Inter-occasion variability"
In campsis: Generic PK/PD Simulation Platform CAMPSIS

if (campsis::onCran()) {
  cat("This vignette was not built on CRAN. Please check out the online version [here](https://calvagone.github.io/campsis.doc/articles/v07_iov.html).")
  knitr::knit_exit()
}

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