Longitudinal and survival sub-models are two building blocks for joint modelling of longitudinal and time to event data. Extensive research indicates separate analysis of these two processes could result in biased outputs due to their associations. Conditional independence between measurements of biomarkers and event time process given latent classes or random effects is a common approach for characterising the association between the two sub-models while taking the heterogeneity among the population into account. However, this assumption is tricky to validate because of the unobservable latent variables. Thus a Gaussian copula joint model with random effects is proposed to accommodate the scenarios where the conditional independence assumption is questionable. In our proposed model, the conventional joint model assuming conditional independence is a special case when the association parameter in the Gaussian copula shrinks to zero. Simulation studies and real data application are carried out to evaluate the performance of our proposed model. In addition, personalised dynamic predictions of survival probabilities are obtained based on the proposed model and comparisons are made to the predictions obtained under the conventional joint model.
翻译:纵观和生存小模型是联合模拟纵向和时间与事件数据的联合模型的两个基石。广泛的研究表明,对这两个过程进行单独分析可能由于其关联而导致有偏差的产出。测量生物标记和事件时间过程之间的有条件独立性,考虑到潜伏类别或随机效应,是确定这两个小模型之间联系的通用方法,同时考虑人口中的异质性。然而,由于不可观测的潜在变量,这一假设难以验证。因此,提议了一个带有随机效应的高斯大千叶联极联合模型,以适应有条件独立假设有疑问的情景。在我们提议的模型中,假定有条件独立的常规联合模型是一个特殊案例,当高斯大交界的关联参数缩为零时,假设有条件独立的传统联合模型是一个特例。进行模拟研究和实际数据应用,以评价我们拟议模型的性能。此外,根据拟议的模型获得对生存概率的个性动态预测,并对根据常规联合模型获得的预测进行比较。