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nlmixr2lib

Version 0.3.0

• Added ability to choose style type when modifying models. Currently supported styles are: “camel” for variablesLikeThis, “snake” for variables_like_this, “dot” for variables.like.this and “blank” for variableslikethis. This can be selected with setCombineType().

• With the new combination style, you can change how eta variables are constructed with the option(nlmixr2lib.etaCombineType="camel") or whatever you wish it to the variable style to be.

• Added new model building framework for building models

  • PK model building functions

    • addTransit()/removeTransit() which were present before, but now modified and made a bit more robust, more closely matching literature method of transit compartments.

    • addDepot()/removeDepot() which were present before, but modified to be a bit more robust.

    • addWeibullAbs() which adds a Weibull absorption to a PK model

    • convertMM() converts linear elimination to Michaelis-Menten elimination

    • transPK() converts the cl style parameter transformations to various other PK transformations like k, aob, alpha, k12

  • PD model building functions

  • addIndirectLin() – this adds an indirect effect model to a PK model that has a concentration Cc in the model. This purposely uses a simple linear effect of Cc*Ek or Cc*Ik so it will be easy to parse and turn into other functional forms (like Emax or Hill). If the PK model is not present it will use Cc as a covariate in a purely PD models.

  • addIndirect() – this builds on addIndirectLin() and adds Emax or Hill models to a PK model. You can also set imax=1 or emax=1 to drop these parameters from being estimated in the model. Additionally hill=TRUE will add a Hill coefficient to the sigmoid model.

  • addEffectCmtLin() – this adds an effect compartment based on the Cc in the model. The linear effect can be modified into other function forms.

  • addDirectLin() – this adds a direct effect model based on the Cc in the model.

  • Changing functional forms of Effect models

    • convertEmax() changes linear effect models to Emax models

    • convertEmaxHill() changes linear effect models to Hill models

    • convertQuad() changes linear effect models to quadratic models

    • convertLogLin() changes linear effect models to log-linear models

  • Changing functional forms of Baselines in non-indirect response models

    • addBaselineConst() changes the zero baseline to a estimated constant

    • addBaselineLin() changes the zero baseline to a estimated constant and a linear constant with respect to time.

    • addBaselineExp() changes the zero baseline to a exponential decay with respect to time

    • addBaseline1exp() – the baseline effect is changed from zero to to an exponential approaching to a constant (with respect to time).

  • Changing model properties (all use addCmtProp())

    • addBioavailability() adds bioavailability property to a compartment

    • addRate() adds a modeled rate to a compartment

    • addDur() adds modeled duration to a compartment

    • addIni() adds an initial value to a compartment

    • addLag() adds a lag time to the a compartment

• Add Carlsson Petri (2021) liraglutide PK model

• Add Cirincione (2017) exenatide immediate-release PK model

• Add a variety of indirect response models

• Add a variety of tumor growth inhibition models and move all oncology models into a new model database directory

• Add a variety of double-absorption PK models

• cp and related cpddSd and cppropSd were renamed to Cc, CcAddSd and CcPropSd (fix #70).

• Multiple-endpoint models will have the DV column in the modeldb separated by commas.

Version 0.2.0

• Work with the new rxode2 version 2.0.12 model() and ini() assignment methods.
• Therapeutic-area specific models have begun being added.
• Models can now give the user some additional information load via the message meta-data.
• Models can now be in different directories. The change is for ease of maintaining the library, it is not a change that affects users.
• A regression where addEta() did not change the parameter, related to a change in rxode2, was fixed.
• addEta() detects where to add etas more robustly when covariates are on the parameter.

Models added

• Add Davda (2014) mAb consensus model
• Add Liu (2017) time-dependent clearance model based on nivolumab
• Add Kovalenko (2020) dupilumab PK model
• Add Soehoel (2022) tralokinumab PK model
• Add Zhu (2017) lebrikizumab PK model

Version 0.1.0

• Initial version

These binaries (installable software) and packages are in development.
They may not be fully stable and should be used with caution. We make no claims about them.