## ----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, eval = FALSE, comment=''---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- # # modelEquations = 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, eval = FALSE, 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, eval = FALSE, comment=''---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- # # errorModelRespPK = Combined1( output = "RespPK", sigmaInter = 0, sigmaSlope = 0.21 ) # # errorModelRespPD = Constant( output = "RespPD", sigmaInter = 9.6 ) # # modelError = list( errorModelRespPK, errorModelRespPD ) ## ----echo = TRUE, eval = FALSE, 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, eval = FALSE, 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, # outputs = list( "RespPK" = "Cc", "RespPD" = "E" ), # designs = list( design1 ), # fimType = "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 ) # plotSensitivityIndices = plotSensitivityIndices( evaluationPop, plotOptions ) # # SE = plotSE( evaluationPop ) # RSE = plotRSE( evaluationPop ) # # # examples # plotOutcomesEvaluationRespPK = plotEvaluation[["design1"]][["20mg Arm"]][["RespPK"]] # plotOutcomesEvaluationRespPD = plotEvaluation[["design1"]][["20mg Arm"]][["RespPD"]] # plotSensitivityIndice_RespPK_Cl = plotSensitivityIndices[["design1"]][["20mg Arm"]][["RespPK"]][["Cl"]] ## ----echo = TRUE, eval = FALSE, comment=''---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- # # outputPath = getwd() # outputFile = "Example01_EvaluationPopFIM.html" # plotOptions = list( unitTime=c("hour"), unitOutcomes = c("mcg/mL","DI%") ) # Report( evaluationPop, outputPath, outputFile, plotOptions ) ## ----echo = TRUE, eval = FALSE, comment=''---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- # # evaluationInd = Evaluation( name = " ", # modelEquations = modelEquations, # modelParameters = modelParameters, # modelError = modelError, # outputs = list( "RespPK" = "Cc", "RespPD" = "E" ), # designs = list( design1 ), # fimType = "individual", # odeSolverParameters = list( atol = 1e-8, rtol = 1e-8 ) ) # # evaluationInd = run( evaluationInd ) # # evaluationBay = Evaluation( name = " ", # modelEquations = modelEquations, # modelParameters = modelParameters, # modelError = modelError, # outputs = list( "RespPK" = "Cc", "RespPD" = "E" ), # designs = list( design1 ), # fimType = "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 = getwd() # # plotOptions = list( unitTime=c("hour"), unitOutcomes= c("mcg/mL","DI%") ) # # outputFile = "Example01_EvaluationIndFIM.html" # Report( evaluationInd, outputPath, outputFile, plotOptions ) # # outputFile = "Example01_EvaluationBayFIM.html" # Report( evaluationBay, outputPath, outputFile, plotOptions ) # ## ----echo = TRUE, eval = FALSE, comment=''---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- # # administrationRespPK = Administration( outcome = "RespPK", timeDose = c(0), dose = c( 6.24 ) ) # ## ----echo = TRUE, eval = FALSE, 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, eval = FALSE, 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, eval = FALSE, comment=''---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- # # initialElementaryProtocols = list( c( 0.25, 0.75, 1, 4 ), c( 1.5, 2, 6, 12 ) ) ## ----echo = TRUE, eval = FALSE, comment=''---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- # # administrationConstraintsRespK = AdministrationConstraints( outcome = "RespPK", # doses = list( 0.2, 0.64, 2, 6.24, 11.24, 20 ) ) # ## ----echo = TRUE, eval = FALSE, comment=''---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- # # # armConstraint = Arm( name = "armConstraint", # size = 30, # administrations = list( administrationRespPK ), # 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 ), numberOfArms = 30 ) ## ----echo = TRUE, eval = FALSE, 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 ), # # fimType = "population", # # outputs = list( "RespPK" = "Cc","RespPD" = "E" ), # # odeSolverParameters = list( atol = 1e-8, rtol = 1e-8 ) ) # # optimizationFWPopFIM = run( optimizationFWPopFIM ) # # saveRDS( optimizationFWPopFIM, "optimizationFWPopFIM.RDS" ) ## ----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 ) # 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, # weightThreshold = 0.01, # delta = 1e-04, showProcess = T ), # # designs = list( designConstraint ), # # fimType = "population", # # outputs = list( "RespPK" = "Cc","RespPD" = "E" ), # # odeSolverParameters = list( atol = 1e-8, rtol = 1e-8 ) ) # ## ----echo = TRUE, eval = FALSE, comment=''---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- # # optimizationMultPopFIM = run( optimizationMultPopFIM ) # saveRDS( optimizationMultPopFIM, "optimizationMultPopFIM.RDS" ) # ## ----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 ) # plotWeights # ## ----echo = TRUE, eval = FALSE, comment=''---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- # # outputPath = getwd() # plotOptions = list( unitTime = c( "hour" ), unitOutcomes= c( "mcg/mL" , "DI%" ) ) # outputFile = "Example01_OptimizationMultPopFIM.html" # Report( optimizationMultPopFIM, outputPath, outputFile, plotOptions ) ## ----global_options_end, echo = FALSE, include = FALSE------------------------ options(backup_options)