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A two-stage approach to the joint analysis of longitudinal and survival data utilising the Coxian phase-type distribution

机译:利用Coxian相型分布进行纵向和生存数据联合分析的两阶段方法

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摘要

The Coxian phase-type distribution is a special type of Markov model which can be utilised both to uncover underlying stages of a survival process and to make inferences regarding the rates of flow of individuals through these latent stages before an event of interest occurs. Such models can be utilised, for example, to identify individuals who are likely to deteriorate faster through a series of disease states and thus require more aggressive medical intervention. Within this paper, a two-stage approach to the analysis of longitudinal and survival data is presented. In Stage 1, a linear mixed effects model is first used to represent how some longitudinal response of interest changes through time. Within this linear mixed effects model, the individuals’ random effects can be considered as a proxy measure for the effect of the individuals’ genetic profiles on the response of interest. In Stage 2, the Coxian phase-type distribution is employed to represent the survival process. The individuals’ random effects, estimated in Stage 1, are incorporated as covariates within the Coxian phase-type distribution so as to evaluate their effect on the individuals’ rates of flow through the system represented by the Coxian. The approach is illustrated using data collected on individuals suffering from chronic kidney disease, where focus is given to an emerging longitudinal biomarker of interest – an individual’s haemoglobin level.
机译:考克斯相型分布是一种特殊的马尔可夫模型,既可以用来揭示生存过程的基础阶段,又可以在感兴趣的事件发生之前推断出个体通过这些潜在阶段的流量。可以利用这样的模型,例如,识别可能因一系列疾病状态而更快恶化并因此需要更积极的医学干预的个体。在本文中,提出了一种纵向和生存数据分析的两阶段方法。在阶段1中,首先使用线性混合效应模型来表示感兴趣的某些纵向响应如何随时间变化。在此线性混合效应模型中,可以将个体的随机效应视为个体遗传特征对目标反应的影响的代理度量。在阶段2中,采用Coxian相类型分布表示生存过程。在阶段1中估算的个体随机效应作为协变量并入到Coxian相类型分布中,以便评估其对个体通过Coxian代表的系统流量的影响。通过收集关于患有慢性肾脏疾病的个体的数据来说明该方法,其中重点关注了新兴的纵向生物标志物-个体的血红蛋白水平。

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