Re: [NMusers] MMRM implementation in nonmem?

Hi Matts, In my experience, a typical MMRM model is made of many unconnected model parameters usually with an unstructured variance/covariance matrix of residual error and a single inter-individual parameter. It would be relatively painful to copy and paste everything, but the general model

[NMusers] Introduction to PKNCA: Automation of Noncompartmental Analysis in R

Hello, In the ISoP study group webinar series, I will be giving a webinar on using the PKNCA R library this Wednesday at noon US Eastern time. If you're interested in automation of NCA in your R-based workflow with open-sourced software, check it out! Thank you, Bill *Title:*Introduction

[NMusers] Minimizing NONMEM Installation Size

Hi, I'm installing NONMEM 7.3.0 in a Docker container under Ubuntu Linux with gfortran. To minimize network bandwidth and as a general best practice, I want to minimize the image size. To do so, I deleted the installation media after installation is complete, and I've also deleted as many

Re: [NMusers] Laplacian, BQL and initial estimates

Hi Mark, Might you have more than one $EST step where Laplacian is not used in one of them? And, can you share your $EST step options? Thanks, Bill On 7/17/2016 4:28 PM, Mark Sale wrote: Question: NONMEM has a function to run a grid search to obtain initial estimates for THETA.

[NMusers] SAEM Problem without Convergence Reports OFV

Hi, I have a challenging PD model that I recently completed working on. In some of the runs, I got a likelihood value when I think NONMEM should have aborted without providing the likelihood. The complete story is below. I was using SAEM, and during some of the runs, I got the following

[NMusers] Dynamically Sized MPI NONMEM Runs?

Hi, I've been setting up Docker for NONMEM with NMQual and PsN (https://github.com/billdenney/Pharmacometrics-Docker). The docker containers work with MPI in a static fashion-- as an example, I can start a run with 4 cores, but I can't add or remove cores from the run. MPI appears to have

Re: [NMusers] Rcpp alongside NONMEM

Hi Mike, Similar to Itziar, I've run into near-equivalent problems. I've not tested this as a solution, but my thought is to setup a specific batch file that runs NONMEM for me, and at the top of the batch file it updates the PATH variable to point to the NONMEM copy of gfortran, and at the

Re: [NMusers] Generating TAD with ADDL dosing format

Hi Camila, It sounds like you've got two questions here-- one related to NONMEM and one related to the other program you're using to create your VPC. The NONMEM question appears to be "How do I get TAD in my data without changing my dataset?" The second question appears to be "How to I

[NMusers] ISoP New England: Novel Drug Modalities and Cookout! August 29 (Sign-up link!)

View this email in your browser [image: https://gallery.mailchimp.com/4dfcc4c80e1a6d31f8e6e4332/images/71f6dff6-9d6c-44d3-a56b-6d36e30f2533.png] Novel Drug Modalities,

[NMusers] DEFDOSE/DEFOBS Required for Many Compartments?

Hi, I have a model with many compartments (42 different compartments are defined). It is currently setup this way to future-proof the dataset in case we want to combine analyses of many drugs (about 20 different drugs with central/peripheral compartments) and several endpoints. In the

Re: [NMusers] DEFDOSE/DEFOBS Required for Many Compartments?

ther fix is to supply the PCMT data item in the data set, and (in my case) set PCMT=2 This is something that can be fixed with a future version of NONMEM (its too late for 7.4). -- Alison On Mon, May 1, 2017, at 09:33 AM, Bill Denney wrote: Hi, I have a model with many compartme

RE: [NMusers] Use of ACCEPT in $DATA

Hi Dennis, I don’t have an elegant solution for you (and I’ve been pining for the use of combined Boolean operations like “TIME.GT.5.9.AND.TIME.LT.6.1” for a long time). An inelegant solution could be to run the model once with a write statement to see if you can identify the value like

RE: [NMusers] Cleaning Up After NONMEM

Hi Mark, The simplest answer that I know of is to use PsN ( https://uupharmacometrics.github.io/PsN/). It runs NONMEM in a subdirectory and will only bring the most useful files back into the main directory. Thanks, Bill *From:* owner-nmus...@globomaxnm.com *On Behalf Of *Mark Tepeck

RE: [NMusers] Cleaning Up After NONMEM

*From:* Mark Tepeck *Sent:* Friday, June 8, 2018 4:36 PM *To:* Bill Denney *Cc:* nmusers@globomaxnm.com *Subject:* Re: [NMusers] Cleaning Up After NONMEM Hi Bill, Thank you for the tip. Is there anyway to avoid those sub-directories? For example, let NONMEM clean it up automatically? let

RE: [NMusers] Context-free lexer for NM-TRAN

Hi Ruben, I’m also interested in a lexer-parser for NONMEM. The regexp-based ones that I’ve used have typically had issues (I’ve tried about 4 different ones including one that I wrote), and they are working for many but not all models. I’m unaware of a reasonably complete lexer-parser for

RE: [NMusers] $ABBR REPLACE Limitations?

