Prediction-corrected visual predictive checks for diagnosing nonlinear mixed-effects models

The AAPS Journal
Martin BergstrandMats O Karlsson

Abstract

Informative diagnostic tools are vital to the development of useful mixed-effects models. The Visual Predictive Check (VPC) is a popular tool for evaluating the performance of population PK and PKPD models. Ideally, a VPC will diagnose both the fixed and random effects in a mixed-effects model. In many cases, this can be done by comparing different percentiles of the observed data to percentiles of simulated data, generally grouped together within bins of an independent variable. However, the diagnostic value of a VPC can be hampered by binning across a large variability in dose and/or influential covariates. VPCs can also be misleading if applied to data following adaptive designs such as dose adjustments. The prediction-corrected VPC (pcVPC) offers a solution to these problems while retaining the visual interpretation of the traditional VPC. In a pcVPC, the variability coming from binning across independent variables is removed by normalizing the observed and simulated dependent variable based on the typical population prediction for the median independent variable in the bin. The principal benefit with the pcVPC has been explored by application to both simulated and real examples of PK and PKPD models. The investigated examp...Continue Reading

References

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Citations

Jan 12, 2013·European Journal of Clinical Pharmacology·Anna-Karin HambergMia Wadelius
Mar 12, 2013·European Journal of Clinical Pharmacology·Daniel F B WrightNicholas H G Holford
Sep 28, 2013·European Journal of Clinical Pharmacology·Elisabet StørsetAnders Åsberg
Nov 2, 2011·Journal of Pharmacokinetics and Pharmacodynamics·Marc Lavielle, Kevin Bleakley
Sep 25, 2012·Journal of Pharmacokinetics and Pharmacodynamics·Jace C NielsenJakob Ribbing
Feb 20, 2013·Clinical Pharmacokinetics·Stefanie HennigAlison H Thomson
Jul 31, 2013·International Journal of Antimicrobial Agents·Antonello Di PaoloRomano Danesi
Nov 17, 2012·British Journal of Anaesthesia·B J AndersonT Engelhardt
Feb 26, 2013·The Journal of Antimicrobial Chemotherapy·Sarah AlghanemAlison H Thomson
Jun 22, 2011·Antimicrobial Agents and Chemotherapy·Siv JönssonHelen McIlleron
May 15, 2013·Antimicrobial Agents and Chemotherapy·Mohamed A KamalAlan Forrest
Mar 21, 2012·Antimicrobial Agents and Chemotherapy·Lena E FribergPing Liu
Jan 19, 2012·Antimicrobial Agents and Chemotherapy·Wynand SmytheUlrika S H Simonsson
Feb 15, 2012·Antimicrobial Agents and Chemotherapy·Kevin T BattyTimothy M E Davis
Aug 6, 2013·Clinical Pharmacokinetics·Stefan WillmannWolfgang Mück
Feb 14, 2014·Cancer Chemotherapy and Pharmacology·Matthias FreiwaldAlexander Staab
Nov 5, 2013·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Bojana GolubovićBranislava Miljković
Mar 19, 2014·Journal of Pharmacokinetics and Pharmacodynamics·Jean-Marie MartinezDavid Fabre
Feb 19, 2014·Pharmacogenomics·Anna-Karin Hamberg, Mia Wadelius

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