Optimal designs for random effect models with correlated errors with applications in population pharmacokinetics

DOI10.1214/09-AOAS324zbMATH Open1202.62101arXiv1011.3333MaRDI QIDQ614158FDOQ614158

Authors: Andrey Pepelyshev, Tim Holland-Letz, Holger Dette 

Publication date: 27 December 2010

Published in: The Annals of Applied Statistics (Search for Journal in Brave)

Abstract: We consider the problem of constructing optimal designs for population pharmacokinetics which use random effect models. It is common practice in the design of experiments in such studies to assume uncorrelated errors for each subject. In the present paper a new approach is introduced to determine efficient designs for nonlinear least squares estimation which addresses the problem of correlation between observations corresponding to the same subject. We use asymptotic arguments to derive optimal design densities, and the designs for finite sample sizes are constructed from the quantiles of the corresponding optimal distribution function. It is demonstrated that compared to the optimal exact designs, whose determination is a hard numerical problem, these designs are very efficient. Alternatively, the designs derived from asymptotic theory could be used as starting designs for the numerical computation of exact optimal designs. Several examples of linear and nonlinear models are presented in order to illustrate the methodology. In particular, it is demonstrated that naively chosen equally spaced designs may lead to less accurate estimation.

Full work available at URL: https://arxiv.org/abs/1011.3333

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zbMATH Keywords

compartmental modelsrandom effects modelscorrelated observationsasymptotic optimal design densitynonlinear least squares estimate

Mathematics Subject Classification ID

Applications of statistics to biology and medical sciences; meta analysis (62P10) Optimal statistical designs (62K05) Kinetics in biochemical problems (pharmacokinetics, enzyme kinetics, etc.) (92C45)

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Cited In (16)

• Sample reuse Simulation in Optimal Design for Tmax in Pharmacokinetic Experiments
• A geometric characterization of optimal designs for regression models with correlated observations
• Robust population designs for longitudinal linear regression model with a random intercept
• Optimal parametric design with applications to pharmacokinetic and pharmacodynamic trials
• Hierarchical optimal designs and modeling for engineering: a case-study in the rail sector
• Efficient algorithms for optimal designs with correlated observations in pharmacokinetics and dose-finding studies
• Optimal designs in regression with correlated errors
• Optimal and Robust Designs for Estimating the Concentration Curve and the AUC
• Optimal design for population PK/PD models
• Optimal design for linear models with correlated observations
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• Experimental design for mixed models with application to population pharmacokinetic studies
• PkStaMp library for constructing optimal population designs for PK/PD studies
• Optimal time plan in accelerated degradation testing
• Robust integer-valued designs for linear random intercept models

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