Re: [NMusers] Problems with a physiologic model

Paul, One immediate problem is S3=VB; most likely, you need S4=VB since you observations are in compartment 4 Also, you do not have observations in A2 in the sample data set. If you do have them elsewhere, you need to define S2 as well. Why would you use ADVAN9 (nonlinear) rather than ADVAN5

Re: [NMusers] Problems with a physiologic model

ese, but I cannot figure out how to model the intravascular esterase inactivation of drug without using the differentials. Leonid Gibiansky wrote: Paul, One immediate problem is S3=VB; most likely, you need S4=VB since you observations are in compartment 4 Also, you do not have observations

Re: [NMusers] Problems with a physiologic model

need to scale it again using VB. Hope that helps. Manoj */Leonid Gibiansky <[EMAIL PROTECTED]>/* wrote: Paul, One immediate problem is S3=VB; most likely, you need S4=VB since you observations are in compartment 4 Also, you do not have observations in A2 in the sample da

[NMusers] ETABAR p-value

Dear All, Could anyone help me to interpret ETAbar p value? I have: TOT. NO. OF OBS RECS:1486 TOT. NO. OF INDIVIDUALS: 213 ETABAR: -0.52E-02 -0.27E-01 -0.93E-01 P VAL.: 0.90E+00 0.24E+00 0.81E-04 ETA1 ETA2 ETA3 ETA1 4.08E-01 ETA2 2.26E-01 2.31E-01 ETA3 0.0

Re: [NMusers] ETABAR p-value

] -Original Message- From: [EMAIL PROTECTED] [mailto:[EMAIL PROTECTED] On Behalf Of Leonid Gibiansky Sent: Tuesday, February 20, 2007 18:25 To: nmusers@globomaxnm.com Subject: [NMusers] ETABAR p-value Dear All, Could anyone help me to interpret ETAbar p value? I have

Re: [NMusers] Best approach with limited data

I am not sure that you can answer this question in general, without seeing the data. It may depend on the ratio of inter- to intra- individual errors. I would try it. One option could be to fix the variances of residual errors at values obtained from the full-profile subject. Also, you will need

Re: [NMusers] parent drug and metabolite

I cannot see any problems with the equations, looks correct to me: K=CL1/V1 DADT1=-K*A(1) S1=V1 etc. Leonid Nick Holford wrote: Sam, There is no problem with using CL1 in this code. This is not a reserved word and CL is not a required variable name when using $DES. I fixed the more obvious e

Re: Antwort: Re: [NMusers] change from mass to molar units

Since theoretically rescaling should not matter, the problem is in details that can not be extracted from the description without seeing the data and control stream. Just as an experiment (and to check your data creation process) run the model with the data where AMT and DV are rescaled by a fact

Re: [NMusers] Improved absorption profile by forcing volume of the central compartment

"The method with interaction does not work due to the small sample size." I do not think that this is correct. Sample size should not be an issue for FOCEI. If you have lag time with random effect, this could be a problem for FOCE, but not the sample size. Leonid [EMAIL PROTECTED] wrote: Hell

Re: [NMusers] trough time same as dosing time

Should not be a problem for oral administration. If IV, make sure that trough observation records are before the dosing records (time can be the same, but they should be ordered correctly). Leonid Ying HONG wrote: Dear NMusers, A single-dose of drug was given to healthy volunteers and a PK mo

Re: [NMusers] How does TIME work for multiple doses in NONMEM?

TIME is not reset, it is counted from the first dose in this example. To describe the model you need to introduce TAD (time after the most recent dose) into the data set and use it for FLAG reset: IF(TAD.GT.LAG) FLAG=1 Same with occasion, it would be best to introduce variable OCC (occasion, 1

Re: [NMusers] tumor growth model

In Nonmem V (and VI as well), you can put a unit dose to compartment 1, and then estimate "bioavailability" F1 F1=THETA(...)*EXP(ETA(...)) In Nonmem VI, you can directly supply initial conditions to the compartmental amounts via parameter A_0(1), e.g., A_0(1)=THETA(...)*EXP(ETA(...)) (see h

Re: [NMusers] Query on model development

Use S2=V/1000 instead of S1=V/1000 Leonid Tausif Ahmed wrote: Dear All, I am new to the field of POP-PK. We are developing a POP-PK model for our in-house drug. The conc. are in ng/mL and dose is in mg. The drug is administered *orally* and follows *1-compartment* model. It has a short hal

