# ncappc

0th

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##### Performs NCA calculations and population PK model diagnosis.

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
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)
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)
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

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

Documentation reproduced from package ncappc, version 0.2.1.1, License: GPL-3

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