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  • [NMusers] How to determine the initial estimates?Thanks
    Aug 2006 17 29 40 0800 Dear all The most puzzle to me when I read the NONMEM User Guide is the initial estimates I don t know why the author knew the initial estimates of THETA ETA OMIGA etc How does he do What about the LOWER BOUND and UPPER BOUND These parameters are exactly what we want NONMEM to work out for us So why I know their

    Original URL path: http://nonmem.org/nonmem/nm/98aug182006.html (2016-04-25)
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  • [NMusers] Can NONMEM compute all pharmacokinetics parameters ?
    17 0800 Dear all I find there are only a few parameters listed in the appendix1 Standard Pharmacokinetic Models and Parameters and appendix2 Alternative Parameterizations in User Guide PartV e g for ADVAN1 just K S1 S2 F1 F0 in

    Original URL path: http://nonmem.org/nonmem/nm/99aug182006.html (2016-04-25)
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  • [NMusers] different results from two computers
    0041BF17 Unknown Unknown Unknnow Estimation omitted Would you please comment on the situation and more importantly provide some advice Thanks Jenny From Mark Sale Next Level Solutions com Subject RE NMusers different results from two computers Date Wed 16 Aug 2006 04 57 22 0700 Nick et al Update on the stability of NONMEM importance of successful minimization After fixing a problem with the summation of the likelihood we have managed to make NONMEM converge successfully indenpendent of sequence of subjects You may recall the discussion that for one problem at least whether NONMEM converged was dependent on the sequence of subjects in the data set Nick appropriately cited this as some evidence of the lack of importance of successful minimization since for this this problem at least it seemed to be a random event since the sequence of subjects was randomly defined We seemed to have solved that source of instability in NONMEM with some fairly simple changes in the code and now have a version of NONMEM VI where convergence is independent of sequence of subjects in the data set and is essentially the best case from the 100 native NONMEM runs Perhaps eventually other sources of numerical instability will be identified and we can all agree that minimization really does mean something about the quality of the model data set I ll post the results of the native NONMEM and the modified NONMEM on my web site www NextLevelSolns com downloads probably tomorrow I m looking for cases to try where this approach will make models that refused to do a covariance step now will do one Anyone with interesting relatively fast problems www NextLevelSolns com From Nandy Partha PRDUS PNandy prdus jnj com Subject RE NMusers different results from two computers Date Fri 18 Aug 2006

    Original URL path: http://nonmem.org/nonmem/nm/99aug142006.html (2016-04-25)
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  • [NMusers] A question about Xpose!
    The user does not accept email in non Western non Latin character sets As you said I open the web http xpose sourceforge net downloads php and find some links listed there as follows Xpose 4 0 for R Windows Binary 4 0 Preview Release 3 Midnight Sun Update 4 Linux Binary 4 0 Preview Release 3 Midnight Sun Update 4 Source 4 0 Preview Release 3 Midnight Sun Update

    Original URL path: http://nonmem.org/nonmem/nm/99aug132006.html (2016-04-25)
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  • [NMusers] Hi,dear all ,some new questions occur !
    In addition I don t understand why there are some characters such as G F H in the Index plot for weight WT And what s the meaning of them What s the meaning of 3 or 2 in the plot of DV VS ID 2 The guide said Many points lie along the line AMT 0 where one sees integers 5 3 3 6 etc as one proceeds along the ID axis each integer indicating the corresponding number of points over plotted at that location My question is why there are so many overlap points in the index plot for AMT VS ID The picture x axis is AMT and its y axis is ID and the dot is corresponding to x coordinate AMT and its y coordinate ID so how does the points over plotted Thank you very much Best Regards Jiang From Mark Sale Next Level Solutions mark nextlevelsolns com Subject RE NMusers Hi dear all some new questions occur Date Fri 11 Aug 2006 03 38 29 0700 Jiang 1 First there are better plotting tools available than the built in plots in NONMEM which are set up for 135 column UNIX text output and upside

