caa a22 4500 445313714 CHVBK 20180317142639.0 cr unu---uuuuu 170323e20110801xx s 000 0 eng 10.1007/s11095-011-0422-9 doi (NATIONALLICENCE)springer-10.1007/s11095-011-0422-9 A New Exact Test for the Evaluation of Population Pharmacokinetic and/or Pharmacodynamic Models Using Random Projections [Elektronische Daten] [Celine Laffont, Didier Concordet] ABSTRACT: Purpose: Within-subject dependency of observations has a strong impact on the evaluation of population pharmacokinetic (PK) and/or pharmacodynamic (PD) models. To our knowledge, none of the current model evaluation tools correctly address this issue. We present a new method with a global test and easy diagnostic plot which relies on the use of a random projection technique that allows the analysis of dependent data. Methods: For each subject, the vector of standardised residuals is calculated and projected onto many random directions drawn uniformly from the unit sphere. Our test compares the empirical distribution of projections with their distribution under the model. Simulation studies assess the level of the test and compare its performance with common metrics including normalised prediction distribution errors and different types of weighted residuals. An application to real data is performed. Results: In contrast to other evaluated methods, our test shows adequate level for all models and designs investigated, which confirms its good theoretical properties. The weakness of other methods is demonstrated and discussed. Conclusions: This new test appears promising and could be used in combination with other tools to drive model evaluation in population PK/PD analyses. Springer Science+Business Media, LLC, 2011 GUD nationallicence model evaluation or diagnostics nationallicence nonlinear mixed effects models nationallicence normalised prediction distribution errors NPDE nationallicence weighted residuals nationallicence KS : Kolmogorov-Smirnov nationallicence VPC : visual predictive check nationallicence GUD : global uniform distance nationallicence Laffont Celine INRA, UMR 1331, Toxalim, F-31027, Toulouse, France aut Concordet Didier INRA, UMR 1331, Toxalim, F-31027, Toulouse, France aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/8(2011-08-01), 1948-1962 0724-8741 28:8<1948 2011 28 11095 https://doi.org/10.1007/s11095-011-0422-9 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0422-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Laffont Celine INRA, UMR 1331, Toxalim, F-31027, Toulouse, France aut NATIONALLICENCE 700 1- Concordet Didier INRA, UMR 1331, Toxalim, F-31027, Toulouse, France aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/8(2011-08-01), 1948-1962 0724-8741 28:8<1948 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer