拟合具有强制函数的动态模型:在胰岛素治疗中的连续血糖监测中的应用。
Fitting dynamic models with forcing functions: application to continuous glucose monitoring in insulin therapy.
机构信息
Medical Research Council Biostatistics Unit, Institute of Public Health, University Forvie Site, Cambridge, U.K.
出版信息
Stat Med. 2011 Aug 15;30(18):2234-50. doi: 10.1002/sim.4254. Epub 2011 May 18.
The artificial pancreas is an emerging technology to treat type 1 diabetes (T1D). It has the potential to revolutionize diabetes care and improve quality of life. The system requires extensive testing, however, to ensure that it is both effective and safe. Clinical studies are resource demanding and so a principle aim is to develop an in silico population of subjects with T1D on which to conduct pre-clinical testing. This paper aims to reliably characterize the relationship between blood glucose and glucose measured by subcutaneous sensor as a major step towards this goal. Blood-and sensor-glucose are related through a dynamic model, specified in terms of differential equations. Such models can present special challenges for statistical inference, however. In this paper we make use of the BUGS software, which can accommodate a limited class of dynamic models, and it is in this context that we discuss such challenges. For example, we show how dynamic models involving forcing functions can be accommodated. To account for fluctuations away from the dynamic model that are apparent in the observed data, we assume an autoregressive structure for the residual error model. This leads to some identifiability issues but gives very good predictions of virtual data. Our approach is pragmatic and we propose a method to mitigate the consequences of such identifiability issues.
人工胰腺是一种治疗 1 型糖尿病(T1D)的新兴技术。它有潜力彻底改变糖尿病的治疗方式并提高生活质量。然而,该系统需要进行广泛的测试,以确保其既有效又安全。临床研究需要大量资源,因此一个主要目标是开发一个包含 T1D 患者的虚拟人群,以便在其上进行临床前测试。本文旨在可靠地描述血糖与皮下传感器测量的葡萄糖之间的关系,这是实现这一目标的重要步骤。血液和传感器中的葡萄糖通过微分方程来表示的动态模型来关联。然而,此类模型可能会对统计推断提出特殊挑战。在本文中,我们利用了 BUGS 软件,该软件可以适应有限类别的动态模型,并在此背景下讨论了此类挑战。例如,我们展示了如何适应涉及强制函数的动态模型。为了说明在观测数据中明显存在的偏离动态模型的波动,我们假设残差模型具有自回归结构。这会导致一些可识别性问题,但对虚拟数据的预测非常好。我们的方法是务实的,我们提出了一种减轻此类可识别性问题后果的方法。