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Tumor growth profiles were simulated for 2 years using the Wang and Claret models under a phase 3 clinical trial design. Profiles were censored when tumor size increased >20% from nadir similar to clinical practice. The percent of patients censored varied from 0% (perfect case) to 100% (real-life case). The model used to generate the data was then fit to(More)
There are many reasons for wishing to determine the rate of uptake of a drug from blood into brain parenchyma. However, when faced with doing so for the first time, choosing a method can be a formidable task. There are at least 7 methods from which to choose: indicator dilution, brain uptake index, microdialysis, external registration, PET scanning, in situ(More)
PURPOSE The receptors for hepatocyte and vascular endothelial cell growth factors (MET and VEGFR2, respectively) are critical oncogenic mediators in gastric adenocarcinoma. The purpose is to examine the safety and efficacy of foretinib, an oral multikinase inhibitor targeting MET, RON, AXL, TIE-2, and VEGFR2 receptors, for the treatment of metastatic(More)
PURPOSE To introduce partially linear mixed effects models (PLMEMs), to illustrate their use, and to compare the power and Type I error rate in detecting a covariate effect with nonlinear mixed effects modeling using NONMEM. METHODS Sparse concentration-time data from males and females (1:1) were simulated under a 1-compartment oral model where clearance(More)
Quality population modeling and simulation analyses and reports are something every modeler desires. However, little attention in the literature has been paid to what constitutes quality regarding population analyses. Very rarely do published manuscripts contain any statement about quality assurance of the modeling results contained therein. The purpose of(More)
Linear mixed-effects models (LMEMs) of concentration-double-delta QTc intervals (QTc intervals corrected for placebo and baseline effects) assume that the concentration measurement error is negligible, which is an incorrect assumption. Previous studies have shown in linear models that independent variable error can attenuate the slope estimate with a(More)
We conducted experiments investigating the role of altered cocaine distribution in behavioral sensitization. The first was designed to determine whether carry-over from one injection to the next occurs after acute cocaine administration. Female, Sprague-Dawley rats were administered 5 mg/kg 3H-cocaine and 24 h later were challenged with either 5 mg/kg(More)
PURPOSE The coverage and precision of parametric Bailer-type confidence intervals (CIs) for area under the curve (AUC) was compared to nonparametric bootstrap confidence intervals. METHODS Concentration-time data was simulated using Monte Carlo simulation under a toxicokinetic paradigm with sparse (SSC) and dense sampling (DSC) conditions. AUC was(More)
We investigated the effect of amphetamine pretreatment on the locomotor response to subsequent cocaine challenge. Rats were administered either 0.75 mg/kg amphetamine in a testing environment and saline in their home cage, saline in the testing environment and 0.75 mg/kg amphetamine in their home cage, or saline in both the testing environment and home(More)