Re: [NMusers] Nonparametric method

If it is indeed similar, one can try to solve is with the similar trick, forcing all etas to work for all subjects: http://www.metrumrg.com/publications/aaps_2004_etabug.pdf Leonid Brian M. Sadler wrote: Dear Tom, How does it differ from the parametric problem of non-influential corre

Re: [NMusers] $MIX and $CONTR

Nick, I am not sure that the entire idea is correct: subject can only belong to one population, it cannot jump from population to population. Therefore, time dependent P() should not be allowed. Record-number dependence in $MIX was probably invented to have an option of defining the Ps either b

Re: [NMusers] $MIX and $CONTR

would be time varying. In the example proposed in the NONMEM help the covariate proposed for use in $MIX is AGE. If AGE is properly recorded in the data set then AGE is guaranteed to be a time varying covariate! Nick Leonid Gibiansky wrote: Nick, I am not sure that the entire idea is correct: s

Re: [NMusers] $MIX and $CONTR

not shift from one distribution to another (as explained in the example above). Nick Leonid Gibiansky wrote: Nick, I think you are reading it incorrectly. I would guess that for a long-term study you may relate probability of response to either baseline age or to the end-of-study age, or t

Re: [NMusers] S-plus multivariate normal distribution

Hi Nick, In R, use mvrnorm (load package MASS first) In S+, use rmvnorm Leonid -- Leonid Gibiansky President QuantPharm LLC www.quantpharm.com Nick Holford wrote: Hi, Can someone give me some clues on how to sample from a multivariate normal

Re: [NMusers] SIMULATION QUESTIONS

PRED should be used for comparison. 6. You data set lists observation compartment as CMT=8, is this correct(given the two-compartment model)? Leonid -- Leonid Gibiansky President QuantPharm LLC www.quantpharm.com [EMAIL PROTECTED] wrote

Re: [NMusers] SIMULATION QUESTIONS

Hi Live, In terms of GOF, look on the eta distributions (histograms and Q-Q plots): they should be centered and reasonably normal. Look on eta correlation (ETAs vs ETAs plots): they should be in agreement with correlations in your OMEGA matrix. Look on DV vs PRED: there should be no obvious bi

Re: [NMusers] Data File

1 14 2.2 0 179.4 0 0 0 If the interval between two last doses is exactly II=6, then both variants are equally good; otherwise, the second one could be a little better Leonid --- Leonid Gibiansky President QuantPharm LLC www.quantpharm.com Ganesh

Re: [NMusers] bug/feature in $AES

Hi Nick, It would help if you prepare a cleaner example that demonstrate the problem. What exactly are you trying to achieve (A(?)=?). A(1) and A(2) are not initialized in the code below, so they are zeros as they should. Is this about A3, A4? If yes, the problem could be in communication bet

Re: [NMusers] bug/feature in $AES

fixed then I would suggest that an extra state be added to the $AEINITIAL INIT variable. If INIT=-1 then this would mean to obtain a solution at time=0 and not bother to obtain solutions at subsequent times (for computational efficiency). Nick and Carl Leonid Gibiansky wrote: Hi Nick, It would h

Re: [NMusers] Error model

; combined error model Leonid -- Leonid Gibiansky, President QuantPharm LLC: www.quantpharm.com e-mail: LGibiansky at quantpharm.com tel: (301) 767 5566 James G Wright wrote: If Y is the original observed data, then the log-transformed error model is LOG (Y) = LOG

Re: [NMusers] Error model

James, Note that EVID=4 at those time points, so they could not influence variance of the residual error, and do not influence parameter estimates. Leonid James G Wright wrote: In regard to Navin's original problem, the most likely cause (in most datasets) is that you have some very small F's

Re: [NMusers] Error model

y big numbers when F is small, I expect this method would perform worse than working on the original scale. Best regards, James James G Wright PhD Scientist Wright Dose Ltd Tel: 44 (0) 772 5636914 www.wright-dose.com -Original Message- From: Leonid Gibiansky [mailto:[EMAIL PROT

Re: [NMusers] permissible band matrix

797 [4,]0079 > det(aa) [1] -2945 Leonid ------ Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:www.quantpharm.com e-mail: LGibiansky at quantpharm.com tel:(301) 767 5566 Sam Liao wrote: Dear NONMEM users: Can someon

Re: [NMusers] different COMRES statements

+1 need to be computed and replaced by a particular number, X is the number of elements required for implementation of PRIOR) etc $TABLE ...COM(x+1)=G11 .. I have not used this combination, so this is the untested idea. Leonid ------ Leonid Gibiansky, Ph.D.

