Dear All:
This is just a brief update regarding the availability of NONMEM 7. We
had hoped to begin distribution of this new version at this time.
However, there are some final code changes to be made followed by
thorough testing. We hope to be able to begin distribution in early
August.
Please be certain that the contact information that we have on file for
your license(s) is up to date. This is the person to whom NONMEM 7 will
be sent . Please send any updates regarding the correct contact person
to [email protected] <mailto:[email protected]> .
Please note that NONMEM 7 will have a licensing system. More details
will be provided as we approach the release date.
Our experience with distributing binary code to the beta testers was
very mixed. Some testers had no problems; others had considerable
difficulty with achieving a successful installation. We are now
considering the distribution of NONMEM 7, for the most part, as
encrypted source code. An installation program will be included. The
SIZES file and several other resource files will be left unencrypted so
that the user can make desired changes prior to compilation as was
possible with previous versions. This change in our method of
distribution will require that a revised licensing agreement be
executed.
Regards,
Bob Bauer
Vice-President, Pharmacometrics
Alison Boeckmann
Consultant
Bill Bachman
Director, Pharmacometrics R&D
Tom Ludden
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
http://emailsignature/stationary/Icon_Development_Solutions.gif
NONMEM 7 Update
Can anyone explain what advantages encryted source code might have?
For me at least, the NONMEM source code is already functionally encrypted
because of my poor understanding of Fortran. But it is unclear to me what
problem encryted source code actually solves. Can anyone enlighten me?
Douglas Eleveld
Quoted reply history
________________________________
From: [email protected] on behalf of Ludden, Thomas
Sent: Wed 01/07/2009 9:21 PM
To: [email protected]
Subject: [NMusers] NONMEM 7 Update
Dear All:
This is just a brief update regarding the availability of NONMEM 7. We had
hoped to begin distribution of this new version at this time. However, there
are some final code changes to be made followed by thorough testing. We hope
to be able to begin distribution in early August.
Please be certain that the contact information that we have on file for your
license(s) is up to date. This is the person to whom NONMEM 7 will be sent .
Please send any updates regarding the correct contact person to
[email protected] <mailto:[email protected]> .
Please note that NONMEM 7 will have a licensing system. More details will be
provided as we approach the release date.
Our experience with distributing binary code to the beta testers was very
mixed. Some testers had no problems; others had considerable difficulty with
achieving a successful installation. We are now considering the distribution
of NONMEM 7, for the most part, as encrypted source code. An installation
program will be included. The SIZES file and several other resource files will
be left unencrypted so that the user can make desired changes prior to
compilation as was possible with previous versions. This change in our method
of distribution will require that a revised licensing agreement be executed.
Regards,
Bob Bauer
Vice-President, Pharmacometrics
Alison Boeckmann
Consultant
Bill Bachman
Director, Pharmacometrics R&D
Tom Ludden
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
ICON Development Solutions has made a considerable financial investment in
the major recoding of NONMEM done for version 7. As a commercial entity, it
believes it should protect the intellectual property via encryption while
still allowing the user to make minor adjustments to the installation.
Bill
_____
Quoted reply history
From: [email protected] [mailto:[email protected]] On
Behalf Of Eleveld, DJ
Sent: Thursday, July 02, 2009 6:11 AM
To: Ludden, Thomas; [email protected]
Subject: RE: [NMusers] NONMEM 7 Update
Can anyone explain what advantages encryted source code might have?
For me at least, the NONMEM source code is already functionally encrypted
because of my poor understanding of Fortran. But it is unclear to me what
problem encryted source code actually solves. Can anyone enlighten me?
Douglas Eleveld
_____
From: [email protected] on behalf of Ludden, Thomas
Sent: Wed 01/07/2009 9:21 PM
To: [email protected]
Subject: [NMusers] NONMEM 7 Update
Dear All:
This is just a brief update regarding the availability of NONMEM 7. We had
hoped to begin distribution of this new version at this time. However,
there are some final code changes to be made followed by thorough testing.
We hope to be able to begin distribution in early August.
Please be certain that the contact information that we have on file for your
license(s) is up to date. This is the person to whom NONMEM 7 will be sent
. Please send any updates regarding the correct contact person to
<mailto:[email protected]> [email protected].
Please note that NONMEM 7 will have a licensing system. More details will
be provided as we approach the release date.
Our experience with distributing binary code to the beta testers was very
mixed. Some testers had no problems; others had considerable difficulty
with achieving a successful installation. We are now considering the
distribution of NONMEM 7, for the most part, as encrypted source code. An
installation program will be included. The SIZES file and several other
resource files will be left unencrypted so that the user can make desired
changes prior to compilation as was possible with previous versions. This
change in our method of distribution will require that a revised licensing
agreement be executed.
Regards,
Bob Bauer
Vice-President, Pharmacometrics
Alison Boeckmann
Consultant
Bill Bachman
Director, Pharmacometrics R&D
Tom Ludden
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
Dear All:
Icon Development Solutions has invested in the further
development of NONMEM. By mutual agreement with the University of
California at San Francisco, NONMEM 7 is intellectual property belonging
to IDS. However, IDS will continue to pay royalties to UCSF.
The business plan under which NONMEM 7 was developed calls for
the protection of the I.P. involved. In addition, NONMEM 7 contains
several updated routines developed and owned by IMSL (Visual Numerics
Inc.). Our agreement with IMSL stipulates that we will not distribute
their source code. The installer will compile the software but will not
allow the unencrypted source code to remain on the users computer. The
licensing agreement will also stipulate that any attempt to access the
source code will be a violation of the agreement.
Some source code will be left unencrypted for various reasons,
one being the need for users to change certain values in SIZES and
perhaps other resource routines.
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
http://emailsignature/stationary/Icon_Development_Solutions.gif
Quoted reply history
________________________________
From: Eleveld, DJ [mailto:[email protected]]
Sent: Thursday, July 02, 2009 6:11 AM
To: Ludden, Thomas; [email protected]
Subject: RE: [NMusers] NONMEM 7 Update
Can anyone explain what advantages encryted source code might have?
For me at least, the NONMEM source code is already functionally
encrypted because of my poor understanding of Fortran. But it is
unclear to me what problem encryted source code actually solves. Can
anyone enlighten me?
Douglas Eleveld
________________________________
From: [email protected] on behalf of Ludden, Thomas
Sent: Wed 01/07/2009 9:21 PM
To: [email protected]
Subject: [NMusers] NONMEM 7 Update
Dear All:
This is just a brief update regarding the availability of NONMEM 7. We
had hoped to begin distribution of this new version at this time.
However, there are some final code changes to be made followed by
thorough testing. We hope to be able to begin distribution in early
August.
Please be certain that the contact information that we have on file for
your license(s) is up to date. This is the person to whom NONMEM 7 will
be sent . Please send any updates regarding the correct contact person
to [email protected] <mailto:[email protected]> .
Please note that NONMEM 7 will have a licensing system. More details
will be provided as we approach the release date.
Our experience with distributing binary code to the beta testers was
very mixed. Some testers had no problems; others had considerable
difficulty with achieving a successful installation. We are now
considering the distribution of NONMEM 7, for the most part, as
encrypted source code. An installation program will be included. The
SIZES file and several other resource files will be left unencrypted so
that the user can make desired changes prior to compilation as was
possible with previous versions. This change in our method of
distribution will require that a revised licensing agreement be
executed.
Regards,
Bob Bauer
Vice-President, Pharmacometrics
Alison Boeckmann
Consultant
Bill Bachman
Director, Pharmacometrics R&D
Tom Ludden
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
Dear Douglas, Thomas and Anyone Else on the List,
The NONMEM _was_ an open software. It was advantageous for scientific
community, because one could (at least in theory) understand and verify
the way the calculations were done.
This way it was free though it was not licensed for free. Now it appears
it will become a blackbox. Science does not like blackboxes.
Note the similar blackboxes already exist in the field. Also, encrypting
(or distruibuting binaries) of IMSL routines does not require encryption
of the remaining part of the distribution.
