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Could fix vignette #58

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Nov 8, 2024
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Could fix vignette #58

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22 changes: 12 additions & 10 deletions vignettes/articles/multiple_endpoints.Rmd
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Original file line number Diff line number Diff line change
Expand Up @@ -22,7 +22,7 @@ library(posologyr)
```

# Introduction
A different error model can be defined for multiple endpoints models (eg.
A different error model can be defined for multiple endpoints models (eg.
PK-PD, parent-metabolite, blood-urine...).

An example can be seen below, utilizing the warfarin data and model (provided by Tomoo Funaki and Nick Holford) from the nlmixr documentation (https://nlmixr2.org/articles/multiple-endpoints.html).
Expand All @@ -32,7 +32,7 @@ An example can be seen below, utilizing the warfarin data and model (provided by
```{r}
mod_warfarin_nlmixr <- function() {
ini({
#Fixed effects: population estimates
#Fixed effects: population estimates
THETA_ktr=0.106
THETA_ka=-0.087
THETA_cl=-2.03
Expand All @@ -41,7 +41,7 @@ mod_warfarin_nlmixr <- function() {
THETA_ec50=0.00724
THETA_kout=-2.9
THETA_e0=4.57

#Random effects: inter-individual variability
ETA_ktr ~ 1.024695
ETA_ka ~ 0.9518403
Expand All @@ -51,7 +51,7 @@ mod_warfarin_nlmixr <- function() {
ETA_ec50 ~ 0.7204165
ETA_kout ~ 0.3563706
ETA_e0 ~ 0.2660827

#Unexplained residual variability
cp.sd <- 0.144
cp.prop.sd <- 0.15
Expand All @@ -67,27 +67,29 @@ mod_warfarin_nlmixr <- function() {
ec50 = exp(THETA_ec50 + ETA_ec50)
kout = exp(THETA_kout + ETA_kout)
e0 = exp(THETA_e0 + ETA_e0)

#Structural model defined using ordinary differential equations (ODE)
DCP = center/v
PD=1-emax*DCP/(ec50+DCP)

effect(0) = e0
kin = e0*kout

d/dt(depot) = -ktr * depot
d/dt(gut) = ktr * depot -ka * gut
d/dt(center) = ka * gut - cl / v * center
d/dt(effect) = kin*PD -kout*effect

cp = center / v
pca = effect

#Model for unexplained residual variability
cp ~ add(cp.sd) + prop(cp.prop.sd)
pca ~ add(pca.sd)
})
}
}

mod_warfarin_nlmixr <- mod_warfarin_nlmixr()
```

## data: first subject from the warfarin dataset
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