NDLI: Conditional Weighted Residuals (CWRES): A Model Diagnostic for the FOCE Method

Content Provider	Springer Nature Link
Author	Hooker, Andrew C. Staatz, Christine E. Karlsson, Mats O.
Copyright Year	2007
Abstract	Population model analyses have shifted from using the first order (FO) to the first-order with conditional estimation (FOCE) approximation to the true model. However, the weighted residuals (WRES), a common diagnostic tool used to test for model misspecification, are calculated using the FO approximation. Utilizing WRES with the FOCE method may lead to misguided model development/evaluation. We present a new diagnostic tool, the conditional weighted residuals (CWRES), which are calculated based on the FOCE approximation.CWRES are calculated as the FOCE approximated difference between an individual’s data and the model prediction of that data divided by the root of the covariance of the data given the model.Using real and simulated data the CWRES distributions behave as theoretically expected under the correct model. In contrast, in certain circumstances, the WRES have distributions that greatly deviate from the expected, falsely indicating model misspecification. CWRES/WRES comparisons can also indicate if the FOCE estimation method will improve the results of an FO model fit to data.Utilization of CWRES could improve model development and evaluation and give a more accurate picture of if and when a model is misspecified when using the FO or FOCE methods.
Starting Page	2187
Ending Page	2197
Page Count	11
File Format	PDF
ISSN	07248741
Journal	Pharmaceutical Research
Volume Number	24
Issue Number	12
e-ISSN	1573904X
Language	English
Publisher	Springer US
Publisher Date	2007-07-06
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	conditional estimation model diagnostics modeling non-linear mixed effect models NONMEM pharmacometrics statistics weighted residuals Biomedical Engineering Medical Law Biochemistry Pharmacy Pharmacology/Toxicology
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Pharmacology Molecular Medicine Pharmacology (medical) Biotechnology Pharmaceutical Science

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