Re: 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 ----------------------------------------------- Juergen Bulitta, PhD, Post-doctoral Fellow Pharmacometrics, University at Buffalo, NY, USA Phone: +1 716 645 2855 ext. 281, [EMAIL PROTECTED]