Re: [NMusers] Reporting Modeling Results

-- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:www.quantpharm.com e-mail: LGibiansky at quantpharm.com tel:(301) 767 5566 John Mondick wrote: I would like to get some feedback from the group concerning the reporting of modeling results. I have a

Re: [NMusers] Reporting Modeling Results

the non-normalized set with the initial conditions closer to the solution (if you choose to use non-normalized problem as the final model). Leonid -- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:www.quantpharm.com e-mail: LGibiansky at

Re: [NMusers] Reporting Modeling Results

nsistent with John's statements. Best regards, Jeroen J. Elassaiss-Schaap Scientist PK/PD Organon NV PO Box 20, 5340 BH Oss, Netherlands Phone: + 31 412 66 9320 Fax: + 31 412 66 2506 e-mail: [EMAIL PROTECTED] -Original Message- From: [EMAIL PROTECTED] [mailto:[EMAIL PROTECTED] On B

Re: [NMusers] R package useful for electronic regulatory submissions

. Leonid ------ Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:www.quantpharm.com e-mail: LGibiansky at quantpharm.com tel:(301) 767 5566 Tim Bergsma wrote: Metrum Institute and Random Technologies LLC are pleased to announce the availability of th

Re: [NMusers] help with modelling of categorical response data

-- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:www.quantpharm.com e-mail: LGibiansky at quantpharm.com tel:(301) 767 5566 - $PRED CE=PROP ; define exposure: concentration, AUC or anything else ;PD EMAX=THETA(1)*EXP

Re: [NMusers] Unix to Windows Model Translation / PK Comp Initialization

not think that it is correct to initialize A(2) with 1 if you do not have IV dose=1 at TIME=0. Leonid -- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:www.quantpharm.com e-mail: LGibiansky at quantpharm.com tel:(301) 767 5566 [EMAIL

Re: [NMusers] Cmax, Tmax, and Time and AUC above threshold such as MIC

A(8) $TABLE ID TIME CMAX TMAX CC2 CC7 CC8 The last record of each patient should provide desired values. Leonid -- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:www.quantpharm.com e-mail: LGibiansky at quantpharm.com tel:(301) 767 5566 P

Re: [NMusers] Multiple amniotic fluid samples

bservation per embryon, it is unlikely that you can distinguish between intra and inter subject variability, so I would put everything to noise (sigma). Leonid ------ Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:www.quantpharm.com e-mail: LGi

Re: [NMusers] "Connect the dots" approach for a time-varying covariate

and assigning bioavailability (Nonmem V and VI) or (with Nonmem VI) using A_0(1)= etc. statements Leonid ------ Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:www.quantpharm.com e-mail: LGibiansky at quantpharm.com tel:(301) 767 5566 Samtani, Ma

Re: [NMusers] Why does covariance fail?

http://www.cognigencorp.com/nonmem/current/2007-July/0335.html -- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:www.quantpharm.com e-mail: LGibiansky at quantpharm.com tel:(301) 767 5566 Mark Sale - Next Level Solutions wrote: I'm thinking

Re: [NMusers] output SE of population PK parameters in Nonmem

Hi Rik, $COV PRINT=E should give you correlation matrix of the population parameter estimates As far as I know, there is no way to get SE (and hence covariance matrix) for individual parameter estimates (ETA values). Leonid -- Leonid Gibiansky, Ph.D

Re: [NMusers] Combined residual model and IWRES.

% for OMEGAs, as it should Leonid -- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:www.quantpharm.com e-mail: LGibiansky at quantpharm.com tel:(301) 767 5566 Paul Westwood wrote: Dear All, I'm working on a one-compartment iv model. I

Re: [NMusers] Combined residual model and IWRES.