And finnally, we are not speaking about just a piece of software. We're
speaking about an (nomen-omen) icon of PK/PD software.
Therefore I'd like to ask the question: What about the previous
versions? Will current and future users have a choice to stay using
previous, open versions? Are they also the property belonging to IDS or
can they be licensed by UCSF?
Best regards
Wojciech Jawien
Jagiellonian University
Krakow, Poland
Ludden, Thomas wrote:
> Dear All:
>
> Icon Development Solutions has invested in the further development
> of NONMEM. By mutual agreement with the University of California
> at San Francisco, NONMEM 7 is intellectual property belonging to
>
> IDS. However, IDS will continue to pay royalties to UCSF. The business plan under which NONMEM 7 was developed calls for the
>
> protection of the I.P. involved. In addition, NONMEM 7 contains
> several updated routines developed and owned by IMSL (Visual
> Numerics Inc.). Our agreement with IMSL stipulates that we will
> not distribute their source code. The installer will compile the
> software but will not allow the unencrypted source code to remain
> on the users computer. The licensing agreement will also
> stipulate that any attempt to access the source code will be a
> violation of the agreement.
>
> Some source code will be left unencrypted for various reasons, one
>
> being the need for users to change certain values in SIZES and
> perhaps other resource routines.
>
> 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] <mailto:[email protected]>*
>
> ***Web:* www.icondevsolutions.com
>
> ------------------------------------------------------------------------
> *From:* Eleveld, DJ [mailto:[email protected]]
> *Sent:* Thursday, July 02, 2009 6:11 AM
> *To:* Ludden, Thomas; [email protected]
> *Subject:* RE: [NMusers] NONMEM 7 Update
>
> Can anyone explain what advantages encryted source code might have?
>
> For me at least, the NONMEM source code is already functionally encrypted because of my poor understanding of Fortran. But it is unclear to me what problem encryted source code actually solves. Can anyone enlighten me? Douglas Eleveld
>
> ------------------------------------------------------------------------
> *From:* [email protected] on behalf of Ludden, Thomas
> *Sent:* Wed 01/07/2009 9:21 PM
> *To:* [email protected]
> *Subject:* [NMusers] NONMEM 7 Update
>
> Dear All:
>
> This is just a brief update regarding the availability of NONMEM 7. We had hoped to begin distribution of this new version at this time. However, there are some final code changes to be made followed by thorough testing. We hope to be able to begin distribution in early August. Please be certain that the contact information that we have on file for your license(s) is up to date. This is the person to whom NONMEM 7 will be sent . Please send any updates regarding the correct contact person to [email protected] < mailto: [email protected] >. Please note that NONMEM 7 will have a licensing system. More details will be provided as we approach the release date. Our experience with distributing binary code to the beta testers was very mixed. Some testers had no problems; others had considerable difficulty with achieving a successful installation. We are now considering the distribution of NONMEM 7, for the most part, as encrypted source code. An installation program will be included. The SIZES file and several other resource files will be left unencrypted so that the user can make desired changes prior to compilation as was possible with previous versions. This change in our method of distribution will require that a revised licensing agreement be executed. Regards, Bob Bauer
>
> Vice-President, Pharmacometrics
>
> Alison Boeckmann
>
> Consultant
>
> Bill Bachman
>
> Director, Pharmacometrics R&D
>
> Tom Ludden
>
> 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] <mailto:[email protected]>*
>
> ***Web:* www.icondevsolutions.com
>
>
Dear all
Just one minor comment from one of the not hard core users of NONMEM.
Only 3 years ago I was afraid that NONMEM would die, since no one really seemed to be interested in investing in the software. Today, in my eyes, NONMEM has been brought back on the scene by IDS - that is highly appreciated.
I think we all have to realize that NONMEM is not open source software, there are both advantages and dis-advantages connected to that. As long as IDS ensures that we are able to make minor adjustments (like nsizes etc), I don't see a big problem.
Right now I run the R software (+census and xpose), together with NONMEM, and find thats some of the best pices of open software I have seen. But I dont think the PKPD community is big enough for us to generate comparable software for PKPD modelling, and if we need professionel companies to develop our software, we will have to accept other terms.
Instead I think we should focus on the positive side, NONMEM is alive, and if anyone wants to run an older version of NONMEM that's fine with me. But I will test version 7.0 - and I look forward to the release.
Hope everyone will have a nice summer
Br henrik
_________________________________
Henrik Agers
Director, Head of Exploratory ADME, BRU
Novo Nordisk A/S
Novo Nordisk Park
DK-2760 Mlv
Denmark
+45 4442 3522 (direct)
+45 3079 3522 (mobile)
hkag
http://www.novonordisk.com/
Changing possibilities in haemophilia
Our formulation remains the only recombinant treatment option for haemophilia patients with inhibitors. Learn http://www.novonordisk.com/about_us/improving_haemophilia/ChangingPossibilitiesActivities/HaemophiliaTreatment1.asp
This e-mail (including any attachments) is intended for the addressee(s) stated above only and may contain confidential information protected by law. You are hereby notified that any unauthorized reading, disclosure, copying or distribution of this e-mail or use of information contained herein is strictly prohibited and may violate rights to proprietary information. If you are not an intended recipient, please return this e-mail to the sender and delete it immediately hereafter. Thank you.
Quoted reply history
________________________________
From: owner-nmusers
Behalf Of Eleveld, DJ
Sent: 02 July 2009 23:32
To: Ludden, Thomas; nmusers
Cc: Krohn, Anthony
Subject: RE: [NMusers] NONMEM 7 Update
Dear all:
There is no debate at all that investment in NONMEM should have a healthy return. I just dont understand how encryption is supposed to help.
NONMEM 6 was not encrypted, what problems resulted from this? Did anything actually happen to the NONMEM 6 source code which must be avoided with NONMEM 7?
The thinking "we must encrypt our souce code so nobody steals our IP" may be suitable for consumer goods where copyright violations are rampant and visibility is very low. But the small, highly specalized and very visible community of PK-PD analysis is a very different thing. My impression is that everyone takes thier NONMEM licences very seriously and I dont see any reason why this would change with NONMEM 7.
There are usually upsides and downsides to these kinds of choices and a balance must be struck. I can think of a number of downsides to encryption but no real upsides. I was hoping to hear from others what the upside was. Just "protecting our IP" is, in my opinion, not a real reason becasue this does not actually generate any revenue.
Douglas Eleveld
-----Oorspronkelijk bericht-----
Van: Ludden, Thomas [mailto:Thomas.Ludden
Verzonden: do 2-7-2009 15:15
Aan: Eleveld, DJ; nmusers
CC: Krohn, Anthony
Onderwerp: RE: [NMusers] NONMEM 7 Update
Dear All:
Icon Development Solutions has invested in the further
development of NONMEM. By mutual agreement with the University of
California at San Francisco, NONMEM 7 is intellectual property belonging
to IDS. However, IDS will continue to pay royalties to UCSF.
The business plan under which NONMEM 7 was developed calls for
the protection of the I.P. involved. In addition, NONMEM 7 contains
several updated routines developed and owned by IMSL (Visual Numerics
Inc.). Our agreement with IMSL stipulates that we will not distribute
their source code. The installer will compile the software but will not
allow the unencrypted source code to remain on the users computer. The
licensing agreement will also stipulate that any attempt to access the
source code will be a violation of the agreement.
Some source code will be left unencrypted for various reasons,
one being the need for users to change certain values in SIZES and
perhaps other resource routines.
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: thomas.ludden
Web: www.icondevsolutions.com
http://emailsignature/stationary/Icon_Development_Solutions.gif
________________________________
From: Eleveld, DJ [mailto:d.j.eleveld
Sent: Thursday, July 02, 2009 6:11 AM
To: Ludden, Thomas; nmusers
Subject: RE: [NMusers] NONMEM 7 Update
Can anyone explain what advantages encryted source code might have?
For me at least, the NONMEM source code is already functionally
encrypted because of my poor understanding of Fortran. But it is
unclear to me what problem encryted source code actually solves. Can
anyone enlighten me?
