Interoccation variation question

Dear colleagues, I'm currently working on a population PK analysis where I probably need to incorporate interoccation variation on one or more parameters. However, I'm wondering about one issue. To put it short, here's the problem: Trial 1: 1 dosing occation, PK observed for 1 week Trial 2: 3 dosing occation (1 x week), not full washout between, PK observed for 1 week after dose 1 and after dose 3. PK varies betw. wk 1 and 3. within subject. Question: Should 1) occasion flag OCC=1 for all subject in trial 1 and OCC=1 (week1) and 2 (week 3) in trial 2? Or should 2) occasion flag OCC be omitted for trial 1 subjects and set to 1 or 2 as in 1) for trial 2. On one hand, 1) would strictly speaking seem correct as these subjects have only a dose 1 occation. On the other hand, my feeling is that NONMEM would be put in trouble with seemingly always two inseparable individual ETAs in trial 1 subjects for parameters with IOV on. (I'm using FOCEI). Ka = TVKA*EXP(ETA(IIV_Ka)) IF (OOC.EQ.1) Ka = Ka*EXP(ETA(Occ_1)) IF (OOC.EQ.2) Ka = Ka*EXP(ETA(Occ_2)) .. $OMEGA .1 .1 SAME If 2) is the better approach of the two, would the simulation model not still be Ka=TVKA*EXP(ETA(IIV_Ka)+ETA(Occ)) for any subject, regards of no. of occasions? (Ie. above manoeuvre would be only to avoid an estimation problem). ?? Thx. for any input Thomas ____________________ Thomas Klitgaard Principal Scientist Biomodelling Novo Nordisk A/S Krogshjvej 53 A DK-2880 Bagsvrd Denmark +45 4442 4960 (direct) +45 3079 4960 (mobile) tkt www.novonordisk.com Changing possibilities in haemophilia Novo Nordisk is focused on the quality of life of people living with haemophilia; for this reason our pipeline continues to evolve, it is why we continue to strengthen our existing formula. Learn http://www.novonordisk.com/about_us/improving_haemophilia/ChangingPossibilitiesActivities/HaemophiliaPatientFocus.asp This e-mail (including any attachments) is intended for the addressee(s) stated above only and may contain confidential information protected by law. You are hereby notified that any unauthorized reading, disclosure, copying or distribution of this e-mail or use of information contained herein is strictly prohibited and may violate rights to proprietary information. If you are not an intended recipient, please return this e-mail to the sender and delete it immediately hereafter. Thank you.