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  • [NMusers] Referenced memory could not be written error
    popup NONMEM then terminates with the message No NONMEM execution There may be error messages in the file df txt When I check df txt it is an empty file I am running Digital Fortran Version 6 6 and have reinstalled the program I still get the same problem Has anyone encountered this problem before or have any ideas how I can fix it Thanks Pete Bonate Peter L Bonate

    Original URL path: http://nonmem.org/nonmem/nm/99may252006.html (2016-04-25)
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  • [NMusers] Dose optimization in drug development (Rajesh Krishna)
    the field this source focuses on two key interfaces in new drug development transition from preclinical to Phase I clinical development and transition from Phase IB IIA proof of concept to Phase IIB III pivotal efficacy trials promotes innovative clinical trial designs that may allow for a more optimal strategy for dose selection covers procedures and best practices in biomarker validation and qualification considers the benefits of novel clinical trial

    Original URL path: http://nonmem.org/nonmem/nm/99may082006.html (2016-04-25)
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  • [NMusers] leverage analysis vs. case deletion
    analysis i e investigation of influence of particular observations on the parameter estimates Leonid From Bonate Peter Peter Bonate genzyme com Subject NMusers leverage analysis vs case deletion Date Tue 2 May 2006 12 26 41 0400 They are not synonyms You can do a leverage analysis using case deletion but with linear models you do not need to do so You can use the HAT matrix in a linear model to get the leverage a subject exerts in a dataset With a nonlinear model with individual level data no repeated data you can get the same measure of influence using the Jacobian matrix With a linear mixed effects model there are ways to do this but they are not easy and require access to software that allows matrix calculations like MATLAB or SAS IML But with a nonlinear mixed effects model I am not aware of how you could get this data without doing case deletion Whenever I can I do a case deletion analysis on my data time permitting since you can also get the jackknife estimate of the standard errors Hope this helps pete Peter L Bonate PhD Genzyme Corporation Director Pharmacokinetics 4545 Horizon Hill Blvd San

    Original URL path: http://nonmem.org/nonmem/nm/99may022006.html (2016-04-25)
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  • [NMusers] Placebo in indirect PD models
    a related class of models which describe disease progression that can be intepreted as having a biological basis e g the rate of bone resorption changes with time growth of tumour cells see Holford et al 2001 These models are extensions to the turnover aka indirect effect model family which incorporate time varying changes in either input or loss which are independent of drug Whether or not one can estimates the model parameters is a question of the design of the study but with suitable designs the structural and randome effects parameters should be estimable Best wishes Nick Holford NHG Mould DR Peck CC Disease Progress Models In Atkinson A editor Principles of Clinical Pharmacology San Diego Academic Press 2001 p 253 62 Nick Holford Dept Pharmacology Clinical Pharmacology University of Auckland 85 Park Rd Private Bag 92019 Auckland New Zealand email n holford auckland ac nz tel 64 9 373 7599x86730 fax 373 7556 http www health auckland ac nz pharmacology staff nholford From Piotrovskij Vladimir PRDBE VPIOTROV PRDBE jnj com Subject RE NMusers Placebo in indirect PD models Date Thu 27 Apr 2006 09 27 39 0200 Dear Ivan There may be no general rule how to implement a placebo effect It depends very much on what is your dependent variable In case it is a score you may try the method presented at the PAGE meeting in Pamplona last year http www page meeting org abstract 773 Best regards Vladimir Vladimir Piotrovsky PhD Research Fellow Clinical Pharmacology Experimental Medicine J J Pharmaceutical Research and Development Beerse Belgium From jeffrey a wald gsk com Subject RE NMusers Placebo in indirect PD models Date Mon 1 May 2006 08 30 07 0400 Mark Thanks for your general thoughts but in the case of Ivan s original posting I do not think they are relevant In the case of drug effects that can be described by a semi physiological model such as an indirect response model the placebo response is typically inextricably linked to the pharmacology and the underlying physiology One of the advantages in physiologically based models is that you basically borrow degrees of freedom from your knowledge of the system So for example if inter individual variability in drug response relates to the measurements under baseline or placebo conditions then you can perhaps share an ETA for these 2 components that would otherwise be considered separate in a phenomenological model Furthermore pain is not a good example for the separability of drug placebo effects How could naloxone be a placebo antagonist if this were the case For example Benedetti F C Arduino and M Amanzio 1999 Somatotopic activation of opioid systems by target directed expectations of analgesia Journal of Neuroscience 19 May 1 3639 is one example from a large set of work addressing this for pain in particular Meta analyses in pain and other diseases depression is one that springs to mind have shown that the magnitude of placebo response correlates with the magnitude of pharmacological response

    Original URL path: http://nonmem.org/nonmem/nm/98apr262006.html (2016-04-25)
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  • [NMusers] Xpose 4.0
    the second preview release codenamed Easter Bunny is now available from http xpose sourceforge net Xpose 4 0 is a ground floor rewrite of Xpose 3 104 with the biggest change being the switch from S PLUS to R http www r project org Others include the adoption of a much more object oriented approach allowing Xpose to be used directly from the R console and much wider customization options which provide the flexibility needed to create publication quality graphics Also the newly opened architecture has made it much easier to use Xpose from within other applications Most of the original features of Xpose are now available for testing along with the traditional menu system with the rest to follow soon Some early installation glitches have been fixed and source code has been made available as usual This is a preview release so bugs are expected but reports of these and feature suggestions are very welcome You will need R version 2 2 0 or better with the add on package Hmisc installed to use Xpose 4 0 PR2 Xpose is a team effort supervised by Niclas Jonsson and Mats Karlsson with frontline support and coding being provided by myself