    Original URL path: http://nonmem.org/nonmem/nm/99aug112006.html (2016-04-25)
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  • [NMusers] How can I determine cl=theta1 or v=theta1?
    then How can I determine cl theta1 or v theta1 If I choose cl theta1 and v theta2 k cl v theta1 theta2 but if I choose v theta1 and cl theta2 then k cl v theta2 theta1 So the value of k will be entirely different at last e g let theta1 4 theta2 2 I ll get 2 different results respectively cl theta1 4 v theta2 2 k cl v theta1 theta2 4 2 2 another v theta1 4 cl theta2 2 then k cl v theta2 theta1 2 4 0 5 Look This is my puzzle Can you give me some directions Thank you very much From NIYI ADEDOKUN niyiadedokun hotmail com Subject RE NMusers How can I determine cl theta1 or v theta1 Date Tue 08 Aug 2006 15 00 39 0000 Hi Think of it this way CL and V and K are primary parameters hence they have fixed values Your thetas are just a reparameterization of the fixed parameters In other words it really does not matter which you call theta1 or theta2 because at the end of the day when you do get your results theta1 and theta2 will representy what you had

    Original URL path: http://nonmem.org/nonmem/nm/98aug082006.html (2016-04-25)
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  • [NMusers] How could I determine which thetan(n=1,2,3...) will be put to K or CL?
    1 K THETA 2 CL THETA 2 V THETA 2 V CL K V CL K K CL V S1 V S1 V S1 V CODE1 CODE2 CODE3 What differences are there between the 3 code above How could I determine which thetan n 1 2 3 will be put to K Thanks From Nick Holford http www health auckland ac nz pharmacology staff nholford From Bachman William MYD bachmanw

    Original URL path: http://nonmem.org/nonmem/nm/99aug082006.html (2016-04-25)
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  • [NMusers] Using BLQ data for SIGMA
    will result in all data being BQL you will get an estimate of CL less than 1 0 because you deleted some the data with CL mean but retained all the data with CL www NextLevelSolns com From Stephen Duffull stephen duffull stonebow otago ac nz Subject RE NMusers Using BLQ data for SIGMA Date Tue 8 Aug 2006 10 41 40 1200 Mark I hadn t thought of IOV as a contributor here But taking your example a little further If you had IOV greater than some arbitrary value that resulted in censoring of data as BLQ then you would presumably also get the other end of the spectrum too with concs that are much higher than expected So you would probably see some signal from IOV to support this phenomena and indeed simulations from your model would predict BLQ observations for some dose levels In this case you would have reason to believe that there is some need to account for BLQ data In the absence of this signal it seems to me that execution error which even happens in academia but of course at a much slower rate is a much more probable cause Steve Professor Stephen Duffull Chair of Clinical Pharmacy School of Pharmacy University of Otago PO Box 913 Dunedin New Zealand E stephen duffull otago ac nz P 64 3 479 5044 F 64 3 479 7034 From bulitta ibmp osn de Subject RE NMusers Using BLQ data for SIGMA Date Tue 08 Aug 2006 03 55 24 0200 Dear Dr Hutson As proposed before I would also rate an error in the clinical part or sample storage sample transport most likely from my experience as a clinical monitor What is written in the final study report or clinical report about the dose of the profile which was completely below the quantification limit BQL By how much was the dose increased in this subject You might try to test the high between occasion variability BOV hypothesis a Estimate the PopPK model with BOV while ignoring the profile which is completely BQL b Estimate the PopPK model with BOV while setting all concentrations of the profile which is completely BQL to zero or to a very small concentration Both a and b will probably yield biased estimates However a and b might give you an idea about the range of possibly true models If these two models yield similar answers to your ultimate modeling objectives this procedure might be sufficient and you might stop here In case a and b yield substantially different answers I would study the distribution of eta s outlier and the variance of the BOV terms in cases a and b If case b yields an extremely large BOV for clearance e g a BOV larger than the population parameter variability reported in literature for your drug and group of patients you might argue that this is objective evidence for a clinical error and that case a is the most appropriate

    Original URL path: http://nonmem.org/nonmem/nm/99aug072006.html (2016-04-25)
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