RE: Successful minimization and covariance

________________________________________ From: [email protected] [[email protected]] on behalf of Ayyappa Chaturvedula [[email protected]] Sent: Thursday, May 24, 2012 2:33 PM To: [email protected] Subject: [NMusers] Successful minimization and covariance Dear Group, This is a topic that has been discussed and different schools of thinking exist to my knowledge. But, I want to restate my case and get some opinions. The question is about how important to have successful minimization and covariance if diagnostics make sense. I have developed a two compartment model with a Phase 3 trial data and minimization was successful but covariance step was not. I went ahead and did a 1000 run bootstrap and wanted to get the confidence intervals of parameters. There are 60% runs that are not successfully minimized and many other do not have covariance step successful. I put together CI from the runs that have successful minimization and also including all 1000 runs. There is no difference in the parameter estimate or the confidence interval (less than 5% change in numbers). The model diagnostics look good including VPC, NPDE plots, basic gof and a simulation to explain another trial data. Now, my question is in this particular case do I have to worry further to make the successful covariance step and increase the number of runs that gets successfully minimized in the bootstrap even though I cannot see much difference in the parameter estimates, diagnostics? My bottom line is not going to change in anyway. I appreciate your expert opinions. Regards, Ayyappa