RE: FW: NONMEM VI 2.x Bug Alert #2 and NONMEM 7.1.0 Bug Alert #1
Dear Tom:
I have a question on the different results from NM5.1 vs. NM6.20. I have PK
data fitted by a two-compartment open model with first-order absorption.
The results from NM5.10 and NM6.20 are quite different in that all BSV of
CL/F, V2/F, V3/F, etc were smaller, yet the proportional residue was higher
(49% vs. 36%) in NM5.10. It appears to me that the results from NM6.20 has
better estimates than that from NM5.10. However, the objective function
from NM5.1 is much smaller than that from NM6.20. Can we compare the
objective function from these two version of NM? I know there were changes
made in the Laplacian method and FOCI.
Best regards,
Sam
Quoted reply history
-----Original Message-----
From: [email protected] [mailto:[email protected]] On
Behalf Of Ludden, Thomas
Sent: Friday, October 23, 2009 4:00 PM
To: [email protected]
Subject: [NMusers] FW: NONMEM VI 2.x Bug Alert #2 and NONMEM 7.1.0 Bug Alert
#1
It has been found that the NONMEM VI 2.x fix for the SS=2 bug described
in the previous Bug Alert (see below) can, in certain cases, result in:
1) the program hanging when the initial steady-state feature is used
with SS=2
2) the failure to provide the intended steady-state dose when SS=2 is
used.
At this time, problem 2) has only been observed with ADVAN12.
If you have made the fix to PRED.for or installed the fixed routine
provided at the IDS ftp site it should be backed out.
Tom
Thomas M. Ludden Ph.D.
Vice-President, Pharmacometrics R&D
ICON Development Solutions
Tel: + 1 410 696 3040
Mob: + 1 410 258 2411
Fax: + 1 410 480 0776
Email: [email protected]
Web: www.icondevsolutions.com
-----Original Message-----
From: Ludden, Thomas
Sent: Thursday, October 15, 2009 3:09 PM
To: Nmusers
Subject: NONMEM VI 2.x Bug Alert #2 and NONMEM 7.1.0 Bug Alert #1
========================================================================
==========
Two bugs that affect NONMEM VI and NONMEM 7.1.0 have recently been
discovered.
Fixes and fixed routines are available for NONMEM VI 2.x as
described below. After all code changes listed here and in NONMNEM VI
2.0
Bug Alert #1 (see
ftp://nonmem.iconplc.com/Public/nonmem/NONMEM_VI_buglist/NONMEM_VI_2.1_B
ug_List.txt
for a cumulative list) are made, the nm\BLKDAT.for routine should be
edited.
The value of LEV in BLKDAT should be changed to 2.2. All routines in
nm, pr and tr
directories should be recompiled. Rerun the CDsetup6.bat or SETUP
script from the
installation directory using the same arguments used for the original
installation
with the exception of the last argument. This argument should be y to
indicated the
need to recompile.
Fix code for NONMEM 7.1.0 will be made available soon.
The NONMEM Development Team
_______________________________________________________________________
PREDPP
There is a PREDPP bug in pr/PRED.for (NONMEM VI 2.x) and pr/PRED.f90
(NONMEM 7.1.0) that affects the behavior of the steady-state (SS) data
item when:
1) SS has a value of 2
and
2) the record with SS=2 precedes all other records with a non-zero SS
data item in an individual record or after a reset record, EVID=3 or 4.
The bug causes the steady state dose to be applied twice.
Fix for NONMEM VI 2.x:
In pr/PRED locate
IF (ISSNOW.NE.0) THEN
ISSNOW=0
GO TO 2200
ENDIF
Change the test from .NE. to .GE.
IF (ISSNOW.GE.0) THEN
ISSNOW=0
GO TO 2200
ENDIF
A fixed subroutine is available at
ftp://nonmem.iconplc.com/Public/nonmem/NONMEM_VI_fixed_routines/
To access this folder point your browser to
ftp://nonmem.iconplc.com/Public/nonmem/ and login.
user: nonmemvi
password: updates
then open the folder named NONMEM_VI_fixed_routines.
The fixed PRED.for routine is in the subfolder named PREDPP_14OCT2009
Workaround:
1) If SS=2 is the first record of the individual
record, then a work around is to specify the AMT value on the
affected record to be one-half the intended dose.
Or, the $PK block could be modified instead. Suppose there is only
one steady state dose record having SS=2, and the dose is for
compartment 1.
Add:
$PK
F1=1
IF (SS.EQ.2) F1=.5
2) If SS=2 is used in a subsequent record (with a change in TIME) and it
is not preceded by a record with a non-zero value for SS then there is
no
workaround. This situation occurs when a transient dose precedes the
steady
state dose.
Suggestion: The behavior of the steady-state data item, even in the
absence of the bug, is relatively complex. A user planning to
incorporate the
SS data item into a data set should review Chapter V, Section F of
NONMEM Users
Guide VI, PREDPP, and Chapter 6, Section 8.2.3 of Guide V, Introductory
Guide.
__________________________________________________________________
NONMEM
There is a bug in NONMEM VI 1.x & 2.x and NONMEM 7.1.0 that results in
the spurious error message below, or a similar message, when certain
band symmetric matrices are defined in $OMEGA.
PROGRAM TERMINATED BY OBJ
OMEGA ESTIMATED TO BE SINGULAR
MESSAGE ISSUED FROM ESTIMATION STEP
AT INITIAL OBJ. FUNCTION EVALUATION
Fix for NONMEM VI 2.x requires changes to several subroutines.
The fixed subroutines are available at
ftp://nonmem.iconplc.com/Public/nonmem/NONMEM_VI_fixed_routines/
To access this folder point your browser to
ftp://nonmem.iconplc.com/Public/nonmem/ and login.
user: nonmemvi
password: updates
then open the folder named NONMEM_VI_fixed_routines.
The fixed CN.for, CN1.for, CN2.for, RESCN.for, and RSCN.for routines are
in the subfolder named NONMEM_14OCT2009.
Workaround:
None is available.