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rxode2 (development version)

rxode2 2.1.3

CRAN release: 2024-05-28

Bug fixes

  • Make sure that the object is a uncompressed rxode2 ui for solving with rxSolve (See #661)

  • Fix #670 by using the last simulated observation residual when there are trailing doses.

New features

  • Create a function to see if a rxode2 solve is loaded in memory (rxode2::rxSolveSetup())

  • Create a new function that fixes the rxode2 population values in the model (and drops them in the initial estimates); rxFixPop()

Other changes

  • Pendantic no-remap (as requested by CRAN)

  • gcc USBAN fix (as requested by CRAN)

rxode2 2.1.2

CRAN release: 2024-01-30

Other changes

  • rxUi compression now defaults to fast compression

  • Fixes String literal formatting issues as identified by CRAN (#643)

  • Removes linear compartment solutions with gradients for intel c++ compiler (since they crash the compiler).

rxode2 2.1.0

CRAN release: 2023-12-11

Breaking changes

  • Steady state with lag times are no longer shifted by the lag time and then solved to steady state by default. In addition the steady state at the original time of dosing is also back-calculated. If you want the old behavior you can bring back the option with ssAtDoseTime=FALSE.

  • “dop853” now uses the hmax/h0 values from the rxControl() or rxSolve(). This may change some ODE solving using “dop853”

  • When not specified (and xgxr is available), the x axis is no longer assumed to be in hours

New features

  • User defined functions can now be R functions. For many of these R functions they can be converted to C with rxFun() (you can see the C code afterwards with rxC("funName"))

  • Parallel solving of models that require sorting (like modeled lag times, modeled duration etc) now solve in parallel instead of downgrading to single threaded solving

  • Steady state infusions with a duration of infusions greater than the inter-dose interval are now supported.

  • Added $symengineModelNoPrune and $symengineModelPrune for loading models into rxode2 with rxS()

  • When plotting and creating confidence intervals for multiple endpoint models simulated from a rxode2 ui model, you can plot/summarize each endpoint with sim. (ie. confint(model, "sim") or plot(model, sim)).

    If you only want to summarize a subset of endpoints, you can focus on the endpoint by pre-pending the endpoint with sim. For example if you wanted to plot/summarize only the endpoint eff you would use sim.eff. (ie confint(model, "sim.eff") or plot(model, sim.eff))

  • Added model$simulationIniModel which prepend the initial conditions in the ini({}) block to the classic rxode2({}) model.

  • Now model$simulationModel and model$simulationIniModel will save and use the initialization values from the compiled model, and will solve as if it was the original ui model.

  • Allow ini(model) <- NULL to drop ini block and as.ini(NULL) gives ini({}) (Issue #523)

  • Add a function modelExtract() to extract model lines to allow modifying them and then changing the model by piping or simply assigning the modified lines with model(ui) <- newModifiedLines

  • Add Algebraic mu-referencing detection (mu2) that allows you to express mu-referenced covariates as:


cl <- exp(tcl + eta.cl + wt_cl * log(WT/70.5))

Instead of the


cl <- exp(tcl + eta.cl + wt_cl * log.WT.div.70.5)

That was previously required (where log.WT.div.70.5 was calculated in the data) for mu expressions. The ui now has more information to allow transformation of data internally and transformation to the old mu-referencing style to run the optimization.

  • Allow steady state infusions with a duration of infusion greater than the inter-dose interval to be solved.

  • Solves will now possibly print more information when issuing a “could not solve the system” error

  • The function rxSetPipingAuto() is now exported to change the way you affect piping in your individual setup

  • Allow covariates to be specified in the model piping, that is mod %>% model(a=var+3, cov="var") will add "var" as a covariate.

  • When calculating confidence intervals for rxode2 simulated objects you can now use by to stratify the simulation summary. For example you can now stratify by gender and race by: confint(sim, "sim", by=c("race", "gender"))

  • When calculating the intervals for rxode2 simulated objects you can now use ci=FALSE so that it only calculates the default intervals without bands on each of the percentiles; You can also choose not to match the secondary bands limits with levels but use your own ci=0.99 for instance

  • A new function was introduced meanProbs() which calculates the mean and expected confidence bands under either the normal or t distribution

  • A related new function was introduced that calculates the mean and confidence bands under the Bernoulli/Binomial distribution (binomProbs())

  • When calculating the intervals for rxode2 simulated objects you can also use mean=TRUE to use the mean for the first level of confidence using meanProbs(). For this confidence interval you can override the n used in the confidence interval by using n=#. You can also change this to a prediction interval instead using pred=TRUE.

  • Also when calculating the intervals for rxode2 simulated object you can also use mean="binom" to use the binomial distributional information (and ci) for the first level of confidence using binomProbs(). For this confidence interval you can override the n used in the confidence interval by using n=#. You can also change this to a prediction interval instead using pred=TRUE. With pred=TRUE you can override the number of predicted samples with m=#

  • When plotting the confint derived intervals from an rxode2 simulation, you can now subset based on a simulated value like plot(ci, Cc) which will only plot the variable Cc that you summarized even if you also summarized eff (for instance).

