# MSToolkit will create ReplicateData, MicroData and MacroData directories 

# under the current working directory

getwd()

library(MSToolkit)

generateData( replicateN = 5, subjects = 100, treatDoses = c(0, 5, 10, 50, 100), 

  genParNames = "E0,ED50,EMAX", genParMean = c(2,50,10), genParVCov = c(.5,30,10), 

  respEqn = "E0 + ((DOSE * EMAX)/(DOSE + ED50))",  respVCov = 2, 

  interimSubj = ".3,.7" 

  )

## Calls emaxfit.R - helper functions for fitting an emax model

##  or linear model if the emax fit does not converge

## Also calculates standard error of predicted effect at each dose

source("emaxfit.R")

emaxCode <- function(data){

    uniDoses <- sort( unique(data$DOSE)) 

obsMean <- tapply(data$RESP, list(data$DOSE), mean)

obsSD <- tapply(data$RESP, list(data$DOSE), sd)                                                                   

    eFit <- emax.fit( data$RESP, data$DOSE )

    outDf <- data.frame( DOSE = uniDoses, 

      MEAN = eFit$fitpred, 

      SE = eFit$sdpred,

  SDDIF = eFit$sddif)

    outDf$LOWER <- outDf$MEAN - 1.96*outDf$SE

    outDf$UPPER <- outDf$MEAN + 1.96*outDf$SE

    outDf$N     <- table(data$DOSE)

outDf$OBSMEAN <- obsMean

outDf$OBSSD <- obsSD

    outDf 

}                                                                                                                   

macroCode <- function(data) {

  # Is effect at highest dose significant?

  success <- data$LOWER[data$INTERIM==max(data$INTERIM) & data$DOSE==max(data$DOSE)] > 7

  data.frame( SUCCESS = success )

}

interimCode <- function( data ){

  # DROP any doses where the lower bound of the difference from placebo is negative

  dropdose  <- with( data , DOSE [ LOWER < 0 & DOSE != 0] )

  outList <- list()

  if( length(dropdose) > 0 ) outList$DROP <- dropdose

  outList$STOP <- length(dropdose) == nrow(data)-1

  outList

}

analyzeData(analysisCode = emaxCode, macroCode = macroCode, 

  interimCode = interimCode )

parseCovMatrix(1,2)

parseCovMatrix(c(1,2),2)

parseCovMatrix(c(1,0.8,2),2)

parseCovMatrix(c(1,3,2),2)