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Re: VPC, NPC or PPC?

From: Leonid Gibiansky <LGibiansky>
Date: Wed, 25 Feb 2009 14:59:07 -0500

Nicolas
I do not know your design, but usually, when you have as many doses as
patients, it means that the dose is individualized and controlled by the
PK or by the PD effect (e.g., dose up to certain concentration level or
up to a certain sedation level). In this case, one has to be careful
with any type of predictive check unless your simulation algorithm
includes the dose-adjustment scheme used in the actual study. If
simulations do not include the same dose adjustment algorithm as the
actual study, you may have apparent discrepancy of your simulation
results and observed data even if the model is perfect.

On the other hand, if indeed the trial was concentration or effect
controlled, you may include the same dose adjustment scheme into the
simulations, and then use VPC for the entire study.

If you provide more details of the design, it would be easier to come up
with some reasonable VPC algorithm.

PPC can be conducted using nonmem PRIOR subroutine (see Nonmem manual)
with priors for population parameters fixed at final estimates, and
variability of the population parameters fixed at SE of the final model.

Thanks
Leonid

--------------------------------------
Leonid Gibiansky, Ph.D.
President, QuantPharm LLC
web: www.quantpharm.com
e-mail: LGibiansky at quantpharm.com
tel: (301) 767 5566




SIMON Nicolas wrote:
> Hi All,
>
>
>
> We have a dataset with as many dosing (amount and length of infusion) as
> patients. Once the final model was defined, I have performed a vpc.
> However, because the dosing are very different between patients, is it
> relevant to perform vpc or shall we compute npc or ppc?
>
>
>
> Can somebody explain the basic difference between vpc, npc and ppc and
> when shall we used one or the other?
>
>
>
> Last point, how to obtain ppc?
>
>
>
>
>
> Best regards
>
> Nicolas
>
>
>
>
>
> Professeur à la Faculté de Médecine de Marseille
>
> Laboratoire de Pharmacologie Médicale et Clinique
>
> 27 Bd Jean Moulin
>
> 13385 Marseille cedex
>
> Tél 0491387893 (Hôpital)
>
> Tél 0491324456 (Faculté)
>
> Fax 0491256526
>
>
>
Received on Wed Feb 25 2009 - 14:59:07 EST

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