NONMEM Users Network Archive

Hosted by Cognigen

Re: VPC appropriateness in complex PK

From: Dider Heine <ddrheine>
Date: Fri, 18 Sep 2009 16:39:00 -0700

Thank you Martin,
It sounds to me as if PC-VPCs trump any benefits of an SVPC. Look forward
to your presentation at ACoP.

Best!
Dider

On Fri, Sep 18, 2009 at 9:50 AM, Martin Bergstrand <
martin.bergstrand

> 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. *Pr=
ediction
> 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 (
> http://www.page-meeting.org/pdf_assets/8694-Karlsson_Holford_VPC_Tutorial=
_hires.pdf).
> A poster on the PC-VPCs principle and the advantage with these is submitt=
ed
> to the ACoP conference (October 2009). A two page abstract regarding that
> poster is available already now via the ACoP webpage (
> http://www.go-acop.org/acop2009/posters - Title: *“Prediction Corrected
> Visual Predictive Checks”* Authors: *Martin Bergstrand, Andrew C. Hooke=
r,
> 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
>
> Sweden
>
> -----------------------------------------------
>
> martin.bergstrand
>
> -----------------------------------------------
>
> Work: +46 18 471 4639
>
> Mobile: +46 709 994 396
>
> Fax: +46 18 471 4003
>
>
>
>
>
> *From:* 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,
> http://www.page-meeting.org/page/page2005/PAGE2005P105.pdf , 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:
> http://www.page-meeting.org/pdf_assets/4050-Standardized%20Visual%20Predi=
ctive%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 paramete=
rs
> – Covariate is a continuous variable which made stratification impossib=
le
> – Study design and execution varies among individuals, such as adaptive
> design, difference in dosing schedule, dose changes and dosing time varie=
s
> during study, protocol violations
> – Different concomitant medicines and food intake among individuals whe=
n
> there are drug-drug interactions and food effect on PK
>
> However, the original VPC articles seem to suggest that these are the exa=
ct
> 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?
>
>
>
> Cheers!
>
> Dider
>

Received on Fri Sep 18 2009 - 19:39:00 EDT

The NONMEM Users Network is maintained by ICON plc. Requests to subscribe to the network should be sent to: nmusers-request@iconplc.com.

Once subscribed, you may contribute to the discussion by emailing: nmusers@globomaxnm.com.