Estimate individual-level residual error from the elimination phase

Performs log-linear regression on the elimination phase of a single individual's or one group's pharmacokinetic concentration–time data to estimate additive and proportional residual standard deviations.

Usage

getsigmas(group_df, nlastpoints = 3)

Arguments

group_df: A data frame for a single group (e.g., one subject or dose), containing columns: EVID (event ID), DV (observed concentration), TIME (time after dose), and routeobs (administration route).
nlastpoints: Integer specifying the number of terminal data points used for regression.

Value

A tibble with the following columns:

intercept: Intercept of the log-linear regression line
slope: Estimate of the terminal elimination rate constant
residual_sd_additive: Standard deviation of additive residuals
residual_sd_proportional: Standard deviation of proportional residuals

Details

Residuals are computed from individual-predicted concentrations (IPRED) and observed concentrations (DV) using the following definitions: $$ \sigma_{add} = \sqrt{Var(C_{obs} - C_{pred})} $$

$$ \sigma_{prop} = \sqrt{Var\left(\frac{C_{obs}}{C_{pred}} - 1\right)} $$

where $C_{obs}$ is the observed concentration and $C_{pred}$ is the model-predicted concentration obtained by back-transformation of the log-linear regression. The additive residual standard deviation ($\sigma_{add}$) and proportional residual standard deviation ($\sigma_{prop}$) are calculated per individual.

Author

Zhonghui Huang

Examples

dat <- Bolus_1CPT
dat <- processData(dat)$dat
#> 
#> 
#> Infometrics                               Value          
#> ----------------------------------------  ---------------
#> Dose Route                                bolus          
#> Dose Type                                 combined_doses 
#> Number of Subjects                        120            
#> Number of Observations                    6951           
#> Subjects with First-Dose Interval Data    120            
#> Observations in the First-Dose Interval   2276           
#> Subjects with Multiple-Dose Data          120            
#> Observations after Multiple Doses         4675           
#> ----------------------------------------  ------
getsigmas(dat[dat$ID == 1 & dat$dose_number == 1 & dat$resetflag == 1 &
              dat$EVID == 0, ])
#> # A tibble: 1 × 4
#>   intercept   slope residual_sd_additive residual_sd_proportional
#>       <dbl>   <dbl>                <dbl>                    <dbl>
#> 1      6.97 -0.0679                 1.70                   0.0750