Inter-occasion variability • campsis

This vignette shows how inter-occasion variability (IOV) can be added on a parameter at each administration.

Treatment IOV on KA

Let’s use a 2-compartment model with absorption compartment for this example.

model <- model_suite$nonmem$advan4_trans4

We’re going to add a term IOV_KA on parameter KA. This can be done as follows:

model <- model %>%
  replace(Equation("KA", "THETA_KA*exp(ETA_KA + IOV_KA)"))

This model will not run unless we give some values for IOV_KA. This can achieved by adding IOV to the dataset. The following code will create a simple dataset with IOV.

ds_iov <- Dataset(50) %>%
  add(Bolus(time = c(0, 24, 48), amount = 1000, compartment = 1)) %>%
  add(Observations(times = seq(0, 72, by = 0.5))) %>%
  add(IOV("IOV_KA", distribution = NormalDistribution(mean = 0, sd = 1)))

To disable IOV on KA, the replace method can be used:

ds_no_iov <- ds_iov %>%
  replace(IOV("IOV_KA", 0))

We can now run the model with IOV on KA and without.

results_iov <- simulate(model = model, dataset = ds_iov, seed = 1)
results_no_iov <- simulate(model = model, dataset = ds_no_iov, seed = 1)
gridExtra::grid.arrange(
  shaded_plot(results_iov, "CONC"),
  shaded_plot(results_no_iov, "CONC"),
  nrow = 1
)