Optimal designs for composed models in pharmacokinetic-pharmacodynamic experiments

Holger Dette, Andrey Pepelyshev, Weng Kee Wong

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

We consider two frequently used PK/PD models and provide closed form descriptions of locally optimal designs for estimating individual parameters. In a novel way, we use these optimal designs and construct locally standardized maximin optimal designs for estimating any subset of the model parameters of interest. We do this by maximizing the minimal efficiency of the estimates across all relevant parameters so that these optimal designs are less dependent on the individual parameter or parameters of interest. Additionally, robust designs are proposed to further reduce the dependence on the nominal values of the parameters. We compare efficiencies of our proposed optimal designs with locally optimal designs and designs used in four real studies from the literature and show that our proposed designs provide advantages over those used in practice.

Original languageEnglish
Pages (from-to)295-311
Number of pages17
JournalJournal of Pharmacokinetics and Pharmacodynamics
Volume39
Issue number3
DOIs
Publication statusPublished - 2012 Jun

All Science Journal Classification (ASJC) codes

  • Pharmacology

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