RE: RE: re: bug in NONMEM VI?
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
Quoted reply history
________________________________
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