some issues about NONMEM

From: Xiaofeng Wang - xiaofeng.wang@bms.com Subject: [NMusers] some issues about NONMEM Date: 2/10/2004 10:23 AM Dear everyone: Recently I was advised about some tricky issues existing in NONMEM. I would like to know more about these issues from you. 1 About NONMEN patches to correct the bugs in NONMEM I was informed that NONMEN has several bugs and there are patches to correct these bugs. Also, I was advised that FDA will not accept the results got from NONMEN without being corrected by these patches. But these patches are not available to the public except a few people in this community. Therefore, my questions are: a) If FDA will not accept the results, is there any guideline issued by FDA which patches that a user has to have? b) Has Globomax advised NONMEM users on these patches? c) Could those people who aware these bugs and have patches make their knowledge public, so the community can be benifited? 2 About FO and FOCE method I was also advised to use the results from FOCE, since the results from FO are not countable (type I error, etc)... From FO and FOCE algorithm, it can see that FO is applicable to the situation where interindividual variability is small, while FOCE handles the case when inter-individual variability is large. Therefore, results from both FO and FOCE should be close if the interindividual variability is small. Thus, I would like to know more why results from FO should not be accepted even when interindividual variability is small. I have a few publications discussing about the type I error. However, when should we consider the Type I error? I will read these publications but wish someone could clarify a little bit more before I start to read. In addition, if results from FO are different from FOCE, permutation (?) has to be done to check the problem. I have zero knowledge about it. What is this permutaion method? How to conduct it? Thank you, xiaofeng