This looks like it would work - it seems to obey the rules around 
mu-referencing. You can simplify the $OMEGA by using SAME(3)


Mike
Michael J. Fossler, Pharm. D., Ph. D., F.C.P.
VP, Quantitative Sciences
Trevena, Inc
mfoss...@trevenainc.com<mailto:mfoss...@trevenainc.com>
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From: owner-nmus...@globomaxnm.com [mailto:owner-nmus...@globomaxnm.com] On 
Behalf Of Leander, Jacob
Sent: Wednesday, April 13, 2016 7:01 AM
To: nmusers@globomaxnm.com
Subject: [NMusers] Link different thetas to same omega using mu referencing

Hi

Consider the case where we have a categorical (potentially time-varying) 
covariate named CAT that can take several values (e.g. 0,1,2,3).
Let's say I want to model CL depending on this categorical covariate (where 
parameters are estimated on log-scale).
A simple solution to this would be

IF(CAT.EQ.1) TVCL = THETA(1)
IF(CAT.EQ.2) TVCL = THETA(2)
IF(CAT.EQ.3) TVCL = THETA(3)

I let CL be described by a log-normal distribution with the same omega element 
for all CAT values.

CL = EXP(TVCL + ETA(1))

With an omega statement:

$OMEGA 0.1

I now want to switch to the mu referencing framework in NONMEM. Each theta 
needs to be reference to a MU value, and to force it to be described by the 
same eta I apply the following approach.

MU_1 = THETA(1)
MU_2 = THETA(2)
MU_3 = THETA(3)

IF(CAT.EQ.1) CL = EXP(MU_1 + ETA(1))
IF(CAT.EQ.2) CL = EXP(MU_2 + ETA(2))
IF(CAT.EQ.3) CL = EXP(MU_3 + ETA(3))

With an omega statement:

$OMEGA BLOCK(1) 0.1
$OMEGA BLOCK(1) SAME
$OMEGA BLOCK(1) SAME

where I force the omega element corresponding to ETA1, ETA2 and ETA3  to be the 
same.

Is this a valid approach to obtain what I need?
Or is there a simpler way in the mu-referencing framework to link different 
thetas to the same omega element?

All the best,
Jacob

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