## rxode2 2.0.11

CRAN release: 2022-11-01

• Give a more meaningful error for ‘rxode2’ ui models with only error expressions

• Break the ABI requirement between roxde2() and rxode2parse()

• The new rxode2parse will fix the sprintf exclusion shown on CRAN.

## rxode2 2.0.10

CRAN release: 2022-10-20

• Time invariant covariates can now contain ‘NA’ values.

• When a column has ‘NA’ for the entire id, now ‘rxode2’ warns about both the id and column instead of just the id.

• To fix some CRAN issues in ‘nlmixr2est’, make the version dependency explicit.

## rxode2 2.0.9

CRAN release: 2022-10-19

• Remove log likelihoods from ‘rxode2’ to reduce compilation time and increase maintainability of ‘rxode2’. They were transferred to ‘rxode2ll’ (requested by CRAN).

• Remove the parsing from ‘rxode2’ and solved linear compartment code and move to ‘rxode2parse’ to reduce the compilation time (as requested by CRAN).

• Remove the random number generation from ‘rxode2’ and move to ‘rxode2random’ to reduce the compilation time (as requested by CRAN).

• Remove the event table translation and generation from ‘rxode2’ and move to ‘rxode2et’ to reduce the compilation time (as requested by CRAN).

• Change the rxode2 ui object so it is a compressed, serialized object by default. This could reduce the C stack size problem that occurs with too many environments in R.

• Warn when ignoring items during simulations

• Export a method to change ‘rxode2’ solve methods into internal integers

• Bug fix for time invariant covariates identified as time variant covariate when the individual’s time starts after 0.

## rxode2 2.0.8

CRAN release: 2022-09-23

### Breaking changes

• rxgamma now only allows a rate input. This aligns with the internal rxode2 version of rxgamma and clarifies how this will be used. It is also aligned with the llikGamma function used for generalized likelihood estimation.

• ui cauchy simulations now follow the ui for normal and t distributions, which means you can combine with transformations. This is because the cauchy is a t distribution with one degree of freedom.

• ui dnorm() and norm() are no longer equivalent to add(). Now it allows you to use the loglik llikNorm() instead of the standard nlmixr2 style focei likelihood. This is done by adding dnorm() at the end of the line. It also means dnorm() now doesn’t take any arguments.

• Vandercorput normal removed (non-random number generator)

### New features

• Allow models in the nlmixr2 form without an ini({}) block

• Allow model piping of an omega matrix by f %>% ini(omegaMatrix)

• Standard models created with rxode2() can no be piped into a model function

• Families of log-likelihood were added to rxode2 so that mixed likelihood nonlinear mixed effects models may be specified and run.

• The memory footprint of a rxode2 solving has been reduced

• Piping now allow named strings (issue #249)

### Bug fixes

• rxode2’s symengine would convert sqrt(2) to M_SQRT_2 when it should be M_SQRT2. This has been fixed; it was most noticeable in nlmixr2 log-likelihood estimation methods

• rxode2 treats DV as a non-covariate with etTran (last time it would duplicate if it is in the model). This is most noticeable in the nlmixr2 log-likelihood estimation methods.

### New features

• A new flag (rxFlag) has been created to tell you where in the rxode2 solving process you are. This is useful for debugging. If outputting this variable it will always be 11 or calculating the left handed equations. If you are using in conjunction with the printf() methods, it is a double variable and should be formatted with "%f".

• An additional option of fullPrint has been added to rxode2() which allows rprintf() to be used in almost all of rxode2() steps (inductive linearization and matrix exponential are the exception here) instead of just the integration ddt step. It defaults to FALSE.

## rxode2 2.0.7

CRAN release: 2022-05-17

• Removed accidental ^S from news as requested by CRAN.

• Bug fix for more complicated mu-referencing.

• Change rxode2 md5 to only depend on the C/C++/Fortran code and headers not the R files. That way if there is binary compatibility between nlmixr2est and rxode2, a new version of nlmixr2est will not need to be submitted to CRAN.

## rxode2 2.0.6

CRAN release: 2022-05-09

### Breaking changes

#### Solving controls

• The options for rxControl and rxSolve are more strict. camelCase is now always used. Old options like add.cov and transit_abs are no longer supported, only addCov is supported.

• A new option, sigdig has been added to rxControl(), which controls some of the more common significant figure options like atol, rtol, ssAtol, ssRtol, with a single option.

• For simulations, $simulationSigma now assumes a diagonal matrix. The sigma values are assumed to be standard normal, and uncorrelated between endpoints. Simulation with uncertainty will still draw from this identity diagonal matrix • Parallel solving now seeds each simulation per each individual based on the initial seed plus the simulation id. This makes the simulation reproducible regardless of the number of cores running the simulation. #### Other breaking changes • Solved objects now access the underlying rxode model with $rxode2 instead of \$rxode

• Since this change names, rxode2, rxode and RxODE all perform the same function.

• Options were changed from RxODE.syntax to rxode2.syntax.

• Assigning states with rxode2.syntax.assign.state (was RxODE.syntax.assign.state) is no longer supported.

• Enforcing “pure” assignment syntax with = syntax is no longer supported so rxode2.syntax.assign is no longer supported (was RxODE.syntax.assign).

• Since R supports ** as an exponentiation operator, the pure syntax without ** can no longer be enabled. Hence rxode2.syntax.star.pow (was RxODE.syntax.star.pow) no longer has any effect.

• The “pure” syntax that requires a semicolon can no longer be enabled. Therefore rxode2.syntax.require.semicolon (was RxODE.syntax.require.semicolon) no longer has any effect.

• The syntax state(0) can no longer be turned off. rxode2.syntax.allow.ini0 (was RxODE.syntax.allow.ini0) has been removed.

• Variable with dots in variable and state names like state.name works in R. Therefore, “pure” syntax of excluding . values from variables cannot be enforced with rxode2.syntax.allow.dots (was RxODE.syntax.allow.dots).

• The mnemonic et(rate=model) and et(dur=model) mnemonics have been removed. rate needs to be set to -1 and -2 manually instead.

• The function rxode2Test() has been removed in favor of using testthat directly.

• Transit compartments need to use a new evid, evid=7. That being said, the transitAbs option is no longer supported.

• ID columns in input parameter data frames are not sorted or merged with original dataset any more; The underlying assumption of ID order should now be checked outside of rxode2(). Note that the event data frame is still sorted.

• The UI functions of nlmixr have been ported to work in rxode2 directly.

• rxModelVars({}) is now supported.

• You may now combine 2 models in rxode2 with rxAppendModel(). In fact, as long as the first value is a rxode2 evaluated ui model, you can use c/rbind to bind 2 or more models together.

• You may now append model lines with piping using %>% model(lines, append=TRUE) you can also pre-pend lines by %>% model(lines, append=NA)

• You may now rename model variables, states and defined parameters with %>% rxRename(new=old) or if dplyr is loaded: %>% rename(new=old)

• You can fix parameters with %>% ini(tcl=fix) or %>% ini(fix(tcl)) as well as unfix parameters with %>% ini(tcl=unfix) or %>% ini(unfix(tcl))

### Internal changes

• Strict R headers are enforced more places

• Since there are many changes that could be incompatible, this version has been renamed to rxode2

• rxode2() printout no longer uses rules and centered headings to make it display better on a larger variety of systems.

### Bug fixes

• tad() and related time features only reset at the start of an infusion (as opposed to starting at the beginning and end of an infusion)