Mitsuo,
I have no idea how to decide if the covariance matrix is reasonable or
not. I leave that to statisticians who are trained to see patterns in
random numbers.
The question of what to do with bootstrap results has been well
investigated in the past. The answer is just ignore all NONMEM's
termination messages except the one about exceeding maximum function
evaluations.
Nick
Higashimori, Mitsuo wrote:
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
--
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