*THETA(3)+THETA(4)) Y=F*(1+SQRT(THETA(3))*ERR(1))+SQRT(THETA(4))*ERR(2). also, if you take the square of SE% in thetas, you will see that it nearly matches SE% for SIGMAs, as it should Leonid -- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web

Re: [NMusers] IIV on %CV-Scale - Standard Error (SE)

Leonid -- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:www.quantpharm.com e-mail: LGibiansky at quantpharm.com tel:(301) 767 5566 Ribbing, Jakob wrote: Hi all, I think that Paul stumbled on a rather important issue. The SE of the residual

Re: [NMusers] System call from R causes loss of cursor control

= FALSE, invisible = TRUE) Leonid -- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:www.quantpharm.com e-mail: LGibiansky at quantpharm.com tel:(301) 767 5566 Nick Holford wrote: Dave, Have you tried using the minimized option for the R

Re: [NMusers] NM VI and NMV gave different results

output (error messages if any) Leonid -- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:www.quantpharm.com e-mail: LGibiansky at quantpharm.com tel:(301) 767 5566 Jian Xu wrote: Dear all, I did a Pop PK a year ago in NM V, and got a stable model

Re: [NMusers] Number of bootstrap runs needed for confidence intervals

ian(temp200v2) # -1.956067 median(temp1000) # -1.966652 median(temp10) # -1.959679 sd(temp200) # 0.1984375 sd(temp200v2) # 0.2052445 sd(temp1000)# 0.08406183 sd(temp10) # 0.008499137 ------ Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:www

Re: [NMusers] truncation & simulation

(correlated, as a vector) instead of PK parameters, and compute PK parameters based on the expected patient covariates. Leonid -- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:www.quantpharm.com e-mail: LGibiansky at quantpharm.com tel:(301) 767 5566

Re: [NMusers] Body weight distribution

/about/major/nhanes/nh3data.htm Data can be sampled from this collection, or if needed, described in a parametric way to sample from a derived distribution. Leonid -- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:www.quantpharm.com e-mail

Re: [NMusers] Differences with ADVAN3 TRANS1 and ADVAN3 TRANS4

explained) Leonid -- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:www.quantpharm.com e-mail: LGibiansky at quantpharm.com tel:(301) 767 5566 Paul Collier wrote: Please could someone explain why I get very different results when using ADVAN3

Re: [NMusers] Visual predictive check!

-- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:www.quantpharm.com e-mail: LGibiansky at quantpharm.com tel:(301) 767 5566 andreas lindauer wrote: Dear NMusers, I have a question regarding simulations for a VPC. When a combined residual error is used it happens that

Re: [NMusers] Sparse (pediatric) and rich (adult) data

dependence of CL on WT (if any is noticeable) for very young kids could be attributed to maturation and explained by AGE covariate Leonid -- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:www.quantpharm.com e-mail: LGibiansky at quantpharm.com tel

Re: [NMusers] Sparse (pediatric) and rich (adult) data

, it is not a substitute for the real data. Even with optimal design of the pediatric study (with the same 20 subjects, 3 optimal sample points) I bet you would gain by using adult data as well. Leonid -- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web

Re: [NMusers] Sparse (pediatric) and rich (adult) data

optimal. I think one should use both datasets together (in the specific case that was described) and it looks like we are in agreement on this point. Regards, Leonid -- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:www.quantpharm.com e-mail

Re: [NMusers] iNTRAVENOUS VS. INTRA-ARTERIAL SAMPLING

difference gradually declined. Apart from the times when the rate of concentration changes was very high (concentration changed significantly within 1-2 minutes) the difference between arterial and venous concentrations was negligible. Leonid -- Leonid Gibiansky

Re: [NMusers] Estimation of standard error

rt can be omitted. Or you can use separate errors for each CMT: > Y1=F+F*EPS(1) > Y2=F+F*EPS(2) > Y=R1*Y1+R2*Y2 -- S2= V2 should help to get SE. If not, try MATRIX=S on $COV line. Leonid ------ Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:

Re: [NMusers] Estimation of standard error

Huali Even if it gives a good fit, S2=V1 is still an error. You may try to assume that V2=V1, and then S2=V2=V1, it is fine, but in the current form, equations are incorrect Thanks Leonid -- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web

Re: [NMusers] algorithm limits

failure. Thanks Leonid -- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:www.quantpharm.com e-mail: LGibiansky at quantpharm.com tel:(301) 767 5566 Mark Sale - Next Level Solutions wrote: General question: What are practical limits on

