Re: Question about interoccation variability
Claire,
It is the traditional assumption that BOV variance does not change with occasion (an assumption implemented with the SAME option). But it would be quite reasonable to look for BOV variance that is different from occasion to occasion eg. BOV in F might be relatively low soon after starting treatment in hospital but increase as patients became more active and had more interesting meals at home.
So its a modelling choice that you can test in the usual way based on OFV.
BTW in the example below if you want to use BOV on F1 the code should be F1=POPF1*EXP(ETA(F1)+BOVF1) where POPF1 would typically be set to 1 (unless you had a better idea of what the actual mean bioavailability of oral doses was) and ETA(F1) is the ETA for BSV of F1.
Nick
Quoted reply history
On 11/07/2012 7:16 a.m., Xu, Claire wrote:
> Hi Klaas and Jean,
>
> Thanks a lot for your immediate response and input. I will definitely test that whether having IOV on F1 will help. But I have a more general question about IOV. Can you comment on having one IOV in the model versus having five different IOVs across five different occasions? Is it reasonable to have different IOVs in the model?
>
> Thanks a lot for your generous help.
> Best,
> Claire
>
> On Tue, Jul 10, 2012 at 6:42 PM, Klaas Prins < [email protected] < mailto: [email protected] >> wrote:
>
> I think I would try IOV on F1 first before putting it on KA like
> Jean suggested but above all I think there is an essential element
> missing in your code. IOV is variability between occasions on top
> of inter individual variability.
>
> So do something like:
> F1=1
> F1=THETA(1)*EXP(ETA(6)+BOVKA)
> $OMEGA 0.25 ; IIV F1
>
> Furthermore, there may be other elements contributing to the
> inability to predict Cmax well, such as more complex absorption
> features. I think we lack info to comment on that.
>
> HTH, Klaas
>
> On 10 jul. 2012, at 23:56, "Lavigne, Jean"
> <[email protected] <mailto:[email protected]>> wrote:
>
> > KA=THETA(1)*EXP(BOVKA)
>
> --
> Xu, Claire
> Ph.D Candidate
> Division of Clinical Pharmacology, Wishard Hospital
> Indiana University School of Medicine
> 1001 West 10th Street, Myers W7122
> Indianapolis, IN 46202
> T - 317/7558242
--
Nick Holford, Professor Clinical Pharmacology
First World Conference on Pharmacometrics, 5-7 September 2012
Seoul, Korea http://www.go-wcop.org
Dept Pharmacology & Clinical Pharmacology, Bldg 505 Room 202D
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