RE: [NMusers] ETABAR p-value

shrinkage is identically large for both positive and negative etas) would we expect the mean of posthoc etas to be zero. Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Div. of Pharmacokinetics and Drug Therapy Dept. of Pharmaceutical Biosciences Faculty of Pharmacy Uppsala

RE: [NMusers] ETABAR p-value

noted mean posthoc eta significantly different from zero even when the model is correct (see reference below for some more discussion on the "uselessness" of posthoc etas). http://www.aapspharmaceutica.com/search/abstract_view.asp?id=941&ct=06Abstra cts Best regards, Mats Mats Karl

RE: [NMusers] Modeling Growth Hormone Pulsatility

cortisol in healthy volunteers. Br J Clin Pharmacol. 2007 Feb 28; [Epub ahead of print] Mats Karlsson, PhD Professor of Pharmacometrics Div. of Pharmacokinetics and Drug Therapy Dept. of Pharmaceutical Biosciences Faculty of Pharmacy Uppsala University Box 591 SE-751 24 Uppsala Sweden phone +46

RE: [NMusers] XPOSE4 cur.db error

Dear Paul, Thanks for the praise. I'd just like to point out that Niclas Jonsson is the main architect around the changes - least credit should go to me. Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Div. of Pharmacokinetics and Drug Therapy Dep

RE: [NMusers] Interindividual variability in residual variance

Dear Mahesh, In order for the IIV in RV to be implemented, it is necessary that you use the INTERACTION option in $EST, even if you use the additive error. Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Div. of Pharmacokinetics and Drug Therapy Dept. of

RE: [NMusers] Interindividual variability in residual variance

regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Div. of Pharmacokinetics and Drug Therapy Dept. of Pharmaceutical Biosciences Faculty of Pharmacy Uppsala University Box 591 SE-751 24 Uppsala Sweden phone +46 18 471 4105 fax +46 18 471 4003 [EM

RE: [NMusers] Model Comparison and Viewing of Output

rds, Mats Mats Karlsson, PhD Professor of Pharmacometrics Div. of Pharmacokinetics and Drug Therapy Dept. of Pharmaceutical Biosciences Faculty of Pharmacy Uppsala University Box 591 SE-751 24 Uppsala Sweden phone +46 18 471 4105 fax +46 18 471 4003 [EMAIL PROTECTED] _ From: [EMAIL

RE: [NMusers] AUC Calculation in Simulation with and without EST

Dear Paul, When using $SIM only, the AUC will be estimated based on the simulated parameter values including the ETA's. With PRED or if you do $SIM+$EST (without POSTHOC), the AUC will be based on parameters with ETA set to zero. Best regards, Mats Mats Karlsson, PhD Profess

RE: [NMusers] AUC Calculation in Simulation with and without EST

Dear Paul, When using $SIM only, the AUC will be estimated based on the simulated parameter values including the ETA's. With PRED or if you do $SIM+$EST (without POSTHOC), the AUC will be based on parameters with ETA set to zero. Best regards, Mats Mats Karlsson, PhD Profess

RE: [NMusers] AUC Calculation in Simulation with and without EST

Dear Paul, When using $SIM only, the AUC will be estimated based on the simulated parameter values including the ETA's. With PRED or if you do $SIM+$EST (without POSTHOC), the AUC will be based on parameters with ETA set to zero. Best regards, Mats Mats Karlsson, PhD Profess

RE: [NMusers] 95% prediction interval and $OMEGA

Just to elaborate slightly on this last suggestion. If you use a $MSFI to input your parameters, use TRUE=FINAL to use the final, as opposed to the initial, estimates from that preceding run. If $MSFI is not used, TRUE=FINAL has no meaning. Mats Mats Karlsson, PhD Professor of Pharmacometrics

RE: [NMusers] unbalanced design

;, "rich+sparse unbalanced design", "sparse unbalanced design". Apart from this effect I know of no reason to expect unbalanced designs not to be robust if the model is correctly specified. Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Bio

RE: [NMusers] Very small P-Value for ETABAR

all diagnostics based individual ETAS are less useful. Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Uppsala University Box 591 751 24 Uppsala Sweden phone: +46 18 4714105 fax: +46 18 471 4003 -Original Message- From: [EMAIL PROTECTED]

