tests/testthat/test-simulate_nocb_locf.R

In campsis: Generic PK/PD Simulation Platform Campsis

library(testthat)

context("Test the simulate method with the NOCB/LOCF switch")

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

test_that("Weight as a time-varying covariate, NOCB vs LOCF", {
  if (skip_long_tests()) {
    return(TRUE)
  }
  model <- model_suite$testing$nonmem$advan4_trans4
  equation <- model %>% find(Equation("CL"))
  model <- model %>% replace(Equation("CL", paste0(equation@rhs, "*pow(BW/70, 0.75)")))

  dataset <- Dataset(4) %>%
    add(Bolus(time = 0, amount = 1000, compartment = 1)) %>%
    add(Bolus(time = 24, amount = 1000, compartment = 1)) %>%
    add(Observations(times = c(0, 3, 9, 16, 24, 26, 48)))

  # Left join time-varying BW column
  table <- dataset %>% export(dest = "rxode2", model = model, seed = seed) # CAREFUL, SEED NEEDED FOR REPRODUCIBILITY
  weight <- data.frame(TIME = c(0, 3, 9, 16, 24, 26, 48), BW = c(150, 20, 100, 250, 40, 170, 10))
  table <- table %>% dplyr::left_join(weight, by = "TIME")

  # Dataset non-regression test
  dataset_regression_test(dataset, model, seed = seed, filename = "wt_as_time_varying_cov")

  # LOCF tests
  regFilename <- "wt_as_time_varying_cov_locf"
  simulation <- expression(simulate(
    model = model,
    dataset = table,
    dest = destEngine,
    settings = Settings(NOCB(FALSE), Declare("BW")),
    seed = seed
  ))
  # Note: argument declare is only needed for mrgsolve
  test <- expression(
    output_regression_test(results, output = "CP", filename = regFilename),
    spaghettiPlot(results, "CP")
  )
  campsis_test(simulation, test, env = environment())

  # NOCB tests
  regFilename <- "wt_as_time_varying_cov_nocb"
  simulation <- expression(simulate(
    model = model,
    dataset = table,
    dest = destEngine,
    settings = Settings(NOCB(TRUE), Declare("BW")),
    seed = seed
  ))
  # Note: argument declare is only needed for mrgsolve
  test <- expression(
    output_regression_test(results, output = "CP", filename = regFilename),
    spaghettiPlot(results, "CP")
  )
  campsis_test(simulation, test, env = environment())
})


test_that("NOCB/LOCF should not have any effect on treatment occasion", {
  if (skip_long_tests()) {
    return(TRUE)
  }
  model <- model_suite$testing$nonmem$advan4_trans4 %>%
    delete(Equation("KA")) %>%
    add(Equation("KA", "0")) %>%
    add(IfStatement("OCC==1", Equation("KA", "THETA_KA*1.5*exp(ETA_KA)"))) %>%
    add(IfStatement("OCC==2", Equation("KA", "THETA_KA*0.5*exp(ETA_KA)"))) %>%
    add(IfStatement("OCC==3", Equation("KA", "THETA_KA*0.1*exp(ETA_KA)")))

  dataset <- Dataset(3) %>%
    add(Bolus(time = 0, amount = 1000, compartment = 1)) %>%
    add(Bolus(time = 12, amount = 1000, compartment = 1)) %>%
    add(Bolus(time = 24, amount = 1000, compartment = 1)) %>%
    add(Occasion("OCC", values = c(1, 2, 3), doseNumbers = c(1, 2, 3))) %>%
    add(Observations(times = seq(24, 36)))

  regFilename <- "occ_as_time_varying_cov"
  # table_rxode <- dataset %>% export(dest="RxODE", model=model, seed=seed)
  # table_mrgsolve <- dataset %>% export(dest="mrgsolve", model=model, seed=seed)

  # Dataset non-regression test
  dataset_regression_test(dataset, model, seed = seed, filename = regFilename)

  # LOCF tests
  simulation <- expression(simulate(
    model = model,
    dataset = dataset,
    dest = destEngine,
    settings = Settings(NOCB(FALSE, "OCC")),
    seed = seed,
    outvars = "KA"
  ))
  test <- expression(
    output_regression_test(results, output = "CP", filename = regFilename),
    spaghettiPlot(results, "CP")
  )
  campsis_test(simulation, test, env = environment())

  # NOCB tests
  simulation <- expression(simulate(
    model = model,
    dataset = dataset,
    dest = destEngine,
    settings = Settings(NOCB(TRUE, "OCC")),
    seed = seed,
    outvars = "KA"
  ))
  test <- expression(
    output_regression_test(results, output = "CP", filename = regFilename),
    spaghettiPlot(results, "CP")
  )
  campsis_test(simulation, test, env = environment())
})

test_that("NOCB/LOCF should not have any effect on IOV, e.g. on clearance", {
  if (skip_long_tests()) {
    return(TRUE)
  }
  regFilename <- "3_boluses_iov_cl"
  model <- model_suite$testing$nonmem$advan4_trans4
  model <- model %>% replace(Equation("CL", rhs = "THETA_CL*exp(ETA_CL + IOV_CL)"))

  for (startTime in c(0, 20, 23, 24, 48)) {
    obsTimes <- seq(startTime, 72, by = 5)

    dataset <- Dataset(3) %>%
      add(Bolus(time = 0, amount = 1000, compartment = 1)) %>%
      add(Bolus(time = 24, amount = 1000, compartment = 1)) %>%
      add(Bolus(time = 48, amount = 1000, compartment = 1)) %>%
      add(Observations(times = obsTimes)) %>% # BEFORE by 0.5, NOW by 5
      add(IOV(colname = "IOV_CL", distribution = FunctionDistribution(fun = "rnorm", args = list(mean = 0, sd = 1))))

    # table_rxode <- dataset %>% export(dest="RxODE", model=model, seed=seed)
    # table_mrgsolve <- dataset %>% export(dest="mrgsolve", model=model, seed=seed)

    # LOCF tests
    simulation <- expression(simulate(
      model = model,
      dataset = dataset,
      dest = destEngine,
      settings = Settings(NOCB(FALSE, "IOV_CL")),
      seed = seed
    ))
    test <- expression(
      output_regression_test(results, output = "CP", filename = regFilename, times = obsTimes),
      spaghettiPlot(results, "CP")
    )
    campsis_test(simulation, test, env = environment())

    # NOCB tests
    simulation <- expression(simulate(
      model = model,
      dataset = dataset,
      dest = destEngine,
      settings = Settings(NOCB(TRUE, "IOV_CL")),
      seed = seed
    ))
    test <- expression(
      output_regression_test(results, output = "CP", filename = regFilename, times = obsTimes),
      spaghettiPlot(results, "CP")
    )
    campsis_test(simulation, test, env = environment())
  }
})