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RE: NONMEM message

From: Martin Fransson <Martin.Fransson>
Date: Thu, 13 Nov 2008 11:36:30 +0100

Dear Mitsuo

This previous, quite comprehensive post by William Bachman (orig. Ken
Kowalski) may help to interpret the COV-step.

http://www.cognigencorp.com/nonmem/nm/99may012003.html

Best regards
Martin Fransson


> -----Original Message-----
> From: owner-nmusers
> On Behalf Of Higashimori, Mitsuo
> Sent: den 13 november 2008 06:27
> To: Nick Holford; nmusers
> Subject: RE: [NMusers] NONMEM message
>
> Dear Nick,
>
> Thank you for your advice.
> In my case, covariance matrix also was displayed without any problem. So,
> I could check whether covariance matrix is reasonable or not, but it was
> difficult to interpret it for me. Therefore, I wanted to know if this
> message is important. In addition, I mused if such a result should be
> excluded from listing and summarizing the result files after bootstrap.
>
> Best regards,
> Mitsuo
>
>
> > -----Original Message-----
> > From: owner-nmusers
> > [mailto:owner-nmusers
> > Sent: Thursday, November 13, 2008 1:58 PM
> > To: nmusers
> > Subject: Re: [NMusers] NONMEM message
> >
> >
> > Mitsuo,
> >
> > This is a special kind of NONMEM error message:
> >
> > MINIMIZATION SUCCESSFUL
> > HOWEVER, PROBLEMS OCCURRED WITH THE MINIMIZATION.
> > REGARD THE RESULTS OF THE ESTIMATION STEP CAREFULLY, AND
> > ACCEPT THEM ONLY
> > AFTER CHECKING THAT THE COVARIANCE STEP PRODUCES REASONABLE OUTPUT.
> >
> > because the message itself seems to be an error.
> >
> > Whenever I see this message the covariance step does not run
> > therefore I
> > cannot decide if the covariance step produces reasonable output. I
> > therefore ignore this message after the word SUCCESSFUL.
> >
> > The numerical oddities in NONMEM are well known so I am not surprised
> > that raising women to a power make them have a different
> > influence from
> > distinguishing them explicitly from men. The power approach is
> > computationally much less efficient than a conditional
> > expression so I
> > never use it if I can avoid it.
> >
> > Nick
> >
> > Higashimori, Mitsuo wrote:
> > > Dear all,
> > >
> > > I have a following error(?) massage on a poplation analysis
> > using NONMEM VI.
> > >
> > > 0MINIMIZATION SUCCESSFUL
> > > HOWEVER, PROBLEMS OCCURRED WITH THE MINIMIZATION.
> > > REGARD THE RESULTS OF THE ESTIMATION STEP CAREFULLY, AND
> > ACCEPT THEM ONLY
> > > AFTER CHECKING THAT THE COVARIANCE STEP PRODUCES REASONABLE OUTPUT.
> > >
> > > I found it when I described a control stream to assess sex
> > difference on oral clearance as shown in below,
> > >
> > > TVCL = THETA(1) * THETA(2) ** SEX
> > > where SEX=0 for male and SEX=1 for female.
> > >
> > > This message was displayed without any error message. It
> > was not dissapeared even though I changed the initial
> > parameters. However, it was solved when I changed the model
> > definition. For example,
> > >
> > > TVCL = THETA(1)
> > > IF (SEX.EQ.1) TVCL = THETA(2)
> > >
> > > Could you please let me know some details regarding the
> > message. Especially, I'd like to know
> > >
> > > 1. What impact does this error message give the analysis result?
> > > 2. Why does it depend on the model definition?
> > >
> > > Thanks,
> > >
> > > _/ _/ _/ Mitsuo Higashimori, Ph.D.
> > > _/ _/ _/ Pharmacokinetic Group, Early Phase Development Department
> > > _/ _/ _/ Clinical Division, Research & Development
> > > _/ _/ _/ AstraZeneca K.K.
> > > _/ _/ _/ E-mail: Mitsuo.Higashimori
> > >
> > >
> > >
> > >
> >
> > --
> > Nick Holford, Dept Pharmacology & Clinical Pharmacology
> > University of Auckland, 85 Park Rd, Private Bag 92019,
> > Auckland, New Zealand
> > n.holford
> > http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford
> >
> >

Received on Thu Nov 13 2008 - 05:36:30 EST

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