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
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
<klaas.pr...@qpharmetra.com <mailto:klaas.pr...@qpharmetra.com>> 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"
<jean.lavi...@celerion.com <mailto:jean.lavi...@celerion.com>> 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
University of Auckland,85 Park Rd,Private Bag 92019,Auckland,New Zealand
tel:+64(9)923-6730 fax:+64(9)373-7090 mobile:+64(21)46 23 53
email: n.holf...@auckland.ac.nz
http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford
