https://blog.nlmixr2.org/blog/ Recent content in The nlmixr2 blog on nlmixr2 Hugo -- gohugo.io en Fri, 27 Feb 2026 00:00:00 +0000 https://blog.nlmixr2.org/blog/2026-02-27-tidyvpc/ Fri, 27 Feb 2026 00:00:00 +0000 https://blog.nlmixr2.org/blog/2026-02-27-tidyvpc/ VPCs – a new method for VPCs in nlmixr2 I am excited to announce a new VPC method available in nlmixr2 – tidyvpc. This method can be built on-top of previous code and provides slightly different visualizations than the vpc package. Below is an example that shows the two different methods: library(nlmixr2) ## ── Attaching packages ───────────────────────────────────────────────────────── nlmixr2 5.0.0 ── ## ✔ lotri 1.0.2 ✔ monolix2rx 0.0.6 ## ✔ nlmixr2data 2. https://blog.nlmixr2.org/blog/2026-01-16-iov/ Fri, 16 Jan 2026 00:00:00 +0000 https://blog.nlmixr2.org/blog/2026-01-16-iov/ Inter-occasion variability Happy new year! With the holidays over we had the opportunity to celebrate many special occasions. I invite you to celebrate a new occasion for nlmixr2 – inter-occasion variability. We now support inter-occasion variability estimation in nlmixr2! Implementing inter-occasion variability in models To implement inter-occasion variability in nlmixr2 models you simply have to specify that the variable is an occasion variable, say occ: iov.cl ~ 0.1 | occ The ~ syntax is similar to how between subject variability is specified, the addition of | tells that this a between occ variability. https://blog.nlmixr2.org/blog/2025-12-12-nlmixr2-5/ Fri, 12 Dec 2025 00:00:00 +0000 https://blog.nlmixr2.org/blog/2025-12-12-nlmixr2-5/ nlmixr2 5.0 As time progresses, dependencies update, dependencies come and go, and sometimes these dependencies change what happens to rxode2/nlmixr2 models. One dependency change (qs being dropped) means that models from before nlmixr2/rxode2 5.0 have the UI/fit models saved to disk will may not be able to load completely in nlmixr2 5.0. This is because internally nlmixr2/rxode2 encoded its models in binary qs format. Why is qs going away? While the maintainer wanted to keep qs and its file format around, R is changing and what is acceptable to access within C/C++ from R has changed. https://blog.nlmixr2.org/blog/2025-11-23-r-consortium/ Mon, 24 Nov 2025 00:00:00 +0000 https://blog.nlmixr2.org/blog/2025-11-23-r-consortium/ nlmixr2 Working Group We are very excited to announce we are joining the R consortium as a Working Group (WG). Our vision will remain the same: The vision of nlmixr2 is to develop a R-based open-source nonlinear mixed-effects modeling software package that can compete with commercial pharmacometric tools and is suitable for regulatory submissions. What is a R Consortium Working Group? A R Consortium ISC working group is a group of volunteers for a project that “requires the skills not possessed by a single individual, or the amount of work required is more than can be accomplished by a single person in a reasonable amount of time. https://blog.nlmixr2.org/blog/2025-10-22-agq/ Wed, 22 Oct 2025 00:00:00 +0000 https://blog.nlmixr2.org/blog/2025-10-22-agq/ nlmixr2 log-likelihood In 2022 we announced the focei log-likelihood. However, in our last advisory committee meeting Mats Karlsson pointed out that focei log-likelihood may not be the best approach. He believed that Stuart L. Beal and Lewis B. Sheiner did not include this method since they may have been trying to protect users from methods that may not make sense (for example, maybe focei log-likelihood is not an accurately enough approximation of the likelihood). https://blog.nlmixr2.org/blog/2025-09-29-mceta/ Sun, 28 Sep 2025 00:00:00 +0000 https://blog.nlmixr2.org/blog/2025-09-29-mceta/ nlmixr2 4.0 mceta Two of popular algorithms for fitting nonlinear fixed effects models in pharmacometrics are first order conditional estimation (with interaction), sometimes called focei. This is often considered a classical estimation method As time progressed, Monte-Carlo methods started being used, such as stochastic approximation estimation-maximization (saem). This uses Mote-Carlo Methods to try to find the maximum expectation of the nonlinear-mixed effects model. The new feature I am discussing is mceta for focei, which combines the Monte-Carlo sampling with focei. https://blog.nlmixr2.org/blog/2025-08-29-nlmixr2-verse/ Thu, 28 Aug 2025 00:00:00 +0000 https://blog.nlmixr2.org/blog/2025-08-29-nlmixr2-verse/ nlmixr2 4.0 verse As promised, I am discussing some other change that are breaking and makes nlmixr2 a major release. First is a very visible change as you load nlmixr2: library(nlmixr2) ## ── Attaching packages ───────────────────────────────────────────────────────── nlmixr2 4.0.1 ── ## ✔ lotri 1.0.2 ✔ monolix2rx 0.0.6 ## ✔ nlmixr2data 2.0.9 ✔ nlmixr2lib 0.3.0 ## ✔ nlmixr2est 4.1.0 ✔ nlmixr2rpt 0.2.1 ## ✔ nlmixr2extra 3.0.3 ✔ nonmem2rx 0.1.8 ## ✔ nlmixr2plot 3. https://blog.nlmixr2.org/blog/2025-07-16-nlmixr2-4/ Wed, 16 Jul 2025 00:00:00 +0000 https://blog.nlmixr2.org/blog/2025-07-16-nlmixr2-4/ nlmixr2 4.0 We at the nlmixr2 team are committed to quality results. This is seen in line with our vision: The vision of nlmixr2 is to develop a R-based open-source nonlinear mixed-effects modeling software package that can compete with commercial pharmacometric tools and is suitable for regulatory submissions. This release furthers the quality by changing linear compartment models the ADVAN solutions to the WNL solutions(both claim to be something that NONMEM is using for the linear solved systems). https://blog.nlmixr2.org/blog/2025-06-30-nlmixr2-ecosystem/ Mon, 30 Jun 2025 00:00:00 +0000 https://blog.nlmixr2.org/blog/2025-06-30-nlmixr2-ecosystem/ nlmixr2 ecosystem I have seen a few new pharmacometrics tools integrated in the nlmixr2 ecosystem recently. I thought I would point out the tools I know that integrate in the nlmixr2 ecosystem. Some are maintained by our nlmixr2 team, and many are not. For each category, these are ordered alphabetically. Tools that Enhance nlmixr2’s language nlmixr2lib In addition to a model library, it has tools to change model components (like add Weibull absorption, add transit compartments, change standard elimination to Michaleis-Menton absorption; maintained by Bill Denney and developed by the nlmixr2 team). https://blog.nlmixr2.org/blog/2025-05-31-rxode2-geom/ Sat, 31 May 2025 00:00:00 +0000 https://blog.nlmixr2.org/blog/2025-05-31-rxode2-geom/ rxode2 and ggplot rxode2 (and nlmixr2) uses ggplot internally. This means most things are compatible with ggplot2. One thing that is not quite as widely known that rxode2 has some custom geom functions that are useful for exploring pharmacometrics data. geom_amt() – exploring when dosing occurs rxode2 will allow exploring time of dosing with the geom_amt(). From the geom_amt() documentation we can see how this is applied: library(rxode2) library(units) ## udunits database from /usr/share/xml/udunits/udunits2. https://blog.nlmixr2.org/blog/2025-04-30-pmxnode-nlmixr2/ Wed, 30 Apr 2025 00:00:00 +0000 https://blog.nlmixr2.org/blog/2025-04-30-pmxnode-nlmixr2/ Neural Network ODEs and nlmixr2 I have had some requests to talk about nlmixr2 using neural network ODEs, since neural networks are something that more people are exploring with the explosion of artificial intelligence LLMs. There is a package, pmxNODE, by Dominic Bräm that adds neural network ODEs to pharmacometric modeling tools like NONMEM, Monolix and nlmixr2. In addition to the code that Dominic has added, I extended this package to allow Neural Networks directly in a rxode2 or nlmixr2 model. https://blog.nlmixr2.org/blog/2025-03-31-more-useful-functions/ Mon, 31 Mar 2025 00:00:00 +0000 https://blog.nlmixr2.org/blog/2025-03-31-more-useful-functions/ This month I will on a single nlmixr2’s plot function that is shared with nlme, augPred(). I think this is useful but also harder to find like the rxode2 plots discussed last month. The example of this feature is the phenobarbitol data: library(nlmixr2) pheno <- function() { ini({ tcl <- log(0.008) # typical value of clearance tv <- log(0.6) # typical value of volume ## var(eta.cl) eta.cl + eta.v ~ c(1, 0. https://blog.nlmixr2.org/blog/2025-02-25-useful-functions/ Tue, 25 Feb 2025 00:00:00 +0000 https://blog.nlmixr2.org/blog/2025-02-25-useful-functions/ This month I will focus on rxode2’s plotting functions. I think these are very useful but not very well known. In general I will focus on three things: plotting single subjects, plotting multiple subjects and plotting confidence bands. Plot functions rxode2 plotting Of course discussion of plotting require a model and simulation, so we will use the model from the original tutorial: library(rxode2) ## Model from rxode2 tutorial m1 <- rxode2({ KA <- 2. https://blog.nlmixr2.org/blog/2025-01-24-udf/ Fri, 24 Jan 2025 00:00:00 +0000 https://blog.nlmixr2.org/blog/2025-01-24-udf/ This month I will talk about a new type of user function. Previously, I spoke of user functions that you can use in your code to extend the functionality of rxode2 and nlmixr2. Recently we released the ability for certain functions to generate code. I will go over examples that could be helpful to extend rxode2 ui models: An example that allows arguments to be named inside of the rxode2 ui models (though classic models still do not allow this). https://blog.nlmixr2.org/blog/2024-12-11-mu3/ Wed, 11 Dec 2024 00:00:00 +0000 https://blog.nlmixr2.org/blog/2024-12-11-mu3/ This month, I will talk about about a new iteration of mu-referencing in nlmixr2, which I call mu3 and mu4. What is mu referencing in nlmixr2 – Review from another post From the last blog post about mu-referencing, I will give a brief overview of mu-referencing and what mu-2 referencing is and how it is expanded a bit more. mu-referencing is combining a fixed effect, random effect and possibly a covariate in the form: https://blog.nlmixr2.org/blog/2024-11-06-poped/ Tue, 05 Nov 2024 00:00:00 +0000 https://blog.nlmixr2.org/blog/2024-11-06-poped/ New babelmixr2 integrates PopED. I am excited to announce today a new version of babelmixr2 has been released that streamlines creating fast, efficient PopED databases for optimal design. With the babelmixr2 package you can: Import your NONMEM model to rxode2/nlmixr2 format using nonmem2rx Import your Monolix model to rxode2/nlmixr2 using monolix2rx Use your existing nlmixr2 model or create your own rxode2/nlmixr2 model With it in the nlmixr2 format, you can then quickly do optimal design https://blog.nlmixr2.org/blog/2024-10-21-monolix2rx/ Mon, 21 Oct 2024 00:00:00 +0000 https://blog.nlmixr2.org/blog/2024-10-21-monolix2rx/ monolix2rx has been released on CRAN. I am excited to announce that as part of the nlmixr2 3.0 series of releases, you now have a way to import a Monolix model into rxode2/nlmixr2. This is similar to how you can import the output of nonmem into a rxode2 model with nonmem2rx. I am also in the process of releasing a bug-fix revision now. Key notes in importing models to rxode2 and nlmixr2 There are a few things to note in any conversion from monolix to rxode2 and nlmixr2: https://blog.nlmixr2.org/blog/2024-09-18-nlmixr2-3.0.0-release/ Wed, 18 Sep 2024 00:00:00 +0000 https://blog.nlmixr2.org/blog/2024-09-18-nlmixr2-3.0.0-release/ nlmixr2 3.0 is here nlmixr2 3.0 has been released and most of the related packages in the nlmixr2 ecosystem have been updated as well. Since there were a few non-backward compatible changes and breaking changes, the version has been bumped from 2 to 3. Most code will run the same, but because of the breaking change, we changed the major version. The big changes are: Non abi binary linkages between every package. https://blog.nlmixr2.org/blog/2024-08-05-rxderived/ Mon, 05 Aug 2024 00:00:00 +0000 https://blog.nlmixr2.org/blog/2024-08-05-rxderived/ One of the things that can be useful from time to time is to calculate different PK parameters based on whatever parameters you have estimated. There is a great function, calc_derived() in pmxTools that allows this calculation of the derived parameters (by my collaborators Justin Wilkins and Bill Denney). I