Dear NONMEM users,
as beginners in NONMEM we have the following questions:
- What is the meaning of "DEL" and "W" (in the subroutine $ERROR)?
- What is the meaning of "TOL" and when should it be used?
- Assumed we need to use $DES, is this possible only with NONMEM version 7 or
can we use it also in NONMEM 6?
Thanks a lot and kind regards from rainy Cologne
Paola & Lisa
<<ATTACHMENT: diGion,Paola.vcf>>
basic questions...
Paola & Lisa,
Please see responses interspersed below.
Best regards from snowy Buffalo,
Luann Phillips
Director PK/PD
Cognigen Corporation
(716) 633-3463 ext 236
di Gion, Paola wrote:
> Dear NONMEM users,
>
> as beginners in NONMEM we have the following questions:
>
> - What is the meaning of "DEL" and "W" (in the subroutine $ERROR)?
I don't think NONMEM has a standard definition for DEL and W. If you can send a copy of the code in which you saw these variables, I would be happy to explain them.
> - What is the meaning of "TOL" and when should it be used?
The TOL subroutine when either ADVAN 6, 8, 9, 10, or 13 is used.
The following section of "NONMEM USERS GUIDE
INTRODUCTION TO NONMEM 7" provides a very nice explanation of how NONMEM utilizes the value of TOL.
Section I.14 Controlling the Precision of the Gradient Evaluation
In classical NONMEM methods (First order, First order conditional
A copy of this guide can be located at: ftp://nonmem.iconplc.com/Public/nonmem7/Release_Notes_Plus/
filename: intro712.pdf
This explanation is helpful even if you're not using NONMEM 7.
> - Assumed we need to use $DES, is this possible only with NONMEM version 7 or can we use it also in NONMEM 6?
NONMEM6 and NONMEM7 have $DES. However, $DES is not always required. NONMEM supplies ADVANs to fit 1 and 2 CMT models and a few others without the use of $DES.
Refer to the nmhelp for ADVAN and TRANS.
Example:
ADVAN1 --> A one compartment model
Combined with TRANS1 --> PK parameter is K
Combined with TRANS2 --> PK parameters are CL and V
> Thanks a lot and kind regards from rainy Cologne
>
> Paola & Lisa
Paola,
Quoted reply history
On 31/03/2011 3:02 p.m., di Gion, Paola wrote:
> Dear NONMEM users,
>
> as beginners in NONMEM we have the following questions:
>
> - What is the meaning of "DEL" and "W" (in the subroutine $ERROR)?
They are sort of like a virus that is spread by copying and pasting from old control streams passed around among beginners.
These are not standard NM-TRAN variables. Some people like to use them to create some diagnostic variables like IWRES. I find no use for them.
> - What is the meaning of "TOL" and when should it be used?
TOL is an option for the differential equation solving subroutines (ADVAN6, ADVAN8, ADVAN9 and ADVAN13 (NM7 only). It specifies the tolerance for the numerical solution of the differential equations. A reasonable starting value is TOL=6 for NM7 (with NSIG=2 and SIGL=6).
> - Assumed we need to use $DES, is this possible only with NONMEM version 7 or can we use it also in NONMEM 6?
You can use $DES with any version of NONMEM. It usually runs faster with NM6 than NM7. However, in some cases ADVAN13 in NONMEM7 will run faster than ADVAN6,8.9. Its hard to predict which ADVAN is best so just try different ones and use the one that runs fastest.
> Thanks a lot and kind regards from rainy Cologne
Its raining in Cape Town too!
> Paola & Lisa
--
Nick Holford, Professor Clinical Pharmacology
Dept Pharmacology& Clinical Pharmacology
University of Auckland,85 Park Rd,Private Bag 92019,Auckland,New Zealand
tel:+64(9)923-6730 fax:+64(9)373-7090 mobile:+64(21)46 23 53
email: [email protected]
http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford
Paola,
I agree with Nick that there may be little use for the DEL and W variables.
The standard coding may be something like:
$ERROR
IPRED = F
IRES = DV-IPRED
W = THETA(#)*F
DEL = 0
IF(W.EQ.0) DEL = 1
IWRES = IRES/(W+DEL)
Y = F+EPS(1)*W
The W represents the “weight” of the error model. In the above example this is
proportional error.
The DEL is used to keep the unlikely divide by zero error from appearing when
IRES/W is calculated. When W=0, IRES=RES.
Like Nick, I’m don’t find too much use in this. If W = 0, I think the IWRES
should be missing instead of calculated as RES.
Matt.
Quoted reply history
From: [email protected] [mailto:[email protected]] On
Behalf Of Nick Holford
Sent: Thursday, March 31, 2011 9:03 AM
To: nmusers
Subject: Re: [NMusers] basic questions...
Paola,
On 31/03/2011 3:02 p.m., di Gion, Paola wrote:
Dear NONMEM users,
as beginners in NONMEM we have the following questions:
- What is the meaning of "DEL" and "W" (in the subroutine $ERROR)?
They are sort of like a virus that is spread by copying and pasting from old
control streams passed around among beginners.
These are not standard NM-TRAN variables. Some people like to use them to
create some diagnostic variables like IWRES. I find no use for them.
