Locally D-optimal designs based on a class of composed models resulted from blending Emax and one-compartment models

• 成果类型: Article
• 署名作者: Fang, X.; Hedayat, A. S.
• 署名单位: University of Illinois System; University of Illinois Chicago; University of Illinois Chicago Hospital
• 刊物名称: ANNALS OF STATISTICS
• ISSN/ISSBN: 0090-5364
• DOI: 10.1214/009053607000000776
• 发表日期: 2008
• 页码: 428-444
• 关键词: exponential regression-models; optical-density data; nonlinear models; population; pharmacokinetics; quinidine; DYNAMICS

摘要

A class of nonlinear models combining a pharmacokinetic compartmental model and a pharmacodynamic Emax model is introduced. The locally D-optimal (LD) design for a four-parameter composed model is found to be a saturated four-point uniform LD design with the two boundary points of the design space in the LD design support. For a five-parameter composed model, a sufficient condition for the LD design to require the minimum number of sampling time points is derived. Robust LD designs are also investigated for both models. It is found that an LD design with k parameters is equivalent to an LD design with k - 1 parameters if the linear parameter in the two composed models is a nuisance parameter. Assorted examples of LD designs are presented.