Gaithersburg, MD 20878 Office: (215) 616-6428 Mobile: (925) 286-0769 robert.ba...@iconplc.com www.iconplc.com *From:* owner-nmus...@globomaxnm.com [mailto:owner-nmus...@globomaxnm.com <owner-nmus...@globomaxnm.com>] *On Behalf Of *Bill Denney *Sent:* Tuesday, January 23, 2018 4:40 P

Re: [NMusers] Failure to execute NONMEM from R

Hi Matthew, Since everything is working when run directly from the command line (cmd), I would guess that it's something like a path issue. Check your path at the command prompt (type "path") and in RStudio ("Sys.getenv("PATH")"). Thanks, Bill > On Dec 20, 2017, at 21:54, HUI, Ka Ho

RE: [NMusers] IMPMAP behavior question

Hi Bob, Leonid, and Mark, Thanks for this interesting conversation! I think that it explains some issues with models I’d not gotten to the bottom of in the past. Bob, can these timeouts be raised to the user in the main output files? Or even better, could the timeout be automatically

RE: [NMusers] $ABBR REPLACE Limitations?

:lu...@cognigencorp.com] *Sent:* Tuesday, January 23, 2018 3:51 PM *To:* Bill Denney <wden...@humanpredictions.com> *Cc:* nmusers <nmusers@globomaxnm.com> *Subject:* Re: [NMusers] $ABBR REPLACE Limitations? Bill, I know at one time NM had a bug (haven't checked to see if it

[NMusers] $ABBR REPLACE Limitations?

Hi, I’m working in NONMEM 7.4.1 with a model where I need to track 4 drugs simultaneously. To increase the model quality, I’m making heavy use of $ABBR REPLACE to keep track of THETA, ETA, and CMT numbers. I traced an issue with my model where there was no gradient on a bioavailability term

[NMusers] CMT Remapping

Hi, In a follow-up to the previous email, I’m still working on the same model where I need to track 4 drugs simultaneously. For this, I’m working from a single data file, and my initial modeling is drug 1 (first control stream), drug 2 (second control stream), drug 3 (third control stream),

RE: [NMusers] CMT Remapping

[mailto:lgibian...@quantpharm.com] Sent: Tuesday, January 23, 2018 5:46 PM To: Bill Denney <wden...@humanpredictions.com>; nmusers@globomaxnm.com Subject: Re: [NMusers] CMT Remapping Hi Bill, I do not think this is possible, but you are making things more complicated than needed. You can

RE: [NMusers] Time-Varying Bioavailability on Zero-Order Infusion

tien.biho...@cognigencorp.com>; Bill Denney <wden...@humanpredictions.com> Cc: NMUsers <nmusers@globomaxnm.com> Subject: Re: [NMusers] Time-Varying Bioavailability on Zero-Order Infusion Hi Bill, I think the proposed original solution is the only one if you would like to implement i

RE: [NMusers] Time-Varying Bioavailability on Zero-Order Infusion

—this solution does that, but I’d like to learn a simpler way than what I suggested. Thanks, Bill *From:* Sebastien Bihorel <sebastien.biho...@cognigencorp.com> *Sent:* Tuesday, March 13, 2018 9:17 PM *To:* Bill Denney <wden...@humanpredictions.com> *Cc:* NMUsers <nmusers@globomaxnm.com

[NMusers] Time-Varying Bioavailability on Zero-Order Infusion

Hi NONMEMers, Is there a good way to assign a time-varying bioavailabilty on a zero-order rate of infusion in NONMEM? The best I’ve been able to come up with is something like the below. It seems like something that should be easier than what I’m doing below (I adjusted it from the real

RE: [NMusers] VPCs confidence intervals?