- What is the meaning of "TOL" and when should it be used?
TOL is an option for the differential equation solving subroutines (ADVAN6,
ADVAN8, ADVAN9 and ADVAN13 (NM7 only).
It specifies the tolerance for the numerical solution of the differential
equations. A reasonable starting value is TOL=6 for NM7 (with NSIG=2 and
SIGL=6).
- Assumed we need to use $DES, is this possible only with NONMEM version 7 or
can we use it also in NONMEM 6?
You can use $DES with any version of NONMEM. It usually runs faster with NM6
than NM7. However, in some cases ADVAN13 in NONMEM7 will run faster than
ADVAN6,8.9. Its hard to predict which ADVAN is best so just try different ones
and use the one that runs fastest.
Thanks a lot and kind regards from rainy Cologne
Its raining in Cape Town too!
Paola & Lisa
--
Nick Holford, Professor Clinical Pharmacology
Dept Pharmacology & Clinical Pharmacology
University of Auckland,85 Park Rd,Private Bag 92019,Auckland,New Zealand
tel:+64(9)923-6730 fax:+64(9)373-7090 mobile:+64(21)46 23 53
email: [email protected]<mailto:[email protected]>
http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford
________________________________
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privileged. If you are not an intended recipient or an authorized
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Thank you.
Dear Matt and all,
In the code you gave, DEL is a protection when F=0 as it may be in a lag-time
model, not only for IWRES but also for the model as such. You can’t have a
proportional error model with a prediction of zero. Add an absolute error
component or switch from a lag to a transit compartment delay model are two
possibilities. In general, I find IWRES useful for diagnosing the residual
error model by plotting abs(IWRES) versus IPRED when I have reasonable amount
of data per subject. An appropriate error model should result in a lack of
trend. Others may have other ways of assuring that the residual error model is
appropriate. Better alternatives are always welcome.
Best regards,
Mats
Mats Karlsson, PhD
Professor of Pharmacometrics
Dept of Pharmaceutical Biosciences
Uppsala University
Sweden
Postal address: Box 591, 751 24 Uppsala, Sweden
Phone +46 18 4714105
Fax + 46 18 4714003
Quoted reply history
From: [email protected] [mailto:[email protected]] On
Behalf Of Fidler,Matt,FORT WORTH,R&D
Sent: Thursday, March 31, 2011 5:30 PM
To: Nick Holford; nmusers
Subject: RE: [NMusers] basic questions...
Paola,
I agree with Nick that there may be little use for the DEL and W variables.
The standard coding may be something like:
$ERROR
IPRED = F
IRES = DV-IPRED
W = THETA(#)*F
DEL = 0
IF(W.EQ.0) DEL = 1
IWRES = IRES/(W+DEL)
Y = F+EPS(1)*W
The W represents the “weight” of the error model. In the above example this is
proportional error.
The DEL is used to keep the unlikely divide by zero error from appearing when
IRES/W is calculated. When W=0, IRES=RES.
Like Nick, I’m don’t find too much use in this. If W = 0, I think the IWRES
should be missing instead of calculated as RES.
Matt.
From: [email protected] [mailto:[email protected]] On
Behalf Of Nick Holford
Sent: Thursday, March 31, 2011 9:03 AM
To: nmusers
Subject: Re: [NMusers] basic questions...
Paola,
On 31/03/2011 3:02 p.m., di Gion, Paola wrote:
Dear NONMEM users,
as beginners in NONMEM we have the following questions:
- What is the meaning of "DEL" and "W" (in the subroutine $ERROR)?
They are sort of like a virus that is spread by copying and pasting from old
control streams passed around among beginners.
These are not standard NM-TRAN variables. Some people like to use them to
create some diagnostic variables like IWRES. I find no use for them.
- What is the meaning of "TOL" and when should it be used?
TOL is an option for the differential equation solving subroutines (ADVAN6,
ADVAN8, ADVAN9 and ADVAN13 (NM7 only).
It specifies the tolerance for the numerical solution of the differential
equations. A reasonable starting value is TOL=6 for NM7 (with NSIG=2 and
SIGL=6).
- Assumed we need to use $DES, is this possible only with NONMEM version 7 or
can we use it also in NONMEM 6?
You can use $DES with any version of NONMEM. It usually runs faster with NM6
than NM7. However, in some cases ADVAN13 in NONMEM7 will run faster than
ADVAN6,8.9. Its hard to predict which ADVAN is best so just try different ones
and use the one that runs fastest.
Thanks a lot and kind regards from rainy Cologne
Its raining in Cape Town too!
Paola & Lisa
--
Nick Holford, Professor Clinical Pharmacology
Dept Pharmacology & Clinical Pharmacology
University of Auckland,85 Park Rd,Private Bag 92019,Auckland,New Zealand
tel:+64(9)923-6730 fax:+64(9)373-7090 mobile:+64(21)46 23 53
email: [email protected]
http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford
_____
This e-mail (including any attachments) is confidential and may be legally
privileged. If you are not an intended recipient or an authorized
representative of an intended recipient, you are prohibited from using, copying
or distributing the information in this e-mail or its attachments. If you have
received this e-mail in error, please notify the sender immediately by return
e-mail and delete all copies of this message and any attachments.
Thank you.