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An approach to joint analysis of longitudinal measurements and competing risks failure time data

机译:纵向测量和竞争风险失效时间数据的联合分析方法

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Joint analysis of longitudinal measurements and survival data has received much attention in recent years. However, previous work has primarily focused on a single failure type for the event time. In this paper we consider joint modeling of repeated measurements and competing risks failure time data to allow for more than one distinct failure type in the survival endpoint which occurs frequently in clinical trials. Our model uses latent random variables and common covariates to link together the sub-models for the longitudinal measurements and competing risks failure time data, respectively. An EM-based algorithm is derived to obtain the parameter estimates, and a profie likelihood method is proposed to estimate their standard errors. Our method enables one to make joint inference on the multiple outcomes which is often necessary in analyses of clinical trials. Furthermore, joint analysis has several advantages compared with separate analysis of either the longitudinal data or competing risks survival data. By modeling the event time, the analysis of longitudinal measurements is adjusted to allow for non-ignorable missing data due to informative dropout, which cannot be appropriately handled by the standard linear mixed effcts models alone. In addition, the joint model utilizes information from both outcomes, and could be substantially more efficient than the separate analysis of the competing risk survival data as shown in our simulation study. The performance of our method is evaluated and compared with separate analyses using both simulated data and a clinical trial for the scleroderma lung disease.
机译:纵向测量和生存数据的联合分析近年来受到了广泛的关注。但是,以前的工作主要集中在事件时间的单一故障类型上。在本文中,我们考虑对重复测量和竞争风险失效时间数据进行联合建模,以在生存终点中考虑一种以上在临床试验中经常发生的独特失效类型。我们的模型使用潜在随机变量和公共协变量将子模型链接在一起,分别进行纵向测量和竞争风险失效时间数据。推导了基于EM的算法以获得参数估计,并提出了一种似然法估计其标准误差。我们的方法使人们可以对多种结果进行联合推断,而这在临床试验分析中通常是必需的。此外,与纵向数据或竞争风险生存数据的单独分析相比,联合分析具有多个优势。通过对事件时间进行建模,可以调整纵向测量的分析,以允许由于信息丢失而导致不可忽略的丢失数据,仅标准线性混合效应模型无法适当地处理这些数据。此外,联合模型利用了两种结果的信息,并且比我们的模拟研究中显示的对竞争风险生存数据的单独分析要有效得多。我们使用模拟数据和硬皮病肺病的临床试验对我们方法的性能进行了评估,并与单独的分析进行了比较。

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