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  • [NMusers] raised globulin levels in diabetics
    Aug 2005 08 46 45 0200 Dear All In various of my studies on type 2 diabetics I find that globulin levels are raised in approximately 90 of my subjects This is evident despite the absence of obvious hepatis conditions

    Original URL path: http://nonmem.org/nonmem/nm/99aug242005.html (2016-04-25)
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  • [NMusers] post hoc pk parameter associations with clinical covariates/response
    of subjects with or without a particular polymorphism or using logistic regression to model toxicity on drug clearance Is this two step approach statistically appropriate For instance a standard assumption of these tests and models is independence between subjects but it would appear that these predicted pk parameters are not independent I ve read some of the discussion of simultaneous versus sequential estimation in pk pd analysis of Karlsson Zhang

    Original URL path: http://nonmem.org/nonmem/nm/99aug192005.html (2016-04-25)
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  • [NMusers] bias and good fit vs centering
    METHOD 1 INT instead of LAPLACIAN In the current version of NONMEM version V LAPLACIAN ignore the interaction between ETA and EPSILON when it does exit If you have a model like Y F eta F eta ERR 1 LAPLACIAN will first simplify the model to Y F eta F 0 ERR 1 and then move on In my opinion for a linear mixed model with a proportional error model LAPLACIAN is equal to FO Despite the better approximation of LAPLACIAN method for the marginal likelihood in general lack of interaction option for LAPLACIAN may ultimately make LAPLACIAN worse than FOCE with interaction when the residual error model includes an interaction Yaning Wang Ph D Pharmacometrician Office of Clinical Pharmacology and Biopharmaceutics Center of Drug Research and Evaluation Food and Drug Administration Office 301 827 9763 From musor000 optonline net mailto musor000 optonline net Subject Re RE NMusers bias and good fit vs centering Sent Friday August 19 2005 8 57 PM Hello Yaning You are right I had to use the interaction option Also I used the same constant CV error for both studies and different additive erors It fixed the problem Thank you Pavel From Mouksassi Mohamad Samer mohamad samer mouksassi umontreal ca Subject NMusers bias and goodfit vs centering Date Fri 19 Aug 2005 11 01 15 0400 Pavel Dr Stuart Beal described a way to use the Laplacian aproximation with interaction in NONMEM V This can be found at http www cognigencorp com nonmem nm 99jul162002 html I have never tried it so far but maybe some other NONMEM users may have some experience in its application and advantages MOUKSASSI Mohamad Samer Pharm D Étudiant Ph D Sciences Parmaceutiques Université de Montréal Faculté de Pharmacie Pavillon Jean Coutu Tel 343 6111 ext 0388 From Wang Yaning

    Original URL path: http://nonmem.org/nonmem/nm/99aug182005.html (2016-04-25)
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  • [NMusers] Upgrading to Intel 9.0 Fortran for Windows
    regards Sam The most difficult part of upgrading your NONMEM and or Pdx Pop Installations to use Intel 9 0 Fortran for Windows is the installation of Intel s new compiler For some reason the instructions they provide are never quite clear IMO and the licensing issue compounds the problems Once the new compiler is installed however installation and running of NONMEM and PDx Pop are trivial The initial problem I encountered with the Intel installation was using the option to use a serial number I kept getting you have used an invalid serial number no matter how many times I contacted Intel support and verified the number Once I switched to the option to use a license file supplied as an email attachment by Intel installation proceeded without further issues The other issue you may encounter is if you have previous versions of Intel Fortran installed on your system The environmental variables may still have settings that point to previous versions of the compiler so that if you run the compiler command ifort from a DOS window it may tell you that you are running version 8 0 instead of 9 0 To circumvent this issue manually edit your system environment variables Remove paths to version 8 0 from the PATH LIB INCLUDE variables and replace as necessary with the correct paths for version 9 0 The ifortvars bat found in the C Program Files Intel Compiler Fortran 9 0 IA32 Bin directory for my installation will provide the information you need for the variables for version 9 0 Once you have modified your environment test that you are getting version 9 0 by running ifort from a DOS window The response should look something like C nmi9 run ifort Intel R Fortran Compiler for 32 bit applications Version

    Original URL path: http://nonmem.org/nonmem/nm/98aug172005.html (2016-04-25)
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  • [NMusers] PRIOR Subroutine
    example and may be also share their experience Thanks a lot for your help Regards Partha Partha Nandy Senior Research Investigator BMS From mari carmen llopis ipsen com Subject Re NMusers PRIOR Subroutine Date Thu 18 Aug 2005 10 37 17 0200 Dear Partha This is a paper about PRIOR Gisleskog PO Karlsson MO Beal SL Use of Prior Information to Stabilize a Population Data Analysis Journal of Pharmacokinetics Biopharmaceutics