Re: [NMusers] algorithm limits

-- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:www.quantpharm.com e-mail: LGibiansky at quantpharm.com tel:(301) 767 5566 Mark Sale - Next Level Solutions wrote: Leonid, This isn't PK, and the model show basically the right shape, and the data suggest reaso

Re: FW: [NMusers] PPC

covariates (such as study, dose, weight as necessary, etc.). Leonid -- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:www.quantpharm.com e-mail: LGibiansky at quantpharm.com tel:(301) 767 5566 [EMAIL PROTECTED] wrote: Dear Dr. Holford

Re: [NMusers] problem with PK fit in a PKPD model

graphically and using various PK-PD models. Leonid -- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:www.quantpharm.com e-mail: LGibiansky at quantpharm.com tel:(301) 767 5566 Fatemeh Akhlaghi, PhD wrote: Dear NMusers group: I am puzzled by the

[NMusers] NONMEM memory vs. run time

uences the run time. Is it better (in terms of the run time) to use standard sizes, or "big" is OK if you have enough RAM? Thanks! Leonid ---------- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:www.quantpharm.com e-mail: LGibiansky at quantpharm.c

Re: [NMusers] NONMEM memory vs. run time

capabilities. I think the OS manages to put active problems to RAM and non-active ones to swap space so that overall performance is not affected, but I am not sure, hence the question. Leonid -- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web

Re: [NMusers] Scaling for pediatric study planning

. Leonid ------ Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:www.quantpharm.com e-mail: LGibiansky at quantpharm.com tel:(301) 767 5566 [EMAIL PROTECTED] wrote: Dear NM_Users, we have all been good students and listened to Nick when he told us again and again the rock-solid

Re: [NMusers] Scaling for pediatric study planning

same equation as DADT(1)= -C1*VM'/(KM+C1) - K10*A(1) then DADT(1)= -A(1)*(VM'/V1)/(KM+C1) - K10*A(1) VM' is indeed should be scaled as WT**0.75 (thus leading to VM scaled as WT**(-0.25). Leonid ------ Leonid Gibiansky, Ph.D. President, Qua

Re: [NMusers] target-mediate model: numerical difficulties

(within the dose/concentration range of your data) Leonid Gibiansky, Ekaterina Gibiansky,Tarundeep Kakkar, Peiming Ma, Approximations of the Target-Mediated Drug Disposition Model and Identifiability of Model Parameters, PAGE 17 (2008) Abstract 1269 [www.page-meeting.org/?abstract=1269] http

Re: [NMusers] a potential bug

-- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:www.quantpharm.com e-mail: LGibiansky at quantpharm.com tel:(301) 767 5566 [EMAIL PROTECTED] wrote: Hello NONMEM Users, Subjects received IV infusion (study 2), IV injection or SQ injection (study1). In

Re: [NMusers] More Levels of Random Effects

the simplest, most reasonable and the most-often used option). Thanks Leonid -- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:www.quantpharm.com e-mail: LGibiansky at quantpharm.com tel:(301) 767 5566 Nick Holford wrote: Xia, There is no

Re: [NMusers] More Levels of Random Effects

cannot be repeated, so your covariate (occasion) will have different value (level) at any future trial. Leonid -- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:www.quantpharm.com e-mail: LGibiansky at quantpharm.com tel:(301) 767 5566 Nick

Re: [NMusers] More Levels of Random Effects

The next level of random effects can be introduced in NONMEM using PRIOR subroutine. It existed as undocumented feature even in Nonmem V. Now (in Nonmem VI) it is official (see help). Leonid -- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web

Re: [NMusers] More Levels of Random Effects

Hi Bill, I think, description in $PRIOR and nwpri help entries are the most helpful. The simplest 1-compartment problem example is below. Good luck! Leonid -- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:www.quantpharm.com e-mail: LGibiansky at

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

. If they are OK than I would not worry about ETABAR. However, small ETABAR p-value often hints that the ETA distribution is not symmetric, or has outliers (non-symmetric long tails). Thanks Leonid -- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web

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

THETA(2) Thanks Leonid -- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:www.quantpharm.com e-mail: LGibiansky at quantpharm.com tel:(301) 767 5566 Xia Li wrote: Hi Nick, My pleasure! This is a topic from Bayesian Hierarchical Model(BHM). If we

Re: [NMusers] Models that abort before convergence Addendum

e you ever used in your report/publication FINAL model that did not converge (YES/NO): 8. Define yourself as novice/intermediate/experienced Nonmem user: Thanks Leonid ------ Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:www.quantpharm.com e-mail: LG

