This thesis concerns five studies where the statistical consequences of violations of modeling assumptions are assessed using experimental and simulated pharmacokinetic-pharmacodynamic data. The... Show moreThis thesis concerns five studies where the statistical consequences of violations of modeling assumptions are assessed using experimental and simulated pharmacokinetic-pharmacodynamic data. The first study describes the development of an open source web application for Bland-Altman analysis of comparison data, which is able to take into account both intra- and interindividual variability. In the second study the behavior of Akaike's information theoretic criterion is investigated in the presence of interindividual variability. The effects of neglecting or allowing for process noise are described in the third and fourth studies, for surrogate measures of clinical endpoints such depth of anesthesia and analgesia. In the fifth study pharmacodynamic model parameter estimates are compared when these are based on venous versus arterial blood samples. Show less
Dahan, A.; Olofsen, E.; Sigtermans, M.; Noppers, I.; Niesters, M.; Aarts, L.; ... ; Sarton, E. 2011
