caa a22 4500 605533849 CHVBK 20210128100840.0 cr unu---uuuuu 210128e20151201xx s 000 0 eng 10.1007/s10928-015-9449-6 doi (NATIONALLICENCE)springer-10.1007/s10928-015-9449-6 Inter occasion variability in individual optimal design [Elektronische Daten] [Anders Kristoffersson, Lena Friberg, Joakim Nyberg] 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) MAPocc—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 MAPocc and POPocc accurately predicted precision and shrinkage. For the investigated designs, the MAPocc method was on average slightly superior to POPocc and was less computationally intensive. The Author(s), 2015 Inter occasion variability (IOV) nationallicence Optimal design (OD) nationallicence Maximum a posteriori (MAP) nationallicence Fisher information nationallicence Bayesian nationallicence Pharmacometrics nationallicence Shrinkage nationallicence Kristoffersson Anders Department of Pharmaceutical Biosciences, Uppsala University, Box 591, 75124, Uppsala, Sweden aut Friberg Lena Department of Pharmaceutical Biosciences, Uppsala University, Box 591, 75124, Uppsala, Sweden aut Nyberg Joakim Department of Pharmaceutical Biosciences, Uppsala University, Box 591, 75124, Uppsala, Sweden aut Journal of Pharmacokinetics and Pharmacodynamics Springer US; http://www.springer-ny.com 42/6(2015-12-01), 735-750 1567-567X 42:6<735 2015 42 10928 https://doi.org/10.1007/s10928-015-9449-6 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10928-015-9449-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kristoffersson Anders Department of Pharmaceutical Biosciences, Uppsala University, Box 591, 75124, Uppsala, Sweden aut NATIONALLICENCE 700 1- Friberg Lena Department of Pharmaceutical Biosciences, Uppsala University, Box 591, 75124, Uppsala, Sweden aut NATIONALLICENCE 700 1- Nyberg Joakim Department of Pharmaceutical Biosciences, Uppsala University, Box 591, 75124, Uppsala, Sweden aut NATIONALLICENCE 773 0- Journal of Pharmacokinetics and Pharmacodynamics Springer US; http://www.springer-ny.com 42/6(2015-12-01), 735-750 1567-567X 42:6<735 2015 42 10928