# RE: Link different thetas to same omega using mu referencing

Date: Wed, 13 Apr 2016 12:25:38 +0000

Hi Jacob,

I suggest:
CAT1=0
CAT2=0
CAT3=0
IF(CAT.EQ.1) CAT1=1
IF(CAT.EQ.2) CAT2=1
IF(CAT.EQ.3) CAT3=1
MU_1 = CAT1*THETA(1) + CAT2*THETA(2) + CAT3*THETA(3)
CL = EXP(MU_1+ETA(1))

That way you have only one OMEGA. This could be more flexible when expandin=
g OMEGA for additional IIV in block format.

Cheers... Brian

From: owner-nmusers
Behalf Of Michael Fossler
Sent: Wednesday, April 13, 2016 7:56 AM
To: Leander, Jacob; nmusers
Subject: [NMusers] RE: Link different thetas to same omega using mu referen=
cing

This looks like it would work - it seems to obey the rules around mu-refere=
ncing. 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
mfossler
Office: 610-354-8840, ext. 249
Cell: 610-329-6636

From: owner-nmusers
ilto:owner-nmusers
Sent: Wednesday, April 13, 2016 7:01 AM
To: nmusers
Subject: [NMusers] Link different thetas to same omega using mu referencing

Hi

Consider the case where we have a categorical (potentially time-varying) co=
variate 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 elem=
ent 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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Received on Wed Apr 13 2016 - 08:25:38 EDT

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