Fattinger K E, Verotta D
Department of Pharmacy and Pharmaceutical Chemistry, University of California San Francisco, California 94143, USA.
J Pharmacokinet Biopharm. 1995 Dec;23(6):611-34. doi: 10.1007/BF02353464.
A lot of attention has been given in the past to deconvolution and in particular to its nonparametric variants. In a companion paper (1), we present a fully nonparametric deconvolution method in which subject specificity is explicitly taken into account. To do so we use so-called "longitudinal splines." A longitudinal spline is a nonparametric function composed of a template spline, in common to all subjects, and of a distortion spline representing the difference of the subject's function from the template. In this paper we concentrate on testing and documenting the performance of this nonparametric methodology in terms of the approximation of unknown functions. We simulate population data using parametric functions, and use longitudinal splines to recover the unknown functions. We consider different estimation methods including (1) parametric nonlinear mixed effect, (2) least squares, and (3) two-stage. Methods 2-3 are more robust than Method 1, and obtain reliable estimates of the unknown functions. The lack of robustness of Method 1 appears to be due to the misspecifications of the distribution of the subjects' parameters. Results also suggest that in a data-rich situation nonparametric nonlinear mixed-effect models should be preferred.
过去,很多注意力都集中在反卷积上,尤其是其非参数变体。在一篇配套论文(1)中,我们提出了一种完全非参数的反卷积方法,其中明确考虑了个体特异性。为此,我们使用了所谓的“纵向样条”。纵向样条是一种非参数函数,由所有个体共有的模板样条以及表示个体函数与模板差异的畸变样条组成。在本文中,我们专注于测试和记录这种非参数方法在未知函数逼近方面的性能。我们使用参数函数模拟总体数据,并使用纵向样条来恢复未知函数。我们考虑了不同的估计方法,包括(1)参数非线性混合效应法、(2)最小二乘法和(3)两阶段法。方法2 - 3比方法1更稳健,并能获得未知函数的可靠估计。方法1缺乏稳健性似乎是由于个体参数分布的错误设定。结果还表明,在数据丰富的情况下,应优先选择非参数非线性混合效应模型。