Douglas Eleveld
________________________________
From: owner-nmusers
Sent: Wed 01/07/2009 9:21 PM
To: nmusers
Subject: [NMusers] NONMEM 7 Update
Dear All:
This is just a brief update regarding the availability of NONMEM 7. We
had hoped to begin distribution of this new version at this time.
However, there are some final code changes to be made followed by
thorough testing. We hope to be able to begin distribution in early
August.
Please be certain that the contact information that we have on file for
your license(s) is up to date. This is the person to whom NONMEM 7 will
be sent . Please send any updates regarding the correct contact person
to IDSSOFTWARE
Please note that NONMEM 7 will have a licensing system. More details
will be provided as we approach the release date.
Our experience with distributing binary code to the beta testers was
very mixed. Some testers had no problems; others had considerable
difficulty with achieving a successful installation. We are now
considering the distribution of NONMEM 7, for the most part, as
encrypted source code. An installation program will be included. The
SIZES file and several other resource files will be left unencrypted so
that the user can make desired changes prior to compilation as was
possible with previous versions. This change in our method of
distribution will require that a revised licensing agreement be
executed.
Regards,
Bob Bauer
Vice-President, Pharmacometrics
Alison Boeckmann
Consultant
Bill Bachman
Director, Pharmacometrics R&D
Tom Ludden
Vice-President, Pharmacometrics R&D
ICON Development Solutions
Tel: + 1 410 696 3040
Mob: + 1 410 258 2411
Fax: + 1 410 480 0776
Email: thomas.ludden
Web: www.icondevsolutions.com
Thomas
Didn't ICON consider that indeed, this decision might stimulate the divergence
of an open-source clade of NONMEM, somewhat like R stemmed out of S-plus? If a
small academic group starts to work in that direction, it would certainly be
quickly joined by many...
Thierry Buclin
Univ. Hospital, Lausanne
Quoted reply history
De : [email protected] [mailto:[email protected]] De la
part de Ludden, Thomas
Envoyé : jeudi, 2. juillet 2009 15:15
À : Eleveld, DJ; [email protected]
Cc : Krohn, Anthony
Objet : RE: [NMusers] NONMEM 7 Update
Dear All:
Icon Development Solutions has invested in the further development of NONMEM.
By mutual agreement with the University of California at San Francisco, NONMEM
7 is intellectual property belonging to IDS. However, IDS will continue to pay
royalties to UCSF.
The business plan under which NONMEM 7 was developed calls for the protection
of the I.P. involved. In addition, NONMEM 7 contains several updated routines
developed and owned by IMSL (Visual Numerics Inc.). Our agreement with IMSL
stipulates that we will not distribute their source code. The installer will
compile the software but will not allow the unencrypted source code to remain
on the users computer. The licensing agreement will also stipulate that any
attempt to access the source code will be a violation of the agreement.
Some source code will be left unencrypted for various reasons, one being the
need for users to change certain values in SIZES and perhaps other resource
routines.
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]<mailto:[email protected]>
Web: www.icondevsolutions.com
Dear all
Just one minor comment from one of the not hard core users of NONMEM.
Only 3 years ago I was afraid that NONMEM would die, since no one really seemed
to be interested in investing in the software. Today, in my eyes, NONMEM has
been brought back on the scene by IDS - that is highly appreciated.
I think we all have to realize that NONMEM is not open source software, there
are both advantages and dis-advantages connected to that. As long as IDS
ensures that we are able to make minor adjustments (like nsizes etc), I don't
see a big problem.
Right now I run the R software (+census and xpose), together with NONMEM, and
find thats some of the best pices of open software I have seen. But I dont
think the PKPD community is big enough for us to generate comparable software
for PKPD modelling, and if we need professionel companies to develop our
software, we will have to accept other terms.
Instead I think we should focus on the positive side, NONMEM is alive, and if
anyone wants to run an older version of NONMEM that's fine with me. But I will
test version 7.0 - and I look forward to the release.
Hope everyone will have a nice summer
Br henrik
_________________________________
Henrik Agersø
Director, Head of Exploratory ADME, BRU
Novo Nordisk A/S
Novo Nordisk Park
DK-2760 Måløv
Denmark
+45 4442 3522 (direct)
+45 3079 3522 (mobile)
[email protected]
http://www.novonordisk.com/
Changing possibilities in haemophilia
Our formulation remains the only recombinant treatment option for haemophilia
patients with inhibitors. Learn
http://www.novonordisk.com/about_us/improving_haemophilia/ChangingPossibilitiesActivities/HaemophiliaTreatment1.asp
This e-mail (including any attachments) is intended for the addressee(s) stated
above only and may contain confidential information protected by law. You are
hereby notified that any unauthorized reading, disclosure, copying or
distribution of this e-mail or use of information contained herein is strictly
prohibited and may violate rights to proprietary information. If you are not an
intended recipient, please return this e-mail to the sender and delete it
immediately hereafter. Thank you.
Quoted reply history
________________________________
From: [email protected] [mailto:[email protected]] On
Behalf Of Eleveld, DJ
Sent: 02 July 2009 23:32
To: Ludden, Thomas; [email protected]
Cc: Krohn, Anthony
Subject: RE: [NMusers] NONMEM 7 Update
Dear all:
There is no debate at all that investment in NONMEM should have a healthy
return. I just dont understand how encryption is supposed to help.
NONMEM 6 was not encrypted, what problems resulted from this? Did anything
actually happen to the NONMEM 6 source code which must be avoided with NONMEM 7?
The thinking "we must encrypt our souce code so nobody steals our IP" may be
suitable for consumer goods where copyright violations are rampant and
visibility is very low. But the small, highly specalized and very visible
community of PK-PD analysis is a very different thing. My impression is that
everyone takes thier NONMEM licences very seriously and I dont see any reason
why this would change with NONMEM 7.
There are usually upsides and downsides to these kinds of choices and a balance
must be struck. I can think of a number of downsides to encryption but no real
upsides. I was hoping to hear from others what the upside was. Just
"protecting our IP" is, in my opinion, not a real reason becasue this does not
actually generate any revenue.
Douglas Eleveld
-----Oorspronkelijk bericht-----
Van: Ludden, Thomas [mailto:[email protected]]
Verzonden: do 2-7-2009 15:15
Aan: Eleveld, DJ; [email protected]
CC: Krohn, Anthony
Onderwerp: RE: [NMusers] NONMEM 7 Update
Dear All:
Icon Development Solutions has invested in the further
development of NONMEM. By mutual agreement with the University of
California at San Francisco, NONMEM 7 is intellectual property belonging
to IDS. However, IDS will continue to pay royalties to UCSF.
The business plan under which NONMEM 7 was developed calls for
the protection of the I.P. involved. In addition, NONMEM 7 contains
several updated routines developed and owned by IMSL (Visual Numerics
Inc.). Our agreement with IMSL stipulates that we will not distribute
their source code. The installer will compile the software but will not
allow the unencrypted source code to remain on the users computer. The
licensing agreement will also stipulate that any attempt to access the
source code will be a violation of the agreement.
Some source code will be left unencrypted for various reasons,
one being the need for users to change certain values in SIZES and
perhaps other resource routines.
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
http://emailsignature/stationary/Icon_Development_Solutions.gif
________________________________
From: Eleveld, DJ [mailto:[email protected]]
Sent: Thursday, July 02, 2009 6:11 AM
To: Ludden, Thomas; [email protected]
Subject: RE: [NMusers] NONMEM 7 Update
Can anyone explain what advantages encryted source code might have?
For me at least, the NONMEM source code is already functionally
encrypted because of my poor understanding of Fortran. But it is
unclear to me what problem encryted source code actually solves. Can
anyone enlighten me?
Douglas Eleveld
________________________________
From: [email protected] on behalf of Ludden, Thomas
Sent: Wed 01/07/2009 9:21 PM
To: [email protected]
Subject: [NMusers] NONMEM 7 Update
Dear All:
This is just a brief update regarding the availability of NONMEM 7. We
had hoped to begin distribution of this new version at this time.
However, there are some final code changes to be made followed by
thorough testing. We hope to be able to begin distribution in early
August.
Please be certain that the contact information that we have on file for
your license(s) is up to date. This is the person to whom NONMEM 7 will
be sent . Please send any updates regarding the correct contact person
to [email protected] <mailto:[email protected]> .
Please note that NONMEM 7 will have a licensing system. More details
will be provided as we approach the release date.
Our experience with distributing binary code to the beta testers was
very mixed. Some testers had no problems; others had considerable
difficulty with achieving a successful installation. We are now
considering the distribution of NONMEM 7, for the most part, as
encrypted source code. An installation program will be included. The
SIZES file and several other resource files will be left unencrypted so
that the user can make desired changes prior to compilation as was
possible with previous versions. This change in our method of
distribution will require that a revised licensing agreement be
executed.
Regards,
Bob Bauer
Vice-President, Pharmacometrics
Alison Boeckmann
Consultant
Bill Bachman
Director, Pharmacometrics R&D
Tom Ludden
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
I do have only one simple question. How many people took advantage from the
fact Nonmem was distributed as open source? If we are talking about a very
small percentage, is this discussion worthwhile? How many people except bob
bauer and may be somebody else I am not aware of are able to follow and
understand the cuirrent nonmem code?
Serge
Quoted reply history
________________________________
From: [email protected]
To: Ludden, Thomas ; [email protected]
Sent: Thu Jul 02 23:46:09 2009
Subject: [NMusers] RE: NONMEM 7 Update
Thomas
Didn't ICON consider that indeed, this decision might stimulate the divergence
of an open-source clade of NONMEM, somewhat like R stemmed out of S-plus? If a
small academic group starts to work in that direction, it would certainly be
quickly joined by many…
Thierry Buclin
Univ. Hospital, Lausanne
De : [email protected] [mailto:[email protected]] De la
part de Ludden, Thomas
Envoyé : jeudi, 2. juillet 2009 15:15
À : Eleveld, DJ; [email protected]
Cc : Krohn, Anthony
Objet : RE: [NMusers] NONMEM 7 Update
Dear All:
Icon Development Solutions has invested in the further development of
NONMEM. By mutual agreement with the University of California at San
Francisco, NONMEM 7 is intellectual property belonging to IDS. However, IDS
will continue to pay royalties to UCSF.
The business plan under which NONMEM 7 was developed calls for the
protection of the I.P. involved. In addition, NONMEM 7 contains several
updated routines developed and owned by IMSL (Visual Numerics Inc.). Our
agreement with IMSL stipulates that we will not distribute their source code.
The installer will compile the software but will not allow the unencrypted
source code to remain on the users computer. The licensing agreement will also
stipulate that any attempt to access the source code will be a violation of the
agreement.
Some source code will be left unencrypted for various reasons, one
being the need for users to change certain values in SIZES and perhaps other
resource routines.
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
--
The information contained in this email message may
contain confidential or legally privileged information and is intended solely
for the use of the named recipient(s). No confidentiality or privilege is
waived or lost by any transmission error. If the reader of this message is
not the intended recipient, please immediately delete the e-mail and all
copies of it from your system, destroy any hard copies of it and notify the
sender either by telephone or return e-mail. Any direct or indirect use,
disclosure, distribution, printing, or copying of any part of this message is
prohibited. Any views expressed in this message are those of the individual
sender, except where the message states otherwise and the sender is
authorized to state them to be the views of XOMA.
Dear NONMEM users,
two years ago when we started (at Merck Serono) to discuss the necessary QA
documents for a "validated" NONMEM system the fact that NONMEM was open-source
played a major role in our risk analysis. In fact we conciously decided in
favor of open-source software also with regards of other tools (R, PsN, XPOSE)
associated with NONMEM.
I do not know to which degree system validation according to GxP standards is
affected in other commercial enterprices by the fact that NONMEM7 will no
longer be open-source. Specifically, I shall address that question here at my
new employer (AstraZeneca). I have also proposed to discuss the question of
NONMEM system validation at the upcoming PKUK meeting in Birmingham.
Please, do not apply the classification 'positive/negative reaction to new
encrypted NONMEM code' to my contribution. My work will not be negatively
affected by encryption, and I welcome the new estimation methods of NONMEM7.
Cheers,
Joachim Grevel
___________________________________________________
AstraZeneca R&D Charnwood
Clinical Pharmacology & DMPK
Bakewell Road, Loughborough, Leics LE11 5RH, England
Tel: +44 (0) 1509 645177
[email protected]
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Quoted reply history
-----Original Message-----
From: [email protected] [mailto:[email protected]]on
Behalf Of Serge Guzy
Sent: 03 July 2009 08:56
To: [email protected]; [email protected]; [email protected]
Subject: Re: [NMusers] RE: NONMEM 7 Update
I do have only one simple question. How many people took advantage from the
fact Nonmem was distributed as open source? If we are talking about a very
small percentage, is this discussion worthwhile? How many people except bob
bauer and may be somebody else I am not aware of are able to follow and
understand the cuirrent nonmem code?
Serge
_____
From: [email protected]
To: Ludden, Thomas ; [email protected]
Sent: Thu Jul 02 23:46:09 2009
Subject: [NMusers] RE: NONMEM 7 Update
Thomas
Didn't ICON consider that indeed, this decision might stimulate the divergence
of an open-source clade of NONMEM, somewhat like R stemmed out of S-plus? If a
small academic group starts to work in that direction, it would certainly be
quickly joined by many…
Thierry Buclin
Univ. Hospital, Lausanne
De : [email protected] [mailto:[email protected]] De la
part de Ludden, Thomas
Envoyé : jeudi, 2. juillet 2009 15:15
À : Eleveld, DJ; [email protected]
Cc : Krohn, Anthony
Objet : RE: [NMusers] NONMEM 7 Update
Dear All:
Icon Development Solutions has invested in the further development of NONMEM.
By mutual agreement with the University of California at San Francisco, NONMEM
7 is intellectual property belonging to IDS. However, IDS will continue to pay
royalties to UCSF.
The business plan under which NONMEM 7 was developed calls for the protection
of the I.P. involved. In addition, NONMEM 7 contains several updated routines
developed and owned by IMSL (Visual Numerics Inc.). Our agreement with IMSL
stipulates that we will not distribute their source code. The installer will
compile the software but will not allow the unencrypted source code to remain
on the users computer. The licensing agreement will also stipulate that any
attempt to access the source code will be a violation of the agreement.
Some source code will be left unencrypted for various reasons, one being the
need for users to change certain values in SIZES and perhaps other resource
routines.
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
_____
The information contained in this email message may contain confidential or
legally privileged information and is intended solely for the use of the named
recipient(s). No confidentiality or privilege is waived or lost by any
transmission error. If the reader of this message is not the intended
recipient, please immediately delete the e-mail and all copies of it from your
system, destroy any hard copies of it and notify the sender either by telephone
or return e-mail. Any direct or indirect use, disclosure, distribution,
printing, or copying of any part of this message is prohibited. Any views
expressed in this message are those of the individual sender, except where the
message states otherwise and the sender is authorized to state them to be the
views of XOMA.
Serge, I am afraid I dont understand what you are getting at.
Are you trying to say that so few people in the world understand the NONMEM
code
and so noone is likely to complain that they cant understand the encrypted code?
Or are you trying to say that so few people in the world understand the NONMEM
code
and so encryption is rather pointless since it changes almost nothing?
Douglas
Quoted reply history
-----Original Message-----
From: [email protected] on behalf of Serge Guzy
Sent: Fri 7/3/2009 9:56 AM
To: [email protected]; [email protected]; [email protected]
Subject: Re: [NMusers] RE: NONMEM 7 Update
I do have only one simple question. How many people took advantage from the
fact Nonmem was distributed as open source? If we are talking about a very
small percentage, is this discussion worthwhile? How many people except bob
bauer and may be somebody else I am not aware of are able to follow and
understand the cuirrent nonmem code?
