See attached message.
On Wed, 2 Jan 2008 23:51:51 -0800, "John Lukas" <[EMAIL PROTECTED]>
said:
> 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
>
>
> ________________________________
>
Quoted reply history
> 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
>
>
>
>
>
--
Alison Boeckmann
[EMAIL PROTECTED]
I was concerned about this issue, and John was kind enough to send me a
control stream and data set. I cannot reproduce his results on my Sun
workstation, but I do see a difference between NONMEM V and NONMEM VI
minimum as NONMEM V. Surprisingly, the minimum value of the objective
function is higher with VI than with V. According to Tom Ludden, "it is
more common, when results differ between V and VI using a conditional
estimation method, that the NONMEM VI results (without SLOW) are
associated with a lower objective function value rather than a higher
value. At least that has been our experience."
My NONMEM V runs are consistent (model A vs. model B).
My NONMEM VI runs are consistent (model A vs. model B).
NONMEM VI reaches a different minimum than does NONMEM V unless the
SLOW option of $ESTIM is used, in which case it reaches the same
minimum as NONMEM V.
There are 130 subjects with ages from <1 to 96. Of these, 31 are under
the age of 21. Age and WT are clearly correlated till roughly that
age, after that there is no strong correlation. (I looked a simple
NONMEM scatter of AGE vs. WT).
I cannot explain why NONMEM VI results differs from NONMEM V, but in my
runs it has nothing to do with the order of thetas (model A vs. model
B.) It is always disturbing when NONMEM VI gets a different result than
NONMEM V, but this is a known problem and I cannot see that this
particular case is evidence for a bug in VI.
Legend for results:
"VI" is NONMEM VI 1.0
"V" is NONMEM V 1.0
"A" uses the model
COV2=THETA(4)*(AGE-36)+THETA(5)*(WT-65)
"B" uses the model
COV2=THETA(5)*(AGE-36)+THETA(4)*(WT-65)
"s" is SLOW
"n" is SLOW option omitted (default).
Minimum value of the objective function:
VInA: mm 45.414
VInB: mm 45.413
VIsA: mm 33.771
VIsB: mm 33.771
V__A: mm 33.771
V__B: mm 33.771
Final values of THETA:
VInA: tf -3.27E-01 -2.85E-02 2.88E-04 -1.04E-03 1.44E-02
VInB: tf -3.27E-01 -2.85E-02 2.88E-04 1.44E-02 -1.05E-03
VIsA: tf -3.13E-01 -2.65E-02 2.87E-04 -1.40E-03 1.45E-02
VIsB: tf -3.13E-01 -2.65E-02 2.87E-04 1.45E-02 -1.40E-03
V__A: tf -3.13E-01 -2.65E-02 2.86E-04 -1.40E-03 1.45E-02
V__B: tf -3.14E-01 -2.65E-02 2.87E-04 1.45E-02 -1.38E-03
Final value of OMEGA:
VInA: of 1.57E-02
VInB: of 1.57E-02
VIsA: of 2.49E-01
VIsB: of 2.49E-01
V__A: of 2.49E-01
V__B: of 2.50E-01
Final value of SIGMA:
VInA: sf 4.51E-01
VInB: sf 4.51E-01
VIsA: sf 2.42E-01
VIsB: sf 2.42E-01
V__A: sf 2.43E-01
V__B: sf 2.42E-01
I use a Sun Solaris 2 workstation, using
f90 (Forte Developer 7 Fortran 95 7.0 Patch 111714-04 2002/12/17)