RE: [NMusers] FO vs FOCE, sequential vs simultaneous

when these share parameters (as PK and PD data does). Therefore the advantage of using sequential will not be as large (if advantageous at all) compared to sequential for FO. Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Uppsala Unive

RE: [NMusers] The Standard Two-Stage and ELS

+2.00E+00 4.50E+01 5.27E+00 4.74E+01 3.70E+00 7.22E+00 -3.52E+00 3.06E-02 23 +2.00E+00 6.00E+01 5.27E+00 4.74E+01 1.80E+00 1.61E+00 1.89E-01 3.74E-02 Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Uppsala

RE: [NMusers] calculation of AUC

magnitude and will typically be: %RV expected AUC difference 10 0.50% 20 2% 30 5% 40 9% 50 14% 70 29% Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Uppsala

RE: [NMusers] calculation of AUC

ifferent if they are calculated in this way. I expect that if the model is correct, the observed NCA AUCs will be more similar to the simulated NCA AUCs. Hope this makes it clearer. Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Uppsala Un

RE: [NMusers] calculation of AUC

Nick, See comments below. Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Uppsala University Box 591 751 24 Uppsala Sweden phone: +46 18 4714105 fax: +46 18 471 4003 -Original Message- From: owner-nmus...@globomaxnm.com [mailto:owner-nmus

RE: [NMusers] VPC with Mixture Model

ssibly what you could do is be more careful in your choice of prediction intervals to display. For example, if you have a subpopulation of poor metabolizers of about 5%, displaying only median and interquartile range PIs may not be a good idea. Best regards, Mats Mats Karlsson, Ph

RE: [NMusers] OMEGA BLOCK with mixture model?

Pharmacol. 2005 Feb;59(2):189-98 Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Uppsala University Box 591 751 24 Uppsala Sweden phone: +46 18 4714105 fax: +46 18 471 4003 From: owner-nmus...@globomaxnm.com [mailto:owner-nmus

RE: [NMusers] VPC with Mixture Model

is 5%, but only 2% are allocated to this subpopulation by the EBE step. Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Uppsala University Box 591 751 24 Uppsala Sweden phone: +46 18 4714105 fax: +46 18 471 4003 -Original Message- Fr

RE: [NMusers] VPC with Mixture Model

Hi Nck, Exactly - when in simulation mode the correct assignment will take place. Here however, was the question about stratifying the VPC based on the value of the POSTHOC estimates based on the real data. Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences

RE: [NMusers] VPC with Mixture Model

e in NONMEM: finding the individual probability of belonging to a subpopulation for the use in model analysis and improved decision making." Carlsson KC, Savić RM, Hooker AC, Karlsson MO. AAPS J. 2009 Mar;11(1):148-54. Epub 2009 Mar 10. Mats Mats Karlsson, PhD Professor of Pharmacometri

RE: [NMusers] OMEGA BLOCK with mixture model?

s Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Uppsala University Box 591 751 24 Uppsala Sweden phone: +46 18 4714105 fax: +46 18 471 4003 From: Diane R Mould [mailto:drmo...@attglobal.net] Sent: Wednesday, April 15, 2009 6:16 PM To: 

RE: [NMusers] OMEGA selection

rrelations, whereas Bill interpreted it as CVs for IIV. It was just not enough info to make the distinction. If the model is so simple, why not show the whole model. Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Uppsala University Box 591 751 24 Upps

RE: [NMusers] OMEGA BLOCK with mixture model?

Hi Nele, So what exactly is the IIV model you are testing? Showing code is probably clearest. A model with only diagonal IIV in CL/F and V/F may well be underparameterized. What happened with the mixture? Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of

RE: [NMusers] OMEGA BLOCK with mixture model?

or two- or three-compartment models the advantages are that if indeed the main covariance structure between CL/F, V1/F, Q/F, V2/F is a joint positive correlation due to variability in bioavailability, fu etc, then a DIAG(5) is more parsimonious than a BLOCK(4). Mats Mats Karlsson, PhD Pr

RE: [NMusers] OMEGA BLOCK with mixture model?

