Skip to contents

This shows an easy work-flow to create a VPC using a NONMEM model:

Step 1: Convert the NONMEM model to rxode2:

library(babelmixr2)
library(nonmem2rx)



# First we need the location of the nonmem control stream Since we are running an example, we will use one of the built-in examples in `nonmem2rx`
ctlFile <- system.file("mods/cpt/runODE032.ctl", package="nonmem2rx")
# You can use a control stream or other file. With the development
# version of `babelmixr2`, you can simply point to the listing file

mod <- nonmem2rx(ctlFile, lst=".res", save=FALSE)
#>  getting information from  '/home/runner/work/_temp/Library/nonmem2rx/mods/cpt/runODE032.ctl'
#>  reading in xml file
#>  done
#>  reading in ext file
#>  done
#>  reading in phi file
#>  done
#>  reading in lst file
#>  abbreviated list parsing
#>  done
#>  reading in grd file
#>  done
#>  splitting control stream by records
#>  done
#>  Processing record $INPUT
#>  Processing record $MODEL
#>  Processing record $gTHETA
#>  Processing record $OMEGA
#>  Processing record $SIGMA
#>  Processing record $PROBLEM
#>  Processing record $DATA
#>  Processing record $SUBROUTINES
#>  Processing record $PK
#>  Processing record $DES
#>  Processing record $ERROR
#>  Processing record $ESTIMATION
#>  Ignore record $ESTIMATION
#>  Processing record $COVARIANCE
#>  Ignore record $COVARIANCE
#>  Processing record $TABLE
#>  change initial estimate of `theta1` to `1.37034036528946`
#>  change initial estimate of `theta2` to `4.19814911033061`
#>  change initial estimate of `theta3` to `1.38003493562413`
#>  change initial estimate of `theta4` to `3.87657341967489`
#>  change initial estimate of `theta5` to `0.196446108190896`
#>  change initial estimate of `eta1` to `0.101251418415006`
#>  change initial estimate of `eta2` to `0.0993872449483344`
#>  change initial estimate of `eta3` to `0.101302674763154`
#>  change initial estimate of `eta4` to `0.0730497519364148`
#>  read in nonmem input data (for model validation): /home/runner/work/_temp/Library/nonmem2rx/mods/cpt/Bolus_2CPT.csv
#>  ignoring lines that begin with a letter (IGNORE=@)'
#>  applying names specified by $INPUT
#>  subsetting accept/ignore filters code: .data[-which((.data$SD == 0)),]
#>  done
#>  read in nonmem IPRED data (for model validation): /home/runner/work/_temp/Library/nonmem2rx/mods/cpt/runODE032.csv
#>  done
#>  changing most variables to lower case
#>  done
#>  replace theta names
#>  done
#>  replace eta names
#>  done (no labels)
#>  renaming compartments
#>  done
#>  solving ipred problem
#>  done
#>  solving pred problem
#>  done

Step 2: convert the rxode2 model to nlmixr2

In this step, you convert the model to nlmixr2 by as.nlmixr2(mod); You may need to do a little manual work to get the residual specification to match between nlmixr2 and NONMEM.

Once the residual specification is compatible with a nlmixr2 object, you can convert the model, mod, to a nlmixr2 fit object:

fit <- as.nlmixr2(mod)
#> → loading into symengine environment...
#> → pruning branches (`if`/`else`) of full model...
#>  done
#> → finding duplicate expressions in EBE model...
#> [====|====|====|====|====|====|====|====|====|====] 0:00:00
#> → optimizing duplicate expressions in EBE model...
#> [====|====|====|====|====|====|====|====|====|====] 0:00:00
#> → compiling EBE model...
#>  done
#> rxode2 4.0.0 using 2 threads (see ?getRxThreads)
#>   no cache: create with `rxCreateCache()`
#> → Calculating residuals/tables
#>  done
#> → compress origData in nlmixr2 object, save 203816
#> → compress parHistData in nlmixr2 object, save 2184

fit

cmt(CENTRAL)cmt(PERI)cl=exp(theta1+eta1)v=exp(theta2+eta2)q=exp(theta3+eta3)v2=exp(theta4+eta4)v1=vscale1=vk21=qv2k12=qvdCENTRALdt=k21×PERIk12×CENTRALcl×CENTRALv1dPERIdt=k21×PERI+k12×CENTRALf=CENTRALscale1ipred=frescv=RSVipredprop(RSV)\begin{align*} cmt({CENTRAL}) \\ cmt({PERI}) \\ {cl} & = \exp\left({theta1}+{eta1}\right) \\ {v} & = \exp\left({theta2}+{eta2}\right) \\ {q} & = \exp\left({theta3}+{eta3}\right) \\ {v2} & = \exp\left({theta4}+{eta4}\right) \\ {v1} & = {v} \\ {scale1} & = {v} \\ {k21} & = \frac{{q}}{{v2}} \\ {k12} & = \frac{{q}}{{v}} \\ \frac{d \: CENTRAL}{dt} & = {k21} {\times} {PERI}-{k12} {\times} {CENTRAL}-\frac{{cl} {\times} {CENTRAL}}{{v1}} \\ \frac{d \: PERI}{dt} & = -{k21} {\times} {PERI}+{k12} {\times} {CENTRAL} \\ {f} & = \frac{{CENTRAL}}{{scale1}} \\ {ipred} & = {f} \\ {rescv} & = {RSV} \\ {ipred} & \sim prop({RSV}) \end{align*}

Step 3: Perform the VPC

From here we simply use vpcPlot() in conjunction with the vpc package to get the regular and prediction-corrected VPCs and arrange them on a single plot:


library(ggplot2)
p1 <- vpcPlot(fit, show=list(obs_dv=TRUE))
#> using C compiler: ‘gcc (Ubuntu 13.3.0-6ubuntu2~24.04) 13.3.0’
#> [====|====|====|====|====|====|====|====|====|====] 0:00:00

p1 <- p1 + ylab("Concentrations") +
  rxode2::rxTheme() +
  xlab("Time (hr)") +
  xgxr::xgx_scale_x_time_units("hour", "hour")

p1a <- p1 + xgxr::xgx_scale_y_log10()

## A prediction-corrected VPC
p2 <- vpcPlot(fit, pred_corr = TRUE, show=list(obs_dv=TRUE))
#> [====|====|====|====|====|====|====|====|====|====] 0:00:00
p2 <- p2 + ylab("Prediction-Corrected Concentrations") +
  rxode2::rxTheme() +
  xlab("Time (hr)") +
  xgxr::xgx_scale_x_time_units("hour", "hour")

p2a <- p2 + xgxr::xgx_scale_y_log10()


library(patchwork)
(p1 * p1a) / (p2 * p2a)