John/All,
Although your problem has been solved, I am not sure this should be the end of this topic or the beginning of a more general discussion on how much we can 'trust' NONMEM and what we can do to standardise at least the basic algorithms we use to analyse data in our scientific community to get comparable and consistent results between individuals and groups. I am very concerned about findings like this: it seems to me that you only found out by chance that there was something wrong with your first fit and you only spotted the error because you used a simple model. How often does something like this happen without us noticing when we use more complex models? I had a similar issue recently when I found out that with another simple model NMV always gave wrong predictions for the first ID in the dataset, whereas NMVI (using exactly the same code) didn't. I still don't know why this happened, but I don't think I would have spotted it had I not compared the 2 NM versions which is obviously not something I would like to do for every analysis I perform. So, this brings me to my more specific point/comment/question: I am intrigued by your PS that you are 'aware of other *important* inconsistencies between version VI and V from university colleagues working on a PK problem with FOCE...', and was wondering if anyone has collated a list of these inconsistencies and also recommendations how to spot and solve them. For example, should we now always use the SLOW option in NMVI (to be honest I had never come across this before) or at least compare SLOW with NOSLOW for every analysis? Thanks, Piet Piet H. van der Graaf Preclinical M&S Pfizer IPC 654 Sandwich CT13 9NJ ++-44-1304-648330 ________________________________ From: [EMAIL PROTECTED] [mailto:[EMAIL PROTECTED] On Behalf Of John Lukas Sent: 03 January 2008 07:52 To: [email protected] Subject: RE: [NMusers] RE: re: bug in NONMEM VI? Hi all, Bill is right. SLOW in NONMEM version 6 works fine giving the better answer in the minimization problem (FO method). Peter is also right in that COV3 and COV4 are more correlated than with the others! I suppose NONMEM version 5 was inherently SLOW (!)? Thanks and have a great new year! John John C Lukas Strategic Consulting Services Pharsight Corp. line: + 33 492 726 495 cell: + 33 626 496 777 ________________________________ From: Bonate, Peter [mailto:[EMAIL PROTECTED] Sent: Wed 1/2/2008 10:03 PM To: Bill Bachman; John Lukas; [email protected] Subject: RE: [NMusers] RE: re: bug in NONMEM VI? I'd also like to see how correlated COV3 and COV4 are. This may be a collinearity issue. pete bonate Peter L. Bonate, PhD, FCP Genzyme Corporation Senior Director Clinical Pharmacology and Pharmacokinetics 4545 Horizon Hill Blvd San Antonio, TX 78229 USA [EMAIL PROTECTED] phone: 210-949-8662 fax: 210-949-8219 crackberry: 210-315-2713 ________________________________ From: [EMAIL PROTECTED] [mailto:[EMAIL PROTECTED] On Behalf Of Bill Bachman Sent: Wednesday, January 02, 2008 2:38 PM To: 'John Lukas'; [email protected] Subject: RE: [NMusers] RE: re: bug in NONMEM VI? Have you tried both of these runs using the SLOW option on the estimation record? ________________________________ From: [EMAIL PROTECTED] [mailto:[EMAIL PROTECTED] On Behalf Of John Lukas Sent: Wednesday, January 02, 2008 2:36 PM To: [email protected] Subject: [NMusers] RE: re: bug in NONMEM VI? ________________________________ From: John Lukas Sent: Mon 12/17/2007 11:51 PM To: [email protected] Subject: re: bug in NONMEM VI? Dear Nmusers, A simple LME model run using NM version VI, FO method, with 4 covariates (5 THETA's) as, . . $PRED SUM1=THETA(2)*COV1+THETA(3)*COV2 SUM2=THETA(4)*COV4+THETA(5)*COV3 TLAU=THETA(1)+SUM1+SUM2 F=TLAU+ETA(1) Y=F+EPS(1) $THETA 4 .1 .1 .1 .1 $OMEGA .1 $SIGMA .1 $ESTIMATION MAXEVALS=1900 PRINT=5 METHOD=0 (let's call this FIT A) gave a different fit from another (FIT B) where only the order of THETA( 4) and 5 was reversed, all else kept the same, as, . . SUM2=THETA(5)*COV4+THETA(4)*COV3 . . (even more strange, FIT B, the reversed order run, proved to be the good run!) NONMEM version V had the same result for both FITS A and B, as expected (and same as FIT B from version 6). FOCE gave good answers always in both NONMEM version V and version VI. But, the question remains about that dependence on ordering of the THETAs with the FO method for version VI. Any comments? Has there been discussion on this earlier that I missed? Thanks in advance. John PS I am aware of other *important* incosistencies between version VI and V from university colleagues working on a PK problem with FOCE... John C Lukas Strategic Consulting Services Pharsight Corp. line: + 33 492 726 495 cell: + 33 626 496 777