Serge
________________________________
From: [email protected]
To: Ludden, Thomas ; [email protected]
Sent: Thu Jul 02 23:46:09 2009
Subject: [NMusers] RE: NONMEM 7 Update
Thomas
Didn't ICON consider that indeed, this decision might stimulate the divergence
of an open-source clade of NONMEM, somewhat like R stemmed out of S-plus? If a
small academic group starts to work in that direction, it would certainly be
quickly joined by many.
Thierry Buclin
Univ. Hospital, Lausanne
De : [email protected] [mailto:[email protected]] De la
part de Ludden, Thomas
Envoyé : jeudi, 2. juillet 2009 15:15
À : Eleveld, DJ; [email protected]
Cc : Krohn, Anthony
Objet : RE: [NMusers] NONMEM 7 Update
Dear All:
Icon Development Solutions has invested in the further development of
NONMEM. By mutual agreement with the University of California at San
Francisco, NONMEM 7 is intellectual property belonging to IDS. However, IDS
will continue to pay royalties to UCSF.
The business plan under which NONMEM 7 was developed calls for the
protection of the I.P. involved. In addition, NONMEM 7 contains several
updated routines developed and owned by IMSL (Visual Numerics Inc.). Our
agreement with IMSL stipulates that we will not distribute their source code.
The installer will compile the software but will not allow the unencrypted
source code to remain on the users computer. The licensing agreement will also
stipulate that any attempt to access the source code will be a violation of the
agreement.
Some source code will be left unencrypted for various reasons, one
being the need for users to change certain values in SIZES and perhaps other
resource routines.
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
--
The information contained in this email message may
contain confidential or legally privileged information and is intended solely
for the use of the named recipient(s). No confidentiality or privilege is
waived or lost by any transmission error. If the reader of this message is
not the intended recipient, please immediately delete the e-mail and all
copies of it from your system, destroy any hard copies of it and notify the
sender either by telephone or return e-mail. Any direct or indirect use,
disclosure, distribution, printing, or copying of any part of this message is
prohibited. Any views expressed in this message are those of the individual
sender, except where the message states otherwise and the sender is
authorized to state them to be the views of XOMA.
Dear all,
The term "open source" has been used in connection with NONMEM. This is
not correct. A better term might be "source distribution".
For the definition of "open source", please see
http://www.opensource.org/docs/osd
NONMEM distribution never complied with any of the rules, e.g., free
redistribution and derived works, nor was it intended to comply with
the spirit of open source. The code was always protected via copyright
and a strict license agreement (see below).
Some historical background: the first version of NONMEM (ca. 1980) was
distributed as pre-compiled binaries for IBM mainframes. Stuart decided
later to distribute as source only because it allowed NONMEM to be run
on more platforms. Comments were stripped to help it fit on the smaller
media (mag tapes; floppies) of the time. Did any users ever look at
the source code to understand what NONMEM was doing, or contact Stuart
to say "the algorithm in such and such a subroutine could be improved,
here is my suggestion"? Maybe, but Stuart did not distribue the source
code to invite collaboration. I believe that, had there been some way
of distributing NONMEM in a form that would allow it to be installed on
all platforms, but without providing the source code, Stuart would have
done so, and Lewis would have agreed.
Perhaps there will be a loss to the NONMEM community and to science when
the source is no longer distributed, but it is not "open source" as such
that is being lost. As Tom Ludden pointed out to me, "The new methods
have all been previously published. Only the specific implementations
of the methods are protected, not the science related to their
development."
Here are some of the provisions of the license agreement that was used
when UCSF distributed the code. As you can see, they were not at all in
the spirit of open source software, and do not allow anyone to take
NONMEM and develop it on their own.
2.1 REGENTS grants to LICENSEE a non-transferable, non-exclusive
license, under REGENTS' Copyright and/or license to use, for
internal use only, LICENSED PRODUCTS. No right to sublicense
REGENTS' LICENSED PRODUCTS is included herein and such right is
expressly withheld.
3. RIGHT TO USE .
3.1 LICENSEE shall have the right to copy and modify the LICENSED
PRODUCTS for use on a single computer of LICENSEE provided that any
portion thereof included in a modified work shall remain subject to
all terms and conditions of this Agreement. LICENSEE agrees to take
all steps necessary to ensure that the LICENSED PRODUCTS, or any
portion thereof, in any form, are not disclosed to others by
LICENSEE. LICENSEE warrants that all individuals having access to the
LICENSED PRODUCTS under this Agreement shall observe and perform this
nondisclosure covenant, and that the LICENSEE will establish adequate
procedures for this purpose.
11. TERMINATION
11.1 LICENSEE agrees that, should this license not be renewed within
thirty (30) days after its anniversary date, LICENSEE will return all
LICENSED PRODUCTS to REGENTS and will destroy all other copies of
LICENSED PRODUCTS and any derivative works of LICENSED PRODUCTS
LICENSEE may have in his possession.
--
Alison Boeckmann
[email protected]
Dear NMusers,
How many of NMusers had to look at the sources routine during their
daily PK/PD modeling? And Why ?
In the past I had to look at the source code to decipher vague errors
that I could not understand until I went to the fortran routine and see
at which circumstances this error is issued.
Other instances where I looked at the source code is when:
I needed to see which commons have the correlation matrix/ the R/ RINV,
S matrices...to be able to output these with more precision. (Happily,
NMVII will allow more control on the outputs precision).
Also I wanted to look at some undocumented features to be able to use
them:
e.g: the PHI function was previously available but undocumented.
Also to see more details about the numerical method used to approximate
the phi function...
In the nonmem help many entries ask the interested user to study the NM
code to understand and see how can use these advanced features.
With the encryption of the source code, can we expect more extensive and
complete documentation and flexible user controls?
Bests,
Samer Mouksassi
Dear Alison,
I agree that open source as defined by Open Source Initiative never
applied to the NONMEM. In my previous email I used the term "open
software", and it was also imprecise.
But until now, NONMEM wasn't a blackbox, either.
You are writing
(the provisions of the former UCSF license agreement) do not allow
anyone to take
NONMEM and develop it on their own.
It's not exactly what the point 3.1 says:
3.1 LICENSEE shall have the right to copy and *modify* the LICENSED
PRODUCTS for use on a single computer of LICENSEE ...
I understand licensees could develop NONMEM on their own provided they never try to disseminate neither original nor modified code.
It makes difference.
Regards
Wojciech
As a heavy NONMEM user since 1993 I never needed to look at the NONMEM code and
I believe that more than 95 percent of the users are the same and are more
interested in the modelling than in understanding the source code.
Ziad
Quoted reply history
------Original Message------
From: Eleveld, DJ
To: Serge Guzy
To: [email protected]
To: Ludden, Thomas
To: [email protected]
Subject: RE: [NMusers] RE: NONMEM 7 Update
Sent: 3 Jul 2009 21:40
Serge, I am afraid I dont understand what you are getting at.
Are you trying to say that so few people in the world understand the NONMEM code
and so noone is likely to complain that they cant understand the encrypted code?
Or are you trying to say that so few people in the world understand the NONMEM
code
and so encryption is rather pointless since it changes almost nothing?
Douglas
-----Original Message-----
From: [email protected] on behalf of Serge Guzy
Sent: Fri 7/3/2009 9:56 AM
To: [email protected]; [email protected]; [email protected]
Subject: Re: [NMusers] RE: NONMEM 7 Update
I do have only one simple question. How many people took advantage from the
fact Nonmem was distributed as open source? If we are talking about a very
small percentage, is this discussion worthwhile? How many people except bob
bauer and may be somebody else I am not aware of are able to follow and
understand the cuirrent nonmem code?
Serge
________________________________
From: [email protected]
To: Ludden, Thomas ; [email protected]
Sent: Thu Jul 02 23:46:09 2009
Subject: [NMusers] RE: NONMEM 7 Update
Thomas
Didn't ICON consider that indeed, this decision might stimulate the divergence
of an open-source clade of NONMEM, somewhat like R stemmed out of S-plus? If a
small academic group starts to work in that direction, it would certainly be
quickly joined by many.
