RE: [NMusers] Questions about identifiability

Hi Silke, If you are looking at model indentifiability, regardless of in-principle or in-practice, you absolutely must use a range of initial estimates. Minimization algorithms can converge to a minimum or a saddle point close to the initial estimates. If your model always finds the 'right' answ

RE: [NMusers] unscientific poll

My guess is the low response is likely an effect of inexperienced and intermediate users remaining silent to allow the most informed users decide the outcome of the poll. This was a consideration for me, even though I eventually decided to participate as an intermediate user. Regular reading of a

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? Doug

RE: [NMusers] NONMEM 7 Update

onplc.com] Verzonden: do 2-7-2009 15:15 Aan: Eleveld, DJ; nmusers@globomaxnm.com 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 S

RE: [NMusers] RE: NONMEM 7 Update

De : owner-nmus...@globomaxnm.com [mailto:owner-nmus...@globomaxnm.com] De la part de Ludden, Thomas Envoyé : jeudi, 2. juillet 2009 15:15 À : Eleveld, DJ; nmusers@globomaxnm.com Cc : Krohn, Anthony Objet : RE: [NMusers] NONMEM 7 Update Dear All: Icon Development Solutions has invest

RE: [NMusers] Parameter Shrinkage

Susan, The one I really liked was: M O Karlsson and R M Savic, Diagnosing Model Diagnostics, Clinical Pharmacology & Therapeutics (2007) 82, 17-20. doi:10.1038/sj.clpt.6100241 Douglas Eleveld Van: owner-nmus...@globomaxnm.com [mailto:owner-nmus...@globomaxnm

RE: [NMusers] Linear VS LTBS

Hi Neil, Well if you compare proportional+additive error model with a logarithmic error model then it shouldnt be suprising that they work differently and give you different residual variance. Logarithmic error model presumes that the accuracy of the observations, in absolute terms, becomes ve

RE: [NMusers] Calculating shrinkage when some etas are zero

Hi Pyry and Jacob, If you exclude zero etas then what happens to infomative individuals who just happen to have the population typical values? This approch would exclude these individuals when trying to indicate how informative an estimation is about a parameter. I know this is unlikely, but

RE: [NMusers] Generating Cmax at end of infusion

Hi, As others have suggested making an additional record at the known desired time is probably the most straightforward manner to get what you want. So this should probably be a preferred solution. If you for some reason you cant to add a record (maybe you dont know the time beforehand), I th

RE: [NMusers] distribution assumption of Eta in NONMEM

I'd like to interject a slightly different point of view to the distributional assumption question here. When I hear people speak in terms of the “distribution assumptions of some estimation method” I think its easy for people to jump to the conclusion that the normal distribution assumptio

RE: [NMusers] How to model observed quantity tha is an average over compartments

Hi Dieter, If you only onserve the average of two quantities you can never estimate the individual contributions. You must have some additional information to be able to do this. Maybe if the time constants are apriori known to be very different, i.e. fast and slow, then it might be possible

RE: [NMusers] How to model observed quantity tha is an average over compartments

different tissues. This can be apriori or determined by some other technique. Doug Eleveld -Oorspronkelijk bericht- Van: Dieter Menne [mailto:dieter.me...@menne-biomed.de] Verzonden: July 30, 2010 8:05 AM Aan: Eleveld, DJ; nmusers@globomaxnm.com Onderwerp: RE: [NMusers] How to model obs

RE: [NMusers] Block versus diagonal omega

Hi Jeroen, If shrinkage induces correlations (which arent "true") in the posthoc ETAs then the data isnt very informative for at least 1 of the parameters. If this (misleading) correlation causes the researcher to test a model with off-diagonal covariance, I would expect that they would not fi

[NMusers] Compiler warnings during recompilation, is this expected?

Hello NONMEM users, I am seeing compiler warnings during recompiling stage of NONMEM 7.2.0 runs. Is this expected? Or should I take this as a sign that something is wrong? I am using Linux (Ubuntu) and G95. best regards, Douglas Eleveld Recompiling certain components /home/deleveld/nm72/pr/S

RE: [NMusers] Compiler warnings during recompilation, is this expected?

Ok, thanks. I guess its a coding style issue, its probably very hard to make automatically generated code that is always warning-free -Original Message- From: Bill Bachman [mailto:bachm...@comcast.net] Sent: Fri 5/27/2011 1:57 PM To: Eleveld, DJ; 'nmusers' Subject: RE

RE: [NMusers] question about shinkage

Hi Li, Well, do you have rich data and a small number of subjects? How much shrinkage exactly? A very small negative number might just be due to (hopefully) non-important numerical issues. It could also be due to early termination of the estimation, not doing enough iterations, problems with

RE: [NMusers] Choice of models

Hi Toufigh, Just a suggestion that you may already be using, do you use the SORT option for estimation. This is i think helpful when the informativeness of individuals vary considerably. I might help stabilise the full data set. Douglas Eleveld From: o

[NMusers] RE: NM7.2 SAEM with LIKE

Hi All, I dont think it is contradictory to use the sample-based densities for integration and then use the classical EBE for reporting individual values. When integrating you want to see the entire individual density so you can give correct weight to large areas of low probability. But when y

RE: [NMusers] RE: Simulation settgin in the precence of Shrinkage in PK when doing PK-PD analysis

Hi All, The strange thing to me about the PPP&D method is that you generate two different posthoc estimates for individual PK, one from the PK modelling alone and another from the PPP&D step. Does anyone know if one of these inferior to the other? Which is the "right" individual posthoc PK est

