In health cohort studies, repeated measures of markers are often used to describe the natural history of a disease. Joint models allow to study their evolution by taking into account the possible informative dropout usually due to clinical events. However, joint modeling developments mostly focused on continuous Gaussian markers while, in an increasing number of studies, the actual marker of interest is non-directly measurable; it consitutes a latent quantity evaluated by a set of observed indicators from questionnaires or measurement scales. Classical examples include anxiety, fatigue, cognition. In this work, we explain how joint models can be extended to the framework of a latent quantity measured over time by markers of different nature (e.g. continuous, binary, ordinal). The longitudinal submodel describes the evolution over time of the quantity of interest defined as a latent process in a structural mixed model, and links the latent process to each marker repeated observation through appropriate measurement models. Simultaneously, the risk of multi-cause event is modelled via a proportional cause-specific hazard model that includes a function of the mixed model elements as linear predictor to take into account the association between the latent process and the risk of event. Estimation, carried out in the maximum likelihood framework and implemented in the R-package JLPM, has been validated by simulations. The methodology is illustrated in the French cohort on Multiple-System Atrophy (MSA), a rare and fatal neurodegenerative disease, with the study of dysphagia progression over time truncated by the occurrence of death.
翻译:在保健组群研究中,反复测量标记往往用于描述疾病自然史。联合模型允许研究其演变过程,方法是考虑到通常由于临床事件而可能出现的信息性失学现象。然而,联合模型发展主要侧重于连续高斯标记,而在越来越多的研究中,实际利益标记是非直接测量的;它含有由一组从调查问卷或测量尺度观察到的指标所评估的潜在数量;典型例子包括焦虑、疲劳、认知。在这项工作中,我们解释如何将联合模型扩展至由不同性质的标记(如连续、二进制、或非常规)测量的随时间测量的潜在数量框架。 纵向子模型描述了在一段时间后利息数量的演变,在一个结构混合模型中被界定为一种潜在过程,并将潜在过程与每个标记通过适当的测量模型或测量尺度反复观察联系起来。同时,多原因事件的风险通过一个比例性因子特定危害模型模型模拟,其中包括混合模型元素的功能,作为线性预测器,以考虑到在时间上由不同性质的标志性标记(如连续、双进、双进、双进、双进 )测量子模型描述了在结构模型中的风险。A-在模拟中,机尾部机变的机变变变的机机机机机机法中,机机机机变的机机变法的概率法。