RxODE Event Types

2021-09-01

Source: vignettes/RxODE-datasets.Rmd

RxODE

Datasets for RxODE & nlmixr

Data for input into nlmixr is the same type of data input for RxODE, and it is similar to data for NONMEM (most NONMEM-ready datasets can be used directly in nlmixr).

Columns Described by Type of Use

Subject Identification Columns

The subject identification column separates subjects for identification of random effects.

  • ID: A subject identifier that may be an integer, character, or factor.

Observation Columns

Observation columns are used to indicate the dependent variable and how to use or measure it.

  • DV: A numeric column with the measurement
  • CENS: A numeric column for indication of censoring, such as below the limit of quantification for an assay.
  • LIMIT: A numeric column for helping indicate the type of censoring, such as below the limit of quantification for an assay.
  • MDV: An indicator for missing DV values
  • CMT: The name or number of the compartment
  • DVID: The dependent variable identifier
  • EVID The event identifier

Dosing Columns

  • AMT: The amount of the dose
  • CMT: The name or number of the compartment
  • EVID: The event identifier
  • ADDL: The number of additional doses
  • RATE or DUR: The rate or duration of a dose

Covariate Columns

Details for Specific Dataset Columns

The details below are sorted alphabetically by column name. For grouping by use, see the documentation above.

AMT Column

The AMT column defines the amount of a dose.

For observation rows, it should be 0 or NA.

For dosing rows, it is the amount of the dose administered to the CMT. If the dose has a zero-order rate (such as a constant infusion), the infusion may be setup using the RATE or DUR column.

CENS/LIMIT Columns

The CENS column is an indicator column indicating if censoring occurred. For pharmacokinetic modeling, censoring is typically when a sample is below the limit of quantification. Internally RxODE saves these values so that nlmixr can use them in likelihood calculations.

CENS = 0 indicates that the value in DV is measured without censoring.

CENS = 1 indicates that a value is left censored (or below the limit of quantitation) and that the value in DV is censoring/quantitation limit.

CENS = -1 indicates that a value is right censored (or above limit of quantitation) and that the value in DV is censoring/quantitation limit.

The LIMIT is additional information about how censoring is handled with nlmixr and is stored in RxODE’s data structure as well. When a value is left censored, like below a limit of 1 you may also believe that the value is above a certain threshold, like zero. In this case, a limit of 0 indicates that the censored value is between 0 and 1.

In short when:

CENS = 0 a LIMIT is ignored because the observation is not censored

CENS = 1 the value is censored between (LIMIT, DV)

CENS = -1 the value is censored between (DV, LIMIT)

CMT Column

The CMT column indicates the compartment where an event occurs. When given as a character string or factor (the preferred method), it is matched by name in the model. When given as an integer, it is matched by the order that compartments appear in the model.

DUR Column

The DUR column defines the duration of an infusion. It is used to set the duration of a zero-order rate of infusion.

DV Column

The DV column indicates the current measurement in the current compartment (see CMT) with the current measurement identifier (see DVID) which may be missing (see MDV) or censored (see CENS).

DVID Column

TODO

EVID Column

The EVID column is the event identifier for a row of data.

For observation records, it will be 0. For normal dosing records, it will be 1. Many more EVID values are detailed in the RxODE Event Types and Classic RxODE Events vignettes.

ID Column

The ID column is a subject identifier. This column is used to separate one individual (usually a single person or animal) from another.

In the model, the ID column is used to separate individuals. The numerical integrator re-initializes with each new individual, and new values for all random effects are selected.

RATE Column

TODO