  • When the rxode2 ui is a compressed ui object, you can modify the ini block with $ini <- or modify the model block with $model <-. These are equivalent to ini(model) <- and model(model) <-, respectively. Otherwise, the object is added to the user defined components in the function (ie $meta). When the object is uncompressed, it simply assigns it to the environment instead (just like before).

  • When printing meta information that happens to be a lotri compatible matrix, use lotri to express it instead of the default R expression.

  • Allow character vectors to be converted to expressions for piping (#552)

  • rxAppendModel() will now take an arbitrary number of models and append them together; It also has better handling of models with duplicate parameters and models without ini() blocks (#617 / #573 / #575).

  • keep will now also keep attributes of the input data (with special handling for levels); This means a broader variety of classes will be kept carrying more information with it (for example ordered factors, data frame columns with unit information, etc)

  • Piping arguments append for ini() and model() have been aligned to perform similarly. Therefore ini(append=) now can take expressions instead of simply strings and model(append=) can also take strings. Also model piping now can specify the integer line number to be modified just like the ini() could. Also model(append=FALSE) has been changed to model(append=NULL). While the behavior is the same when you don’t specify the argument, the behavior has changed to align with ini() when piping. Hence model(append=TRUE) will append and model(append=FALSE) will now pre-pend to the model. model(append=NULL) will modify lines like the behavior of ini(append=NULL). The default of model(line) modifying a line in-place still applies. While this is a breaking change, most code will perform the same.

  • Labels can now be dropped by ini(param=label(NULL)). Also parameters can be dropped with the idiom model(param=NULL) or ini(param=NULL) changes the parameter to a covariate to align with this idiom of dropping parameters

  • rxRename has been refactored to run faster

Internal new features

  • Add as.model() for list expressions, which implies model(ui) <- ui$lstExpr will assign model components. It will also more robustly work with character vectors

  • Simulated objects from rxSolve now can access the model variables with $rxModelVars

  • Simulation models from the UI now use rxerr.endpoint instead of err.endpoint for the sigma residual error. This is to align with the convention that internally generated variables start with rx or nlmixr

  • Sorting only uses timsort now, and was upgraded to the latest version from Morwenn

Bug fixes

  • Simulating/solving from functions/ui now prefers params over omega and sigma in the model (#632)

  • Piping does not add constants to the initial estimates

  • When constants are specified in the model({}) block (like k <- 1), they will not be to the ini block

  • Bug fix for geom_amt() when the aes transformation has x

  • Bug fix for some covariate updates that may affect multiple compartment models (like issue #581)

Maintenance fixes

  • Modify plot code to work with development xgxr

rxode2 2.0.14

CRAN release: 2023-10-07

  • CRAN requested that FORTRAN kind be changed as it was not portable; This was commented code, and simply removed the comment.

  • Bug-fix for geom_amt(); also now uses linewidth and at least ggplot2 3.4.0

  • Some documentation was cleaned up from rxode2 2.0.13

rxode2 2.0.13

CRAN release: 2023-04-22

Bug fixes

  • A bug was fixed so that the zeroRe() function works with correlated omega values.

  • A bug was fixed so that the rename() function works with initial conditions for compartments (cmt(0))

New features

  • 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).

Internal changes

  • If lower/upper bounds are outside the required bounds, the adjustment is displayed.

  • When initial values are piped that break the model’s boundary condition reset the boundary to unbounded and message which boundary was reset.

  • Added as.rxUi() function to convert the following objects to rxUi objects: rxode2, rxModelVars, function. Converting nlmixr2 fits to rxUi will be placed in the s3 method in the corresponding package.

  • assertRxUi(x) now uses as.rxUi() so that it can be extended outside of rxode2/nlmixr2.

  • rxode2 now supports addl with ss doses

  • Moved rxDerived to rxode2parse (and re-exported it here).

  • Added test for transit compartment solving in absence of dosing to the transit compartment (fixed in rxode2parse but solving tested here)

  • Using ini() without any arguments on a rxode2 type function will return the ini() block. Also added a method ini(mod) <- iniBlock to modify the ini block is you wish. iniBlock should be an expression.

  • Using model() without any arguments on a rxode2 type function will return the model() block. Also added a new method model(mod) <- modelBlock

  • Added a new method rxode2(mod) <- modFunction which allows replacing the function with a new function while maintaining the meta information about the ui (like information that comes from nonmem2rx models). The modFunction should be the body of the new function, the new function, or a new rxode2 ui.

  • rxode2 ui objects now have a $sticky item inside the internal (compressed) environment. This $sticky tells what variables to keep if there is a “significant” change in the ui during piping or other sort of model change. This is respected during model piping, or modifying the model with ini(mod)<-, model(mod)<-, rxode2(mod)<-. A significant change is a change in the model block, a change in the number of estimates, or a change to the value of the estimates. Estimate bounds, weather an estimate is fixed or estimate label changes are not considered significant.

  • Added as.ini() method to convert various formats to an ini expression. It is used internally with ini(mod)<-. If you want to assign something new that you can convert to an ini expression, add a method for as.ini().

  • Added as.model() method to convert various formats to a model expression. It is used internally with model(mod)<-. If you want to assign something new that you can convert to a model expression, add a method for as.model().

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.

Simulations

  • 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.

Additional features

  • 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)