RE: [NMusers] Peculiar output file - no doubt I'm missing something obvious - help requested

Hi Steven,

 

I think this problem was indeed captured by NONMEM, but at the posthoc step.
With FO, there is no attempt to estimate individual parameters while
estimating the population parameters. Only after finding the final
population parameter estimates, which may be successful, is an attempt to
estimate individual parameters made if requested (that's why it is called
"POSTHOC").

 

Working with Volumes and Clearances, as opposed to micro constants, usually
makes the parameters easier to constrain appropriately and keep you away
from problems like the one encountered here.

 

Best regards,

Mats

 


Mats Karlsson, PhD
Professor of Pharmacometrics
Div. of Pharmacokinetics and Drug Therapy
Dept. of Pharmaceutical Biosciences
Faculty of Pharmacy
Uppsala University
Box 591
SE-751 24 Uppsala
Sweden
phone +46 18 471 4105
fax +46 18 471 4003
mats.karlsson_at_farmbio.uu.se

  _____


From: owner-nmusers_at_globomaxnm.com [mailto:owner-nmusers_at_globomaxnm.com] On
Behalf Of Charnick, Steven B
Sent: Wednesday, January 24, 2007 21:19
To: nmusers_at_globomaxnm.com
Subject: [NMusers] Peculiar output file - no doubt I'm missing something
obvious - help requested

 

Hi everyone,

In running a basic control stream, FO, on a relatively small .csv dataset
from a single dose trial, I get the following in my NONMEM results file:

0MINIMIZATION SUCCESSFUL
 NO. OF FUNCTION EVALUATIONS USED: 2319
 NO. OF SIG. DIGITS IN FINAL EST.: 3.5
0PRED EXIT CODE = 1


0INDIVIDUAL NO. 51 ID=0.60000000E+01 (WITHIN-INDIVIDUAL) DATA REC NO.
3

 THETA=


  3.38E+01 4.87E-01 4.30E-01 4.99E+01 9.73E+02


 OCCURS DURING SEARCH FOR ETA AT A NONZERO VALUE OF ETA


 A ROOT OF THE CHARACTERISTIC EQUATION IS ZERO BECAUSE


 K*K32 IS MUCH SMALLER THAN (K+K23+K32)**2.


 PERHAPS K OR K32 IS VERY SMALL, OR K23 IS VERY LARGE.


0PROGRAM TERMINATED BY FNLETA
 MESSAGE ISSUED FROM TABLE STEP

As you can probably see, and as was confirmed when this was run within
PDx-POP as opposed to within NONMEM itself, while minimization was
'successful', there is a problem. As a result, no tables for xpose were
generated and termination occurred. The problem may be a bound on one of
the micro constants, but I'm not sure.

Has anyone run into this before, and if so, what did you do to workaround
it?
Steven Charnick, PhD
Senior Investigator
Merck Research Laboratories
WP75B-1305
PO Box 4
West Point PA 19486

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Received on Wed Jan 24 2007 - 16:23:39 EST