Hi Elena, VPCs are accurately called prediction intervals not confidence intervals. The difference is that a prediction interval shows what you would expect for the next individual in a study while a confidence interval shows what you would expect for the result of a statistic (often confidence

RE: [NMusers] Mailing list about pharmacometrics

Hi Sebastien, The best I know for general PMx questions is the ISoP message boards: https://discuss.go-isop.org/ Thanks, Bill -Original Message- From: owner-nmus...@globomaxnm.com On Behalf Of Sebastien Bihorel Sent: Thursday, January 31, 2019 11:01 AM To: nmusers@globomaxnm.com

RE: [NMusers] bootstrap

Hi Niurys, The simplest method to ensure a good bootstrap is often to simplify the data file by removing rows that should not be used for the modeling before running the bootstrap. Notably, if you exclude an entire subject either based on the ID column or another column, usually the boostrap

[NMusers] Installing NONMEM with Intel Fortran 2019.4

Hi everyone, With the recent discussion of installing NONMEM with Windows MPI, I have a somewhat similar question on Linux: Has anyone had success installing NONMEM with Intel Fortran 2019 update 4 on Linux? I was updating Pharmacometrics-Docker (

RE: [NMusers] NonMem and EVID=2

Hi Johan, Since I answered the original message, I’ll respond here, too, though with a less specific answer at this point. If you could provide the control stream and data (or example of the data), that would help. My guess is generally similar to my guess in 2016. The integration steps

RE: [NMusers] Using evid 0 before dosing

Hi Carlos, It is commonly used. For most datasets, there will be at least one observation that occurs before dosing to estimate the baseline value, and in almost every scenario, the modeling dataset should mirror the real world actions. So, there is no issue with it, and usually you will have

RE: [NMusers] error message from xpose

Hi Mark, The tidyselect package has recently undergone some significant changes. I would guess that may have caused an issue with xpose which heavily uses the tidyverse. As Duy indicated, I’d suggest posting an issue to GitHub so that Ben can help. Thanks, Bill *From:*

RE: [NMusers] M3 method - WRES, and CWRES

Hi Mutaz, Matt Hutmacher described it well here: https://www.cognigen.com/nmusers/2010-April/2448.html A very brief summary of his excellent post is that subjects with a combination of censored (BLQ) an uncensored (above the LLOQ and below the ULOQ) will be biased in their reporting of CWRES

RE: [NMusers] Negative concentration from simulation

Hi Nyein, Negative concentrations can be expected from simulations if the model includes additive residual error. I assume that you mean additive and proportional error when you say "combined error model". If the error structure does not include additive error, then we'd need to know more. How

Re: [NMusers] Install problem 7.5.0 on Ubuntu 19.10

Hi DJ, Richard and I have experienced the same issue. I believe that simply replacing libfortran.so.3 with libfortran.so will fix it, but we haven't worked out exactly where to do it yet: https://github.com/billdenney/Pharmacometrics-Docker/pull/4 Thanks, Bill On Sun, Oct 25, 2020, 11:56 AM

RE: [NMusers] Variability on infusion duration

Similar to Leonid's solution, you can try using an exponential distribution: D1 = DUR*(1-EXP(-EXP(ETA(1 The exponential within an exponential gives left skew and ensures that D1 ≤ DUR. For subjects who you know had an incomplete infusion duration, I would add an indicator variable (1 if

RE: [NMusers] Variability in Dosing Rate (and amount)

Hi Paul, Martin’s ideas are great ones. My first thought on the “clever coding” would be to treat it like bioavailability. You should be sure that you split it between days rather than estimate it completely separately between days. I would think of doing it in general like: ; Fraction of

RE: [NMusers] Assessment of elimination half life of mAb

Hi Pete, I agree that it is hard to communicate. I like the general idea of C90 you propose. I tend to choose something in between your and Leonid's answer, when possible. I target an answer of "when is the pharmacodynamic effect <5% of the maximum or therapeutic effect". It does require more

RE: [NMusers] Time-varying input/flexibility to change input rate on the fly

/flexibility to change input rate on the fly Dear all, I was wondering if any progress has been made on the topic raised originally by Bill Denney in 2018: https://www.mail-archive.com/nmusers@globomaxnm.com/msg06990.html Are there any simpler ways in NM 7.5 to adapt input (e.g. infusion rates) in $DES

RE: [NMusers] relation of numerical error to gfortran?

Hi Tong, The general issue of floating point instability is generally a problem for models that are hard to fit (3 days with full parallelization sounds hard to fit). It’s discussed in the intro7.pdf document in section I.70, “Stable Model Development for Monte Carlo Methods”. Given that

Re: [NMusers] Clarification on performance of mu referencing

Hi Sébastien, My understanding is that keeping all thetas additive makes mu r referencing more efficient. The underlying mu reference math is then accurate for matrix linear formulations. My understanding is not perfect for this, so I'll defer to others if there is a different answer. Thanks,

RE: [NMusers] Condition number

Hi everyone, This has been a great discussion! Bob: I’d like to clarify something that Pete, Matt, Ken, and Leonid were discussing about how the covariance matrix is calculated. I believe that NONMEM rescales the values for estimation and then reverses the rescaling for reporting. Is the