nlmixr2est

Nonlinear Mixed Effects Models in Population PK/PD, Estimation Routines


License
CNRI-Python-GPL-Compatible

Documentation

output
github_document

nlmixr2est: The core estimation routines for nlmixr2

R build status CodeFactor CRAN version CRAN total downloads CRAN total downloads

codecov

The goal of nlmixr2est is to provide the nlmixr2 core estimation routines.

Installation

You can install the development version of nlmixr2est from GitHub with:

# install.packages("remotes")
remotes::install_github("nlmixr2/nlmixr2data")
remotes::install_github("nlmixr2/lotri")
remotes::install_github("nlmixr2/rxode2")
remotes::install_github("nlmixr2/nlmixr2est")

For most people, using nlmixr2 directly would be likely easier.

library(nlmixr2est)
#> Loading required package: nlmixr2data

## The basic model consiss of an ini block that has initial estimates
one.compartment <- function() {
  ini({
    tka <- 0.45 # Log Ka
    tcl <- 1 # Log Cl
    tv <- 3.45    # Log V
    eta.ka ~ 0.6
    eta.cl ~ 0.3
    eta.v ~ 0.1
    add.sd <- 0.7
  })
  # and a model block with the error sppecification and model specification
  model({
    ka <- exp(tka + eta.ka)
    cl <- exp(tcl + eta.cl)
    v <- exp(tv + eta.v)
    d/dt(depot) = -ka * depot
    d/dt(center) = ka * depot - cl / v * center
    cp = center / v
    cp ~ add(add.sd)
  })
}

## The fit is performed by the function nlmixr/nlmix2 specifying the model, data and estimate
fit <- nlmixr2(one.compartment, theo_sd,  est="saem", saemControl(print=0))
#> 
#>  
#> 
#> ℹ parameter labels from comments will be replaced by 'label()'
#> 
#> → loading into symengine environment...
#> → pruning branches (`if`/`else`) of saem model...
#> ✔ done
#> → finding duplicate expressions in saem model...
#> → optimizing duplicate expressions in saem model...
#> ✔ done
#> rxode2 2.0.7 using 4 threads (see ?getRxThreads)
#> Calculating covariance matrix
#> → loading into symengine environment...
#> → pruning branches (`if`/`else`) of saem model...
#> ✔ done
#> → finding duplicate expressions in saem predOnly model 0...
#> → finding duplicate expressions in saem predOnly model 1...
#> → optimizing duplicate expressions in saem predOnly model 1...
#> → finding duplicate expressions in saem predOnly model 2...
#> ✔ done
#> 
#> → Calculating residuals/tables
#> ✔ done
#> → compress origData in nlmixr2 object, save 5952
#> → compress phiM in nlmixr2 object, save 62360
#> → compress parHist in nlmixr2 object, save 9560
#> → compress saem0 in nlmixr2 object, save 24688

# Since the fit is performed in `nlmixr2est` this code works
print(fit)
#> ── nlmixr SAEM OBJF by FOCEi approximation ──
#> 
#>  Gaussian/Laplacian Likelihoods: AIC() or $objf etc. 
#>  FOCEi CWRES & Likelihoods: addCwres() 
#> 
#> ── Time (sec $time): ──
#> 
#>            setup covariance  saem table compress    other
#> elapsed 0.001189   0.007003 2.188 0.019    0.022 1.381808
#> 
#> ── Population Parameters ($parFixed or $parFixedDf): ──
#> 
#>        Parameter  Est.     SE %RSE Back-transformed(95%CI) BSV(CV%) Shrink(SD)%
#> tka       Log Ka 0.454  0.196 43.1       1.57 (1.07, 2.31)     71.5   -0.0203% 
#> tcl       Log Cl  1.02 0.0853  8.4       2.76 (2.34, 3.26)     27.6      3.46% 
#> tv         Log V  3.45 0.0454 1.32       31.5 (28.8, 34.4)     13.4      9.89% 
#> add.sd           0.693                               0.693                     
#>  
#>   Covariance Type ($covMethod): linFim
#>   No correlations in between subject variability (BSV) matrix
#>   Full BSV covariance ($omega) or correlation ($omegaR; diagonals=SDs) 
#>   Distribution stats (mean/skewness/kurtosis/p-value) available in $shrink 
#> 
#> ── Fit Data (object is a modified tibble): ──
#> # A tibble: 132 × 19
#>   ID     TIME    DV  PRED    RES IPRED   IRES  IWRES eta.ka eta.cl   eta.v    cp
#>   <fct> <dbl> <dbl> <dbl>  <dbl> <dbl>  <dbl>  <dbl>  <dbl>  <dbl>   <dbl> <dbl>
#> 1 1      0     0.74  0     0.74   0     0.74   1.07   0.103 -0.491 -0.0820  0   
#> 2 1      0.25  2.84  3.27 -0.426  3.87 -1.03  -1.48   0.103 -0.491 -0.0820  3.87
#> 3 1      0.57  6.57  5.85  0.723  6.82 -0.246 -0.356  0.103 -0.491 -0.0820  6.82
#> # … with 129 more rows, and 7 more variables: depot <dbl>, center <dbl>,
#> #   ka <dbl>, cl <dbl>, v <dbl>, tad <dbl>, dosenum <dbl>

# But plots are in the helper package `nlmixr2plot`, and therefore:
plot(fit)

plot of chunk example

# does not give the standard goodness of fit plots