Re: [NMusers] Minimization terminated ?

Dear Nick, Dear Mahesh, Dear Mark,

I also noticed that SIGDIG=3 is more reliable in NONMEM VI than it was in
NONMEM V. In some bootstrap runs I did in NONMEM V, SIGDIG=5 gave
lower objective functions than SIGDIG=3 for more complex models. For
simpler and stable models, both SIGDIG choices yielded the same OBJ.

I do not know what exactly is affected in the estimation process in NONMEM
when changing SIGDIG=3 to SIGDIG=5. However, I think to remember that
the stepsize of the path on which NONMEM minimizes the OBJ is larger for
SIGDIG=3 than for SIGDIG=5. A smaller stepsize during the estimation process
seems preferable which might have been the reason why the SIGDIG=5
performed better in more complex bootstrap problems.
Mahesh, I would therefore tend to use SIGDIG=5, even though this is likely
to cause a non-successful termination message.

I am not sure, if a successful termination message and a successful $COV
step should be a criterion for publishing a model. As Nick wrote, WinBugs
and Monolix do not provide such a termination message.
There is a convergence test in the latest version of S-Adapt and this is
helpful for the user. The convergence criterion in NPAG is based on a change
in the OBJ. However, as far as I know, nonparametric algorithms do not
provide standard errors of parameter estimates, unless one bootstraps.

I also prefer to have successful convergence messages and confidence
intervals. However, some programs do not report convergence messages,
because there does not seem to be a natural way to tell a model converged
successfully or not.

In my opinion the criterion of qualifying a model depends on the planned
application of the model. Using a model for simulation purposes or showing
that two groups of patients have a significantly different average Michaelis-Menten
constant most likely requires different methods of model qualification.

Best regards
Juergen

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Juergen Bulitta, PhD, Post-doctoral Fellow
Pharmacometrics, University at Buffalo, NY, USA
Phone: +1 716 645 2855 ext. 281, j_at_bulitta.com
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Received on Sat Jul 21 2007 - 20:05:34 EDT