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RE: NONMEM 7.1.0 Bug Alert #2 - Cumulative Bug List

From: Michael Karol <MKarol>
Date: Tue, 10 Nov 2009 13:56:30 -0500

Tom:

   When can we expect release of 7.1.1 ?

Regards, 
Michael
-------------------------------------------------------------
Michael D. Karol, Ph.D.
Senior Director, Clinical Pharmacology
Synta Pharmaceuticals Corp.
45 Hartwell Ave
Lexington, MA 02421
 
MKarol
(781) 541-7952


-----Original Message-----
From: owner-nmusers
On Behalf Of Ludden, Thomas
Sent: Tuesday, November 10, 2009 9:46 AM
To: nmusers
Subject: [NMusers] NONMEM 7.1.0 Bug Alert #2 - Cumulative Bug List

NONMEM 7.1.0 Bug List as of 05NOV2009

This list is also available at
ftp://nonmem.iconplc.com/Public/nonmem7/Release_Notes_Plus/

Fixed code for NONMEM 7.1.0 will be made available at a future time
with the release of 7.1.1.

The NONMEM Development Team
________________________________________________________________________
NONMEM
1. There is a bug in NONMEM VI 1.x & 2.0 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

Workaround:
None is available.

2. When single subject data was analyzed, NONMEM VI would impose
the use of the SLOW gradient feature, without this option appearing
explicitly on the $ESTIMATION record. In NONMEM 7.1.0, the SLOW
option is not imposed unless it appears on the $ESTIMATION record.
Small differences in results may occur for some single subject
analyses.

Workaround:
Include the SLOW option on the $ESTIMATION record.

3. In NONMEM 7.1.0, whenever MAXEVAL=0 appears on the $ESTIMATION
record, the table number in the raw output files is 0.

Workaround:
Use MAXEVAL=1 on the $ESTIMATION record if it is important to correct
the table number.

4. If the SAEM or MCMC method is the first method used in a
problem and the INTERACTION option is not specified (even with
homoscedastic residual error), the model initialization will not
be complete and will result in a failed analysis.

Workaround:
Always specify INTERACTION for the new methods. This option does
not impact the analysis time.

5. In NONMEM 7.1.0, if a problem is run, completed and saved in an
msf file and then later the msf file is used to implement the
Covariance Step without an Estimation Step, the results would not
be consistent with those obtained when both Estimation and
Covariance Steps were implemented in the same control stream.

Workaround:
Add an Estimation Step to the control stream using the msf file to
implement the Covariance Step, and specify the same method that
was used when the msf was created.
E.g.,

$MSFI myfile.msf
$EST METHOD=0 MAXEVAL=0
$COV

or

$MSFI myfile.msf
$EST METHOD=0 MAXEVAL=1
$COV

6. For METHOD=MCMC the inverse covariance matrix of the estimates
is not calculated. The inverse covariance matrix associated with
the MCMC method that is displayed in the <root>.coi file should be
ignored.

_________________________________________________________
PREDPP

1. There is a PREDPP bug in pr/PRED.for (NONMEM VI 2.0) 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.


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, in the
absence of the bug, is relatively complex. A user planning to
incorporate the SS data item into a data set should review
Section V.F in NONMEM Users Guide VI, PREDPP, and Chapter 6,
Section 8.2.3 of Guide V, Introductory Guide.

___________________________________________________________

NMTRAN

1. In some cases the $COVARIANCE record may be incorrectly parsed
resulting in an NM-TRAN error message.

Workarounds:
1) Place the $COVARIANCE record prior to the $ESTIMATION record in
the control stream.

Or

2) Include the option COND or UNCOND on the $COVARIANCE record.
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Received on Tue Nov 10 2009 - 13:56:30 EST

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