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Interoccation variation question

From: TKT <tkt>
Date: Mon, 6 Apr 2009 10:21:12 +0200

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 observe=
d for 1 week after dose 1 and after dose 3. PK varies betw. wk 1 and 3. wit=
hin 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 i=
n 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 tri=
al 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 sti=
ll be Ka=TVKA*EXP(ETA(IIV_Ka)+ETA(Occ)) for any subject, regards of no. o=
f 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
Krogshøjvej 53 A
DK-2880 Bagsværd
Denmark
+45 4442 4960 (direct)
+45 3079 4960 (mobile)
tkt
www.novonordisk.com

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Received on Mon Apr 06 2009 - 04:21:12 EDT

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