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Re: NONMEM message

From: Nick Holford <n.holford>
Date: Thu, 13 Nov 2008 22:43:47 +1300

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: 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
>>
>>
>>

--
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 - 04:43:47 EST

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