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. This is the same idiom that NONMEM uses for simulation from these matrices.

• With that new feature, a new function zeroRe() allows simple setting of omega and/or sigma values to zero for a model (#456). This is a similar idiom to mrgsolve which should allow easier transitioning of code.

Model piping changes

Model piping is still one of my favorite features of rxode2, and I would like to highlight a few more features.

• Add the ability to append model statements with piping using %>% model(x=3, append=d/dt(depot)), still supports appending with append=TRUE and pre-pending with append=NA (the default is to replace lines with append=FALSE)

library(rxode2)

## rxode2 2.0.12.9000 using 8 threads (see ?getRxThreads)
##   no cache: create with `rxCreateCache()`

# using the nlmixr2 theo example:
one.compartment <- function() {
  ini({
    tka <- 0.45 # Log Ka
    tcl <- 1 # Log Cl
    tv <- 3.45    # Log V
    eta.ka ~ 0.6
    eta.cl ~ 0.3
    eta.v ~ 0.1
    add.sd <- 0.7
  })
  model({
    ka <- exp(tka + eta.ka)
    cl <- exp(tcl + eta.cl)
    v <- exp(tv + eta.v)
    d/dt(depot) = -ka * depot
    d/dt(center) = ka * depot - cl / v * center
    cp = center / v
    cp ~ add(add.sd)
  })
}

one.compartment |> # could use %>% as well
  model(x<-20+ka, append=d/dt(depot))

## ℹ parameter labels from comments will be replaced by 'label()'

##  ── rxode2-based free-form 2-cmt ODE model ────────────────────────────────────────────────────────────── 
##  ── Initalization: ──  
## Fixed Effects ($theta): 
##    tka    tcl     tv add.sd 
##   0.45   1.00   3.45   0.70 
## 
## Omega ($omega): 
##        eta.ka eta.cl eta.v
## eta.ka    0.6    0.0   0.0
## eta.cl    0.0    0.3   0.0
## eta.v     0.0    0.0   0.1
## 
## States ($state or $stateDf): 
##   Compartment Number Compartment Name
## 1                  1            depot
## 2                  2           center
##  ── μ-referencing ($muRefTable): ──  
##   theta    eta level
## 1   tka eta.ka    id
## 2   tcl eta.cl    id
## 3    tv  eta.v    id
## 
##  ── Model (Normalized Syntax): ── 
## function() {
##     ini({
##         tka <- 0.45
##         label("Log Ka")
##         tcl <- 1
##         label("Log Cl")
##         tv <- 3.45
##         label("Log V")
##         add.sd <- c(0, 0.7)
##         eta.ka ~ 0.6
##         eta.cl ~ 0.3
##         eta.v ~ 0.1
##     })
##     model({
##         ka <- exp(tka + eta.ka)
##         cl <- exp(tcl + eta.cl)
##         v <- exp(tv + eta.v)
##         d/dt(depot) = -ka * depot
##         x <- 20 + ka
##         d/dt(center) = ka * depot - cl/v * center
##         cp = center/v
##         cp ~ add(add.sd)
##     })
## }

• Add the ability to pipe model estimates from another model by parentModel %>% ini(modelWithNewEsts)

• Parameter labels may now be modified via ini(param = label("text")) (#351).

• Parameter order may be modified via the append argument to ini() when piping a model. For example, ini(param = 1, append = 0) or ini(param = label("text"), append = "param2") (#352).

nlmixr2 estimation changes

• nlmixr2 fits now include both the correlation and covariance condition numbers; nlmixr2 has included the covariance condition numbers (https://doi.org/10.1080/16000870.2019.1696646 and https://en.wikipedia.org/wiki/Condition_number). However, correlation matrix condition numbers have been used as well and are what are used in NONMEM (as discussed in the NONMEM help https://nmhelp.tingjieguo.com/$covar.htm). This release will report both

• vpcSim() which is used for NPDE and VPC calculations will now re-simulate anything that is not solved correctly (solved with replacement).