Hi Steve, See below. Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Uppsala University Box 591 751 24 Uppsala Sweden phone: +46 18 4714105 fax: +46 18 471 4003 -Original Message- From: Stephen Duffull [mailto:stephen.duff...@otago.ac.nz] Sent

RE: [NMusers] OMEGA BLOCK with mixture model?

Hi Leonid, Pls see below. Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Uppsala University Box 591 751 24 Uppsala Sweden phone: +46 18 4714105 fax: +46 18 471 4003 -Original Message- From: Leonid Gibiansky [mailto:lgibian...@quantpharm.com] Sent

RE: [NMusers] Resetting af single compartment

Dear Thomas, Compartments can be turned on and off by specifying extra events (EVID=2) in the data set. To turn off CMT N use CMT column equal to –N, to turn it on use N in CMT column. Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical

RE: [NMusers] Time to event analysis using NONMEM

Dear Anubha, You need to have a record at time zero so that the integration can start. This record can be a EVID=2 Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Uppsala University Box 591 751 24 Uppsala Sweden phone: +46 18

RE: [NMusers] estimating Ka from dataset combining rich sample study and sparse sampling study

mplex structural model that a single profile indicated. Maybe you need to go to a two-compartment for example. Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Uppsala University Box 591 751 24 Uppsala Sweden phone: +46 18 4714105 fax: +

[NMusers] Post-doctoral positions available at Uppsala Univeristy

please contact me. Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Uppsala University Box 591 751 24 Uppsala Sweden phone: +46 18 4714105 fax: +46 18 471 4003

RE: [NMusers] Modeling of two time-to-event outcomes

hy it would be worse than a copula function. Nick's example is such a situation, like all examples where death is one event... Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Uppsala University Box 591 751 24 Uppsala Sweden phone: +46 18 4

RE: AW: [NMusers] Simulations with/without residual error

UNCCL UNCV CL V As for the error model this was of course intentional - checking impact of model misspecification is one of the reasons we do these kinds of simulation studies. :) Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Uppsala

RE: [NMusers] COND LAPLACE LIKELIHOOD

Dear Wang Did you put proper boundaries on B2 & B3? Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Uppsala University Box 591 751 24 Uppsala Sweden phone: +46 18 4714105 fax: +46 18 471 4003 -Original Message- From: owner-

RE: [NMusers] Re: count simulations

ments have incorrect type No nonmem execution. Is it that nonmem can give random number 0 and not 1? I can see only the numerical issue of log(0). ;-- Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Uppsala University Box 591 751

RE: [NMusers] Linear VS LTBS

Nick, Pls see below. Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Uppsala University Box 591 751 24 Uppsala Sweden phone: +46 18 4714105 fax: +46 18 471 4003 From: owner-nmus...@globomaxnm.com [mailto:owner-nmus

RE: [NMusers] Linear VS LTBS

esign. Error models for concentrations below LO? are not entirely unimportant, but will not have the properties you mention below. Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Uppsala University Box 591 751 24 Uppsala Sweden phone: +46 18 471410

RE: [NMusers] Linear VS LTBS

Hi Nick, Maybe Leonid's suggestion to agree to disagree was a good one but here we go again :) See below Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Uppsala University Box 591 751 24 Uppsala Sweden phone: +46 18 4714105 fax: +46 18 471

RE: [NMusers] Honest measurements

Nick, So the advice regarding handling of error models actually concerns a study that is to be done in your lab where negative concentrations are to be reported. Not the million of studies with LOQ limits. Could have been useful to know. Best regards, Mats Mats Karlsson, PhD Professor of

RE: [NMusers] Honest measurements

Steve, And we need to design our studies to what is reported, which means taking into account that for some observations, the only information you will get is that they are below a limit. Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences

RE: [NMusers] What does convergence/covariance show?

Nick, Pls see below. Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Uppsala University Box 591 751 24 Uppsala Sweden phone: +46 18 4714105 fax: +46 18 471 4003 -Original Message- From: owner-nmus...@globomaxnm.com [mailto:owner-nmus...@globomaxnm.com

RE: [NMusers] What does convergence/covariance show?

OFV as a measure of goodness-of-fit is central and look at the risk something improved the fit by chance, but I would not use it as measure of clinical importance. Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Uppsala University Box 591 7

RE: [NMusers] What does convergence/covariance show?

, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Uppsala University Box 591 751 24 Uppsala Sweden phone: +46 18 4714105 fax: +46 18 471 4003 -Original Message- From: owner-nmus...@globomaxnm.com [mailto:owner-nmus...@globomaxnm.com] On Behalf Of

RE: [NMusers] What does convergence/covariance show?

this that have no practical impact. You do not indicate what else in the survival analysis convinced you that the OFV was associated with something of practical consequence. I trust your decision was not based only on the OFV! Nick Mats Karlsson wrote: > Nick, > > I agree that small

RE: [NMusers] What does convergence/covariance show?

Nick, Could you elaborate on how you reason around the necessity of showing a priori power when you find a significant effects from the study data? How would you show it? Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Uppsala University Box

RE: [NMusers] time-dependent residual error models

(and alternatives such as residual error magnitude related to rate of change) in these publications: J Pharmacokinet Biopharm. 1995 Dec;23(6):651-72. J Pharmacokinet Biopharm. 1998 Apr;26(2):207-46 Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosci

[NMusers] researcher in PBPK modelling

within a week after application deadline. Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Uppsala University Box 591 751 24 Uppsala Sweden phone: +46 18 4714105 fax: +46 18 471 4003

RE: [NMusers] Modeling biomarker data below the LOQ

71-80. Epub 2009 May 19. Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Uppsala University Box 591 751 24 Uppsala Sweden phone: +46 18 4714105 fax: +46 18 471 4003 From: owner-nmus...@globomaxnm.com [mailto:owner

RE: [NMusers] BSV and BOV interaction

ion model should include such a correlation. If shrinkage is high (>20% or so) I would tend to use simulation-based or CWRES based diagnostics instead of posthoc eta's. Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Uppsala University Box 5

RE: [NMusers] Dilemma with PPK parameters

y, it is always appreciated to learn if and how the problem was solved. Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Uppsala University Box 591 751 24 Uppsala Sweden phone: +46 18 4714105 fax: +46 18 471 4003 -Original Message-

RE: [NMusers] distribution assumption of Eta in NONMEM

dissimilar to a cumulative normal are things to look out for. Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Uppsala University Box 591 751 24 Uppsala Sweden phone: +46 18 4714105 fax: +46 18 471 4003 From: owner-nmus

RE: [NMusers] distribution assumption of Eta in NONMEM

non-parametric methods where very little distributional assumption is being made. Semi-parametric methods are essentially parametric but parameters are estimated that relates not just the magnitude, but also the shape of the distribution.) Best regards, Mats Mats Karlsson, PhD Professo

RE: [NMusers] distribution assumption of Eta in NONMEM

results Stuart were basing his thoughts on, do you? Maybe the keyword in Stuart’s sentence is “largely”. Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Uppsala University Box 591 751 24 Uppsala Sweden phone: +46 18 4714105 fax

RE: [NMusers] distribution assumption of Eta in NONMEM

Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Uppsala University Box 591 751 24 Uppsala Sweden phone: +46 18 4714105 fax: +46 18 471 4003 From: owner-nmus...@globomaxnm.com [mailto:owner-nmus...@globomaxnm.com] On Behalf Of Nick Holford Sent: Monday

RE: [NMusers] distribution assumption of Eta in NONMEM

transformation TVCL=THETA(1) HTPAR=THETA(2) ETATR=ETA(1)*SQRT(ETA(1)*ETA(1))**HTPAR CL=TVCL*EXP(ETATR) Logit transformation TVCL=THETA(1) LGPAR1 = THETA(2) LGPAR2 = THETA(3) PHI = LOG(LGPAR1/(1-LGPAR1)) PAR1 = EXP(PHI+ETA(1)) ETATR = (PAR1/(1+PAR1)-LGPAR1)*LGPAR2 CL=TVCL*EXP(ETATR) Mats Mats Karlsson, PhD