think this is an underrated function that can help many people with typical calculations. rxode2 has the same type of function, which can be helpful to test the linCmt() functions, rxDerived(). https://blog.nlmixr2.org/blog/2024-07-08-mu2/ Mon, 08 Jul 2024 00:00:00 +0000 https://blog.nlmixr2.org/blog/2024-07-08-mu2/ This month, I will talk about about a new iteration of mu-referencing in nlmixr2, which I call mu2. What is mu referencing in nlmixr2 mu-referencing is combining a fixed effect, random effect and possibly a covariate in the form: \[ \theta_\mathsf{pop}+\eta_\mathsf{individual}+\theta_\mathsf{covariate}\times \mathsf{DataCovariate} \] Often they are placed in exponentials for these to be log-normally distributed like: \[ \exp\left(\theta_\mathsf{pop}+\eta_\mathsf{individual}+\theta_\mathsf{covariate}\times \mathsf{DataCovariate}\right) \] In optimization routines like saem, these are switched out with a single parameter during optimization classically called \(\phi\) in both NONMEM and Monolix. https://blog.nlmixr2.org/blog/2024-06-05-nlmixr2-2.1.2-release/ Thu, 06 Jun 2024 00:00:00 +0000 https://blog.nlmixr2.org/blog/2024-06-05-nlmixr2-2.1.2-release/ Both nlmixr2 and rxode2 have been updated, the below describes all the nlmixr2 related packages (maintained by the nlmixr2 team). Most of items in this release are bug fixes. One of the changes will make random number generation platform independent. Unfortunately, this means simulations from within rxode2/nlmixr2 will have different numbers drawn from random distributions but I think platform independence is important enough to push this change through. Versions of new packages nlmixr2 2. https://blog.nlmixr2.org/blog/2024-05-08-user-functions/ Wed, 08 May 2024 00:00:00 +0000 https://blog.nlmixr2.org/blog/2024-05-08-user-functions/ One of the exciting new features of the recent rxode2 is user functions. This allows you to define your own R functions for use in nlmixr2 or rxode2. This new feature can really help make your code more concise by reusing custom transformations or apply more complex routines. This can call R functions directly, but at a cost – single threaded and slower execution. However, you can reduce the cost by converting the R functions to C automatically with rxFun(). https://blog.nlmixr2.org/blog/2024-04-04-steady-state/ Thu, 04 Apr 2024 00:00:00 +0000 https://blog.nlmixr2.org/blog/2024-04-04-steady-state/ One of the things that I changed in the last release was steady state. Once I created the nonmem2rx package, I searched for NONMEM control streams that we could test the import from, especially those with attached data. I ran across nmtests that uses NONMEM to test against mrgsolve and how it behaves. During that test I noticed that rxode2 did not follow the convention of NONMEM in lagged steady state doses. https://blog.nlmixr2.org/blog/2024-03-05-aws/ Tue, 05 Mar 2024 00:00:00 +0000 https://blog.nlmixr2.org/blog/2024-03-05-aws/ Running large population PK/PD analyses on laptops and desktops often requires long computational times. This is quite tedious. In addition, when using parallel computing on your machine, it can slow it down for a while, creating further nuisances. Outsourcing computation to the cloud is a solution to this problem. Among the various cloud providers, Amazon Web Service (AWS) is one of the most famous and used by industries in various fields. https://blog.nlmixr2.org/blog/2024-02-07-new-estimation-methods/ Wed, 07 Feb 2024 00:00:00 +0000 https://blog.nlmixr2.org/blog/2024-02-07-new-estimation-methods/ nlmixr2 2.1.0 was released and I promised to talk about the new features. One of the things that can impact many peoples work-flow is new estimation methods for population-only data. Many people use population-only estimation methods before changing the model to a mixed effect model, so I believe these can be useful for many people trying to find the best model to the data at hand. I will talk about the new ones (and why you may want to use them). https://blog.nlmixr2.org/blog/2024-01-09-nlmixr2-2.1.0-release/ Tue, 09 Jan 2024 00:00:00 +0000 https://blog.nlmixr2.org/blog/2024-01-09-nlmixr2-2.1.0-release/ nlmixr2 2.1.0 was released 9 Jan 2024 which requires the newest (and recently released) engine packages nlmixr2est 2.2.0 (released 12 Dec 2023) and rxode2 2.0.10 (released 13 Dec 2023). I will be blogging about a few new features but want to mention a few now: More flexible mu referencing User defined functions can now be used with nlmixr2 and rxode2 Event handling changes Many new estimation methods for population only fitting The truncated changelog for these packages are below: https://blog.nlmixr2.org/blog/2023-06-02-nonmem2rx-and-babelmixr2/ Fri, 02 Jun 2023 00:00:00 +0000 https://blog.nlmixr2.org/blog/2023-06-02-nonmem2rx-and-babelmixr2/ nonmem2rx/babelmixr2 I am really excited to announce that the nlmixr2 team has released a new version of babelmixr2 and a new package nonmem2rx that allows you to convert NONMEM to rxode2 or even a nlmixr2 object. To install, simply upgrade babelmixr2 with: install.packages(c("nonmem2rx", "babelmixr2")) What you can do with nonmem2rx/babelmixr2 You can do many useful tasks directly converting between nlmixr2 and NONMEM models; you can: Convert a NONMEM model to a rxode2 model https://blog.nlmixr2.org/blog/2023-04-14-nlmixr2est-and-related-packages/ Fri, 14 Apr 2023 00:00:00 +0000 https://blog.nlmixr2.org/blog/2023-04-14-nlmixr2est-and-related-packages/ This is another release of a group of nlmixr2-related packages. Feature Highlights There are a few things I would like to highlight in this release: Highly requested feature(s) A much requested feature has been added for rxode2; Diagonal zeros in the omega and sigma matrices are treated as zeros in the model. The corresponding omega and sigma matrices drop columns/rows where the diagonals are zero to create a new omega and sigma matrix for simulation. https://blog.nlmixr2.org/blog/2022-12-07-automated-reporting-of-nlmixr2-fit-results-in-word-and-powerpoint/ Tue, 06 Dec 2022 00:00:00 +0000 https://blog.nlmixr2.org/blog/2022-12-07-automated-reporting-of-nlmixr2-fit-results-in-word-and-powerpoint/ I’m happy to announce the initial release of nlmixr2rpt: a package designed to automate reporting of nlmixr2 results to Word and PowerPoint. The nlmixr2rpt package is attempting to save you time on the back-end of your analysis so you can focus on the analysis itself. There are three main issues we are attempting to address: Interoperability: While I am personally a fan of LaTeX, corporations tend to favor Word and PowerPoint. https://blog.nlmixr2.org/blog/2022-12-05-babelmixr2-monolix/ Mon, 05 Dec 2022 00:00:00 +0000 https://blog.nlmixr2.org/blog/2022-12-05-babelmixr2-monolix/ As with NONMEM, it is important to be able to compare nlmixr2 to industry standard software like Monolix. With that , in mind, I am proud to announce the first nlmixr2 to Monolix translator in babelmixr2. As with NONMEM, while this has been done before, the method whereby we are converting between the two is novel and has some surprising advantages. How to use Monolix with nlmixr2 To use Monolix in nlmixr, you do not need to change your data or your nlmixr2 dataset. https://blog.nlmixr2.org/blog/2022-11-11-babelmixr2-nonmem/ Fri, 11 Nov 2022 00:00:00 +0000 https://blog.nlmixr2.org/blog/2022-11-11-babelmixr2-nonmem/ I remember attending a virtual ACoP where Tim Waterhouse said “This person is so convincing that the could sell NONMEM to a nlmixr developer”. I was in the wrong meeting so I laughed and connected to the correct meeting. While he is correct, I don’t really want to purchase a NONMEM license, and I would think that individual pharmacometricians are the same: they don’t want to buy a personal license for the software they use at work (although CROs might be different here). https://blog.nlmixr2.org/blog/2022-11-10-nlmixr2-nonmem/ Thu, 10 Nov 2022 00:00:00 +0000 https://blog.nlmixr2.org/blog/2022-11-10-nlmixr2-nonmem/ This is more of a methodology post, pointing out how things