inst/doc/Example01.R

In PFIM: Population Fisher Information Matrix

## ----global_options, echo = FALSE, include = FALSE--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
backup_options <- options()
options(width = 3000)
knitr::opts_chunk$set(collapse = TRUE,
comment = "#>",echo = FALSE, warning = FALSE, message = FALSE,
cache = FALSE, tidy = FALSE, size = "small")
library(PFIM)

## ----echo = TRUE, comment=''------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
modelEquations = list(
  
  outcomes = list( "RespPK"  = "Cc",
                   "RespPD"  = "E" ),
  
  equations = list(  "Deriv_Cc" = "dose_RespPK/V*ka*exp(-ka*t) - Cl/V*Cc",
                     "Deriv_E" = "Rin*(1-Imax*(Cc**gamma)/(Cc**gamma + IC50**gamma))-kout*E" ) )

## ----echo = TRUE, comment=''------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
modelParameters = list(
  
  ModelParameter( name = "V",
                  distribution = LogNormal( mu = 0.74, omega = 0.316 ) ),
  
  ModelParameter( name = "Cl",
                  distribution = LogNormal( mu = 0.28, omega = 0.456 ) ),
  
  ModelParameter( name = "ka",
                  distribution = LogNormal( mu = 10, omega = sqrt( 0 ) ), fixedMu = TRUE ),
  
  ModelParameter( name = "kout",
                  distribution = LogNormal( mu = 6.14, omega = 0.947 ) ),
  
  ModelParameter( name = "Rin",
                  distribution = LogNormal( mu = 614, omega = sqrt( 0 ) ), fixedMu = TRUE ),
  
  ModelParameter( name = "Imax",
                  distribution = LogNormal( mu = 0.76, omega = 0.439 ) ),
  
  ModelParameter( name = "IC50",
                  distribution = LogNormal( mu = 9.22, omega = 0.452 ) ),
  
  ModelParameter( name = "gamma",
                  distribution = LogNormal( mu = 2.77, omega = 1.761 ) ) )


## ----echo = TRUE, comment=''------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
errorModelRespPK = Combined1( outcome = "RespPK", sigmaInter = 0, sigmaSlope = 0.21 )

errorModelRespPD = Constant( outcome = "RespPD", sigmaInter = 9.6 )

modelError = list( errorModelRespPK, errorModelRespPD )

## ----echo = TRUE, comment=''------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

# sampling times
samplingTimesRespPK = SamplingTimes( outcome = "RespPK",
                                     samplings = c( 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4 ) )

samplingTimesRespPD = SamplingTimes( outcome = "RespPD",
                                     samplings = c( 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4 ) )

# Define the arms and the administrations

administrationRespPK1 = Administration( outcome = "RespPK", timeDose = c(0), dose = c( 0.2 ) )

arm1 = Arm( name = "0.2mg Arm",
            size = 6,
            administrations = list( administrationRespPK1 ) ,
            samplingTimes   = list( samplingTimesRespPK, samplingTimesRespPD ),
            initialCondition = list( "Cc" = 0,
                                     "E" = 100 ) )

administrationRespPK2 = Administration( outcome = "RespPK", timeDose = c(0), dose = c( 0.64 ) )

arm2 = Arm( name = "0.64mg Arm",
            size = 6,
            administrations = list( administrationRespPK2 ) ,
            samplingTimes   = list( samplingTimesRespPK, samplingTimesRespPD ),
            initialCondition = list( "Cc" = 0,
                                     "E" = 100 ) )

administrationRespPK3 = Administration( outcome = "RespPK", timeDose = c(0), dose = c( 2 ) )

arm3 = Arm( name = "2mg Arm",
            size = 6,
            administrations = list( administrationRespPK3 ) ,
            samplingTimes   = list( samplingTimesRespPK, samplingTimesRespPD ),
            initialCondition = list( "Cc" = 0,
                                     "E" = 100 ) )

administrationRespPK4 = Administration( outcome = "RespPK", timeDose = c(0), dose = c( 6.24 ) )