RE: [NMusers] distribution assumption of Eta in NONMEM

0.08444 1.74E-24 0.001808 LGPAR1 = THETA(2) LGPAR2 = THETA(3) PHI = LOG(LGPAR1/(1-LGPAR1)) PAR1 = EXP(PHI+ETA(1)) ETATR = (PAR1/(1+PAR1)-LGPAR1)*LGPAR2 HILL=THETA(1)*EXP(ETATR) Y=1.1**HILL/(1.1**HILL+1) + EPS(1) Best regards, Mats Mats Karlsson, PhD

FW: [NMusers] distribution assumption of Eta in NONMEM

It seems my mails are not appearing on nmusers – maybe a sign that the thread has gone on too long. Anyway the one below is from yesterday. /Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Uppsala University Box 591 751 24 Uppsala Sweden phone: +46

RE: [NMusers] ALAG with transit model

Dear Ann, Change to ALAG4. Note that you could use ADVAN 5 or 7 for this model if you specify all rate constants. These should be faster. Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Uppsala University Sweden Postal

RE: [NMusers] Baseline as a covariate

more complex than easily handled via a covariance, then I suggest that you use the baseline observation as a covariate with error (Dansirikul et al Pharmacokinet Pharmacodyn. 2008 Jun;35(3):269-83.) Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical

RE: [NMusers] Rational of using IOV

IOV may not be modeled ideally. Then however, not only IOV, but also IIV and RV become “nuisance” parameters as they will not represent the true IIV or RV. Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Uppsala University Sweden

RE: [NMusers] Rational of using IOV

Seems like the mail below from last week never appeared on the nmusers. Probably the discussion became too long (or too hair-splitting.). Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Uppsala University Sweden Postal address

RE: [NMusers] Autoinduction model - An increased clearance(day 1- 14)

nt on the concentration of drug rather than an on/off ). The number of parameters is no more than the one you're using now, but avoids the change-point which often cause numerical problems. Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical B

RE: [NMusers] basic questions...

assuring that the residual error model is appropriate. Better alternatives are always welcome. Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Uppsala University Sweden Postal address: Box 591, 751 24 Uppsala, Sweden Phone +46

[NMusers] PhD student positions in pharmacometrics open for application

The pharmacometrics research group at Uppsala University are enrolling new PhD students. Information at http://www.personalavd.uu.se/ledigaplatser/engindex.html Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Uppsala University

RE: [NMusers] Confidence intervals of PsN bootstrap output

this upper boundary. If, as you say, the analyst has carefully thought through the boundaries, an estimate at the boundary should represent the global minimum within the reasonable parameter range. I think one can make a strong argument for not discarding such runs. Best regards, Mats Mats Karlsson, PhD

[NMusers] Eight Postdoctoral research positions in Pharmacometrics at Uppsala Univeristy

, 2012. Please specify a time window for possible starting dates. For further information and applications please contact Mats Karlsson mats.karls...@farmbio.uu.se. Some general information about the research group can be found at http://www.farmbio.uu.se/research/researchgroups/pharmacometrics/ and

RE: [NMusers] Output EPS(1) after an $EST step?

) and the agreement between epsilon and the residual is lost. Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Faculty of Pharmacy Uppsala University Box 591 75124 Uppsala Phone: +46 18 4714105 Fax + 46 18 4714003 From

RE: [NMusers] OMEGA priors using modes of inverse Wishart matrix

User's Guides, you may find useful info in Gisleskog et al J Pharmacokinet Pharmacodyn. 2002 Dec;29(5-6):473-505. Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Faculty of Pharmacy Uppsala University Box 591 75124 Up

FW: [NMusers] OMEGA priors using modes of inverse Wishart matrix

SE = Standard error of Omega^2 (from output f previous) Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Faculty of Pharmacy Uppsala University Box 591 75124 Uppsala Phone: +46 18 4714105 Fax + 46 18 4714003 From: Bauer,

RE: [NMusers] Coding delayed covariate effects

ETA10 ONEHEADER NOPRINT FILE=patab31 Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Faculty of Pharmacy Uppsala University Box 591 75124 Uppsala Phone: +46 18 4714105 Fax + 46 18 4714003 -Original Message- From: owner

RE: [NMusers] time-dependent clearance model

simple starting model, you can try combining the two. Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Faculty of Pharmacy Uppsala University Box 591 75124 Uppsala Phone: +46 18 4714105 Fax + 46 18 4714003 From: owner

