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Computing normalised prediction distribution errors to evaluate nonlinear mixed-effect models: The npde add-on package for R.

机译:计算归一化的预测分布误差以评估非线性混合效应模型:R的npde附加软件包。

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摘要

Pharmacokinetic/pharmacodynamic data are often analysed using nonlinear mixed-effect models, and model evaluation should be an important part of the analysis. Recently, normalised prediction distribution errors (npde) have been proposed as a model evaluation tool. In this paper, we describe an add-on package for the open source statistical package R, designed to compute npde. npde take into account the full predictive distribution of each individual observation and handle multiple observations within subjects. Under the null hypothesis that the model under scrutiny describes the validation dataset, npde should follow the standard normal distribution. Simulations need to be performed before hand, using for example the software used for model estimation. We illustrate the use of the package with two simulated datasets, one under the true model and one with different parameter values, to show how npde can be used to evaluate models. Model estimation and data simulation were performed using NONMEM version 5.1.
机译:通常使用非线性混合效应模型来分析药代动力学/药效学数据,并且模型评估应是分析的重要组成部分。近来,已经提出了归一化的预测分布误差(npde)作为模型评估工具。在本文中,我们描述了用于统计npde的开源统计软件包R的附加软件包。 npde考虑到每个观察值的完整预测分布,并处理受试者中的多个观察值。在审查模型描述验证数据集的零假设下,npde应该遵循标准正态分布。需要事先使用例如用于模型估计的软件进行仿真。我们说明了该软件包与两个模拟数据集(一个在真实模型下,一个具有不同参数值)的用法,以显示如何使用npde评估模型。使用NONMEM 5.1版进行模型估计和数据模拟。

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