RE: 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 ($OMEGA), "If FIXED appears anywhere among the list of values,
the entire block is fixed."
that Andreas pointed out is that internally Nonmem parameterizes the Omega
matrix by its
Cholesky factor elements, not the elements of the Omega matrix itself. The
Cholesky factor has the
same block diagonal structure as the Omega matrix, but due to the 'fill-in'
phenomenon during
a factorization, an internal zero element inside an Omega block will not
necessarily be preserved
as a zero in the Cholesky factor. So there is no way to force an internal
element in an Omega block to be zero.
Robert H. Leary, PhD
Fellow
Pharsight - A Certara(tm) Company
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Cary, NC 27511
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Quoted reply history
-----Original Message-----
From: [email protected] [mailto:[email protected]]on
Behalf Of [email protected]
Sent: Wednesday, April 15, 2009 6:6 AM
To: [email protected]
Cc: [email protected]
Subject: Re: [NMusers] OMEGA BLOCK with mixture model?
Nele,
going by the nonmem user manual, part VIII, p 94 ($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
[email protected] / www.actelion.com
[email protected]
Sent by: [email protected]
04/14/2009 05:08 PM
To
[email protected]
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: [email protected]
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