arm4 = Arm( name = "6.24mg Arm",
            size = 6,
            administrations = list( administrationRespPK4 ) ,
            samplingTimes   = list( samplingTimesRespPK, samplingTimesRespPD ),
            initialCondition = list( "Cc" = 0,
                                     "E" = 100 ) )

administrationRespPK5 = Administration( outcome = "RespPK", timeDose = c(0), dose = c( 11.24 ) )

arm5 = Arm( name = "11.24mg Arm",
            size = 6,
            administrations = list( administrationRespPK5 ) ,
            samplingTimes   = list( samplingTimesRespPK, samplingTimesRespPD ),
            initialCondition = list( "Cc" = 0,
                                     "E" = 100 ) )

administrationRespPK6 = Administration( outcome = "RespPK", timeDose = c(0), dose = c( 20 ) )

arm6 = Arm( name = "20mg Arm",
            size = 6,
            administrations = list( administrationRespPK6 ) ,
            samplingTimes   = list( samplingTimesRespPK, samplingTimesRespPD ),
            initialCondition = list( "Cc" = 0,
                                     "E" = 100 ) )

## ----echo = TRUE, comment=''------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
design1 = Design( name = "design1", arms = list( arm1, arm2, arm3, arm4, arm5, arm6 ) )

## ----echo = TRUE, eval = FALSE, comment=''----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
#  evaluationPop = Evaluation( name = "",
#                              modelEquations = modelEquations,
#                              modelParameters = modelParameters,
#                              modelError = modelError,
#                              outcomes = list( "RespPK"  = "Cc", "RespPD"  = "E" ),
#                              designs = list( design1 ),
#                              fim = "population",
#                              odeSolverParameters = list( atol = 1e-8, rtol = 1e-8 ) )
#  
#  evaluationPop = run( evaluationPop )

## ----echo = TRUE, eval = FALSE, comment=''----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
#  
#  show( evaluationPop )
#  
#  fisherMatrix = getFisherMatrix( evaluationPop )
#  getCorrelationMatrix( evaluationPop )
#  getSE( evaluationPop )
#  getRSE( evaluationPop )
#  getShrinkage( evaluationPop )
#  getDeterminant( evaluationPop )
#  getDcriterion( evaluationPop )

## ----echo = TRUE, eval = FALSE, comment=''----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
#  
#  plotOptions = list( unitTime = c("hour"), unitOutcomes = c("mcg/mL","DI%")  )
#  
#  plotEvaluation = plotEvaluation( evaluationPop, plotOptions )
#  
#  plotSensitivityIndice = plotSensitivityIndice( evaluationPop, plotOptions )
#  
#  SE = plotSE( evaluationPop )
#  RSE = plotRSE( evaluationPop )
#  
#  # examples
#  plotOutcomesEvaluationRespPK = plotEvaluation[["design1"]][["20mg Arm"]][["RespPK"]]
#  
#  plotOutcomesEvaluationRespPD = plotEvaluation[["design1"]][["20mg Arm"]][["RespPD"]]
#  
#  plotSensitivityIndice_RespPK_Cl =  plotSensitivityIndice[["design1"]][["20mg Arm"]][["RespPK"]][["Cl"]]
#  
#  SE = SE[["design1"]]
#  RSE = RSE[["design1"]]

## ----echo = TRUE, eval = FALSE, comment=''----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
#  
#  outputPath = "C:/...."
#  outputFile = "Example01_EvaluationPopFIM.html"
#  plotOptions = list( unitTime=c("hour"), unitResponses= c("mcg/mL","DI%") )
#  
#  Report( evaluationPop, outputPath, outputFile, plotOptions )
#  

