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Re: VPC appropriateness in complex PK

From: Dider Heine <ddrheine>
Date: Mon, 21 Sep 2009 13:58:40 -0700

So to summarize,
1. The VPC (Holford NHG. PAGE. 2005;14) is appropriate for screening of al=
l
pk models, and is complementary to:
2. The SPC (original method by Mentre et. al J Pharmacokinet Pharmacodyn.
2006;33(3):345-67, subsequently re-presented by Wang et al, PAGE, 2009)
which should be used to identify if the distribution of discrepancies
between model predictions and observations is uniform.
3. The PC-VPC (implemented from within PSN) offers similar advantages to 1
and 2 above (combined) with the additional advantage of being automated.
4. In the case of adaptive trial desings, a VPC with an adaptive algorithm
should be implemented for model evaluation.

Agreed?
Cheers!
Dider


On 9/21/09, Martin Bergstrand <martin.bergstrand
>
> Dear Marco,
>
>
>
> It is correct that PC-VPCs is currently not a feature in PsN. The standar=
d
> VPC command in PsN can still be used for most of the calculations needed =
to
> produce a PC-VPC, however calculation of median PRED in each bin must
> currently be calculated outside of PsN. This calculation is needed once f=
or
> a data-set and a specific choice of binning. The calculated median PRED i=
s
> appended together with PRED in the data-file.
>
>
>
> In the model file used to construct the VPC the following code is added:
>
>
>
> IF(ICALL.EQ.4) THEN
>
> PCDV = Y * MPR/PR
>
> ELSE
>
> PCDV = DV * MPR/PR
>
> ENDIF
>
>
>
> ;; PR = Typical model prediction (PRED) for the current observation
> (appended in the input data)
>
> ;; MPR = Median PRED in the current bin (appended in the input data)
>
>
>
> When the VPC command in PsN is executed you add ”-dv=PCDV” at the c=
ommand
> line. It is important that you chose binning options in PsN so that it
> corresponds to the binning you have done when calculating median PRED (MP=
R).
>
>
>
> PRED correction will from my understanding eventually be an option in the
> PsN VPC functionality. Currently however all programming efforts for PsN =
are
> focused on making the existing functionalities compatible with NONMEM 7.
> Therefore I am not sure if PRED correction is going to be included alread=
y
> in the next release.
>
>
>
> Best regards,
>
> Martin
>
>
>
> *From:* marco.campioni
> marco.campioni
> *Sent:* den 21 september 2009 17:44
> *To:* Martin Bergstrand
> *Cc:* 'Dider Heine'; nmusers
> *Subject:* RE: [NMusers] VPC appropriateness in complex PK
>
>
>
>
> Dear Martin and Uppsala group,
>
> Maybe I’m wrong, but I guess PC-VPC is not available in the current ver=
sion
> of PsN.
>
> Did you plan to implement it in the new PsN version?
>
> Many thanks
>
> Kind Regards
>
> Marco
>
>
> -------------------------------------------------------------------------=
-----
> 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
>

Received on Mon Sep 21 2009 - 16:58:40 EDT

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