Luo Sheng
Division of Biostatistics, University of Texas School of Public Health, 1200 Pressler St., Houston, TX 77030, U.S.A.
Stat Med. 2014 Feb 20;33(4):580-94. doi: 10.1002/sim.5956. Epub 2013 Sep 6.
Impairment caused by Parkinson's disease (PD) is multidimensional (e.g., sensoria, functions, and cognition) and progressive. Its multidimensional nature precludes a single outcome to measure disease progression. Clinical trials of PD use multiple categorical and continuous longitudinal outcomes to assess the treatment effects on overall improvement. A terminal event such as death or dropout can stop the follow-up process. Moreover, the time to the terminal event may be dependent on the multivariate longitudinal measurements. In this article, we consider a joint random-effects model for the correlated outcomes. A multilevel item response theory model is used for the multivariate longitudinal outcomes and a parametric accelerated failure time model is used for the failure time because of the violation of proportional hazard assumption. These two models are linked via random effects. The Bayesian inference via MCMC is implemented in 'BUGS' language. Our proposed method is evaluated by a simulation study and is applied to DATATOP study, a motivating clinical trial to determine if deprenyl slows the progression of PD.
帕金森病(PD)所导致的损害具有多维度性(如感觉、功能和认知方面)且呈进行性发展。其多维度特性使得无法用单一结果来衡量疾病进展。PD的临床试验采用多种分类和连续的纵向结果来评估治疗对整体改善情况的效果。诸如死亡或退出试验等终末事件会中断随访过程。此外,发生终末事件的时间可能取决于多变量纵向测量结果。在本文中,我们考虑针对相关结果的联合随机效应模型。由于违反了比例风险假设,对于多变量纵向结果使用多级项目反应理论模型,对于失效时间则使用参数化加速失效时间模型。这两个模型通过随机效应相联系。通过马尔可夫链蒙特卡罗(MCMC)进行的贝叶斯推断是用“BUGS”语言实现的。我们所提出的方法通过模拟研究进行评估,并应用于DATATOP研究,这是一项旨在确定丙炔苯丙胺是否能减缓PD进展的具有启发性的临床试验。