are done in nlmixr2 and how it likely doesn’t match what is done in NONMEM (and at least one reason why a drop-in replacement of rxode2 by another tool like PKPDsim, mrgsolve, or deSolve is not an easy project). For the impatient, adding focei lag time (and other dose-based events) have improved in stability for this release of nlmixr2. https://blog.nlmixr2.org/blog/2022-10-25-nlmixr-objf/ Tue, 25 Oct 2022 00:00:00 +0000 https://blog.nlmixr2.org/blog/2022-10-25-nlmixr-objf/ Last time I blogged promised to talk about a few other things, including: Likelihood based on each observation (and how to get it) Standard Errors / Hessians, etc for between subject variabilities or etas (and how to get them) Hessians for the individual between subject variability is also used for the focei calculation. So, if you are impatient, I will give you brief instructions on where to get each component of the likelihood: https://blog.nlmixr2.org/blog/2022-10-23-nlmixr2-llik/ Mon, 24 Oct 2022 00:00:00 +0000 https://blog.nlmixr2.org/blog/2022-10-23-nlmixr2-llik/ I am pretty excited abut the new nlmixr2 release (2.0.8). When I joined the the nlmixr2 team, I wanted to do a fancy heavy tailed, skewed model in an open source tool so I could figure out how to do even more with it. With this release, it is possible to do a heavy tailed (t-distribution dt()) skewed (coxBox(lambda)) distribution: my old wish is now possible with focei! A few other things that people may be interested in are: https://blog.nlmixr2.org/blog/2022-10-19-rxode2-2.0.9-release/ Wed, 19 Oct 2022 00:00:00 +0000 https://blog.nlmixr2.org/blog/2022-10-19-rxode2-2.0.9-release/ rxode2 2.0.9 has been released, and rxode2 2.0.10 will be released soon! I want to personally thank all those who have submitted issues, and helped with the development. Without the support rxode2 wouldn’t be the tool it is today. This is the first CRAN-visible release since rxode2 2.0.7 and I would like to highlight a few new interesting features: ‘rxode2’ can now have more flexible model functions The key features are: https://blog.nlmixr2.org/blog/2022-10-13-mrgsolve-vs-rxode2/ Thu, 13 Oct 2022 00:00:00 +0000 https://blog.nlmixr2.org/blog/2022-10-13-mrgsolve-vs-rxode2/ mrgsolve vs rxode2 One of the most common questions I get is, “What are the differences between mrgsolve (1) and rxode2?”. The most common reasons for this question are: I really don’t know what tool to use, what are the advantages of each? I really like one of the tools (either mrgsolve or rxode2) and I want to let my colleagues know how nice my favorite tool is. I am not really the best person to answer this question since I am most familiar with rxode2 and can’t answer all the questions about mrgsolve. https://blog.nlmixr2.org/blog/2022-10-12-rxode-and-rxode2/ Wed, 12 Oct 2022 00:00:00 +0000 https://blog.nlmixr2.org/blog/2022-10-12-rxode-and-rxode2/ RxODE vs rxode2 Since rxode2 came out recently, I am getting many questions about what is the difference between rxode2 and RxODE. I think the biggest reason for the question is – is this update going to break all the nice things I already do with RxODE? Or maybe why should I bother to change? I feel the same way when I have big changes in things I use. For me, I love the ability to pipe and change data with the tidyverse, and similar tools, but hate when they change things that affect my code. https://blog.nlmixr2.org/blog/2022-06-08-nlmixr2-is-here/ Wed, 08 Jun 2022 00:00:00 +0000 https://blog.nlmixr2.org/blog/2022-06-08-nlmixr2-is-here/ Over the past half year, a lot of changes have been happening behind the scenes, and the time has finally come to reveal them! nlmixr2 nlmixr2 will be the version in active development going forward, taking over from nlmixr, starting with the current CRAN version, 2.0.6. Our new home on GitHub is here, and on CRAN, we’re here. The reasons for the name and format change are many, but most importantly, we’ve taken this step to improve overall user experience and to help us maintain the project more effectively.