nlmixr2/rxode2 mu referencing 2.0

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.

nlmixr2 2.1.2/ rxode2 2.1.3

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.

nlmixr2/rxode2 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().

nlmixr2/rxode2 steady state changes

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.

nlmixr2, tidyverse and RStudio on 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.

By Nicola Melillo and Hitesh Mistry in nlmixr2 AWS

March 5, 2024