Thierry Buclin
Univ. Hospital,
------Original Message Truncated------
Hi,
I think some interesting issues have been raised about Icon's plan to
distribute encrypted source code. I would like to ask what does this really hide and how can it benefit Icon and the user community?
First -- what is being hidden?
1. The 'old' estimation methods (METHOD=ZERO, METHOD=CONDITIONAL) with
their various options such as LAPLACE were revealed to previous licensees
of NONMEM. As far as I can tell these 'old' methods, in NONMEM7, function
very similarly to earlier versions but have been just been tweaked with some
changes in convergence options (NSIG, SIGL).
2. The 'new' ITS and MCPEM methods presumably came from the S-ADAPT package (developed by Bob Bauer) whose licensing agreement says "No part of the sofware may be repackaged into a non open-source version, and no part of the software may be sold for profit.". It remains to be seen how these new methods will help users but I am hopeful that incorporating these methods will give us new opportunities to improve the science.
3. I cannot be sure about the origins of the NONMEM SAEM method in
Monolix but the SAEM code in Monolix is distributed under a Free Software license agreement and it seems likely that this has been helpful for the NONMEM implentation. I am hopeful that the pioneering efforts of the Monolix team will benefit NONMEM users.
Thus the core methods of NONMEM, both old and new, are already available
to others who may want to compete with Icon so I wonder what the
encrypted source will really hide?
It is clear that the IMSL source code cannot be distributed to users
because that is the contract that Icon have with IMSL. Would it be
possible to distribute the licensed NONMEM source code with object code
libraries for the IMSL routines?
Serge asked " How many people took advantage from the fact Nonmem was
distributed as open source?". Under the earlier NONMEM license I was able to make modifications to the code to fix minor problems with compilers, improve the output formatting and compute interesting things like the determinant of the information matrix. These changes could be made without understanding the whole NONMEM system and no doubt others like me without formal training in fortran or
statistical software development were also able to personalise things.
After the major recoding effort of NONMEM into a modern fortran dialect
(thanks to Icon) it is likely that the code will no longer be
"functionally encrypted" and indeed might be usefully extended by others
developing new methods in this area. So even if only a few people have
been able to take advantage of the source code for NONMEM in the past it
is more likely that in the future more people will be able to contribute
to its development. Furthermore, inability to access the source code will also make it harder for 3rd party developers to help users (e.g. NMQUAL) to fix known bugs and to create qualified installations using different SIZES.
Second -- How does it aid Icon?
Hiding the source code might reduce the potential user base and thus license fees for Icon because statistical algorithm development has frequently had its roots outside of proprietary implementations. As Thierry pointed out (comparing S-Plus with R) isn't there a risk that hiding NONMEM will encourage others to
develop an competing alternative?
Once again I want to congratulate Bob, Tom and Alison for their efforts
to modernize NONMEM and prepare us for a new and more powerful tool. But
hiding the source code seems against the community spirit of nmusers who give freely of their experiences and expertise and the advantages, if any, to Icon remain obscure.
Best wishes,
Nick
--
Nick Holford, Professor Clinical Pharmacology
Dept Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand
[email protected] tel:+64(9)923-6730 fax:+64(9)373-7090
mobile: +33 64 271-6369 (Apr 6-Jul 20 2009)
http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford
The fact that NONMEM7 will not be open source code is very unfortunate,
it has not been often, but there have been occasions when by going over the
source code I was able to understand aspects of NONMEM programming that were
still unclear to me,
being able to get a look at the actual algorithms in software had been a major
advantage for NONMEM!!!!
Alice I Nichols, PhD
Sr Director
Early Development and Clinical Pharmacology
Wyeth Research
500 Arcola Rd
Collegeville, PA 19426
tel: 484-865-8741/ fax: 484-865-9075
[email protected]
>>> "Serge Guzy" <[email protected]> 7/3/2009 3:56 AM >>>
I do have only one simple question. How many people took advantage from the
fact Nonmem was distributed as open source? If we are talking about a very
small percentage, is this discussion worthwhile? How many people except bob
bauer and may be somebody else I am not aware of are able to follow and
understand the cuirrent nonmem code?
Serge
Quoted reply history
From: [email protected]
To: Ludden, Thomas ; [email protected]
Sent: Thu Jul 02 23:46:09 2009
Subject: [NMusers] RE: NONMEM 7 Update
Thomas Didn't ICON consider that indeed, this decision might stimulate the
divergence of an open-source clade of NONMEM, somewhat like R stemmed out of
S-plus? If a small academic group starts to work in that direction, it would
certainly be quickly joined by many* Thierry BuclinUniv. Hospital, Lausanne De
: [email protected] [mailto:[email protected]] De la part
de Ludden, Thomas
Envoyé : jeudi, 2. juillet 2009 15:15
À : Eleveld, DJ; [email protected]
Cc : Krohn, Anthony
Objet : RE: [NMusers] NONMEM 7 Update
Dear All:Icon Development Solutions has invested in the further development of
NONMEM. By mutual agreement with the University of California at San
Francisco, NONMEM 7 is intellectual property belonging to IDS. However, IDS
will continue to pay royalties to UCSF. The business plan under which NONMEM
7 was developed calls for the protection of the I.P. involved. In addition,
NONMEM 7 contains several updated routines developed and owned by IMSL (Visual
Numerics Inc.). Our agreement with IMSL stipulates that we will not distribute
their source code. The installer will compile the software but will not allow
the unencrypted source code to remain on the users computer. The licensing
agreement will also stipulate that any attempt to access the source code will
be a violation of the agreement. Some source code will be left unencrypted for
various reasons, one being the need for users to change certain values in SIZES
and perhaps other resource routines.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]: www.icondevsolutions.com
The information contained in this email message may contain confidential or
legally privileged information and is intended solely for the use of the named
recipient(s). No confidentiality or privilege is waived or lost by any
transmission error. If the reader of this message is not the intended
recipient, please immediately delete the e-mail and all copies of it from your
system, destroy any hard copies of it and notify the sender either by telephone
or return e-mail. Any direct or indirect use, disclosure, distribution,
printing, or copying of any part of this message is prohibited. Any views
expressed in this message are those of the individual sender, except where the
message states otherwise and the sender is authorized to state them to be the
views of XOMA.
Alice Nichols.vcf
Description:
Binary data
On Mon, Jul 6, 2009 at 2:35 PM, Alice Nichols<[email protected]> wrote:
> The fact that NONMEM7 will not be open source code is very unfortunate,
>
> it has not been often, but there have been occasions when by going over the
> source code I was able to understand aspects of NONMEM programming that were
> still unclear to me,
>
> being able to get a look at the actual algorithms in software had been a
> major advantage for NONMEM!!!!
I agree that having the source code available, even though released
under a restrictive license, can be valuable for a few people (myself
included). I would assume that the majority (at least 51%) of users
don't care, and probably shouldn't.
The comment about open source release of comparable tools -- well,
such do exist, and while some are suboptimal to NONMEM in their
current implementations, they could be improved if the right people
had time and interest -- but this is difficult, as the models and
statistical framework is fragile, given the pressure most of us (in
Pharma) have to use the minimal amount of information to get the most
robust answer feasible.
For example, the R packages nlmeODE, PKfit provide a starting point
which could be brought up to speed with the right people supporting
them, and other basic tools could be enhanced to provide a friendlier
environment.
People have pointed out Monolix, but that's more like NONMEM -- still
requires a commercial blackbox to run. No problem with blackboxes
for validation, SAS being the most famous.
Anyway, there are serious discrepancies between the published
algorithms and the implementations. So it isn't necessarily possible
to use the published work alone to figure out how to reconstruct
estimates except for straightforward model/data combinations.
unless the community is willing to put in (after-hours) effort for a
real open source solution, let's enjoy the strong support we currently
get from our commercial providers, and support and work with them.
After all, they are working to get our support (and funding!).
best,
-tony
(Stacey, for you:
Group Head, M&S Statistics, Novartis Pharma AG).
[email protected]
Muttenz, Switzerland.
