Huang Yangxin, Chen Ren, Dagne Getachew, Zhu Yiliang, Chen Henian
a Department of Epidemiology & Biostatistics , College of Public Health, University of South Florida , Tampa , Florida , USA.
J Biopharm Stat. 2015;25(3):373-96. doi: 10.1080/10543406.2014.920660.
Bivariate correlated (clustered) data often encountered in epidemiological and clinical research are routinely analyzed under a linear mixed-effected (LME) model with normality assumptions for the random-effects and within-subject errors. However, those analyses might not provide robust inference when the normality assumptions are questionable if the data set particularly exhibits skewness and heavy tails. In this article, we develop a Bayesian approach to bivariate linear mixed-effects (BLME) models replacing the Gaussian assumptions for the random terms with skew-normal/independent (SNI) distributions. The SNI distribution is an attractive class of asymmetric heavy-tailed parametric structure which includes the skew-normal, skew-t, skew-slash, and skew-contaminated normal distributions as special cases. We assume that the random-effects and the within-subject (random) errors, respectively, follow multivariate SNI and normal/independent (NI) distributions, which provide an appealing robust alternative to the symmetric normal distribution in a BLME model framework. The method is exemplified through an application to an AIDS clinical data set to compare potential models with different distribution specifications, and clinically important findings are reported.
在流行病学和临床研究中经常遇到的双变量相关(聚类)数据,通常在线性混合效应(LME)模型下进行常规分析,该模型对随机效应和个体内误差有正态性假设。然而,如果数据集特别呈现出偏态和重尾,当正态性假设存在疑问时,这些分析可能无法提供稳健的推断。在本文中,我们开发了一种贝叶斯方法用于双变量线性混合效应(BLME)模型,用偏态正态/独立(SNI)分布取代随机项的高斯假设。SNI分布是一类有吸引力的非对称重尾参数结构,包括偏态正态、偏态t、偏态斜线和偏态污染正态分布作为特殊情况。我们假设随机效应和个体内(随机)误差分别遵循多元SNI和正态/独立(NI)分布,这在BLME模型框架中为对称正态分布提供了一个有吸引力的稳健替代方案。通过应用于一个艾滋病临床数据集来举例说明该方法,以比较具有不同分布规范的潜在模型,并报告了具有临床重要性的发现。