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Main Authors: Alt, Ethan M., Qu, Yixiang, Damone, Emily, Liu, Jing-ou, Wang, Chenguang, Ibrahim, Joseph G.
Format: Preprint
Published: 2024
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Online Access:https://arxiv.org/abs/2409.13873
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author Alt, Ethan M.
Qu, Yixiang
Damone, Emily
Liu, Jing-ou
Wang, Chenguang
Ibrahim, Joseph G.
author_facet Alt, Ethan M.
Qu, Yixiang
Damone, Emily
Liu, Jing-ou
Wang, Chenguang
Ibrahim, Joseph G.
contents 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 for the longitudinal and survival models, adding significant flexibility. Adopting a Bayesian approach, we propose an efficient Hamiltonian Monte Carlo 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.
format Preprint
id arxiv_https___arxiv_org_abs_2409_13873
institution arXiv
publishDate 2024
record_format arxiv
spellingShingle Jointly modeling time-to-event and longitudinal data with individual-specific change points: a case study in modeling tumor burden
Alt, Ethan M.
Qu, Yixiang
Damone, Emily
Liu, Jing-ou
Wang, Chenguang
Ibrahim, Joseph G.
Methodology
Applications
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 for the longitudinal and survival models, adding significant flexibility. Adopting a Bayesian approach, we propose an efficient Hamiltonian Monte Carlo 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.
title Jointly modeling time-to-event and longitudinal data with individual-specific change points: a case study in modeling tumor burden
topic Methodology
Applications
url https://arxiv.org/abs/2409.13873