## ----echo = TRUE, eval = FALSE, comment=''----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
#  evaluationInd = Evaluation( name = "",
#                              modelEquations = modelEquations,
#                              modelParameters = modelParameters,
#                              modelError = modelError,
#                              outcomes = list( "RespPK"  = "Cc", "RespPD"  = "E" ),
#                              designs = list( design1 ),
#                              fim = "individual",
#                              odeSolverParameters = list( atol = 1e-8, rtol = 1e-8 ) )
#  
#  evaluationInd = run( evaluationInd )
#  
#  evaluationBay = Evaluation( name = "",
#                              modelEquations = modelEquations,
#                              modelParameters = modelParameters,
#                              modelError = modelError,
#                              outcomes = list( "RespPK"  = "Cc", "RespPD"  = "E" ),
#                              designs = list( design1 ),
#                              fim = "Bayesian",
#                              odeSolverParameters = list( atol = 1e-8, rtol = 1e-8 ) )
#  
#  evaluationBay = run( evaluationBay )

## ----echo = TRUE, eval = FALSE, comment=''----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
#  
#  show( evaluationInd )
#  show( evaluationBay )
#  
#  fisherMatrix = getFisherMatrix( evaluationInd )
#  getCorrelationMatrix( evaluationInd )
#  getSE( evaluationInd )
#  getRSE( evaluationInd )
#  getShrinkage( evaluationInd )
#  getDeterminant( evaluationInd )
#  getDcriterion( evaluationInd )
#  
#  fisherMatrix = getFisherMatrix( evaluationBay )
#  getCorrelationMatrix( evaluationBay )
#  getSE( evaluationBay )
#  getRSE( evaluationBay )
#  getShrinkage( evaluationBay )
#  getDeterminant( evaluationBay )
#  getDcriterion( evaluationBay )

## ----echo = TRUE, eval = FALSE, comment=''----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
#  
#  outputPath = "C:/...."
#  
#  plotOptions = list( unitTime=c("hour"), unitResponses= c("mcg/mL","DI%") )
#  
#  outputFile = "Example01_EvaluationIndFIM.html"
#  Report( evaluationInd, outputPath, outputFile, plotOptions )
#  
#  outputFile = "Example01_EvaluationBayFIM.html"
#  Report( evaluationBay, outputPath, outputFile, plotOptions )
#  

## ----echo = TRUE, comment=''------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
samplingTimesRespPK = SamplingTimes( outcome = "RespPK", samplings = c( 0.25, 0.75, 1, 1.5, 2, 4, 6 ) )

samplingTimesRespPD = SamplingTimes( outcome = "RespPD", samplings = c( 0.25, 0.75, 1.5, 2, 3, 6, 8, 12 ) )

## ----echo = TRUE, comment=''------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
samplingConstraintsRespPK  = SamplingTimeConstraints( outcome = "RespPK",
                                                      initialSamplings = c( 0.25, 0.75, 1, 1.5, 2, 4, 6 ),
                                                      fixedTimes = c( 0.25, 4 ),
                                                      numberOfsamplingsOptimisable = 4 )

samplingConstraintsRespPD  = SamplingTimeConstraints( outcome = "RespPD",
                                                      initialSamplings = c( 0.25, 0.75, 1.5, 2, 3, 6, 8, 12 ),
                                                      fixedTimes = c( 2, 6 ),
                                                      numberOfsamplingsOptimisable = 4 )

## ----echo = TRUE, comment=''------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
initialElementaryProtocols = list( c( 0.25, 0.75, 1, 4 ), c( 1.5, 2, 6, 12 ) )

## ----echo = TRUE, comment=''------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
administrationConstraintsRespK = AdministrationConstraints( outcome = "RespPK", 
                                                           doses = c( 0.2, 0.64, 2, 6.24, 11.24, 20 ) )


## ----echo = TRUE, comment=''------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

armConstraint = Arm( name = "armConstraint",
                     size = 30,
                     administrations = list( administrationRespPK1 ),
                     samplingTimes   = list( samplingTimesRespPK, samplingTimesRespPD ),
                     administrationsConstraints = list( administrationConstraintsRespK ),
                     samplingTimesConstraints = list( samplingConstraintsRespPK, samplingConstraintsRespPD ),
                     initialCondition = list( "Cc" = 0,
                                              "E" = "Rin/kout"  ) )

designConstraint = Design( name = "designConstraint", 
                           arms = list( armConstraint ) )

## ----echo = TRUE, comment=''------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
numberOfSubjects = c(30)
proportionsOfSubjects = c(30)/30

