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VPC appropriateness in complex PK

From: Dider Heine <ddrheine>
Date: Fri, 18 Sep 2009 08:53:52 -0700

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 no=
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 - 11:53:52 EDT

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