RE: [NMusers] Two sequential absorption processes

Hello, I think that the model that you refer to is called the KOKA absorption model (Holford et al. J Pharmacokinet Biopharm. 1992; 20:421-42). You don't need $DES, it can be easily coded using ADVAN4 (it will greatly reduce your run time). I guess you know what fraction of the dose enters as a

RE: [NMusers] Mixture model for Disease Progression

xture model makes about the existence of different sub-populations. Nick On 15/01/2011 11:12 a.m., Samtani, Mahesh [PRDUS] wrote: Hello, I am trying some simple linear disease progression analysis and the data suggests that there are 2 populations in the dataset (Low Baseline

[NMusers] Mixture model for Disease Progression

Hello, I am trying some simple linear disease progression analysis and the data suggests that there are 2 populations in the dataset (Low Baseline, Low Slope vs. High Baseline, High Slope). It appears that that population consists of progressers and non-progressers (The Pharmacometrics textbook de

RE: [NMusers] Predicting body weight as a function of gestational age

Hello, You can use the CDC growth charts that can be found here: http://www.cdc.gov/growthcharts/percentile_data_files.htm The interesting files from the website are: 1. WTAGEINF [XLS - 34 KB] : birth to 36 months 2. WTAGE

[NMusers] INCLUDE Functionality and Multiple-Dose Data

Dears, I was testing out the following code, presented by Tom at a meeting a while back, for independent estimation of individual PK data. The code works just fine with Single dose data, even when there are multiple periods, but it fails to analyze the true "multiple dose" data. For the sin

RE: [NMusers] Trial optimization across multiple endpoints

Dear Dr. Corrigan, Could you kindly elaborate what is the other co-primary end-point? I can understand that you may not be able to share this additional information. I will therefore try to illustrate my concern with this secondary end-point optimization assuming that your drug of interest is an a

[NMusers] Difficulty with gam and step.gam

Hello, I have 21 covariates that I would like to screen using GAM in xpose. I tried using the extra file in xpose. I couldn't figure out how to communicate with xpose and tell it to use the additional variables in the extra file as covariates during GAM. Could someone comment on how to use the ext

RE: [NMusers] Baseline as a covariate

Dear Dr. Bonate, Could you kindly elaborate on the structural model that is being used to characterize your PD system? In my limited experience, I have seen the behavior that you describe under 2 circumstances: a) Simple inhibitory Emax PD model with a baseline: Here patients with a higher baselin

RE: [NMusers] Constrain PD values using a logistic transformation

illes...@nc.rr.com] Sent: Fri 7/2/2010 3:04 PM To: Samtani, Mahesh [PRDUS] Cc: nmusers@globomaxnm.com Subject: Re: [NMusers] Constrain PD values using a logistic transformation Hi Mahesh, If you plan to use one of the approximate likelihood methods, e.g., FO or FOCE, you may prefer to transform the dat

[NMusers] Constrain PD values using a logistic transformation

Dear NMusers, I am trying to model some PD data, which has a lower bound of zero and an upper bound of 100. I was wondering how to implement this restriction and if it was possible to use the general logistic transformation in the $ERROR block shown below: $ERROR IPRE=A(1) LT=LOG(IPRE/(100-IPR

RE: [NMusers] Customize the design aspects of the VPC plots in xpose

mg","G mg","H mg")),scales = list(x = list(at=seq(0,3360,by=336) , labels=seq(0,20,by=2)), y = list(at=log(c(.3,1,3,7.5,20,50,150)), labels=c(.3,1,3,7.5,20,50,150)) )) Sincere Thanks, Mahesh From: martin [mailto:m.g.john...@rug.nl] Sent: Thu 4/1

[NMusers] Customize the design aspects of the VPC plots in xpose

Hello, I am trying to customize the design aspects of the VPC plots being made with xpose after a PsN run. This is how far I have reached: xpose.VPC (vpc.info="vpc1/vpc_results.csv", vpctab="vpc1/vpctab1", PI="NULL", by="STRT", PI.ci="area", PI.real=TRUE,type="p",main ="Visual Predictive Check\nPS

RE: [NMusers] How to calculate t1/2, z?

