NONMEM Users Network Archive

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Re: OMEGA BLOCK with mixture model?

From: Nick Holford <n.holford>
Date: Wed, 15 Apr 2009 14:28:04 +0200

Hi,

It is indeed a nuisance to have to renumber all the ETAs if you have a
complex model and you change the sequence of $OMEGA.

You can of course choose to use the awk script which comes with WFN
(http://wfn.sourceforge.net) translate an extended NM-TRAN control
stream, which uses parameter names for THETA, ETA and EPS (or ERR)
references in the abbreviated code, into a standard NM-TRAN format with
all the renumbering taken care of automatically.

This awk script can be used with any installation of NONMEM that runs an
operating system that has a version of awk available. It is not
necessary to use WFN. Typically a one or two line change is needed in
your favourite script for running NONMEM to allow the translation to
take place.

Nick

andreas.krause
>
> 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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--
Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand
n.holford
mobile: +33 64 271-6369 (Apr 6-Jul 17 2009)
http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford

Received on Wed Apr 15 2009 - 08:28:04 EDT

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