NONMEM Users Network Archive

Hosted by Cognigen

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
(CL1,CL2).

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

 

Hope this helps.

 

Christian

****************************************************************************
*******************************************

Christian Laveille

Senior Consultant

Exprimo NV

 

Tel: +33 474 68 81 84

Mob: +33 610 55 31 09

Fax: +33 959 106 261

Email: christian.laveille

Web: www.exprimo.com <http://www.exprimo.com/>

 

This e-mail is confidential. It is also privileged or otherwise protected by
work product immunity or other legal rules. The information is intended to
be for use of the individual or entity named above. If you are not the
intended recipient, please be aware that any disclosure, copying,
distribution or use of the contents of this information is prohibited. You
should therefore delete this message from your computer system. If you have
received the message in error, please notify us by reply e-mail. The
integrity and security of this message cannot be guaranteed on the Internet.
Thank you for your co-operation.

 

  _____

From: owner-nmusers
Behalf Of Bob Leary
Sent: mercredi 15 avril 2009 15:16
To: andreas.krause
nmusers
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
Fellow

Pharsight - A CertaraT Company

5625 Dillard Dr., Suite 205
Cary, NC 27511

Phone/Voice Mail: (919) 852-4625, Fax: (919) 859-6871
Email: bleary

This email message (including any attachments) is for the sole use of the
intended recipient and may contain confidential and proprietary
information. Any disclosure or distribution to third parties that is not
specifically authorized by the sender is prohibited. If you are not the
intended recipient, please contact the sender by reply email and destroy all
copies of the original message.

-----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?


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





----------------------------------------------------------------------
Proprietary or confidential information belonging to Nycomed Group may
be contained in this message. If you are not the addressee indicated
in this message, please do not copy or deliver this message to anyone.
In such case, please destroy this message and notify the sender by
reply e-mail. Please advise the sender immediately if you or your
employer do not consent to Internet e-mail for messages of this kind.
Opinions, conclusions and other information in this message that
pertain to the sender's employer and its products and services
represent the opinion of the sender and do not necessarily represent
or reflect the views and opinions of the employer.
----------------------------------------------------------------------

The information of this email and in any file transmitted with it is
strictly confidential and may be legally privileged.
It is intended solely for the addressee. If you are not the intended
recipient, any copying, distribution or any other use of this email is
prohibited and may be unlawful. In such case, you should please notify the
sender immediately and destroy this email.
The content of this email is not legally binding unless confirmed by letter.
Any views expressed in this message are those of the individual sender,
except where the message states otherwise and the sender is authorised to
state them to be the views of the sender's company. For further information
about Actelion please see our website at http://www.actelion.com


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

The NONMEM Users Network is maintained by ICON plc. Requests to subscribe to the network should be sent to: nmusers-request@iconplc.com.

Once subscribed, you may contribute to the discussion by emailing: nmusers@globomaxnm.com.