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: [EMAIL PROTECTED] 
> [mailto:[EMAIL PROTECTED] Behalf Of Nick Holford
> 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: [EMAIL PROTECTED]
> >
> >
> >  
> >   
> 
> -- 
> Nick Holford, Dept Pharmacology & Clinical Pharmacology
> University of Auckland, 85 Park Rd, Private Bag 92019, 
> Auckland, New Zealand
> [EMAIL PROTECTED] tel:+64(9)923-6730 fax:+64(9)373-7090
> http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford
> 
> 

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