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Re: OMEGA BLOCK with mixture model?

From: andreas.krause
Date: Wed, 15 Apr 2009 12:06:05 +0200

Nele,

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


-----

Andreas Krause, PhD
Lead Scientist Modeling and Simulation

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




nele.plock
Sent by: owner-nmusers
04/14/2009 05:08 PM

To
nmusers
cc

Subject
[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:
$OMEGA BLOCK(3)
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
Nele
______________________________________________________________

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
http://www.nycomed.com

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





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Received on Wed Apr 15 2009 - 06:06:05 EDT

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