RE: [NMusers] Reducing ETAs actually decreased OFV

You mean you removed an eta and the objective function went down? I dont think this can really happen in a straightforward way. In NONMEM, the minimum of the objective function is found and if having all etas to zero gives a lower objective function than some other eta values then barring coverg

RE: [NMusers] Time-varing covariate and renal function as a covariate

Hi Matt and Everyone, Whether or not "just using weight and CLCR should be enough" depends on whether you think that people who lost weight because of a drug (the formerly obese) are physilogically the same (with respect to the drugs in question) as those who were never obese. Are the formerly-

RE: [NMusers] OMEGA - CORR MATRIX FOR RANDOM EFFECTS - ETAS

Hi Jules, If the correlation between two ETAs is 0 then you should be able to remove one ETA and replace it by a scaled version of the other ETA and get the same objective function value. This model would not have a correlation problem (since only one ETA) so your problem would be "solved" in a

[NMusers] RE: Simulations with OMEGA BLOCK

Hi Andreas, You cant fix part of a block in NONMEM, you have to fix the whole block. So the trick is to construct the covaiance matrix structure you want out of smaller blocks. And when you fix an ETA on the diagonal to zero the corresponding covariances have to be zero as well. (i.e. the left-

[NMusers] Slow PRED in tables?

Hello everyone, I have a curious problem with slow PRED calculations in tables. The estimations are reasonably fast, 471 seconds for 23 iterations. If there is no PRED in any tables then NONMEM finishes a moment after the message about elapsed estimation time. But if is PRED in a table then it

[NMusers] RE: Slow PRED in tables?

there could be all sorts of practical considerations with legacy code. warm regards, Douglas Eleveld Van: Bauer, Robert [mailto:robert.ba...@iconplc.com] Verzonden: January 29, 2014 10:34 PM Aan: Eleveld, DJ; nmusers@globomaxnm.com Onderwerp: RE: Slow PRED in tables

[NMusers] RE: Slow PRED in tables?

Hi Robert, I can confirm that using WRESCHOL solves the problem. Thanks! warm regards Douglas Eleveld From: Bauer, Robert [robert.ba...@iconplc.com] Sent: Thursday, January 30, 2014 5:21 PM To: Eleveld, DJ; nmusers@globomaxnm.com Subject: RE: Slow PRED in

RE: [NMusers] OMEGA matrix

Hi Pavel, My question is: Why is it desirable to fit a complete omega matrix if its physical interpretation is unclear? Etas are variation of unknown origin i.e. not explained by the structural model. A full omega matrix allows the unknown variation of one paramater to have a (linear?) relations

RE: [NMusers] OMEGA matrix

; Eleveld, DJ Onderwerp: Re: [NMusers] OMEGA matrix Dear Pavel, others, The underlying technical difference is that SAEM is in its core a sampling methodology. Off-diagonal elements (as explained by Bob Bauer) are available as sample correlations and do not have to be separately computed in contrast

[NMusers] RE: IIV on res error

Hi Yuma, My experience is that some model modifications can greatly reduce objfn but make prediction actually worse. I like to use repeated 2-fold cross-validation since I am usually interested in accurate predictions for out-of-sample data. This may or may not be what you want your model to do

RE: [NMusers] Covariate lead to increase in Eta shrinkage

it sounds like that covariate provides information for the parameter influenced by eta. you have taken something that was unexplained population variation and explained part of it with the covariate. this is usually a good thing. if the covariate helps so much to predict the parameter that the et

[NMusers] RE: Standard errors of estimates for strictly positive parameters

Hi Aziz, Just some comments off the top of my head in a quite informal way: I'm not really sure that these are the same problem because they dont start with the same information in the form of parameter constraints. In model 1 you are asking the optimizer for the unconstrained maximum likelihoo

RE: [NMusers] Phsysiological model

Hi Andre, Hopefully you can see that (1) QCO=15.87*(BW)**0.75 calculates very different values for QCO compared to (2)QCO=15.87*(WT/WTstd)**0.75 unless of course WTstd is 1kg. In that case (WTstd is 1 kg) then they are exactly the same. The easiest way to separate these situations is to

RE: [NMusers] flip-flop without absorption information?

Hi Jakob and Everyone, In the no-covariate case flip and flop 😊 represent equal likelihoods i.e. two local minimums of equal depth. I agree that distributional assumptions would likely be useful to discriminate between two different parameters values that have equal likelihoods. Depending on how

[NMusers] Historical question

Hi All, I am writing a paper on some C language code I have written that does FOCE. I want to write a few sentences about the history of NONMEM but I'm not 100% sure it is correct. Can someone knowledgeable give me some feedback on this? "NONMEM software was developed at USCF in the late 1970s a

[NMusers] Re: Question about ETA on residual error

5 Aan: Eleveld, DJ ; nonmem usersgroup Onderwerp: RE: Question about ETA on residual error Hello Douglas: The off-diagonals of ETA(4, XXX) should be zero, as the variance-covariance of etas (phc) is the inverse of the information matrix that is calculated as: Ey(2nd derivative partial

[NMusers] Question about ETA on residual error

Hi All, I am having trouble understanding an aspect of NONMEM FOCEI estimation and I didn’t find anything in the documentation to get me started. When I add an ETA() on residual error everything estimates as I expect. I call this "composite error model", I dont know if there is another terminolog