Hello, There is an Excel spread sheet convert.xls for doing this, developed by Dr. Steven Shafer. Please see this NMusers posting to download the spread sheet (Terminal half-life will be 0.693 divided by the slowest lambda rate constant from the excel spread-sheet): http://cognigencorp.com/nonmem/

[NMusers] Coding a triple absorption model

> Dear NMusers, I am using a dual absorption model as follows (The dose is split into 2 fractions and the splitting fraction, THETA(.), is an estimated parameter in the model): TPH = LOG(THETA(.)/(1-THETA(.))) TH = EXP(TPH+ETA(.))/(1+EXP(TPH+ETA(.))) F2 = TH F1 = 1-TH However, upon prolonge

RE: [NMusers] Resetting of single compartment

Dear Dr. Bachman, My thinking was that the amount in these compartments is "emptied" i.e. set to zero and turned off (and hence the CMT needs to turned back on again). There are some nice postings by Drs. Karlsson and Gibiansky on how to "empty" the urine compartment when modeling urine sample c

[NMusers] Schwartz formulae

Dear NMusers, I am having difficulty with the Schwartz formulae for computing GFR in kids. Some references state that the formula gives GFR in mL/min while others say it is mL/min/1.73 m². Also the value of k varies between references. This is what I plan on using. Are these formulas in the righ

RE: [NMusers] ETA on ALAG1

Hello, The easy fix is to use the Hybrid option. See this posting: http://www.cognigencorp.com/nonmem/nm/99jun022003.html The key messages are at the very end of this thread: "you might try the hybrid method specifying that t

RE: [NMusers] Simultaneous vs sequential for modeling parent AND metabolites in pop PK

Dear Dr. Holford, All I was suggesting was that once you have decided on which assumption you like the most and start modeling the metabolite data then shouldn't simultaneous modeling of the parent + metabolite be more preferable? The model will take long run time any ways because it will be a $

[NMusers] sequential vs simultaneous

Dear NMusers, I think in trying to generalize the case between sequential PK/PD vs. sequential parent/metabolite we maybe forgetting some PK concepts. 1) In the case of parent/metabolite modeling the metabolite data often carries important information about the parent drug. Eg.a. If the

RE: [NMusers] adding error term to covariate

Hello, I was bit by this problem once in the past. My quick fix was to put etas on Smax & baseline (both parameters were estimated) and then put a block between these etas. It has a few limitations a) A fixed effect is modeled as a random effect; b) post-hoc plots of individual Smax and baseline

RE: FW: [NMusers] PPC

Dear Susan, The cut function in S-plus is quite useful for binning. The cut function creates a category object by dividing continuous data into intervals. One can use the nominal (protocol) times as breakpoints and labels in the cut function. To read more about binning please see the abstract by

RE: FW: [NMusers] PPC

Dear Nick, Thank-you for teaching these important concepts. Could you and others kindly comment on the following 2 aspects: a) The variance-covariance matrix based on the estimated standard errors and their correlation will generate a multi-variate normal distribution for the parameters. Howeve

[NMusers] Non-influential Eta

Dear NMusers, I am trying to sequentially model the PD of a drug that has a simple inhibitory Emax effect. There is a clear placebo response from the control group and placebo effect goes away once patients stop taking their placebo pills (Hence the TY code below). Both drug & placebo effect (de

RE: [NMusers] Condition numbers and eigenvalues

Dear Katharina, Please see the best practices posting by Dr. Kowalski on nmusers, which contains some references: http://www.cognigencorp.com/nonmem/nm/99may012003.html The second useful resource is Dr. Bonate's text-book (Pharmacok

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

Dear Bo, If the runs are already completed you could use nmsee to extract the needed information from the NONMEM output. Using nmsee and grep the extracted information will be stored in a text file which is readily amenable for use with read.table in S-plus. I learnt the usage of nmsee by readin

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

Dear NMusers, I wish to model a biomarker that is controlled by a time-varying variable. The temporal pattern of this time-varying variable is irregular which makes a parametric description of its profile somewhat difficult. I am hoping to use a "connect the dots" approach for this exercise i.e.

