format: Artículo Open Access
Published: Wiley 2025
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author Ethan M. Alt
Yixiang Qu
Emily Meghan Damone
Jing‐ou Liu
Chenguang Wang
Joseph G. Ibrahim
author_facet Ethan M. Alt
Yixiang Qu
Emily Meghan Damone
Jing‐ou Liu
Chenguang Wang
Joseph G. Ibrahim
Ethan M. Alt
Yixiang Qu
Emily Meghan Damone
Jing‐ou Liu
Chenguang Wang
Joseph G. Ibrahim
collection Wiley Open Access
contents Jointly Modeling Time‐To‐Event and Longitudinal Data With Individual‐Specific Change Points: A Case Study in Modeling Tumor Burden Ethan M. Alt Yixiang Qu Emily Meghan Damone Jing‐ou Liu Chenguang Wang Joseph G. Ibrahim Statistics in Medicine ABSTRACT In oncology clinical trials, tumor burden (TB) stands as a crucial longitudinal biomarker, reflecting the toll a tumor takes on a patient's prognosis. With certain treatments, the disease's natural progression shows the tumor burden initially receding before rising once more. Biologically, the point of change may be different between individuals and must have occurred between the baseline measurement and progression time of the patient, implying a random effects model obeying a bound constraint. However, in practice, patients may drop out of the study due to progression or death, presenting a non‐ignorable missing data problem. In this paper, we introduce a novel joint model that combines time‐to‐event data and longitudinal data, where the latter is parameterized by a random change point augmented by random pre‐slope and post‐slope dynamics. Importantly, the model is equipped to incorporate covariates across the longitudinal and survival models, adding significant flexibility. Adopting a Bayesian approach, we propose an efficient Hamiltonian Monte Carlo (HMC) algorithm for parameter inference. We demonstrate the superiority of our approach compared to a longitudinal‐only model via simulations and apply our method to a data set in oncology. The code for implementation is publicly available on https://github.com/quyixiang/chgptModel . 10.1002/sim.70021 http://onlinelibrary.wiley.com/termsAndConditions#vor
doi_str_mv 10.1002/sim.70021
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spellingShingle Jointly Modeling Time‐To‐Event and Longitudinal Data With Individual‐Specific Change Points: A Case Study in Modeling Tumor Burden
Ethan M. Alt
Yixiang Qu
Emily Meghan Damone
Jing‐ou Liu
Chenguang Wang
Joseph G. Ibrahim
Statistics in Medicine
Jointly Modeling Time‐To‐Event and Longitudinal Data With Individual‐Specific Change Points: A Case Study in Modeling Tumor Burden Ethan M. Alt Yixiang Qu Emily Meghan Damone Jing‐ou Liu Chenguang Wang Joseph G. Ibrahim Statistics in Medicine ABSTRACT In oncology clinical trials, tumor burden (TB) stands as a crucial longitudinal biomarker, reflecting the toll a tumor takes on a patient's prognosis. With certain treatments, the disease's natural progression shows the tumor burden initially receding before rising once more. Biologically, the point of change may be different between individuals and must have occurred between the baseline measurement and progression time of the patient, implying a random effects model obeying a bound constraint. However, in practice, patients may drop out of the study due to progression or death, presenting a non‐ignorable missing data problem. In this paper, we introduce a novel joint model that combines time‐to‐event data and longitudinal data, where the latter is parameterized by a random change point augmented by random pre‐slope and post‐slope dynamics. Importantly, the model is equipped to incorporate covariates across the longitudinal and survival models, adding significant flexibility. Adopting a Bayesian approach, we propose an efficient Hamiltonian Monte Carlo (HMC) algorithm for parameter inference. We demonstrate the superiority of our approach compared to a longitudinal‐only model via simulations and apply our method to a data set in oncology. The code for implementation is publicly available on https://github.com/quyixiang/chgptModel . 10.1002/sim.70021 http://onlinelibrary.wiley.com/termsAndConditions#vor
title Jointly Modeling Time‐To‐Event and Longitudinal Data With Individual‐Specific Change Points: A Case Study in Modeling Tumor Burden
topic Statistics in Medicine
url https://onlinelibrary.wiley.com/doi/10.1002/sim.70021