Evaluation of an Extended Grid Method for Estimation Using Nonparametric Distributions
Journal Title: The AAPS Journal - Year 2009, Vol 11, Issue 3
Abstract
A nonparametric population method with support points from the empirical Bayes estimates (EBE) has recently been introduced (default method). However, EBE distribution may, with sparse and small datasets, not provide a suitable range of support points. This study aims to develop a method based on a prior parametric analysis capable of providing a nonparametric grid with adequate support points range. A new method extends the nonparametric grid with additional support points generated by simulation from the parametric distribution, hence the name extended-grid method. The joint probability density function is estimated at the extended grid. The performance of the new method was evaluated and compared to the default method via Monte Carlo simulations using simple IV bolus model and sparse (200 subject, two samples per subject) or small (30 subjects, three samples per subjects) datasets and two scenarios based on real case studies. Parameter distributions estimated by the default and the extended-grid method were compared to the true distributions; bias and precision were assessed at different percentiles. With small datasets, the bias was similar between methods (<10%); however, precision was markedly improved with the new method (by 43%). With sparse datasets, both bias (from 5.9% to 3%) and precision (by 60%) were improved. For simulated scenarios based on real study designs, extended-grid predictions were in a good agreement with true values. A new approach to obtain support points for the nonparametric method has been developed, and it displayed good estimation properties. The extended-grid method is automated, using the program PsN, for implementation into the NONMEM.
Authors and Affiliations
Radojka M. Savic, Mats O. Karlsson
Keywords
Related Articles
- EP ID EP681492
- DOI 10.1208/s12248-009-9138-8
- Views 89
- Downloads 0
A Method to Evaluate Fetal Erythropoiesis from Postnatal Survival of Fetal RBCs
Fetal RBCs are produced during a period of very rapid growth and stimulated erythropoiesis under hypoxic intrauterine conditions. Fetal RBC life span varies with gestational age (GA) and is shorter than that in healthy a...
A Review of Clinical Translation of Inorganic Nanoparticles
Inorganic nanoparticles are widely used for therapeutic and diagnostic purposes as they offer unique features as compared with their organic and polymeric counterparts. As such, inorganic nanoparticles represent...
Vesicular monoamine transporter 2: Role as a novel target for drug development
In the central nervous, system, vesicular monoamine transporter 2 (VMAT2) is the only transporter that moves cytoplasmic dopamine (DA) into synaptic vesicles for storage and subsequent exocytotic release. Pharmacological...
Choice of LC-MS Methods for the Absolute Quantification of Drug-Metabolizing Enzymes and Transporters in Human Tissue: a Comparative Cost Analysis
The online version of this article (doi:10.1208/s12248-014-9712-6) contains supplementary material, which is available to authorized users.
Intranasal Delivery of Exendin-4 Confers Neuroprotective Effect Against Cerebral Ischemia in Mice
The online version of this article (doi:10.1208/s12248-015-9854-1) contains supplementary material, which is available to authorized users.