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RE: VPC appropriateness in complex PK

From: Martin Bergstrand <martin.bergstrand>
Date: Fri, 18 Sep 2009 18:50:01 +0200

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
ires.pdf). 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





Work: +46 18 471 4639

Mobile: +46 709 994 396

Fax: +46 18 471 4003



From: owner-nmusers
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:
ve%20Check%20in%20Model%20Evaluation%20-%20PAGE2009%20submit.pdf .
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?




Received on Fri Sep 18 2009 - 12:50:01 EDT

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