In clinical trials, studies often present longitudinal data or clustered data. These studies are commonly analyzed using linear mixed models (LMMs), usually considering Gaussian assumptions for random effect and error terms. Recently, several proposals extended the restrictive assumptions from traditional LMM by more flexible ones that can accommodate skewness and heavy-tails and consequently are more robust to outliers. This work proposes a canonical fundamental skew-t linear mixed model (ST-LMM), that allows for asymmetric and heavy-tailed random effects and errors and includes several important cases as special cases, which are presented and considered for model selection. For this robust and flexible model, we present an efficient EM-type algorithm for parameter estimation via maximum likelihood, implemented in a closed form by exploring the hierarchical representation of the ST-LMM. In addition, the estimation of standard errors and random effects is discussed. The methodology is illustrated through an application to schizophrenia data and some simulation studies.
翻译:在临床试验中,研究往往提供纵向数据或集群数据。这些研究通常使用线性混合模型(LMMs)进行分析,通常考虑到高斯的随机效应和误差假设。最近,若干提案将传统的LMMM的限制性假设从传统的LMM扩大为更灵活的假设,能够容纳扭曲和重尾,因此对外线更为有力。这项工作提出了一种Canonic 基本Skew-t线性混合模型(ST-LMMM),允许不对称和重尾随机效应和错误,包括作为特例的几例重要案例,这些案例被介绍和考虑用于模型选择。对于这一强健和灵活的模型,我们提出了一个有效的EM型参数估算算法,通过探索ST-LMMM的等级代表,以封闭的形式尽可能地执行。此外,还讨论了标准误差和随机效应的估计。该方法通过对精神分裂症数据的应用和一些模拟研究加以说明。