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Joint modeling of multivariate longitudinal measurements and survival data with applications to Parkinson’s disease

机译:多元纵向测量和生存数据的联合建模及其在帕金森氏病中的应用

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摘要

In many clinical trials, studying neurodegenerative diseases including Parkinson’s disease (PD), multiple longitudinal outcomes are collected in order to fully explore the multidimensional impairment caused by these diseases. The follow-up of some patients can be stopped by some outcome-dependent terminal event, e.g. death and dropout. In this article, we develop a joint model that consists of a multilevel item response theory (MLIRT) model for the multiple longitudinal outcomes, and a Cox’s proportional hazard model with piecewise constant baseline hazards for the event time data. Shared random effects are used to link together two models. The model inference is conducted using a Bayesian framework via Markov Chain Monte Carlo simulation implemented in BUGS language. Our proposed model is evaluated by simulation studies and is applied to the DATATOP study, a motivating clinical trial assessing the effect of tocopherol on PD among patients with early PD.
机译:在许多临床研究中,包括帕金森氏病(PD)在内的神经退行性疾病的研究均收集了多个纵向结果,以全面探讨由这些疾病引起的多维损伤。一些患者的随访可以通过某些依赖于结果的终末事件来停止,例如死亡和辍学。在本文中,我们将开发一个联合模型,该模型包括用于多个纵向结果的多级项目响应理论(MLIRT)模型,以及用于事件时间数据的具有分段恒定基线风险的Cox比例风险模型。共享随机效应用于将两个模型链接在一起。使用贝叶斯框架通过以BUGS语言实现的Markov Chain Monte Carlo模拟进行模型推断。我们提出的模型通过模拟研究进行了评估,并应用于DATATOP研究,该研究是一项评估生育酚对早期PD患者中PD对PD影响的激励性临床试验。

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