    Original URL path: http://nonmem.org/nonmem/nm/99apr262006.html (2016-04-25)
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  • [NMusers] Installation of NONMEM using NMQual.
    at line 46 code is written like CLOSE UN 28 If not and is written like CLOSE UN 28 STATUS DELETED then change code at line as CLOSE UN 28 15 Allow SETUP to proceed to a successful termination by typing Y at step 6 16 Change to the run directory cd run 17 Test the installation with the nmfe5 C shell script nmfe5 CONTROL5 report5 txt If successful and you set up NONMEM for PDx Pop the file OUTPUT will contain the results of the run If successful and you set up NONMEM for running with nmfe5 the file report5 txt will contain the results of the run But now one of our clients wants to install NONMEM using NMQual In that case the changes in step 12 above is done by NMQual But the other changes in steps 13 and 14 are not done Now the Question is what is the need of installing NONMEM with NMQual If the changes mentioned in step 13 and 14 are not done how it will effect the NONMEM execution Thanks in advance Ramajogi ramajogi clinapps com www clinapps com From Gastonguay Marc marcg metrumrg com Subject Re NMusers Installation of NONMEM using NMQual Date Mon 24 Apr 2006 22 06 52 0400 Dear Ramajogi I ll try to answer your general questions about NMQual and then the specific questions about the code changes you are trying to implement NMQual is an open source GPL tool to implement and track whatever NONMEM code changes install options a user wishes to make for a given installation NMQual also links each specific installation to a specific NONMEM run command and provides a mechanism for ensuring installation code integrity at each run time NMQual 4 1 is provided with templates with typical code changes for all reported NONMEM V bug fixes and some of the common setup options compiler or operating system specific changes as well I believe that NMQual is the only publicly available tool that automates the processes of keeping your NONMEM installation up to date and maintaining a record of all code changes For more information on how to use NMQual please read the User Guide and see the FAQ on the NMQual resources web site http metruminstitute org downloads nmqual You might also be interested in attending the upcoming web cast training sessions on NMQual http metruminstitute org training html A fee based Professional Services Package with extended support is also available from Metrum Research Group LLC nmqual services metrumrg com The code changes you ve identified in steps 13 and 14 are not part of the standard recommended code changes for NONMEM installation on linux but I think I ve found the sources for these Your Step 13 is related to display of iteration results to the terminal and is not a required installation step on linux As Bill Bachman points out this is a recommended code change if you are running with the PDxPop interface See http www cognigencorp

    Original URL path: http://nonmem.org/nonmem/nm/99apr242006.html (2016-04-25)
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  • [NMusers] Weighting in NONMEM
    in the ERROR what does NONMEM use OLS ELS or something else Can somebody comment on it Thank you very much Pat From GIRARD PASCAL PASCAL GIRARD adm univ lyon1 fr Subject RE NMusers Weighting in NONMEM Date Thu 20 Apr 2006 08 12 57 0200 Dear Pat Writing W whatever in ERROR has no action at all on NONMEM weightings The purpose of writing this is simply to compute individual weighted residuals IWRES which are not part of NONMEM output as opposed to population WRES provided by NONMEM IWRES have to be computed according to individual predictions F evaluated according to POSTHOC ETAs which are evaluated either with POSTHOC option if you use FO or are part of the computation with FOCE Best regards Pascal Dr Pascal Girard EA 3738 Ciblage Thérapeutique en Oncologie Fac Médecine Lyon Sud BP12 69921 OULLINS Cedex France Tel 33 0 4 26 23 59 54 Fax 33 0 4 26 23 59 76 From Bill Bachman bachmanw comcast net Subject RE NMusers Weighting in NONMEM Date Thu 20 Apr 2006 08 02 06 0400 As Pascal suggests weighting is accomplished in NONMEM via the variance model that you code in your model This

    Original URL path: http://nonmem.org/nonmem/nm/99apr192006.html (2016-04-25)
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  • [NMusers] ADAPT II with SAMPLE option
    is there any literature available on how to use the SAMPLE option because that is somehow neglected in the user s guide I would really appreciate if anybody could clarify what I m doing wrong Thanks a lot for your help Best regards Nele From bulitta ibmp osn de Subject Re NMusers ADAPT II with SAMPLE option Date Tue 18 Apr 2006 18 32 19 0200 I remember that those chapters of the Adapt II user manual helped me in the past chapters and pages refer to Release 4 of the Adapt manual Examples for D optimal sampling Chapter 4 7 Example pk7 SAMPLE D Optimal Design page 91 Chapter 6 5 Example 2compcl SAMPLE D Optimal Design page 167 Specification of dosage regimens Chapter 2 3 Preparing Data to be used with ADAPT page 13 Chapter 3 2 Model Inputs Bolus Inputs and Others page 34 Best regards many greetings Juergen From Stephen Duffull sduffull pharmacy uq edu au Subject RE NMusers ADAPT II with SAMPLE option Date Wed 19 Apr 2006 08 02 40 1000 Hi Nele I have no experience at using ADAPT ADAPT II But I can confirm that your model with 8 sampling times does not produce a singular matrix Indeed I tried this example in POPT for Population OPTimal design http www uq edu au pharmacy sduffull POPT htm and your original 8 sampling times was sufficient to provide good estimates for all your fixed and random effects parameters I perturbed the zero time to 0 01 and assumed a lognormal variance for all of your BSV terms of 0 1 And this optimizes fine as well I used 1200 as the dose However you mention a constant rate of 1200 which doesn t exist in your first order input model CL 6 6

    Original URL path: http://nonmem.org/nonmem/nm/99apr182006.html (2016-04-25)
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