RE: [NMusers] Question about handling BLOQ data with mixture model

Hi Martin, If you write P(3) =1-P(1)-P(2) you reduce the risk of writing something incorrect J Mats Karlsson Mats Karlsson, PhD Professor of Pharmacometrics FIRST WORLD CONFERENCE ON PHARMACOMETRICS, 5-7 September 2012, Seoul ( <http://www.go-wcop.org/> www.go-wcop.org) D

RE: [NMusers] Priors and covariate model building

lable. Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics FIRST WORLD CONFERENCE ON PHARMACOMETRICS, 5-7 September 2012, Seoul (www.go-wcop.org) Dept of Pharmaceutical Biosciences Faculty of Pharmacy Uppsala University Box 591 75124 Uppsala Phone: +46 18 4714105 Fax + 46 18 47

RE: [NMusers] Question about interoccation variability

Dear Claire, If you have data only from oral doses and covariances between disposition parameters (CL; V), then you will not get any further improvement by introducing variability in F1. Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics FIRST WORLD CONFERENCE ON

RE: [NMusers] Question about mixture model of Ka

to keep this parameterization for P(1), maybe you should try switching initial est's between THETA3 and THETA4. Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics FIRST WORLD CONFERENCE ON PHARMACOMETRICS, 5-7 September 2012, Seoul ( <http://www.go-wcop.org/&

[NMusers] Covariate modeling course in Philadelphia Oct 22-23, 2012

bayes estimates for diagnostics: problems and solutions. AAPS J. 2009 ;11:558-69. Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Faculty of Pharmacy Uppsala University Box 591 75124 Uppsala http://www.farmbio

[NMusers] Covariate modeling course in Philadelphia Oct 22-23, 2012

558-69. Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Faculty of Pharmacy Uppsala University Box 591 75124 Uppsala http://www.farmbio.uu.se/research/researchgroups/pharmacometrics/ Phone: +46 18 4714105 Fax +

RE: [NMusers] single-patient AUC

population PK model as prior, NONMEM and other non-linear mixed effects models are probably preferable. Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics FIRST WORLD CONFERENCE ON PHARMACOMETRICS, 5-7 September 2012, Seoul ( <http://www.go-wcop.org/> www.go-wc

RE: [NMusers] time-to-event simulation based diagnostic

Dear Francois, Unless you create a new data set where events are allowed to occur at any possible time (usually a dense time grid), then the result that you have got is rather the expected (i.e. too good to be true). Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics

RE: [NMusers] VPC question

ieve that the psn user guide for npc/vpc (npc_vpc_userguide.pdf) contains the information you seek. Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Faculty of Pharmacy Uppsala University Box 591 75124 Uppsala Phone: +46 18 4714

RE: [NMusers] RE: Proper way to handle the pre-first dose PK observation for non-endogenous drug

more relevant. If it is not, Nick's is more appropriate. Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Faculty of Pharmacy Uppsala University Box 591 75124 Uppsala Phone: +46 18 4714105 Fax + 46 18 4714003 -Original Message- F

RE: [NMusers] M3 method with log transformed data

Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Faculty of Pharmacy Uppsala University Box 591 75124 Uppsala Phone: +46 18 4714105 Fax + 46 18 4714003 From: owner-nmus...@globomaxnm.com [mailto:owner-nmus...@globomaxnm.com] On Behalf Of

RE: [NMusers] FW: Intersubject Variability in Logistic Regression

M you can just specify > $ESTIMATION MET=0 LIKE MAX=500 You should omit or rename the "ID" column, as NONMEM would expect ETAs when ID as in the data set. Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Faculty of

RE: [NMusers] Bootstrap, re-using inital model run results

, you could use the "-out=xxx.yyy" to point to the correct file if that does not follow naming conventions. If you have not run it and really don't want to run it, you could substitute xxx.yyy for some other output file with similar structure. Best regards, Mats Mats Karlsso

RE: [NMusers] Bootstrap, re-using inital model run results

Hi Anuba, I would agree with your suggestion. That is how I usually do it. Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Faculty of Pharmacy Uppsala University Box 591 75124 Uppsala Phone: +46 18 4714105 Fax + 46 18