Re: [NMusers] Models that abort before convergence Addendum

the poll beyond this simple statement. In addition, questions 4-7 will help us to understand how widespred is the use of models with failed convergence step and/or with failed minimization step. Thanks Leonid ------ Leonid Gibiansky, Ph.D. President, Qua

[NMusers] unscientific poll

-pasted after the summary of replies. Part 3: CSV file with the original data is copy-pasted after the comments Part 4: R code that I used to summarize the results is provided Thanks to all who participated. Leonid -- Leonid Gibiansky, Ph.D. President, QuantPharm

Re: [NMusers] Modelling intracellular and plasma data

DADT(1) = -K*A(1) ; plasma C1=A(1)/V1 DADT(2) = K2*A(1)-K23*A(2) ;"transit"(can be duplicated to increase delay) DADT(3) = K23*A(3)-K30*A(3) ; intracellular C3=A(3)/V3 Thanks Leonid ------ Leonid Gibiansky, Ph.D. President, QuantPha

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

-- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:www.quantpharm.com e-mail: LGibiansky at quantpharm.com tel:(301) 767 5566 Xiao, Alan wrote: Dear All, I know this is an old topic, too, but would like to see the statistics. When you have a dataset with

Re: [NMusers] CrcL or Cr in pediatric model

nce: TVCL=THETA(X)*(WT/70)**0.75+THETA(Y)*CRCL ------ Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:www.quantpharm.com e-mail: LGibiansky at quantpharm.com tel:(301) 767 5566 Bonate, Peter wrote: I have an interesting question I'd like to

Re: [NMusers] CrcL or Cr in pediatric model

dels on CL for each level of renal function? The suggestion was to define the renal disease as categorical variable, and then correct CL, for example: TCL ~ THETA(1) (for healthy) TCL ~ THETA(2) (for patients with severe renal impairment) Thanks Leonid ---------- Leoni

Re: [NMusers] CrcL or Cr in pediatric model

categorical description does not show any renal impairment effect, it makes no sense to use more complicated models, and it makes sense to explain dependence of CL on CRCL by WT, AGE or other available covariates. Best Leonid -- Leonid Gibiansky, Ph.D

Re: [NMusers] CrcL or Cr in pediatric model

Jakob, The model that I mentioned is not additive; it is multiplicative: Parameter= MeanValue*Effect1(WT)*Effect2(RF) but the effect of RF is expressed as a linear function of RF Effect2(RF) = 1 + THETA()*RF Leonid -- Leonid Gibiansky, Ph.D. President

Re: [NMusers] CrcL or Cr in pediatric model

. Leonid ------ Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:www.quantpharm.com e-mail: LGibiansky at quantpharm.com tel:(301) 767 5566 Ribbing, Jakob wrote: Leonid, As I understand the linear model you suggested it can be simplified* to this structure: THETA(1)*((W

Re: [NMusers] Identifiablity of parent / metabolite PK with interconversion

missing VS=V2, VA=V3 somewhere. Thanks Leonid -- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:www.quantpharm.com e-mail: LGibiansky at quantpharm.com tel:(301) 767 5566 Dong-Seok Yim wrote: > > Hi, colleagues, > > I am current

Re: [NMusers] Identifiablity of parent / metabolite PK with interconversion

. Thanks Leonid -- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:www.quantpharm.com e-mail: LGibiansky at quantpharm.com tel:(301) 767 5566 Dong-Seok Yim wrote: Leonid, Thank you for your comprehensive comment. Once I raised this, I wish to ask

Re: [NMusers] simulation question

files needed to run nonmem (in R, use setwd(NonmemDirName) to do it) Leonid -- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:www.quantpharm.com e-mail: LGibiansky at quantpharm.com tel:(301) 767 5566 Ethan Wu wrote: Dear users, I am trying

Re: [NMusers] Theoretical questions about Beal's M2 method

eads to l(t) below. As to the 0 to 1 restriction, l(t) is the density, not probability. It should integrate to one but can be smaller or greater than 1 (any positive number). Leonid ------ Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:www.qua

Re: [NMusers] var-cov matrix issue?

parameters, this use of the inverse variance-covariance matrix is somewhat limited. -- ------ Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:www.quantpharm.com e-mail: LGibiansky at quantpharm.com tel:(301) 767 5566 Bachman, William wrote: As a cla

Re: [NMusers] VPC, NPC or PPC?

-- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:www.quantpharm.com e-mail: LGibiansky at quantpharm.com tel:(301) 767 5566 SIMON Nicolas wrote: Hi All, We have a dataset with as many dosing (amount and length of infusion) as patients. Once the final model was defined, I

Re: [NMusers] VPC, NPC or PPC?

to get higher doses in this design). Thanks Leonid -- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:www.quantpharm.com e-mail: LGibiansky at quantpharm.com tel:(301) 767 5566 SIMON Nicolas wrote: Hi Leonid, Thanks for your help. The

Re: [NMusers] Log transformation of concentration

estimates): you can find the poster on PAGE web site. Still, for several real data sets, I've seen that the log-transformed model provided slightly better fit, especially for data with large residual error. Leonid -- Leonid Gibiansky, Ph.D. Pres

Re: [NMusers] Log transformation of concentration

should allow (in theory, given sufficient amount of data) to recover the true model, including the true error model. Log-transformation is just the trick that allows to implement the exponential error model in nonmem. Thanks Leonid ------ Leonid Gibiansky, Ph.D.

Re: [NMusers] OMEGA BLOCK with mixture model?

-- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:www.quantpharm.com e-mail: LGibiansky at quantpharm.com tel:(301) 767 5566 nele.pl...@nycomed.com wrote: Dear all, I am trying to fit a PK model to oral data. In the data, we observed two things: First, CL seems to be

Re: [NMusers] VPC with Mixture Model

ation than other model diagnostics) Thanks Leonid ------ Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:www.quantpharm.com e-mail: LGibiansky at quantpharm.com tel:(301) 767 5566 Mats Karlsson wrote: Dear Satyendra, Interesting question. I d

Re: [NMusers] OMEGA BLOCK with mixture model?

arm)? Is it always stable (or at least as stable as BLOCK(2))? Thanks Leonid -- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:www.quantpharm.com e-mail: LGibiansky at quantpharm.com tel:(301) 767 5566 Mats Karlsson wrote: Hi Steve, For a

Re: [NMusers] OMEGA BLOCK with mixture model?

-- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:www.quantpharm.com e-mail: LGibiansky at quantpharm.com tel:(301) 767 5566 Mats Karlsson wrote: Hi Leonid, Pls see below. Mats Karlsson, PhD Professor of Pharmacometrics Dept of Pharmaceutical

Re: [NMusers] Bootstrap analysis

probability of observing the value as extreme as the final-model parameter estimates based on the bootstrap distribution (using a percent of bootstrap estimates that are below or above the final-model. estimate). Thanks Leonid -- Leonid Gibiansky, Ph.D

Re: [NMusers] Resetting af single compartment

(although I never tried it) Leonid -- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:www.quantpharm.com e-mail: LGibiansky at quantpharm.com tel:(301) 767 5566 Elassaiss - Schaap, J. (Jeroen) wrote: Thomas, Two solutions (their smart

Re: [NMusers] forrtl: error (73): floating divide by zero

I would try IF(W.LE.0.01) W = 1 Leonid -- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:www.quantpharm.com e-mail: LGibiansky at quantpharm.com tel:(301) 767 5566 hoxu8...@mail.usyd.edu.au wrote: Dear Nonmem users, I have been

Re: [NMusers] Coding a triple absorption model

SUM=1+ EXP(THETA(1)+ETA(1)) + EXP(THETA(2)+ETA(2)) F1=EXP(THETA(1)+ETA(1))/SUM F2=EXP(THETA(2)+ETA(2))/SUM F3=1/SUM -- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:www.quantpharm.com e-mail: LGibiansky at quantpharm.com tel:(301) 767 5566

Re: [NMusers] Time to event analysis using NONMEM

Anubha You do not have time=0 records, therefore, A(1)=0 Try HZ=BASE*TIME (and use $PRED rather than $PK) Leonid -- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:www.quantpharm.com e-mail: LGibiansky at quantpharm.com tel:(301) 767 5566

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

You can try IF(RICH data) THEN KA=THETA(1)*EXP(ETA(1)) ELSE KA=THETA(1) ENDIF -- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web:www.quantpharm.com e-mail: LGibiansky at quantpharm.com tel:(301) 767 5566 Ethan Wu wrote: Dear Juergen

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