"Commit early,commit often, and commit in a repository from which we
can easily roll-back your mistakes" (AJR, 4Jan05).
Drink Coffee: Do stupid things faster with more energy!
Allow me to respond to questions 2 and 3 regarding source code legacy.
2.
The new methods were originally written by me for S-ADAPT, so as author,
I was free to use them for other purposes. The reworking of the code to
fit NONMEM was then performed by me as a paid employee of ICON. This
code for NONMEM is therefore fully owned by ICON, and while it functions
mathematically similar to that in S-ADAPT, is now quite different in
appearance from that in S-ADAPT.
Nonetheless, S-ADAPT itself (which is not owned by ICON, and therefore
has no claim on S-ADAPT) and its source code that I wrote for it, along
with the legacy ADAPT II code that originally came from Dave D'Argenio
and Alan Schumitzky, continues to be open-source, and continues to be
forbidden from being sold for profit as is. This is in accordance with
the agreement that I arranged with Dave D'Argenio.
3.
The FORTRAN algorithms I wrote for the SAEM method were also originally
written for S-ADAPT. They are completely based on my reading the
MONOLIX manual on Marc Lavielle's description of the kernel density
setups, and the general literature on Bayesian analysis. I never read
the MATLAB source code of Monolix to implement these algorithms.
Robert J. Bauer, Ph.D.
Vice President, Pharmacometrics
ICON Development Solutions
Tel: (215) 616-6428
Mob: (925) 286-0769
Email: [email protected]
Web: www.icondevsolutions.com
Quoted reply history
-----Original Message-----
From: [email protected] [mailto:[email protected]]
On Behalf Of Nick Holford
Sent: Saturday, July 04, 2009 2:01 PM
To: nmusers
Subject: Re: [NMusers] NONMEM 7 Update
Hi,
I think some interesting issues have been raised about Icon's plan to
distribute encrypted source code. I would like to ask what does this
really hide
and how can it benefit Icon and the user community?
First -- what is being hidden?
1. The 'old' estimation methods (METHOD=ZERO, METHOD=CONDITIONAL) with
their various options such as LAPLACE were revealed to previous
licensees
of NONMEM. As far as I can tell these 'old' methods, in NONMEM7,
function
very similarly to earlier versions but have been just been tweaked with
some
changes in convergence options (NSIG, SIGL).
2. The 'new' ITS and MCPEM methods presumably came from the S-ADAPT
package
(developed by Bob Bauer) whose licensing agreement says "No part of the
sofware
may be repackaged into a non open-source version, and no part of the
software
may be sold for profit.". It remains to be seen how these new methods
will help
users but I am hopeful that incorporating these methods will give us new
opportunities to improve the science.
3. I cannot be sure about the origins of the NONMEM SAEM method in
Monolix but the SAEM code in Monolix is distributed under a Free
Software
license agreement and it seems likely that this has been helpful for the
NONMEM
implentation. I am hopeful that the pioneering efforts of the Monolix
team will
benefit NONMEM users.
Thus the core methods of NONMEM, both old and new, are already available
to others who may want to compete with Icon so I wonder what the
encrypted source will really hide?
It is clear that the IMSL source code cannot be distributed to users
because that is the contract that Icon have with IMSL. Would it be
possible to distribute the licensed NONMEM source code with object code
libraries for the IMSL routines?
Serge asked " How many people took advantage from the fact Nonmem was
distributed as open source?". Under the earlier NONMEM license I was
able to
make modifications to the code to fix minor problems with compilers,
improve
the output formatting and compute interesting things like the
determinant of the
information matrix. These changes could be made without understanding
the whole
NONMEM system and no doubt others like me without formal training in
fortran or
statistical software development were also able to personalise things.
After the major recoding effort of NONMEM into a modern fortran dialect
(thanks to Icon) it is likely that the code will no longer be
"functionally encrypted" and indeed might be usefully extended by others
developing new methods in this area. So even if only a few people have
been able to take advantage of the source code for NONMEM in the past it
is more likely that in the future more people will be able to contribute
to its development. Furthermore, inability to access the source code
will also
make it harder for 3rd party developers to help users (e.g. NMQUAL) to
fix known
bugs and to create qualified installations using different SIZES.
Second -- How does it aid Icon?
Hiding the source code might reduce the potential user base and thus
license
fees for Icon because statistical algorithm development has frequently
had its
roots outside of proprietary implementations. As Thierry pointed out
(comparing
S-Plus with R) isn't there a risk that hiding NONMEM will encourage
others to
develop an competing alternative?
Once again I want to congratulate Bob, Tom and Alison for their efforts
to modernize NONMEM and prepare us for a new and more powerful tool. But
hiding the source code seems against the community spirit of nmusers who
give
freely of their experiences and expertise and the advantages, if any, to
Icon
remain obscure.
Best wishes,
Nick
--
Nick Holford, Professor Clinical Pharmacology
Dept Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New
Zealand
[email protected] tel:+64(9)923-6730 fax:+64(9)373-7090
mobile: +33 64 271-6369 (Apr 6-Jul 20 2009)
http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford
I would strongly urge that ONLY the small segments which ICON considers their
proprerty by encypted,
all other code should be readable as fortran source code....
from prevous emails it sounded like only a small section of code related to
dimensioning of certain variables was to be readable by users,
Alice I Nichols, PhD
Sr Director
Early Development and Clinical Pharmacology
Wyeth Research
500 Arcola Rd
Collegeville, PA 19426
tel: 484-865-8741/ fax: 484-865-9075
[email protected]
>>> "Bauer, Robert" <[email protected]> 7/8/2009 5:40 PM >>>
Allow me to respond to questions 2 and 3 regarding source code legacy.
2.
The new methods were originally written by me for S-ADAPT, so as author,
I was free to use them for other purposes. The reworking of the code to
fit NONMEM was then performed by me as a paid employee of ICON. This
code for NONMEM is therefore fully owned by ICON, and while it functions
mathematically similar to that in S-ADAPT, is now quite different in
appearance from that in S-ADAPT.
Nonetheless, S-ADAPT itself (which is not owned by ICON, and therefore
has no claim on S-ADAPT) and its source code that I wrote for it, along
with the legacy ADAPT II code that originally came from Dave D'Argenio
and Alan Schumitzky, continues to be open-source, and continues to be
forbidden from being sold for profit as is. This is in accordance with
the agreement that I arranged with Dave D'Argenio.
3.
The FORTRAN algorithms I wrote for the SAEM method were also originally
written for S-ADAPT. They are completely based on my reading the
MONOLIX manual on Marc Lavielle's description of the kernel density
setups, and the general literature on Bayesian analysis. I never read
the MATLAB source code of Monolix to implement these algorithms.
Robert J. Bauer, Ph.D.
Vice President, Pharmacometrics
ICON Development Solutions
Tel: (215) 616-6428
Mob: (925) 286-0769
Email: [email protected]
Web: www.icondevsolutions.com
Quoted reply history
-----Original Message-----
From: [email protected] [mailto:[email protected]]
On Behalf Of Nick Holford
Sent: Saturday, July 04, 2009 2:01 PM
To: nmusers
Subject: Re: [NMusers] NONMEM 7 Update
Hi,
I think some interesting issues have been raised about Icon's plan to
distribute encrypted source code. I would like to ask what does this
really hide
and how can it benefit Icon and the user community?
First -- what is being hidden?
1. The 'old' estimation methods (METHOD=ZERO, METHOD=CONDITIONAL) with
their various options such as LAPLACE were revealed to previous
licensees
of NONMEM. As far as I can tell these 'old' methods, in NONMEM7,
function
very similarly to earlier versions but have been just been tweaked with
some
changes in convergence options (NSIG, SIGL).
2. The 'new' ITS and MCPEM methods presumably came from the S-ADAPT
package
(developed by Bob Bauer) whose licensing agreement says "No part of the
sofware
may be repackaged into a non open-source version, and no part of the
software
may be sold for profit.". It remains to be seen how these new methods
will help
users but I am hopeful that incorporating these methods will give us new
opportunities to improve the science.
