Huang Yangxin, Wu Hulin
Department of Epidemiology & Biostatistics, College of Public Health MDC 56, University of South Florida Tampa FL 33612, U.S.A.,
J Stat Plan Inference. 2008 Jan 1;138(1):105-113. doi: 10.1016/j.jspi.2007.05.019.
The study of HIV dynamics is one of the most important developments in recent AIDS research for understanding the pathogenesis of HIV-1 infection and antiviral treatment strategies. Currently a large number of AIDS clinical trials on HIV dynamics are in development worldwide. However, many design issues that arise from AIDS clinical trials have not been addressed. In this paper, we use a simulation-based approach to deal with design problems in Bayesian hierarchical nonlinear (mixed-effects) models. The underlying model characterizes the long-term viral dynamics with antiretroviral treatment where we directly incorporate drug susceptibility and exposure into a function of treatment efficacy. The Bayesian design method is investigated under the framework of hierarchical Bayesian (mixed-effects) models. We compare a finite number of feasible candidate designs numerically, which are currently used in AIDS clinical trials from different perspectives, and provide guidance on how a design might be chosen in practice.
对艾滋病毒动态变化的研究是近期艾滋病研究中最重要的进展之一,有助于理解HIV-1感染的发病机制和抗病毒治疗策略。目前,全球范围内正在开展大量关于艾滋病毒动态变化的艾滋病临床试验。然而,艾滋病临床试验中出现的许多设计问题尚未得到解决。在本文中,我们采用基于模拟的方法来处理贝叶斯分层非线性(混合效应)模型中的设计问题。基础模型描述了抗逆转录病毒治疗下的长期病毒动态变化,我们将药物敏感性和暴露情况直接纳入治疗效果函数中。在分层贝叶斯(混合效应)模型框架下研究贝叶斯设计方法。我们从不同角度对目前艾滋病临床试验中使用的有限数量的可行候选设计进行数值比较,并为在实际中如何选择设计提供指导。