Adding exposure to an IQRaedataER initial dataset

Adding exposure metrics Cmin, Cavg, Cmax, Cavg_accumulated, Cae to an IQRaedataER dataset. Cae: Actual concentration at time of observed AE.

  • Placebo subjects exposure metrics: all 0

  • Set exposure metrics for AE starting at TIME<0 to 0

  • No AE occurred during observed period (censored)

    • Cmax: maximum overall simulated Cmax (first occurrence if several)

    • Cavg: average concentration over INTERVAL_EXPOSURE ending at time of maximum overall simulated Cmax

    • Cmin: minumum concentration over INTERVAL_EXPOSURE ending at time of maximum overall simulated Cmax

    • Cavg_accumulated: average concentration over whole observation period

    • Cae: NA

  • AE occurred during observartion period (not censored)

    • Cmax: maximum concentration in INTERVAL_EXPOSURE prior to AE

    • Cavg: average concentration in INTERVAL_EXPOSURE prior to AE

    • Cmin: minumum concentration in INTERVAL_EXPOSURE prior to AE

    • Cavg_accumulated: average concentration from 0 to time of AE

    • If AE happened at time < INTERVAL_EXPOSURE then use interval 0-AE TIME for Cmin, Cmax, Cavg, Cavgacc

    • Cae: actual concentration a time of AE

  • Use time step DELTA_EXPOSURE to determine Cmin, Cmax, Cavg, Cavg_accumulated Multiple models can be defined and for each model a different output can be used and weighted. The sum of the different weighted outputs of the models is used to calculate the exposure.

addExposure_IQRaedataER(
  data,
  modelinfo,
  INTERVAL_EXPOSURE,
  DELTA_EXPOSURE,
  pathname = "info",
  FLAGduplicateDoses = FALSE,
  opt_abstol = 1e-06,
  opt_reltol = 1e-06
)

Arguments

data

IQRaedataER dataset generated with createAEdata_IQRdataGENERAL()

modelinfo

A list of lists. Each sublist contains the elements NLMEPROJECT, OUTPUT, and WEIGHTING. Example: modelinfo <- list( list(NLMEPROJECT = "ExampleData/NLMEPROJECT1", OUTPUT = "cc_ngmL", WEIGHTING = 1), list(NLMEPROJECT = "ExampleData/NLMEPROJECT2", OUTPUT = "cc_ngmL", WEIGHTING = 2) ) This leads to the exposure used defined as 1cc_ngml(model1) + 2cc_ngml(model2). For single models it is possible to avoid the highest level list as follows: modelinfo <- list(NLMEPROJECT = "ExampleData/NLMEPROJECT1", OUTPUT = "cc_ngmL", WEIGHTING = 1)

INTERVAL_EXPOSURE

Interval over which to calculate the exposure metrics (in TIMEUNIT units)

DELTA_EXPOSURE

Time step delta to use for simulation of exposure metrics

pathname

Path to which to store information about removed subjects (missing individual PK parameters) and removed AEs (missing TIME information)

FLAGduplicateDoses

If TRUE then each dose is duplicated once. Useful for parallel absorption processes. Currently implemented to work when only a single drug is given using one route of administration (ADM=1). Will be duplicated to ADM=2

opt_abstol

Absolute integrator tolerances

opt_reltol

Relative integrator tolerances

Value

Updated IQRaedataER dataset with exposure metrics added

See also