nlmixr2 2.1.2/ rxode2 2.1.3

By Matthew Fidler in rxode2 nlmixr2

June 6, 2024

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 2.1.2 was released 30 May 2024 which requires the newest (and recently released) engine packages:

  • nlmixr2plot 2.0.9 (released 29 May 2024)

  • nlmixr2extra 2.0.10 (released 29 May 2024)

  • nlmixr2est 2.2.2 (released 28 May 2024)

And rxode2 2.1.3 was released on 28 May 2024 and requires the newest engine packages:

  • rxode2et 2.0.13 (released on 27 May 2024)

  • rxode2random 2.1.0 (released on 27 May 2024)

  • rxode2parse 2.0.19 (released on 25 May 2024)

The related package nonmem2rx has also been updated, though the rest of the nlmixr2 related CRAN packages have not been updated.

New features

I will be blogging about a few new features but want to mention a few now:

  • Random number generation is now platform independent. Unfortunately this means that this changes simulation results in this release, though the upside is that mac and linux/pc will no longer give different results for simulated values.

  • If you forget to add the est to the nlmixr2 model, it can infer the estimation method from the nlmixr2 control type (like foceiControl())

  • saem has a fix to handle certain non-mu covariates to have more reasonable results.

  • The time after dose calculation some edge cases with the MDV were fixed.


The truncated changelog for these packages are below:

nlmixr2 2.1.2

  • Re-export the population only estimation control methods.

nlmixr2plot 2.0.9

  • Bug fix for vpcPlot() where input data frame for models did not stratify all the time when the columns were upper case.

nlmixr2extra 2.0.10

  • bootstrapFit() fixes se option (Issue #66)

nlmixr2est 2.2.2

Breaking changes

  • Saem non-mu reference input parameters/covariates were fixed so they work correctly with fixed parameters (Issue #445)

  • Focei changed back to having a lower bound for standard deviations when not specified. This means that best model fits may change. You can revert to the old settings by using foceiControl(sdLowerFact=0.0). You can also change the factors to other values than the default value, that is foceiControl(sdLowerFact=0.000001) for instance which would multiply the initial value by 0.000001 when either the lower bound isn’t specified or the lower bound is specified as zero for the error estimates related to error-based standard deviations.

  • In nlmixr2, expressions are optimized. Because of that optimization, numerical rounding differences can cause different directions in optimization when fixing parameters in the model vs. fixing the parameters manually.

    This means that the fixed parameters in a model vs hard-coded fixed parameters could give different values in the final model.

    A new option literalFix was introduced which change the fixed population parameters to constants in the model while running the optimization. This makes the output of fixing within the model and fixing manually the same (which is what is likely expected). The default is for this to be turned on (ie. literalFix=TRUE). You can get back the old behavior by using the option literalFix=FALSE.

  • In saem, the monte-carlo sampling occurs for all parameters including non-informative ETAs. A fix ensure that non-informative etas in saem are fixed to zero while sampling the phi values. This may change results for models with uninformative etas. To ignore the uninformative etas with saem you ca use use the prior saem handling with saemControl(handleUninformativeEtas=FALSE).

New features

  • Gracefully degrade when $cov is not in the right form (see #423)

  • Add support for PopED in place solving (used in babelmixr2)

  • If est=foceiControl() or other nlmixr2 control with the class foceiControl infer the estimation method is focei

rxode2et 2.0.13

  • Fix import of data where there are NA times

rxode2parse 2.0.19

  • Added a evid suffix of 60 for cases where evid=2 adds an on event (fixes tad() calculation in certain edge cases)

  • Initialize all variables to NA

Posted on:
June 6, 2024
4 minute read, 667 words
rxode2 nlmixr2
See Also:
nlmixr2 2.1.0/ rxode2 2.1.1
nonmem2rx and babelmixr2
nlmixr2 family releases