correct.conc {qpNCA}

Correct Missing Concentration

Description

Corrects missing concentration at critical time points (e.g, predose, TAU, start and end of user selected AUC interval).

Usage

correct.conc(
  x,
  by = character(0),
  nomtimevar = "ntad",
  tau = NA,
  tstart = NA,
  tend = NA,
  teval = NA,
  th = NA,
  reg = "SD",
  ss = "N",
  route = "EV",
  method = 1
)

Arguments

x

input dataset name (after Time Deviation Correction Rules have been applied by correct.time)

by

column names in x indicating grouping variables

nomtimevar

variable name containing the nominal sampling time after dose

tau

dosing interval (for multiple dosing); NA (default) for if single dose; x$tau overrides

tstart

start time of partial AUC (start>0); NA (default) if not requested; x$tstart overrides

tend

end time of partial AUC; NA (default) if not requested; x$tend overrides

teval

user selected AUC interval; NA (default) if not requested; x$teval overrides

th

lamdba_z information for each curve; like output of est.thalf

reg

regimen, "sd" or "md"; x$reg overrides

ss

is steady state reached (y/n); x$ss overrides

route

route of drug administration ("EV","IVB","IVI"); x$route overrides

method

method for trapezoidal rule; x$method overrides

• 1: linear up - linear down

• 2: linear up - logarithmic down

• 3: linear before first Tmax, logarithmic after first Tmax

Details

• Use interpolation if there is a measurable concentration BEFORE and AFTER the missing concentration

• Use extrapolation if there is NO measurable concentration AFTER the missing concentration

• Set missing concentration at predose to 0 (SD, non-endogenous) or value at t=TAU (steady state only)

• Set missing concentration at t=TAU to value at t=0 (steady state only)

The following Concentration Deviation Correction Rules will be applied to critical time points (t=0, tau, tstart, tend, teval), if needed:

Rule	Regimen	Description	Applied to
SDC-1	sd	Set concentration to 0 (only non-endogenous compounds)	t=0
SDC-2	sd	impute missing concentration by interpolation	t=tau,tstart,tend,teval
SDC-3	sd	impute missing concentration by extrapolation	t=tau,tend,teval
SDC-4	sd (IVB)	impute missing concentration by back-extrapolation	t=0
MDC-1	md	impute missing concentration by existing conc at t=0 or t=tau (only if steady state has been reached)	t=0,tau
MDC-2	md	impute missing concentration by interpolation	t=tau,tstart,tend,teval
MDC-3	md	impute missing concentration by extrapolation	t=tau,tend,teval
MDC-4	md (IVB)	impute missing concentration by back-extrapolation	t=0

Value

a dataset with missing concentrations imputed. The following variables are added:

Variable	Description
crule.nr	correction rule number
crule.txt	text explaining what was altered
applies.to.conc	lists all critical time points to which the concentration correction rule applies

Examples

example(correct.time)
x %<>% mutate(ss = 'N', route = 'EV')
# route redefined for completeness
x %<>% correct.conc(by = 'subject') # ignoring th
x %>% head