    Original URL path: http://nonmem.org/nonmem/nm/99aug172005.html (2016-04-25)
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  • [NMusers] faster PC to run nmv
    2005 12 14 59 0400 Sam NONMEM is virtually all double precision floating point calculations While the buffers in NONMEM are set to be pretty small extremely small by today standards disc I O is essentially a non issue as modern operating systems will provide the buffering that makes disc I O irrelevant That makes selecting a machine CPU pretty easy compared to more modern applications with some of this

    Original URL path: http://nonmem.org/nonmem/nm/99aug152005.html (2016-04-25)
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  • [NMusers] Simulating different populations
    AUCT FLG EPS 1 ENDIF TRL IREP trial replicate number THETA 100 TYPICAL REFERENCE AUC 0 8 MODE OF POSTERIOR DISTRIBUTION POINT ESTIMATE OF FR1 0 075 THETA 3 IS SD OF UNCERTAINTY OR STANDARD ERROR FROM NONMEM COV OMEGA 100 100 SIGMA 10 1 SIMULATION 437565 NEW 47003 NORMAL ONLYSIM SUBPROBLEMS 100 TABLE ID DAY FLG AUCR AUCT F1 TRL DV FILE SIMUNCERT tab NOAPPEND NOPRINT NOHEADER From Liping Zhang ZHANG LIPING lilly com Subject Re NMusers Simulating different populations Date Wed 10 Aug 2005 11 09 16 0500 Hi Max what I typically do is to sample let s say 1000 replicates from the distribution of fixed effects parameters in Splus given estimated population parameter value and their variance covariance matrix generated by NONMEM So now you have a 1000 different population each has different fixed effects but overall they reflect the population parameter estimates and their uncertainty Then through some simple Unix C shell script I simulate the outcome from each population with fixed population parameters and BSV and WSV and do statistical summary according to modeling needs As Ken Kowalski pointed out not long ago this procedure is computer labor intensive you need to simulate large number of population and within each population a sufficient number trials I would not go for this route unless I know for my modeling need it requires this kind of truthful representation best regards Liping Liping Zhang PhD Global PK PD Modeling and Trial Simulation ELi Lilly Company Work 317 277 8687 Fax 317 433 6661 DC 0734 Email zhang liping lilly com From Kowalski Ken Ken Kowalski pfizer com Subject RE NMusers Simulating different populations Date Wed 10 Aug 2005 13 12 09 0400 Liping Just to clarify I indicated that simulating different sets of population estimates based on the var cov matrix from NONMEM and then assuming multivariate normal and possibly inverse Wishart for the variance parameters in Omega and or Sigma distributions for the parameter estimates is NOT computationally intensive However it is laborious to use these population estimates and feed them back in to NONMEM to perform simulations that take into account this parameter uncertainty because it requires custom coding Based on Marc s comments it sounds like he and others are working on developing utilities that will automate this process in NONMEM which would make it a lot easier to do this as a general practice If on the other hand we do not wish to make a parametric assumption using the var cov matrix and multivariate Normal Inverse Wishart distribution we could perform parametric or nonparametric bootstrap simulations and re fit the model in NONMEM for each of say 1000 bootstrap datasets to obtain 1000 estimates of the population parameters from the posterior distribution and use these in subsequent simulations to account for parameter uncertainty This approach IS computationally intensive because of having to re fit the model in NONMEM My feeling is that it is better to routinely do something to take into

    Original URL path: http://nonmem.org/nonmem/nm/99aug102005.html (2016-04-25)
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  • [NMusers] Part 11 compliance
    data change One can store scripts and other analysis files as PKS libraries to share them across studies and analyses There is more information available at www pharsight com Best regards Simon Simon Davis Senior Scientific Consultant Mobile 44 7980 832 666 Facsimile 1 801 991 7145 Home Office 44 113 274 1198 From Terri J Fisher tjfisher clinapps com Subject RE NMusers Part 11 compliance Date Mon 8 Aug 2005 09 30 09 0700 Hi Phil Without a doubt the most advanced choice for this is a product called SmartPK developed by Clinapps Inc This web based software brings 21 CFR Part 11 compliant electronic recordkeeping to your NONMEM environment All input and output files are stored electronically in read only format including the data and control stream files used to produce the results Full audit trail capability captures a record of each transaction in a relational database In addition to being able to create user accounts and assign roles to control project study level access Smart PK v2 0 allows you to move your NONMEM analysis from the desktop to a clustered server environment allowing you to execute multiple runs simultaneously accelerating your modeling and analysis process This

    Original URL path: http://nonmem.org/nonmem/nm/99aug082005.html (2016-04-25)
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