tests/testthat/test-simulate_dose_adaptation.R

In campsis: Generic PK/PD Simulation Platform Campsis

library(testthat)

context("Test simple dose adaptations (based on a covariate present in dataset)")

seed <- 1
source(file.path(getwd(), test_path(), "test-utils.R"))

test_that("Dose adaptations based on weight work well", {
  model <- model_suite$testing$nonmem$advan4_trans4 %>% disable("IIV")
  regFilename <- "dose_adaptation_by_bw"

  dataset <- Dataset(2) %>%
    add(Bolus(time = seq(0, 6) * 24, amount = 0.5)) %>% # 0.5mg / kg
    add(Observations(times = seq(0, 7 * 24, by = 4))) %>%
    add(Covariate("WT", c(100, 50))) %>%
    add(DoseAdaptation("AMT*WT"))

  dataset_regression_test(dataset, model, seed = seed, filename = regFilename)

  simulation <- expression(simulate(model = model, dataset = dataset, dest = destEngine, seed = seed))
  test <- expression(
    output_regression_test(results, output = "CP", filename = regFilename)
  )
  campsis_test(simulation, test, env = environment())
})

test_that("Dose adaptations preserve specified infusion duration", {
  model <- model_suite$testing$nonmem$advan3_trans4 %>% disable("IIV")
  regFilename <- "dose_adaptation_by_bw_infusion"

  dataset <- Dataset(2) %>%
    add(Infusion(time = seq(0, 6) * 24, amount = 0.5, duration = 10)) %>% # 0.5mg/kg, 10 hours
    add(Observations(times = seq(0, 7 * 24, by = 4))) %>%
    add(Covariate("WT", c(100, 50))) %>%
    add(DoseAdaptation("AMT*WT"))

  dataset_regression_test(dataset, model, seed = seed, filename = regFilename)

  simulation <- expression(simulate(model = model, dataset = dataset, dest = destEngine, seed = seed))
  test <- expression(
    output_regression_test(results, output = "CP", filename = regFilename)
  )
  campsis_test(simulation, test, env = environment())
})

test_that("Dose adaptations preserve specified infusion rate", {
  model <- model_suite$testing$nonmem$advan3_trans4 %>% disable("IIV")
  regFilename <- "dose_adaptation_by_bw_infusion"

  subj1 <- Arm(subjects = 1) %>%
    add(Infusion(time = seq(0, 6) * 24, amount = 0.5, rate = 5)) %>% # 0.5mg/kg, 50mg/10h=5mg/h
    add(Observations(times = seq(0, 7 * 24, by = 4))) %>%
    add(Covariate("WT", 100)) %>%
    add(DoseAdaptation("AMT*WT"))

  subj2 <- Arm(subjects = 1) %>%
    add(Infusion(time = seq(0, 6) * 24, amount = 0.5, rate = 2.5)) %>% # 0.5mg/kg, 25mg/10h=2.5mg/h
    add(Observations(times = seq(0, 7 * 24, by = 4))) %>%
    add(Covariate("WT", 50)) %>%
    add(DoseAdaptation("AMT*WT"))

  dataset <- Dataset() %>% add(c(subj1, subj2))

  simulation <- expression(simulate(model = model, dataset = dataset, dest = destEngine, seed = seed))
  test <- expression(
    output_regression_test(results, output = "CP", filename = regFilename)
  )
  campsis_test(simulation, test, env = environment())
})

test_that("Dose adaptations based on weight work well, check argument compartments works as expected", {
  model <- model_suite$testing$nonmem$advan4_trans4 %>% disable("IIV")
  regFilename <- "dose_adaptation_by_bw"

  # Add independant ODE
  model <- model %>% add(Ode("A_TEST", "-log(2)/100*A_TEST"))
  model <- model %>% update_compartments()

  # Dataset with unnamed compartments
  times <- seq(0, 7 * 24, by = 4)
  dataset <- Dataset(2) %>%
    add(Bolus(time = 0, amount = 0.5, compartment = 1, ii = 24, addl = 6)) %>%
    add(Bolus(time = 0, amount = 1000, compartment = 5)) %>%
    add(Observations(times = times)) %>%
    add(Covariate("WT", c(100, 50)))

  # Dose adaptation only for compartment 1 (not 5!)
  dataset <- dataset %>%
    add(DoseAdaptation("AMT*WT", compartments = 1))

  # Unnamed compartments
  simulation <- expression(simulate(model = model, dataset = dataset, dest = destEngine, seed = seed))
  test <- expression(
    output_regression_test(results, output = "CP", filename = regFilename),
    output_regression_test(results %>% dplyr::filter(TIME != 0), output = "A_TEST", filename = regFilename), # Remove first time (RxODE:0, mrgsolve:1000)
    spaghettiPlot(results, "A_TEST", "ID")
  )
  campsis_test(simulation, test, env = environment())

  # Same test but with named compartments
  # Dataset with unnamed compartments
  times <- seq(0, 7 * 24, by = 4)
  dataset <- Dataset(2) %>%
    add(Bolus(time = 0, amount = 0.5, compartment = "DEPOT", ii = 24, addl = 6)) %>%
    add(Bolus(time = 0, amount = 1000, compartment = "TEST")) %>%
    add(Observations(times = times)) %>%
    add(Covariate("WT", c(100, 50)))

  # Dose adaptation only for compartment 1 (not 5!)
  dataset <- dataset %>%
    add(DoseAdaptation("AMT*WT", compartments = "DEPOT"))

  # Unnamed compartments
  simulation <- expression(simulate(model = model, dataset = dataset, dest = destEngine, seed = seed))
  test <- expression(
    output_regression_test(results, output = "CP", filename = regFilename),
    output_regression_test(results %>% dplyr::filter(TIME != 0), output = "A_TEST", filename = regFilename), # Remove first time (RxODE:0, mrgsolve:1000)
    spaghettiPlot(results, "A_TEST", "ID")
  )
  campsis_test(simulation, test, env = environment())
})