Inter occasion variability in individual optimal design
2015 (English)In: Journal of Pharmacokinetics and Pharmacodynamics, ISSN 1567-567X, E-ISSN 1573-8744, Vol. 42, no 6, 735-750 p.Article in journal (Refereed) Published
Inter occasion variability (IOV) is of importance to consider in the development of a design where individual pharmacokinetic or pharmacodynamic parameters are of interest. IOV may adversely affect the precision of maximum a posteriori (MAP) estimated individual parameters, yet the influence of inclusion of IOV in optimal design for estimation of individual parameters has not been investigated. In this work two methods of including IOV in the maximum a posteriori Fisher information matrix (FIMMAP) are evaluated: (i) MAP(occ)-the IOV is included as a fixed effect deviation per occasion and individual, and (ii) POPocc-the IOV is included as an occasion random effect. Sparse sampling schedules were designed for two test models and compared to a scenario where IOV is ignored, either by omitting known IOV (Omit) or by mimicking a situation where unknown IOV has inflated the IIV (Inflate). Accounting for IOV in the FIMMAP markedly affected the designs compared to ignoring IOV and, as evaluated by stochastic simulation and estimation, resulted in superior precision in the individual parameters. In addition MAP(occ) and POPocc accurately predicted precision and shrinkage. For the investigated designs, the MAP(occ) method was on average slightly superior to POPocc and was less computationally intensive.
Place, publisher, year, edition, pages
2015. Vol. 42, no 6, 735-750 p.
Inter occasion variability (IOV), Optimal design (OD), Maximum a posteriori (MAP), Fisher information, Bayesian, Pharmacometrics, Shrinkage
Pharmacology and Toxicology
IdentifiersURN: urn:nbn:se:uu:diva-268393DOI: 10.1007/s10928-015-9449-6ISI: 000363982800010PubMedID: 26452548OAI: oai:DiVA.org:uu-268393DiVA: diva2:878646
FunderSwedish Research CouncilEU, European Research Council, Health-F3-2011-278348