Re: [NMusers] Minimization terminated ?

Navin,

NONMEM is quite unreliable when it comes to deciding if it has converged. Minor changes in initial estimates with essentially no difference in the final estimates and OBJ can produce 1) SUCCESSFUL + COVARIANCE 2) SUCCESSFUL + FAILED COVARIANCE 3) TERMINATED.

My guess this is because of numerical rounding errors (not the ones that NONMEM refers to in its error message) so that essentially it becomes a random event which of these outcomes you get. The bottom line is NOT to pay attention to NONMEM's declarations of success but to focus on whether the parameters make sense, whether the fits look good, does a VPC look OK
http://www.page-meeting.org/page/page2005/PAGE2005P105.pdf
and even (if you have got lots of spare time) does the npde fail to reject the null.
http://www.page-meeting.org/pdf_assets/9146-ecomets_a4page07.pdf

Several investigations of bootstraps have shown that it makes little difference if you include successful runs only or if you include all runs. The advantage of all runs is that is simpler to process the results and perhaps the confidence intervals are more precisely estimated
because you have more runs.
http://www.cognigencorp.com/nonmem/nm/99jul152003.html
http://www.nature.com/clpt/journal/v77/n2/abs/clpt200514a.html
http://www.page-meeting.org/?abstract=992

Nick

navin goyal wrote:
>
> Dear NM Users,
> I am using trying to model some POPPK data in NONMEM vi
> Sometimes I get the following message in the output file
>
> MINIMIZATION TERMINATED
> DUE TO ROUNDING ERRORS (ERROR=134)
> NO. OF FUNCTION EVALUATIONS USED: 1103
> NO. OF SIG. DIGITS UNREPORTABLE
>
> But when I change the SIGDIGITS to a lower value the minimization is successful. What exactly
is happening in this case ? Is there something I am missing out?
>
> what about the parameter estimates obtained in such a run ?
>
> Another question related to this is that when I bootstrap a model in wings for nonmem WFN, I
get few runs with similar message where in it also says the same message as above
..MINIMIZATION TERMINATED DUE TO ROUNDING ERRORS (ERROR=134) NO. OF SIG. DIGITS UNREPORTABLE.
> This means that I discard these runs from the calculations ?
>

--
Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand
n.holford_at_auckland.ac.nz tel:+64(9)373-7599x86730 fax:+64(9)373-7090
www.health.auckland.ac.nz/pharmacology/staff/nholford
Received on Fri Jul 20 2007 - 17:04:04 EDT