## ----echo = TRUE, eval = FALSE, comment=''----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
#  optimizationFWPopFIM = Optimization(  name = "PKPD_ODE_multi_doses_populationFIM",
#                                        modelEquations = modelEquations,
#                                        modelParameters = modelParameters,
#                                        modelError = modelError,
#  
#                                        optimizer = "FedorovWynnAlgorithm",
#  
#                                        optimizerParameters = list( elementaryProtocols = initialElementaryProtocols,
#                                                                    numberOfSubjects = numberOfSubjects,
#                                                                    proportionsOfSubjects = proportionsOfSubjects,
#                                                                    showProcess = T ),
#  
#                                        designs = list( designConstraint ),
#  
#                                        fim = "population",
#  
#                                        outcomes = list( "RespPK" = "Cc","RespPD" = "E" ),
#  
#                                        odeSolverParameters = list( atol = 1e-8, rtol = 1e-8 ) )
#  
#  optimizationFWPopFIM = run( optimizationFWPopFIM )

## ----echo = TRUE, eval = FALSE, comment=''----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
#  show( optimizationFWPopFIM )
#  
#  fisherMatrix = getFisherMatrix( optimizationFWPopFIM )
#  getCorrelationMatrix( optimizationFWPopFIM )
#  getSE( optimizationFWPopFIM )
#  getRSE( optimizationFWPopFIM )
#  getShrinkage( optimizationFWPopFIM )
#  getDeterminant( optimizationFWPopFIM )
#  getDcriterion( optimizationFWPopFIM )
#  
#  # plot the frequencies
#  plotFrequencies = plotFrequencies( optimizationFWPopFIM, threshold = 0.001 )
#  plotFrequencies
#  

## ----echo = TRUE, eval = FALSE, comment=''----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
#  outputFile = "Example01_OptimizationFWPopFIM.html"
#  Report( optimizationFWPopFIM, outputPath, outputFile, plotOptions )

## ----echo = TRUE, eval = FALSE, comment=''----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
#  
#  optimizationMultPopFIM = Optimization( name = "PKPD_ODE_multi_doses_populationFIM",
#                                         modelEquations = modelEquations,
#                                         modelParameters = modelParameters,
#                                         modelError = modelError,
#  
#                                         optimizer = "MultiplicativeAlgorithm",
#  
#                                         optimizerParameters = list( lambda = 0.99,
#                                                                     numberOfIterations = 1000,
#                                                                     delta = 1e-04, showProcess = T ),
#  
#                                         designs = list( designConstraint ),
#  
#                                         fim = "population",
#  
#                                         outcomes = list( "RespPK" = "Cc","RespPD" = "E" ),
#  
#                                         odeSolverParameters = list( atol = 1e-8, rtol = 1e-8 ) )
#  

## ----echo = TRUE, eval = FALSE, comment=''----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
#  optimizationMultPopFIM = run( optimizationMultPopFIM )

## ----echo = TRUE, eval = FALSE, comment=''----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
#  show( optimizationMultPopFIM )
#  
#  fisherMatrix = getFisherMatrix( optimizationMultPopFIM )
#  getCorrelationMatrix( optimizationMultPopFIM )
#  getSE( optimizationMultPopFIM )
#  getRSE( optimizationMultPopFIM )
#  getShrinkage( optimizationMultPopFIM )
#  getDeterminant( optimizationMultPopFIM )
#  getDcriterion( optimizationMultPopFIM )
#  
#  # plot the weight
#  plotWeights = plotWeights( optimizationMultPopFIM, threshold = 0.001 )
#  plotWeights
#  

## ----echo = TRUE, eval = FALSE, comment=''----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
#  
#  outputPath = "C:/...."
#  
#  plotOptions = list( unitTime = c( "hour" ), unitResponses= c( "mcg/mL" , "DI%" ), threshold = 0.01 )
#  
#  outputFile = "Example01_OptimizationMultPopFIM.html"
#  
#  Report( optimizationMultPopFIM, outputPath, outputFile, plotOptions )

## ----global_options_end, echo = FALSE, include = FALSE------------------------
options(backup_options)