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Re: NONMEM message

From: Nick Holford <n.holford>
Date: Thu, 13 Nov 2008 17:58:19 +1300

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 Wed Nov 12 2008 - 23:58:19 EST

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