RE: NONMEM 7 Update

-----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