RE: [NMusers] Multiple amniotic fluid samples

Dear Dr. Hutson, The general methodological approach with amniotic fluid PK modeling is to pool the fluid from all the sacs at a given time point and measure the concentration in that pooled fluid. The concentrations in the amniotic fluid are generally modeled as a single compartment with other

[NMusers] Is the use of II, SS, and ADDL allowed simultaneously

Dear NMusers, Is the use of II, SS, and ADDL allowed simultaneously in NONMEM? I wish to assess PK profiles at SS with and without compliance. Here is the potential scenario I am interested in: i) Patients come in at SS and take their 1st two doses correctly ii) Patients then remain compliant O

[NMusers] Simulation for future populations and diagnostics

Dear NMusers, I had to recently run an exercise with simulations across uncertainty in not just THETA, but also OMEGA and SIGMA. I simply parameterized the omegas and sigmas as thetas (many thanks to Dr. Gibiansky's posting on NMusers on how to implement this with omegas and sigmas fixed to one)

[NMusers] Automated way to extract NM output

Dear NMusers, I wish to run a $EST NM.ctl with 500 $PROBLEMs. Is there an automated way to extract the 500 sets of thetas, omegas, sigmas, and minimization statuses from the single output that NONMEM provides? Two related questions are: a) What is the machinery that runs behind WFN for extractin

RE: [NMusers] Minimization terminated ?

Dear NMusers, There have been some elegant references posted to the usersnet in response to this question. However, one question has generally gone unanswered. Navin tells us that NONMEM says MINIMIZATION TERMINATED DUE TO ROUNDING ERRORS (ERROR=134); then he change the SIGDIGITS to a lower val

[NMusers] Interindividual variability in residual variance

Dear NMusers, I have run in to an old problem that Vladimir once described here on the users net. I am trying to implement inter-individual variability in residual variance and the corresponding OMEGA is not being iterated. Usually, in Dr. Karlsson's work this error structure is implemented on

[NMusers] Additive model for IOV and IIV within a logit-transform

Dear NMusers, In a paper by Kerbusch, Wählby, Milligan, & Karlsson (BJCP 56 (6), 639-652) the authors state that: "The bioavailability (F) depended on the formulation (immediate = IR or extended = CR), the dose, and CYP2D6 genotype. Interindividual variation for FIR and FCR, and interoccasion va

[NMusers] IOV and covariate effects on logit TVF

Dear NMusers, In the past I have used the logit transform to obtain IIV on F in NONMEM and used the following equations to get F1 and the SD on F1: TVF = THETA(.)/(1-THETA(.)) LTVF= LOG(TVF) + ETA(.) F1 = EXP(LTVF)/(1+EXP(LTVF)) ~ s.d.F1=SQRT(OMEGA)*THETA(.

[NMusers] Absorption delay NOT completed before the next dose is given

Dear NM users, NM help files says the following about ALAG "When additional doses are specified on a dose event record, the absorption lag time applies to the dose and to all the additional doses. In this case the lag time should not exceed the (length of the) interdose interval" My ques

RE: [NMusers] WARNING 48

-Original Message- From: [EMAIL PROTECTED] [mailto:[EMAIL PROTECTED] Behalf Of Samtani, Mahesh [PRDUS] Sent: Monday, February 26, 2007 12:09 PM To: nmusers@globomaxnm.com Subject: [NMusers] WARNING 48 Dear NM group, I am running my own DES defined PD model and Nonmem generates the fo

[NMusers] WARNING 48

Dear NM group, I am running my own DES defined PD model and Nonmem generates the following warning. What does this warning mean and does it have any implications even if I get successful minimization. (WARNING 48) DES-DEFINED ITEMS ARE COMPUTED ONLY WHEN EVENT TIME INCREASES. E.G., DISPLAYED VA