## ----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=''----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- administrationRespPK = Administration( outcome = "RespPK", timeDose = c(0), dose = c( 6.24 ) ) ## ---- 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( 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 ) ) ## ---- 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 ) # 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)