Peter L. Bonate

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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 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)
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)
The purpose of this work was to present a consolidated set of guidelines for the analysis of uncontrolled concomitant medications (ConMed) as a covariate and potential perpetrator in population pharmacokinetic (PopPK) analyses. This white paper is the result of an industry-academia-regulatory collaboration. It is the recommendation of the working group that(More)
The effect of extrapolated area (%AUCextrap) on estimating mean AUCinf in a simulated single-dose clinical trial was examined. Concentration–time (C–t) profiles from 12 to 36 subjects for 1- and 2-compartment models after single dose administration were simulated with increasing right-tailed censoring. Each subject’s %AUCextrap and AUCinf was calculated(More)
We have all seen the numbers. At least a billion dollars to develop a new medicine and bring it to market [1]. More than 10,000 compounds screened for every new drug approval [2]. The number of new chemical entities approved by the Food and Drug Administration has been declining for a long period to record lows and only now appears to be rebounding [3]. The(More)
Monte Carlo simulation was used to assess the performance of linear mixed effect models (LMEMs) to characterize the concentration–effect relationship when both parent and metabolite concentrations were available. Parent and metabolite concentrations were simulated under an experimental design that mimicked a thorough QT study. Simulations were done where(More)