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NONMEM VI 2.x Bug Alert #2 and NONMEM 7.1.0 Bug Alert #1 - Revised

From: Ludden, Thomas <Thomas.Ludden>
Date: Mon, 9 Nov 2009 14:37:59 -0500


Two bugs that affect NONMEM VI and NONMEM 7.1.0 have 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.

Fixed code for NONMEM 7.1.0 will be made available at a future time.

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.

The fix for NONMEM VI 2.x requires two code changes:

In pr/PRED locate

IF (ISSNOW.NE.0) THEN
ISSNOW=0
GO TO 2200
ENDIF

Change the test from .NE. to .GT. Note that this change is different
from the one described in the original bug alert.

IF (ISSNOW.GT.0) THEN
ISSNOW=0
GO TO 2200
ENDIF

In pr/SSS locate

        IF (II.NE.JJ.AND.((ISSNOW.EQ.0.AND.EVTREC(N,JSS).EQ.2)
     x .OR.ISSNOW.EQ.2)) THEN

Change ISSNOW.EQ.0 to ISSNOW.LE.0

        IF (II.NE.JJ.AND.((ISSNOW.LE.0.AND.EVTREC(N,JSS).EQ.2)
     x .OR.ISSNOW.EQ.2)) THEN

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 PRED.for and SSS.for routines are in the subfolder named
PREDPP_4NOV2009

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.
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Received on Mon Nov 09 2009 - 14:37:59 EST

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