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

From: Rupert Austin <rupert.austin>
Date: Wed, 13 Apr 2016 16:44:28 +0100

I’m not sure that Brian’s suggestion is acceptable due =
to the following constraint I quote from one of the NONMEM manuals:


“Time dependent covariates cannot be part of the MU_ =


If CAT is time-varying (as suggested by Jacob) then “MU_1 = =
CAT1*THETA(1) + CAT2*THETA(2) + CAT3*THETA(3)” includes time =
dependent covariates. Rather worryingly, I don’t think NONMEM =
will trap this problem since I have fallen foul of it with no resulting =
NONMEM warnings, and I have no idea what the consequences are for the =
resulting NONMEM run and results.




Rupert Austin, PhD

Senior Scientist

BAST Inc Limited

Loughborough University Science and Enterprise Park

Charnwood Wing

Holywell Park

Ashby Road

Loughborough, LE11 3AQ, UK

Tel: +44 (0)1509 222908


From: owner-nmusers
On Behalf Of Sadler, Brian
Sent: 13 April 2016 13:26
To: nmusers
Subject: [NMusers] RE: Link different thetas to same omega using mu =


Hi Jacob,


I suggest:







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 =
expanding OMEGA for additional IIV in block format.


Cheers… Brian



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


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




Michael J. Fossler, Pharm. D., Ph. D., F.C.P.

VP, Quantitative Sciences

Trevena, Inc


Office: 610-354-8840, ext. 249

Cell: 610-329-6636


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




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






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




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:






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,




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Received on Wed Apr 13 2016 - 11:44:28 EDT

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