NONMEM Users Network Archive

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RE: VPC appropriateness in complex PK

From: marco.campioni
Date: Mon, 21 Sep 2009 17:44:01 +0200

Dear Martin and Uppsala group,

Maybe I’m wrong, but I guess PC-VPC is not available in the current
version of PsN.

Did you plan to implement it in the new PsN version?

Many thanks

Kind Regards


Marco Campioni, PhD
Modelling & Simulations
Exploratory Medicine

Merck Serono S.A. - Geneva
9, Chemin des Mines
1202 Geneva, Switzerland
Location: B1.4
Phone: +41 22 414 4554
Fax: +41 22 414 3059
Email: marco.campioni

"Martin Bergstrand" <martin.bergstrand
Sent by: owner-nmusers
18/09/2009 18:50

"'Dider Heine'" <ddrheine

RE: [NMusers] VPC appropriateness in complex PK

Dear Dider,
In my opinion the PAGE 2009 abstract by Diane Wang does highlight
weaknesses with the standard VPC under certain circumstances. However, I
don’t think that the SVPC represent the answer to those weaknesses.
Prediction corrected VPCs (PC-VPCs) are a better way of addressing these
issues and was first mentioned in the Karlsson and Holford tutorial on
VPCs at PAGE 2008 (
). A poster on the PC-VPCs principle and the advantage with these is
submitted to the ACoP conference (October 2009). A two page abstract
regarding that poster is available already now via the ACoP webpage ( - Title: “Prediction Corrected
Visual Predictive Checks” Authors: Martin Bergstrand, Andrew C. Hooker,
Johan E. Wallin, Mats O. Karlsson). Please have a look at this abstract
and contact me if you have any further questions.
Kind regards,
Martin Bergstrand, MSc, PhD student
Pharmacometrics Research Group,
Department of Pharmaceutical Biosciences,
Uppsala University
P.O. Box 591
SE-751 24 Uppsala
martin.bergstrand e
Work: +46 18 471 4639
Mobile: +46 709 994 396
Fax: +46 18 471 4003
From: owner-nmusers ilto:owner-nmusers
On Behalf Of Dider Heine
Sent: den 18 september 2009 17:54
To: nmusers
Subject: [NMusers] VPC appropriateness in complex PK
Dear NMusers:
The Visual predictive check (VPC, , and JPKPD,
Volume 35, Number 2 / April, 2008) has been touted as a useful tool for
assessing the perfomance of population pharmacokinetic models. However I
recently came across this abstract from the 2009 PAGE meeting:
This abstract states that situations when VPC is not feasible but a
"Standardized Visual Predictive Check (SVPC) can be used are as follows:
– Patients received individualized dose or there are a small number of
patients per dose group and PK or PD is nonlinear, thus observations can
not be normalized for dose
– There are multiple categorical covariate effects on PK or PD parameters
– Covariate is a continuous variable which made stratification impossible
– Study design and execution varies among individuals, such as adaptive
design, difference in dosing schedule, dose changes and dosing time varies
during study, protocol violations
– Different concomitant medicines and food intake among individuals when
there are drug-drug interactions and food effect on PK

However, the original VPC articles seem to suggest that these are the
exact situations when the VPC alone is an ideal tool for model validation.
 Is there any justification for one approach over the other? Has anyone
ever seen an SVPC utilized elsewhere, I have found nothing. Are these
truly weaknesses of a VPC?

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Received on Mon Sep 21 2009 - 11:44:01 EDT

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