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RE: OMEGA BLOCK with mixture model?

From: Christian Laveille <christian.laveille>
Date: Wed, 15 Apr 2009 15:47:35 +0200

Dear all,


There is an undocumented option in NONMEM called Band, allowing to fix at
least one correlation to zero in a block(n).

In the specific case you just have to put zero as initial estimate for Omega

It should work I used it in the past with NONMEM V!


Hope this helps.




Christian Laveille

Senior Consultant

Exprimo NV


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From: owner-nmusers
Behalf Of Bob Leary
Sent: mercredi 15 avril 2009 15:16
To: andreas.krause
Subject: RE: [NMusers] OMEGA BLOCK with mixture model?


If you want both CL1 and CL2 to be correlated with F (i.e. allow
Omega(CL1,F) and Omega(CL2,F) to be free in

the objective function optimization),

then I don't think there is any simple reordering of the random effects
that will allow the correlation

between CL1 and CL2 to be fixed to zero - i.e. the element Omega(CL1,CL2)
must also be free.


The reason for the Nonmem manual entry

 part VIII, p 94 ($OMEGA), "If FIXED appears anywhere among the list of
values, the entire block is fixed."
that Andreas pointed out is that internally Nonmem parameterizes the Omega
matrix by its

Cholesky factor elements, not the elements of the Omega matrix itself. The
Cholesky factor has the

same block diagonal structure as the Omega matrix, but due to the 'fill-in'
phenomenon during

a factorization, an internal zero element inside an Omega block will not
necessarily be preserved

as a zero in the Cholesky factor. So there is no way to force an internal
element in an Omega block to be zero.


Robert H. Leary, PhD

Pharsight - A CertaraT Company

5625 Dillard Dr., Suite 205
Cary, NC 27511

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-----Original Message-----
From: owner-nmusers
Behalf Of andreas.krause
Sent: Wednesday, April 15, 2009 6:6 AM
To: nele.plock
Cc: nmusers
Subject: Re: [NMusers] OMEGA BLOCK with mixture model?


going by the nonmem user manual, part VIII, p 94 ($OMEGA), "If FIXED appears
anywhere among the list of values, the entire block is fixed."
I did not see anyone pointing that out yet.

This does in fact imply that you need to reorder the sequence of random
effects (which can be quite a nuisance if you have a sequence of models and
the parameters do not correspond any more across models).



Andreas Krause, PhD
Lead Scientist Modeling and Simulation

Actelion Pharmaceuticals Ltd / Gewerbestrasse 16 / CH-4123 Allschwil /
phone +41 61 565 6891 / fax +41 61 565 66 96

Sent by: owner-nmusers

04/14/2009 05:08 PM






[NMusers] OMEGA BLOCK with mixture model?




Dear all,

I am trying to fit a PK model to oral data. In the data, we observed two
things: First, CL seems to be negatively correlated with F1. Secondly, there
seem to be two subpopulations in the exposure, let's say a large group with
'normal' and a second group with high exposure. I would like to identify the
subpopulations using a mixture model, but keep the correlation between CL
and F1. Now I ran into problems when coding the $OMEGA BLOCK.

I figured the block to be something like:
0.1 ;CL1
0 FIX 0.1 ;CL2
0.01 0.01 0.1 ;F1

The error message that appears is:
a covariance is zero, but the block is not a band matrix

I assume that this means that I am not allowed to fix the correlation
between the two clearance-omegas to zero. However, it would be unreasonable
to allow a correlation, because the omegas belong to different
subpopulations, so there can't be a correlation. On the other hand, I did
not include subpopulations for F1, so how can I keep this correlation to
both CL-subgroups?

Any thoughts on this would be highly appreciated!
Best wishes

Dr. Nele Plock
Pharmacometrics -- Modeling and Simulation

Nycomed GmbH
Byk-Gulden-Str. 2
D-78467 Konstanz, Germany

Fon: (+49) 7531 / 84 - 4759
Fax: (+49) 7531 / 84 - 94759

mailto: nele.plock

County Court: Freiburg, Commercial Register HRB 701257
Chairman Supervisory Board: Charles Depasse
Management Board: Dr. Barthold Piening, Gilbert Rademacher, Dr. Anders

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Received on Wed Apr 15 2009 - 09:47:35 EDT

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