3. I cannot be sure about the origins of the NONMEM SAEM method in
Monolix but the SAEM code in Monolix is distributed under a Free
Software
license agreement and it seems likely that this has been helpful for the
NONMEM
implentation. I am hopeful that the pioneering efforts of the Monolix
team will
benefit NONMEM users.
Thus the core methods of NONMEM, both old and new, are already available
to others who may want to compete with Icon so I wonder what the
encrypted source will really hide?
It is clear that the IMSL source code cannot be distributed to users
because that is the contract that Icon have with IMSL. Would it be
possible to distribute the licensed NONMEM source code with object code
libraries for the IMSL routines?
Serge asked " How many people took advantage from the fact Nonmem was
distributed as open source?". Under the earlier NONMEM license I was
able to
make modifications to the code to fix minor problems with compilers,
improve
the output formatting and compute interesting things like the
determinant of the
information matrix. These changes could be made without understanding
the whole
NONMEM system and no doubt others like me without formal training in
fortran or
statistical software development were also able to personalise things.
After the major recoding effort of NONMEM into a modern fortran dialect
(thanks to Icon) it is likely that the code will no longer be
"functionally encrypted" and indeed might be usefully extended by others
developing new methods in this area. So even if only a few people have
been able to take advantage of the source code for NONMEM in the past it
is more likely that in the future more people will be able to contribute
to its development. Furthermore, inability to access the source code
will also
make it harder for 3rd party developers to help users (e.g. NMQUAL) to
fix known
bugs and to create qualified installations using different SIZES.
Second -- How does it aid Icon?
Hiding the source code might reduce the potential user base and thus
license
fees for Icon because statistical algorithm development has frequently
had its
roots outside of proprietary implementations. As Thierry pointed out
(comparing
S-Plus with R) isn't there a risk that hiding NONMEM will encourage
others to
develop an competing alternative?
Once again I want to congratulate Bob, Tom and Alison for their efforts
to modernize NONMEM and prepare us for a new and more powerful tool. But
hiding the source code seems against the community spirit of nmusers who
give
freely of their experiences and expertise and the advantages, if any, to
Icon
remain obscure.
Best wishes,
Nick
--
Nick Holford, Professor Clinical Pharmacology
Dept Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New
Zealand
[email protected] tel:+64(9)923-6730 fax:+64(9)373-7090
mobile: +33 64 271-6369 (Apr 6-Jul 20 2009)
http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford
I would vote for this.
Alan
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Quoted reply history
-----Original Message-----
From: [email protected] [mailto:[email protected]]on
Behalf Of Alice Nichols
Sent: Thursday, July 09, 2009 9:15 AM
To: nmusers; Robert Bauer
Subject: RE: [NMusers] NONMEM 7 Update
I would strongly urge that ONLY the small segments which ICON considers their
proprerty by encypted,
all other code should be readable as fortran source code....
from prevous emails it sounded like only a small section of code related to
dimensioning of certain variables was to be readable by users,
Alice I Nichols, PhD
Sr Director
Early Development and Clinical Pharmacology
Wyeth Research
500 Arcola Rd
Collegeville, PA 19426
tel: 484-865-8741/ fax: 484-865-9075
[email protected]
>>> "Bauer, Robert" <[email protected]> 7/8/2009 5:40 PM >>>
Allow me to respond to questions 2 and 3 regarding source code legacy.
2.
The new methods were originally written by me for S-ADAPT, so as author,
I was free to use them for other purposes. The reworking of the code to
fit NONMEM was then performed by me as a paid employee of ICON. This
code for NONMEM is therefore fully owned by ICON, and while it functions
mathematically similar to that in S-ADAPT, is now quite different in
appearance from that in S-ADAPT.
Nonetheless, S-ADAPT itself (which is not owned by ICON, and therefore
has no claim on S-ADAPT) and its source code that I wrote for it, along
with the legacy ADAPT II code that originally came from Dave D'Argenio
and Alan Schumitzky, continues to be open-source, and continues to be
forbidden from being sold for profit as is. This is in accordance with
the agreement that I arranged with Dave D'Argenio.
3.
The FORTRAN algorithms I wrote for the SAEM method were also originally
written for S-ADAPT. They are completely based on my reading the
MONOLIX manual on Marc Lavielle's description of the kernel density
setups, and the general literature on Bayesian analysis. I never read
the MATLAB source code of Monolix to implement these algorithms.
Robert J. Bauer, Ph.D.
Vice President, Pharmacometrics
ICON Development Solutions
Tel: (215) 616-6428
Mob: (925) 286-0769
Email: [email protected]
Web: www.icondevsolutions.com
-----Original Message-----
From: [email protected] [ mailto:[email protected]]
On Behalf Of Nick Holford
Sent: Saturday, July 04, 2009 2:01 PM
To: nmusers
Subject: Re: [NMusers] NONMEM 7 Update
Hi,
I think some interesting issues have been raised about Icon's plan to
distribute encrypted source code. I would like to ask what does this
really hide
and how can it benefit Icon and the user community?
First -- what is being hidden?
1. The 'old' estimation methods (METHOD=ZERO, METHOD=CONDITIONAL) with
their various options such as LAPLACE were revealed to previous
licensees
of NONMEM. As far as I can tell these 'old' methods, in NONMEM7,
function
very similarly to earlier versions but have been just been tweaked with
some
changes in convergence options (NSIG, SIGL).
2. The 'new' ITS and MCPEM methods presumably came from the S-ADAPT
package
(developed by Bob Bauer) whose licensing agreement says "No part of the
sofware
may be repackaged into a non open-source version, and no part of the
software
may be sold for profit.". It remains to be seen how these new methods
will help
users but I am hopeful that incorporating these methods will give us new
opportunities to improve the science.
3. I cannot be sure about the origins of the NONMEM SAEM method in
Monolix but the SAEM code in Monolix is distributed under a Free
Software
license agreement and it seems likely that this has been helpful for the
NONMEM
implentation. I am hopeful that the pioneering efforts of the Monolix
team will
benefit NONMEM users.
Thus the core methods of NONMEM, both old and new, are already available
to others who may want to compete with Icon so I wonder what the
encrypted source will really hide?
It is clear that the IMSL source code cannot be distributed to users
because that is the contract that Icon have with IMSL. Would it be
possible to distribute the licensed NONMEM source code with object code
libraries for the IMSL routines?
Serge asked " How many people took advantage from the fact Nonmem was
distributed as open source?". Under the earlier NONMEM license I was
able to
make modifications to the code to fix minor problems with compilers,
improve
the output formatting and compute interesting things like the
determinant of the
information matrix. These changes could be made without understanding
the whole
NONMEM system and no doubt others like me without formal training in
fortran or
statistical software development were also able to personalise things.
After the major recoding effort of NONMEM into a modern fortran dialect
(thanks to Icon) it is likely that the code will no longer be
"functionally encrypted" and indeed might be usefully extended by others
developing new methods in this area. So even if only a few people have
been able to take advantage of the source code for NONMEM in the past it
is more likely that in the future more people will be able to contribute
to its development. Furthermore, inability to access the source code
will also
make it harder for 3rd party developers to help users (e.g. NMQUAL) to
fix known
bugs and to create qualified installations using different SIZES.
Second -- How does it aid Icon?
Hiding the source code might reduce the potential user base and thus
license
fees for Icon because statistical algorithm development has frequently
had its
roots outside of proprietary implementations. As Thierry pointed out
(comparing
S-Plus with R) isn't there a risk that hiding NONMEM will encourage
others to
develop an competing alternative?
Once again I want to congratulate Bob, Tom and Alison for their efforts
to modernize NONMEM and prepare us for a new and more powerful tool. But
hiding the source code seems against the community spirit of nmusers who
give
freely of their experiences and expertise and the advantages, if any, to
Icon
remain obscure.
Best wishes,
Nick
--
Nick Holford, Professor Clinical Pharmacology
Dept Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New
Zealand
[email protected] tel:+64(9)923-6730 fax:+64(9)373-7090
mobile: +33 64 271-6369 (Apr 6-Jul 20 2009)
http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford