Powers of the likelihood ratio test and the correlation test using empirical bayes estimates for various shrinkages in population pharmacokinetics.
We compared the powers of the likelihood ratio test (LRT) and the Pearson correlation test (CT) from empirical Bayes estimates (EBEs) for various designs and shrinkages in the context of nonlinear mixed-effect modeling. Clinical trial simulation was performed with a simple pharmacokinetic model with various weight (WT) effects on volume (V). Data sets were analyzed with NONMEM 7.2 using first-order conditional estimation with interaction and stochastic approximation expectation maximization algorithms. The powers of LRT and CT in detecting the link between individual WT and V or clearance were computed to explore hidden or induced correlations, respectively. Although the different designs and variabilities could be related to the large shrinkage of the EBEs, type 1 errors and powers were similar in LRT and CT in all cases. Power was mostly influenced by covariate effect size and, to a lesser extent, by the informativeness of the design. Further studies with more models are needed.
1] IAME UMR 1137, INSERM, Paris, France [2] IAME UMR 1137, Université Paris Diderot, Sorbonne Paris Cité, Paris, France [3] Institut Roche de Recherche et Médecine Translationnelle, Boulogne-Billancourt, France [4] Pharma Research and Early Development, Clinical Pharmacology, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
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Combes
1] Institut Roche de Recherche et Médecine Translationnelle, Boulogne-Billancourt, France [2] Pharma Research and Early Development, Clinical Pharmacology, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
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Pharma Research and Early Development, Clinical Pharmacology, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
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Frey
1] IAME UMR 1137, INSERM, Paris, France [2] IAME UMR 1137, Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
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