More features

There some more features and bug-fixes for certain problems you may have had in this release. You can see a more in-depth look at these in the consolidated news below.

nlmixr2 2.0.9

• The new function nlmixr2CheckInstall() helps to check if your installation is setup correctly with the required compilers and packages.

• This version adds crayon as an imported dependency

nlmixr2est 2.1.4

• Breaking change, now calculate condition number based on covariance and correlation, the names have changed to be more explicit. conditionNumber changed to conditionNumberCov and a new metric conditionNumberCor has been added.

• A bug in boundary value detection prevented automatic covariance calculation with FOCEi estimation (#318)

• Fix vpcSim so that it will be a bit more robust when it is difficult to simulate.

• A bug in model piping which did not allow models to be appended to was fixed (rxode2#364)

• An internal change was made in nlmixr2.rxUi() to better support the babelmixr2 PKNCA estimation method (babelmixr2#75)

• Fixed bug where $iniUi did not return the initial ui when running non focei related methods. Also added alias of $uiIni to the same function.

• Dropped Stan headers for this package, also updated to C++17

rxode2 2.0.12

• A new function zeroRe() allows simple setting of omega and/or sigma values to zero for a model (#456)

• 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. This is the same idiom that NONMEM uses for simulation from these matrices.

• Add the ability to pipe model estimates from another model by parentModel %>% ini(modelWithNewEsts)

• Add the ability to append model statements with piping using %>% model(x=3, append=d/dt(depot)), still supports appending with append=TRUE and pre-pending with append=NA (the default is to replace lines with append=FALSE)

• rxSolve’s keep argument will now maintain character and factor classes from input data with the same class (#190)

• Parameter labels may now be modified via ini(param = label("text")) (#351).

• Parameter order may be modified via the append argument to ini() when piping a model. For example, ini(param = 1, append = 0) or ini(param = label("text"), append = "param2") (#352).

rxode2random 2.0.11

• Fix qassert LTO

rxode2random 2.0.10

• Moved fast factor to rxode2parse to allow etTrans to be moved there

rxode2parse 2.0.16

• Import data.table explicitly in the R code (before was imported only in C/C++ code)

rxode2parse 2.0.15

• Updates the make flags to support CXX17.

rxode2parse 2.0.14

• ‘linCmt()’ translations of ‘alpha’, ‘beta’, ‘gamma’, ‘k21’, ‘k31’, ‘vc’ now error instead of ignoring ‘gamma’ and ‘k31’ to give 2 cmt solution

• transit compartment internal code now changes dose to 0.0 when no dose has been administered to the depot compartment. This way dosing to the central compartment (without dosing to the transit compartment) will not give a NA for the depot compartment (and consequently for the central compartment)

• Moved rxDerived here and added tests for it here as well.

• Moved etTransParse here and added tests for it here as well (makes up most of etTrans). In addition the following changes were made to etTransParse()/etTrans():

  • The internal translation (etTrans()) will not drop times when infusions stop. Before, if the infusion stopped after the last observation the time when the infusion stopped would be dropped. This interferes with linCmt() models.

  • Breaking change/bug fix evid=2 are considered observations when translating data to internal rxode2 event structure

  • Fix edge case to find infusion duration when it is the first item of the dosing record at time 0.

• Fixed a bug for certain infusions where the rate, ii and/or ss data items were dropped from the output when addDosing=TRUE

• Also have internal functions to convert between classic NONMEM events and rxode2 events

• Have an internal function that gives information on the linear compartmental model translation type, which could be useful for babelmixr2

• ‘time’ in model is now case insensitive

• Use function declaration in rxode2parseGetTranslation() to determine thread safety of functions available to rxode2

• Add check for correct number of function arguments to parser.

• Like R, known functions can be assigned as a variable and the function can still be called (while not changing the variable value). For example you can have a variable gamma as well as a function gamma().

• Fix garbled error messages that occur with certain messages.

• Fixed errors that occurred when using capitalized AMT variables in the model.

rxode2ll 2.0.11

• Update compile flags based on CRAN C++17 requirement (Issue #5)

rxode2ll 2.0.10

• Update compile flags based on StanHeaders change.

lotri 0.4.3

• Bug fix for etas that were not named correctly for large order problems