Re: Question about interoccation variability

On Wed, Jul 11, 2012 at 9:33 AM, Nick Holford <[email protected]>wrote: > 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 >> <[email protected]<mailto: >> klaas.prins@**qpharmetra.com <[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:jean.lavigne@celerion.**com<[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 > 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: [email protected] > http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford > > > > > -- 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