[NMusers] Pharmacometrician - Brisbane, Australia

[Bruce Green]

PHARMACOMETRICIAN - BRISBANE, AUSTRALIA

Model Answers Pty Ltd is seeking applications for a pharmacometrician to join 
their team in Brisbane, Australia. The successful candidate will work with an 
inspiring group providing a range of pharmacometric solutions to a global 
client network. The position is suited to highly motivated individuals who are 
looking for a challenging opportunity to facilitate model based drug 
development. 

Applicants should have excellent time management and communication skills and 
be able to innovatively support pharmacometric development. Applicants should 
also have a strong programming background in R or SPlus and demonstrated 
modelling experience using NONMEM / BUGS together with a PhD or equivalent 
qualification/experience in the pharmacometrics area.

The position is based in the central business district of Brisbane, Australia, 
renowned for a superb sub-tropical climate with an emphasis on an outdoor 
lifestyle.

Interested applicants should contact Bruce Green at i...@model-a.com.au or 
refer to the website (www.model-a.com.au) for further information.

[NMusers] basic questions...

[di Gion, Paola]

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
 
 <>

[NMusers] Allrecords.txt

[di Gion, Paola]

Dear NONMEM Users,
 
we try to start a NONMEM run. An error report tells us that:
 
"FILE=Allrecords.txt this option is already been specified"
 
Do you have an idea how could we avoid this error?
 
Thanks a lot and many greetings from still rainy Cologne.
 
Paola and Lisa<>

Re: [NMusers] basic questions...

[Luann Phillips]

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

 

 

Re: [NMusers] basic questions...

[Nick Holford]

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: n.holf...@auckland.ac.nz
http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford

Re: [NMusers] Allrecords.txt

[Paul Matthias Diderichsen]

Hi Paola and Lisa,

On 3/31/2011 3:47 PM, di Gion, Paola wrote:
> "FILE=Allrecords.txt this option is already been specified"
> Do you have an idea how could we avoid this error?

As you've already noticed, nmusers is full of people just waiting to 
help you. :-) In order to make this easier for them (us), consider 
providing:


1) Example control stream

2) Example dataset structure: The header or maybe the first 10 lines of 
the dataset you are working with, if it's not confidential


3) As much information about the error as you can find; either grabbed 
from the command line or from nonmem output (file ends with "lst")


4) If you suspect that something is wrong with your nonmem installation, 
provide information on


4a) which version of nonmem you're trying to work with,
4b) the platform (windows/linux),
4c) the fortran compiler, and
4d) any frontend (wfn, psn, pdxpop) that you use.

PS: A great source of information is the HTML help files in your nonmem 
installation (probably C:\nm712\html\index.htm or similar)


Kind regards and good luck.

--
Paul Matthias Diderichsen, PhD
Quantitative Solutions B.V.
+31 624 330 706

RE: [NMusers] Allrecords.txt

I’m assuming that you may have specified the AllRecords.txt twice in your 
$TABLE statement


$TABLE …  FILE … FILE=AllRecords.txt

Could be a possibility.

Please send a control stream for a better diagnosis.

Matt.

From: owner-nmus...@globomaxnm.com [mailto:owner-nmus...@globomaxnm.com] On 
Behalf Of di Gion, Paola
Sent: Thursday, March 31, 2011 8:47 AM
To: non...@optonline.net; nmusers@globomaxnm.com
Cc: Junge, Lisa
Subject: [NMusers] Allrecords.txt


Dear NONMEM Users,



we try to start a NONMEM run. An error report tells us that:



"FILE=Allrecords.txt this option is already been specified"



Do you have an idea how could we avoid this error?



Thanks a lot and many greetings from still rainy Cologne.



Paola and Lisa


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.

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: owner-nmus...@globomaxnm.com [mailto:owner-nmus...@globomaxnm.com] 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: n.holf...@auckland.ac.nz

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.

RE: [NMusers] basic questions...

[mats karlsson]

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

 

From: owner-nmus...@globomaxnm.com [mailto:owner-nmus...@globomaxnm.com] 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: owner-nmus...@globomaxnm.com [mailto:owner-nmus...@globomaxnm.com] 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: n.holf...@auckland.ac.nz
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.