Journal ArticleDOI
A Two-Step Iterative Algorithm For Estimation In Nonlinear Mixed-Effect Models With An Evaluation In Population Pharmacokinetics
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This article proposes an EM-like algorithm for estimating, by maximum likelihood, the population parameters of a nonlinear mixed-effect model given sparse individual data using a linearization about those Bayesian estimates.Abstract:
This article proposes an EM-like algorithm for estimating, by maximum likelihood, the population parameters of a nonlinear mixed-effect model given sparse individual data The first step involves Bayesian estimation of the individual parameters During the second step, population parameters are estimated using a linearization about those Bayesian estimates This algorithm (implemented in P-PHARM) is evaluated on simulated data, mimicking pharmacokinetic analyses and compared to the First-Order method and the First-Order Conditional Estimates method (both implemented in NONMEM) The accuracy of the results, within few iterations, shows the estimation capabilities of the proposed approachread more
Citations
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Journal ArticleDOI
Optimal design in random-effects regression models
Alain Mallet,Doha Baccar +1 more
TL;DR: In this article, an approach is proposed to optimal design of experiments for estimating randomeffects regression models, where the population designs are defined by the number of subjects and the individual designs to be performed.
Journal ArticleDOI
A survey of population analysis methods and software for complex pharmacokinetic and pharmacodynamic models with examples
TL;DR: An overview is provided of the present population analysis methods and an assessment of which software packages are most appropriate for various PK/ PD modeling problems, and which algorithms and software are most suitable for which types of PK/PD problems are discussed.
Journal ArticleDOI
Estimation of population pharmacokinetic parameters of saquinavir in HIV patients with the MONOLIX software.
TL;DR: MONOLIX is applied to the analysis of the pharmacokinetics of saquinavir from concentrations measured after single dose administration in 100 HIV patients, some with advance disease and it is illustrated how to use MONOLIX to build the covariate model using the Bayesian Information Criterion.
Journal ArticleDOI
Population Pharmacokinetics II: Estimation Methods
Ene I. Ette,Paul J. Williams +1 more
TL;DR: PPK estimation methods that rely on the characterizing of mixed (fixed and random) effects are known to produce PPK parameter estimates that are less biased than those obtained using the naïve and standard two-stage approaches.
Journal ArticleDOI
The Use of Population Pharmacokinetics in Drug Development
TL;DR: This article outlines the population approach, and discusses how it can be implemented within the framework of the studies currently performed as part of the clinical phases of new drug development, and considers study design and performance, based on real-life experiences.
References
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Journal ArticleDOI
Maximum likelihood from incomplete data via the EM algorithm
Journal ArticleDOI
Random-effects models for longitudinal data
Nan M. Laird,James H. Ware +1 more
TL;DR: In this article, a unified approach to fitting two-stage random-effects models, based on a combination of empirical Bayes and maximum likelihood estimation of model parameters and using the EM algorithm, is discussed.
Journal ArticleDOI
Maximum likelihood estimation via the ECM algorithm: A general framework
Xiao-Li Meng,Donald B. Rubin +1 more
TL;DR: In many cases, complete-data maximum likelihood estimation is relatively simple when conditional on some function of the parameters being estimated as mentioned in this paper, and convergence is stable, with each iteration increasing the likelihood.
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