diff --git a/vignettes/articles/multiple_endpoints.Rmd b/vignettes/articles/multiple_endpoints.Rmd index 6966a8c..a71f5ad 100644 --- a/vignettes/articles/multiple_endpoints.Rmd +++ b/vignettes/articles/multiple_endpoints.Rmd @@ -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). @@ -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 @@ -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 @@ -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 @@ -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