RE: [NMusers] M3 method and multiple LOQ values

$ERROR IPRED=F LOQ=LLOQ DUM=(LOQ-IPRED)/(SQRT(SIGMA(1,1))*IPRED) CUMD=PHI(DUM) IF (BQL.EQ.0) THEN F_FLAG=0 Y=IPRED*(1+ ERR(1)) ENDIF IF (BQL.EQ.1) THEN F_FLAG=1 Y=CUMD ENDIF $EST METHOD=COND INTER LAPLACIAN $SIGMA .1 Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics

RE: [NMusers] Mixture model simulation

*(CL1 + CLr)* EXP(ETA(1)) CL=(1.0-Z)*(CL2 + CLr)* EXP(ETA(2)) V2 = THETA(4)*(WT/70)*EXP(ETA(3)) (I'm not sure about your ETA variance structure as it is not entirely provided, but if you use a covariance between CL and V use also separate ETAs for V between mixtures) Best regards, Mats Mats Kar

[NMusers] Covariate model building course before PAGE

Registration for a course on Covariate model building and evaluation in Glasgow June 10-11 has just opened at www.uppsala-pharmacometrics.com Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Faculty of Pharmacy Uppsala University

RE: [NMusers] Time-varing covariate

inear interpolation between observed covariate values $ERROR OCOV =COV;store previous time OTIM =TIME ;store previous time (NB haven't tested the code). Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Faculty o

Re: [NMusers] Time-varing covariate

gt; Leonid > Original email: > ----- > From: Mats Karlsson mats.karls...@farmbio.uu.se > Date: Sat, 24 Aug 2013 10:02:00 +0200 > To: william.s.den...@pfizer.com, ellen.siwei...@gmail.com, > nmusers@globomaxnm.com > Subject: RE: [NMusers] Time-varing covariate > > > Dear

RE: [NMusers] Time-varing covariate

Pharmacol. 2004 Oct;58(4):367-77. Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Faculty of Pharmacy Uppsala University Box 591 75124 Uppsala Phone: +46 18 4714105 Fax + 46 18 4714003 <http://www.farmbio.uu.se/resea

RE: [NMusers] Time-varing covariate

, you may not need to have to use EVID=2 to make the covariate change at other times than event times (as my example code tried to illustrate). Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Faculty of Pharmacy Uppsala University Box

RE: [NMusers] Parameter Estimation in IF Conditioning Statement

mechanism-based approach for absorption modeling: the Gastro-Intestinal Transit Time (GITT) model. STEP = EXP(X*GAM)/(EXP(X*GAM)+EXP(X50*GAM)) Where X50 (inflection point) would be estimated and GAM (steepness) typically fixed. Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics

RE: [NMusers] Prediction with parameter estimates on new data

population and individual). Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Faculty of Pharmacy Uppsala University Box 591 75124 Uppsala Phone: +46 18 4714105 Fax + 46 18 4714003 www.farmbio.uu.se/research/researchgroups/pharmacometrics/<h

SV: [NMusers] OMEGA matrix

nonparametric option does allow a fuller description of the correlation than the linear one though, so if that was the problem, $NONP may offer a solution. Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical Biosciences Faculty of Pharmacy Uppsala University Box

RE: [NMusers] Genotype data missing in some individuals

lsson MO. AAPS J. 2013 Oct;15(4):1035-42. doi: 10.1208/s12248-013-9508-0. Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics   Dept of Pharmaceutical Biosciences Faculty of Pharmacy Uppsala University Box 591 75124 Uppsala   Phone: +46 18 4714105 Fax + 46 18 4714003 www.farmbio.

[NMusers] Stockholm Uppsala Pharmacometrics meeting April 15th

nt model for the immunogenicity of certolizumab pegol in rheumatoid arthritis subjects Mats Karlsson, Uppsala University Welcome, Sofia Friberg Hietala Fredrik Jonsson Mats Karlsson Marie Sandström Janet Wade Johan Wallin Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical

RE: [NMusers] variation of time values in output data

Dear Diane-Charlotte, NONMEM interprets DATE in your in-data and makes use of it. If you don’t want that, rename DATE to something that is not recognized. Each date aboce the first adds 24 h to your time column Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics Dept of

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