Re: Problems with an apparent compiler-senstive model

From: Nick Holford n.holford@auckland.ac.nz Subject: Re: [NMusers] Problems with an apparent compiler-senstive model Date: Wed, 02 Aug 2006 15:25:26 +1200 Leonid, The not so slim evidence comes from 3 sources: 1. An investigation reported by Mark Gastonguay and Ahmed El-Tahtawy "Minimization status had minimal impact on the resulting BS [bootstrap] parameter distributions" http://metrumrg.com/publications/Gastonguay.BSMin.ASCPT2005.pdf 2. An investigation of 13 data sets reported by myself with Carl Kirkpatrick and Steve Duffull "NONMEM Termination Status is Not an Important Indicator of the Quality of Bootstrap Parameter Estimates" http://www.page-meeting.org/default.asp?abstract=992 3. The work described in this thread by Mark Sale and Tom Ludden in which NONMEM converged about 50% of the time with identical data (but randomly re-ordered) and identical model. The parameter estimates were essentially identical whether or not NONMEM claimed to converge. All of these experimental investigations has found that NONMEM's own diagnosis of successful minimization is not a reliable indicator of the quality of the parameter estimates. Contrary evidence that NONMEM is good at diagnosing the quality of the fit is not known to me. It seems to me that support for NONMEM doing a good job here is based on "pretty slim evidence". If you wish to make claims such as "non-convergence indicates problems with the model or with the data" then I ask you to provide some concrete experimental evidence for this assertion :-) Nick -- Nick Holford, Dept Pharmacology & Clinical Pharmacology University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand email:n.holford@auckland.ac.nz tel:+64(9)373-7599x86730 fax:373-7556 http://www.health.auckland.ac.nz/pharmacology/staff/nholford/