Köhler Meike, Umlauf Nikolaus, Beyerlein Andreas, Winkler Christiane, Ziegler Anette-Gabriele, Greven Sonja
Institute of Diabetes Research, Helmholtz Zentrum München, and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Neuherberg, Germany.
Department of Statistics, Faculty of Economics and Statistics, Universität Innsbruck, Innsbruck, Austria.
Biom J. 2017 Nov;59(6):1144-1165. doi: 10.1002/bimj.201600224. Epub 2017 Aug 10.
The joint modeling of longitudinal and time-to-event data is an important tool of growing popularity to gain insights into the association between a biomarker and an event process. We develop a general framework of flexible additive joint models that allows the specification of a variety of effects, such as smooth nonlinear, time-varying and random effects, in the longitudinal and survival parts of the models. Our extensions are motivated by the investigation of the relationship between fluctuating disease-specific markers, in this case autoantibodies, and the progression to the autoimmune disease type 1 diabetes. Using Bayesian P-splines, we are in particular able to capture highly nonlinear subject-specific marker trajectories as well as a time-varying association between the marker and event process allowing new insights into disease progression. The model is estimated within a Bayesian framework and implemented in the R-package bamlss.
纵向数据和事件发生时间数据的联合建模是一种越来越受欢迎的重要工具,用于深入了解生物标志物与事件过程之间的关联。我们开发了一个灵活的加法联合模型的通用框架,该框架允许在模型的纵向和生存部分指定各种效应,如平滑非线性效应、时变效应和随机效应。我们的扩展是由对波动的疾病特异性标志物(在这种情况下是自身抗体)与自身免疫性疾病1型糖尿病进展之间关系的研究推动的。使用贝叶斯P样条,我们尤其能够捕捉高度非线性的个体特异性标志物轨迹,以及标志物与事件过程之间的时变关联,从而为疾病进展提供新的见解。该模型在贝叶斯框架内进行估计,并在R包bamlss中实现。