A Bayesian joint model of multiple nonlinear longitudinal and competing risks outcomes for dynamic prediction in multiple myeloma: joint estimation and corrected two-stage approaches

Fuente: arXiv
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Autori principali: Alvares, Danilo, Barrett, Jessica K., Mercier, François, Roumpanis, Spyros, Yiu, Sean, Castro, Felipe, Schulze, Jochen, Zhu, Yajing
Natura: Preprint
Pubblicazione: 2024
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author Alvares, Danilo
Barrett, Jessica K.
Mercier, François
Roumpanis, Spyros
Yiu, Sean
Castro, Felipe
Schulze, Jochen
Zhu, Yajing
author_facet Alvares, Danilo
Barrett, Jessica K.
Mercier, François
Roumpanis, Spyros
Yiu, Sean
Castro, Felipe
Schulze, Jochen
Zhu, Yajing
contents Predicting cancer-associated clinical events is challenging in oncology. In Multiple Myeloma (MM), a cancer of plasma cells, disease progression is determined by changes in biomarkers, such as serum concentration of the paraprotein secreted by plasma cells (M-protein). Therefore, the time-dependent behaviour of M-protein and the transition across lines of therapy (LoT) that may be a consequence of disease progression should be accounted for in statistical models to predict relevant clinical outcomes. Furthermore, it is important to understand the contribution of the patterns of longitudinal biomarkers, upon each LoT initiation, to time-to-death or time-to-next-LoT. Motivated by these challenges, we propose a Bayesian joint model for trajectories of multiple longitudinal biomarkers, such as M-protein, and the competing risks of death and transition to next LoT. Additionally, we explore two estimation approaches for our joint model: simultaneous estimation of all parameters (joint estimation) and sequential estimation of parameters using a corrected two-stage strategy aiming to reduce computational time. Our proposed model and estimation methods are applied to a retrospective cohort study from a real-world database of patients diagnosed with MM in the US from January 2015 to February 2022. We split the data into training and test sets in order to validate the joint model using both estimation approaches and make dynamic predictions of times until clinical events of interest, informed by longitudinally measured biomarkers and baseline variables available up to the time of prediction.
format Preprint
id arxiv_https___arxiv_org_abs_2405_20418
institution arXiv
publishDate 2024
record_format arxiv
spellingShingle A Bayesian joint model of multiple nonlinear longitudinal and competing risks outcomes for dynamic prediction in multiple myeloma: joint estimation and corrected two-stage approaches
Alvares, Danilo
Barrett, Jessica K.
Mercier, François
Roumpanis, Spyros
Yiu, Sean
Castro, Felipe
Schulze, Jochen
Zhu, Yajing
Applications
Methodology
Predicting cancer-associated clinical events is challenging in oncology. In Multiple Myeloma (MM), a cancer of plasma cells, disease progression is determined by changes in biomarkers, such as serum concentration of the paraprotein secreted by plasma cells (M-protein). Therefore, the time-dependent behaviour of M-protein and the transition across lines of therapy (LoT) that may be a consequence of disease progression should be accounted for in statistical models to predict relevant clinical outcomes. Furthermore, it is important to understand the contribution of the patterns of longitudinal biomarkers, upon each LoT initiation, to time-to-death or time-to-next-LoT. Motivated by these challenges, we propose a Bayesian joint model for trajectories of multiple longitudinal biomarkers, such as M-protein, and the competing risks of death and transition to next LoT. Additionally, we explore two estimation approaches for our joint model: simultaneous estimation of all parameters (joint estimation) and sequential estimation of parameters using a corrected two-stage strategy aiming to reduce computational time. Our proposed model and estimation methods are applied to a retrospective cohort study from a real-world database of patients diagnosed with MM in the US from January 2015 to February 2022. We split the data into training and test sets in order to validate the joint model using both estimation approaches and make dynamic predictions of times until clinical events of interest, informed by longitudinally measured biomarkers and baseline variables available up to the time of prediction.
title A Bayesian joint model of multiple nonlinear longitudinal and competing risks outcomes for dynamic prediction in multiple myeloma: joint estimation and corrected two-stage approaches
topic Applications
Methodology
url https://arxiv.org/abs/2405.20418