Monolix Controller for nlmixr2

Monolix Controller for nlmixr2

Usage

monolixControl(
  nbSSDoses = 7,
  useLinearization = FALSE,
  stiff = FALSE,
  addProp = c("combined2", "combined1"),
  exploratoryAutoStop = FALSE,
  smoothingAutoStop = FALSE,
  burnInIterations = 5,
  smoothingIterations = 200,
  exploratoryIterations = 250,
  simulatedAnnealingIterations = 250,
  exploratoryInterval = 200,
  exploratoryAlpha = 0,
  omegaTau = 0.95,
  errorModelTau = 0.95,
  variability = c("none", "firstStage", "decreasing"),
  runCommand = getOption("babelmixr2.monolix", ""),
  rxControl = NULL,
  sumProd = FALSE,
  optExpression = TRUE,
  calcTables = TRUE,
  compress = TRUE,
  ci = 0.95,
  sigdigTable = NULL,
  absolutePath = FALSE,
  modelName = NULL,
  muRefCovAlg = TRUE,
  ...
)

Arguments

nbSSDoses

Number of steady state doses (default 7)

useLinearization

Use linearization for log likelihood and fim.

stiff

boolean for using the stiff ODE solver

addProp

specifies the type of additive plus proportional errors, the one where standard deviations add (combined1) or the type where the variances add (combined2).

The combined1 error type can be described by the following equation:

$$y = f + (a + b\times f^c) \times \varepsilon$$

The combined2 error model can be described by the following equation:

$$y = f + \sqrt{a^2 + b^2\times f^{2\times c}} \times \varepsilon$$

Where:

- y represents the observed value

- f represents the predicted value

- a is the additive standard deviation

- b is the proportional/power standard deviation

- c is the power exponent (in the proportional case c=1)

exploratoryAutoStop

logical to turn on or off exploratory phase auto-stop of SAEM (default 250)

smoothingAutoStop

Boolean indicating if the smoothing should automatically stop (default FALSE)

burnInIterations

Number of burn in iterations

smoothingIterations

Number of smoothing iterations

exploratoryIterations

Number of iterations for exploratory phase (default 250)

simulatedAnnealingIterations

Number of simulating annealing iterations

exploratoryInterval

Minimum number of iterations in the exploratory phase (default 200)

exploratoryAlpha

Convergence memory in the exploratory phase (only used when exploratoryAutoStop is TRUE)

omegaTau

Proportional rate on variance for simulated annealing

errorModelTau

Proportional rate on error model for simulated annealing

variability

This describes the methodology for parameters without variability. It could be: - Fixed throughout (none) - Variability in the first stage (firstStage) - Decreasing until it reaches the fixed value (decreasing)

runCommand

is a shell command or function to run monolix; You can specify the default by options("babelmixr2.monolix"="runMonolix"). If it is empty and 'lixoftConnectors' is available, use lixoftConnectors to run monolix. See details for function usage.

rxControl

`rxode2` ODE solving options during fitting, created with `rxControl()`

sumProd

Is a boolean indicating if the model should change multiplication to high precision multiplication and sums to high precision sums using the PreciseSums package. By default this is FALSE.

optExpression

Optimize the rxode2 expression to speed up calculation. By default this is turned on.

calcTables

This boolean is to determine if the foceiFit will calculate tables. By default this is TRUE

compress

Should the object have compressed items

ci

Confidence level for some tables. By default this is 0.95 or 95% confidence.

sigdigTable

Significant digits in the final output table. If not specified, then it matches the significant digits in the `sigdig` optimization algorithm. If `sigdig` is NULL, use 3.

absolutePath

Boolean indicating if the absolute path should be used for the monolix runs

modelName

Model name used to generate the NONMEM output. If NULL try to infer from the model name (could be x if not clear). Otherwise use this character for outputs.

muRefCovAlg

This controls if algebraic expressions that can be mu-referenced are treated as mu-referenced covariates by:

1. Creating a internal data-variable `nlmixrMuDerCov#` for each algebraic mu-referenced expression

2. Change the algebraic expression to `nlmixrMuDerCov# * mu_cov_theta`

3. Use the internal mu-referenced covariate for saem

4. After optimization is completed, replace `model()` with old `model()` expression

5. Remove `nlmixrMuDerCov#` from nlmix2 output

In general, these covariates should be more accurate since it changes the system to a linear compartment model. Therefore, by default this is `TRUE`.

...

Ignored parameters

Value

A monolix control object

Details

If runCommand is given as a string, it will be called with the system() command like:

runCommand mlxtran.

For example, if runCommand="'/path/to/monolix/mlxbsub2021' -p " then the command line used would look like the following:

'/path/to/monolix/mlxbsub2021' monolix.mlxtran

If runCommand is given as a function, it will be called as FUN(mlxtran, directory, ui) to run Monolix. This allows you to run Monolix in any way that you may need, as long as you can write it in R. babelmixr2 will wait for the function to return before proceeding.

If runCommand is NA, nlmixr() will stop after writing the model files and without starting Monolix.

Note that you can get the translated monolix components from a parsed/compiled rxode2 ui object with ui$monolixModel and ui$mlxtran

Author

Matthew Fidler