Performs NCA calculations and population PK model diagnosis.

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Description

ncappc is a flexible tool, to

  1. perform a traditional NCA

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

Usage

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ncappc(obsFile = "nca_original.npctab.dta",
  simFile = "nca_simulation.1.npctab.dta", str1Nm = NULL, str1 = NULL,
  str2Nm = NULL, str2 = NULL, str3Nm = NULL, str3 = NULL,
  concUnit = NULL, timeUnit = NULL, doseUnit = NULL,
  doseNormUnit = NULL, obsLog = FALSE, simLog = FALSE, psnOut = TRUE,
  idNmObs = "ID", timeNmObs = "TIME", concNmObs = "DV", idNmSim = "ID",
  timeNmSim = "TIME", concNmSim = "DV", AUCTimeRange = NULL,
  backExtrp = FALSE, LambdaTimeRange = NULL, LambdaExclude = NULL,
  doseAmtNm = NULL, adminType = "extravascular", doseType = "ns",
  doseTime = NULL, Tau = NULL, TI = NULL, method = "linear-log",
  blqNm = NULL, blqExcl = 1, evid = TRUE, evidIncl = 0, mdv = FALSE,
  filterNm = NULL, filterExcl = NULL, negConcExcl = FALSE,
  param = c("AUClast", "Cmax"), timeFormat = "number", dateColNm = NULL,
  dateFormat = NULL, spread = "npi", tabCol = c("AUClast", "Cmax", "Tmax",
  "AUCINF_obs", "Vz_obs", "Cl_obs", "HL_Lambda_z"), figFormat = "tiff",
  noPlot = FALSE, printOut = TRUE, studyName = NULL,
  new_data_method = TRUE, overwrite_SIMDATA = NULL, outFileNm = NULL)

Arguments

obsFile

Observed concentration-time data from an internal data frame or an external table with comma, tab or space as separator ("nca_original.npctab.dta")

simFile

NONMEM simulation output with the simulated concentration-time data from an internal data frame or an external table ("nca_simulation.1.npctab.dta"). NULL produces just the traditional NCA output, a filename or data frame prduces the NCA output as well as the PopPK diagnosis. If new_data_method=TRUE then this can be a compressed file as well.

str1Nm

Column name for 1st level population stratifier (NULL)

str1

Stratification ID of the members within 1st level stratification (e.g c(1,2)) (NULL)

str2Nm

Column name for 2nd level population stratifier (NULL)

str2

Stratification ID of the members within 2nd level stratification (e.g c(1,2)) (NULL)

str3Nm

Column name for 3rd level population stratifier (NULL)

str3

Stratification ID of the members within 3rd level stratification (e.g c(1,2)) (NULL)

concUnit

Unit of concentration (e.g. "ng/mL") ("M.L^-3")

timeUnit

Unit of time (e.g. "h") ("T")

doseUnit

Unit of dose amount (e.g. "ng") ("M")

doseNormUnit

Normalization factor of dose amount if used (e.g. "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) (TRUE)

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. This argument lets the user to choose a specific window of time to be used to estimate the elimination rate constant (Lambda) in the elimination phase. The accepted format for the input to this argument is a numeric array of two elements; c(14,24) will estimate the Lambda using the data within the time units 14 to 24. If NULL then all times are considered.

LambdaExclude

User-defined excluded observation time points for estimation of elimination rate-constant (NULL)

doseAmtNm

Column name to specify dose amount (NULL)

adminType

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

doseType

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

doseTime

Dose time prior to the first observation for steady-state data (NULL)

Tau

Dosing interval for steady-state data (NULL)

TI

Infusion duration (NULL)

method

linear, log or linear-log ("linear-log")

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) (TRUE)

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 ("ppi" (95% parametric prediction interval) or "npi" (95% nonparametric prediction interval))

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"))

figFormat

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

noPlot

Perform only NCA calculations without any plot generation (TRUE or FALSE)

printOut

Write/print output on the disk. No plot will be saved if noPlot is set to TRUE (TRUE, FALSE) (TRUE)

studyName

Name of the study to be added as a description in the report (NULL)

new_data_method

TRUE or FALSE. For testing a faster method of reading data. (TRUE)

overwrite_SIMDATA

Can be TRUE, to create new information in the SIMDATA directory, FALSE, to use the information in the SIMDATA directory or NULL to have a dialog come up to ask the user what to do. (NULL)

outFileNm

Additional tag to the name of the output html and pdf output file hyphenated to the standard ncappc report file name standard ncappc report file name (Name of the observed data file)

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 the Useage section of this document and/or in bold in the Arguments section.

Value

NCA results and diagnostic test results

Examples

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ncappc(obsFile=system.file("extdata","pkdata.csv",package="ncappc"),
psnOut=FALSE,noPlot=TRUE,printOut=FALSE)