ncappc: Performs NCA calculations and population PK model diagnosis.

Description

ncappc is a flexible tool, to

perform a traditional NCA
perform simulation-based posterior predictive checks for a population PK model using NCA metrics.

Usage

ncappc(obsFile = NULL, simFile = NULL, grNm = NULL, grp = NULL,
  flNm = NULL, flag = NULL, doseNm = NULL, dose = NULL,
  concUnit = NULL, timeUnit = NULL, doseUnit = NULL,
  doseNormUnit = NULL, obsLog = "FALSE", simLog = "FALSE",
  psnOut = "FALSE", idNmObs = "ID", timeNmObs = "TIME",
  concNmObs = "DV", idNmSim = "ID", timeNmSim = "TIME",
  concNmSim = "DV", AUCTimeRange = NULL, backExtrp = "FALSE",
  LambdaTimeRange = NULL, LambdaExclude = NULL,
  adminType = "extravascular", doseType = "ns", Tau = NULL, TI = NULL,
  doseAmtNm = NULL, doseAmt = NULL, method = "linear", blqNm = NULL,
  blqExcl = 1, evid = "FALSE", evidIncl = 0, mdv = "FALSE",
  filterNm = NULL, filterExcl = NULL, negConcExcl = "FALSE",
  param = c("AUClast", "Cmax"), timeFormat = "number", dateColNm = NULL,
  dateFormat = NULL, spread = "pi", tabCol = c("AUClast", "Cmax", "Tmax",
  "AUCINF_obs", "Vz_obs", "Cl_obs", "HL_Lambda_z"), printOut = "TRUE",
  figFormat = "tiff")

Arguments

obsFile

Observed concentration-time data from an internal data frame or an external table with comma, tab or space as separator

simFile

NONMEM simulation output with the simulated concentration-time data from an internal data frame or an external table ("NULL")

grNm

Column name for population stratifier ("NULL")

grp

Stratification ID (e.g c(1,2)) ("NULL")

flNm

Column name for popualtion stratifier ("NULL")

flag

Stratification ID (e.g. c(1,2)) ("NULL")

doseNm

Column name to specify dose identifiers ("NULL")

dose

Dose identifiers to be used (c(1,2)) ("NULL")

concUnit

Unit of concentration ("ng/mL") ("[M].[L]^-3")

timeUnit

Unit of time ("h") ("[T])

doseUnit

Unit of dose amount ("ng") ("[M]")

doseNormUnit

Normalization factor of dose amount if used (kg) ("NULL")

obsLog

Concentration in observed data in logarithmic form (TRUE, FALSE) ("FALSE")

simLog

Concentration in simulated data in logarithmic form (TRUE, FALSE) ("FALSE")

psnOut

observed data is an output from PsN or in NONMEM output format (TRUE, FALSE) ("FALSE")

idNmObs

Column name for ID in observed data ("ID")

timeNmObs

Column name for time in observed data ("TIME")

concNmObs

Column name for concentration in observed data ("DV")

idNmSim

Column name for ID in simulated data ("ID")

timeNmSim

Column name for time in simulated data ("TIME")

concNmSim

Column name for concentration in simulated data ("DV")

AUCTimeRange

User-defined window of time used to estimate AUC ("NULL")

backExtrp

If back-extrapolation is needed for AUC (TRUE or FALSE) ("FALSE")

LambdaTimeRange

User-defined window of time to estimate elimination rate-constant ("NULL")

LambdaExclude

User-defined excluded observations during estimation of elimination rate-constant ("NULL")

adminType

Route of administration (iv-bolus,iv-infusion,ss,extravascular) ("extravascular")

doseType

Steady-state (ss) or nonsteady-state (ns) dose ("ns")

Tau

Dosing interval for steady-state data ("NULL")

Infusion duration ("NULL")

doseAmtNm

Column name to specify dose amount ("NULL")

doseAmt

Dose amounts ("NULL")

method

linear, loglinear or mixed ("linear")

blqNm

Name of BLQ column if used ("NULL")

blqExcl

Excluded BLQ value or logical condition (e.g. 1 or ">=1" or c(1,">3")) ("1")

evid

Use EVID (TRUE, FALSE) ("FALSE")

evidIncl

Included EVID ("0")

mdv

Use MDV (TRUE(includes data for MDV==0), FALSE) ("FALSE")

filterNm

Column name for filter ("NULL")

filterExcl

Filter identifier or logical condition used for row exclusion (e.g. c(1,2,"<20",">=100","!=100") ) ("NULL")

negConcExcl

Exclude -ve conc ("FALSE")

param

NCA parameters (AUClast, AUClower_upper, AUCINF_obs, AUCINF_pred, AUMClast, Cmax, Tmax, HL_Lambda_z) (c("AUClast", "Cmax"))

timeFormat

time format (number, H:M, H:M:S) ("number")

dateColNm

colunm name for date if used (Date, DATE) ("NULL")

dateFormat

date format (D-M-Y, D/M/Y or any other combination of D,M,Y) ("NULL")

spread

Measure of the spread of simulated data (sd or pi (95% nonparametric prediction interval)) ("pi")

tabCol

Output columns to be printed in the report in addition to ID, dose and population strata information (list of NCA metrics in a string array) (c("AUClast", "Cmax", "Tmax", "AUCINF_obs", "Vz_obs", "Cl_obs", "HL_Lambda_z"))

printOut

Write/print output on the disk (TRUE, FALSE) ("TRUE")

figFormat

format of the produced figures (bmp, jpeg, tiff, png) ("tiff")

Value

NCA results and diagnostic test results

Details

Non-compartmental analysis (NCA) calculates pharmacokinetic (PK) metrics related to the systemic exposure to a drug following administration, e.g. area under the concentration-time curve and peak concentration. ncappc performs a traditional NCA using the observed plasma concentration-time data. In the presence of simulated plasma concentration-time data, ncappc also performs simulation-based posterior predictive checks (ppc) using NCA metrics for the corresponding population PK (PopPK) model used to generate the simulated data. The diagnostic analysis is performed at the population as well as the individual level. The distribution of the simulated population means of each NCA metric is compared with the corresponding observed population mean. The individual level comparison is performed based on the deviation of the mean of any NCA metric based on simulations for an individual from the corresponding NCA metric obtained from the observed data. Additionaly, ncappc reports the normalized prediction distribution error (NPDE) of the simulated NCA metrics for each individual and their distribution within a population. ncappc produces two default outputs depending on the type of analysis performed, i.e., traditional NCA and PopPK diagnosis. The PopPK diagnosis feature of ncappc produces 7 sets of graphical outputs to assess the ability of a population model to simulate the concentration-time profile of a drug and thereby identify model misspecification. In addition, tabular outputs are generated showing the values of the NCA metrics estimated from the observed and the simulated data, along with the deviation, NPDE, regression parameters used to estimate the elimination rate constant and the related population statistics. The default values of the arguments used in ncappc are shown in bold.