R/Data-methods.R

#####################################################################################
## Author: Daniel Sabanes Bove [sabanesd *a*t* roche *.* com],
##         Wai Yin Yeung [ w *.*yeung1 *a*t* lancaster *.* ac *.* uk]
## Project: Object-oriented implementation of CRM designs
##
## Time-stamp: <[Data-methods.R] by DSB Mon 11/05/2015 17:43>
##
## Description:
## Methods for handling the data. Plot ideas taken from bcrm package.
##
## History:
## 30/01/2014   file creation
## 06/02/2014   add method for conversion to list
## 17/02/2014   add update methods
## 21/07/2015   add plots using data and pseudo models
###################################################################################


## ============================================================

## --------------------------------------------------
## Converting Data object to list
## --------------------------------------------------


##' as.list method for the "GeneralData" class
##'
##' @param x the \code{\linkS4class{GeneralData}} object we want to convert
##' @param \dots unused
##' @return a list of all slots in \code{x}
##'
##' @example examples/Data-method-asList.R
##' @export
##' @keywords methods
setMethod("as.list",
          signature=
          signature(x="GeneralData"),
          def=
          function(x, ...){
              nams <- slotNames(x)
              ret <- lapply(nams,
                            function(n){
                                slot(x, n)
                            })
              names(ret) <- nams
              return(ret)
          })



## ============================================================

## --------------------------------------------------
## Plotting the Data objects
## --------------------------------------------------


##' Plot method for the "Data" class
##'
##' @param x the \code{\linkS4class{Data}} object we want to plot
##' @param y missing
##' @param blind Logical (default FALSE) if to blind the data. If TRUE, then placebo
##' subjects are reported by the active dose level of the corresponding cohort and
##' DLEs are always assigned to the firsts subjects.
##' @param \dots not used
##' @return the \code{\link[ggplot2]{ggplot}} object
##'
##' @importFrom ggplot2 ggplot geom_point scale_colour_manual xlab ylab aes
##' scale_y_continuous scale_x_continuous
##'
##' @example examples/Data-method-plot-Data.R
##' @export
##' @keywords methods
setMethod("plot",
          signature=
          signature(x="Data", y="missing"),
          def=
          function(x, y, blind=FALSE, ...){
              if(x@nObs == 0)
              {
                  return()
              }

              df <- data.frame(patient=seq_along(x@x),
                               dose=x@x,
                               toxicity=ifelse(x@y==1, "Yes", "No"),
                               ID=paste(" ", x@ID))
              cols <- c("No" = "black","Yes" = "red")
              
              # If there are placebo, consider this a y=0.0 for the plot
              if(x@placebo & !blind)
                df$dose[df$dose == x@doseGrid[1]] <- 0.0
              
              # This is to blind the data
              # For each cohort, the placebo is set to the active dose level for that cohort.
              # In addition, all DLTs are assigned to the first subjects in the cohort
              if(x@placebo & blind){
                cohort.id <- unique(x@cohort)
                for(iCoh in seq(a=cohort.id)){
                  filter.coh <- which(x@cohort == cohort.id[iCoh]) 
                  df[filter.coh,"dose"] <- max(df[filter.coh,"dose"])
                  df[filter.coh,"toxicity"] <- sort(df[filter.coh,"toxicity"],
                                                    decreasing=TRUE)
                }
              }

              a <- ggplot(df, aes(x=patient,y=dose)) +
                  scale_y_continuous(breaks=
                                     sort(unique(c(0, df$dose))),
                                     minor_breaks=numeric(),
                                     limits=c(0, max(df$dose) * 1.1))

              a <- a +
                  geom_point(aes(shape=toxicity,colour=toxicity),
                             size=3) +
                                 scale_colour_manual(values=cols) +
                                     xlab("Patient") + ylab("Dose Level")

              if(!blind)
                a <- a + geom_text(aes(label=ID, size=2),
                                   data=df,
                                   hjust=0, vjust=0.5,
                                   angle=90, colour=I("black"),
                                   show.legend = FALSE)

              a <- a + scale_x_continuous(breaks=df$patient,
                                          minor_breaks=numeric())
              
              # add a vertical lines separating sub-sequent cohorts
              if(x@placebo & length(unique(x@cohort)) > 1)
                a <- a + geom_vline(xintercept=head(cumsum(table(x@cohort)),n=-1) + 0.5, 
                                    colour="green",
                                    linetype = "longdash")
              
              return(a)
          })


## --------------------------------------------------
## Subclass with additional biomarker information
## --------------------------------------------------

##' Plot method for the "DataDual" class
##'
##' @param x the \code{\linkS4class{DataDual}} object we want to plot
##' @param y missing
##' @param blind Logical (default FALSE) if to blind the data
##' @param \dots not used
##' @return the \code{\link[ggplot2]{ggplot}} object
##'
##' @importFrom ggplot2 ggplot geom_point scale_colour_manual xlab ylab aes
##' @importFrom gridExtra arrangeGrob
##'
##' @example examples/Data-method-plot-DataDual.R
##' @export
##' @keywords methods
setMethod("plot",
          signature=
          signature(x="DataDual", y="missing"),
          def=
          function(x, y, blind=FALSE, ...){
              ## call the superclass method, to get the first plot
              plot1 <- callNextMethod(x, blind=blind, ...)

              ## now to get the second plot
              df <- data.frame(patient=seq_along(x@x),
                               dose=x@x,
                               biomarker=x@w,
                               toxicity=ifelse(x@y==1, "Yes", "No"))
              cols <- c("No" = "black","Yes" = "red")
              
              # If there are placebo, consider this a y=0.0 for the plot
              if(x@placebo & !blind)
                df$dose[df$dose == x@doseGrid[1]] <- 0.0 
              if(x@placebo & blind){
                  cohort.id <- unique(x@cohort)   
                  for(iCoh in seq(a=cohort.id)){
                      filter.coh <- which(x@cohort == cohort.id[iCoh])  
                      df[filter.coh,"dose"] <- max(df[filter.coh,"dose"])
                  }
              }
              
              # This is to blind the data
              # For each cohort, the placebo is set to the active dose level for that cohort.

              plot2 <- ggplot(df, aes(x=dose, y=biomarker))

              plot2 <- plot2 +
                  geom_point(aes(shape=toxicity, colour=toxicity),
                             size=3) +
                      scale_colour_manual(values=cols) +
                          xlab("Dose Level") + ylab("Biomarker")
              
              if(!blind)
                plot2 <- plot2 +
                  geom_text(data=df,
                            aes(label=patient, y=biomarker+0.02 * diff(range(biomarker)), size=2), hjust=0,
                            vjust=0.5, angle=90, colour=I("black"),
                            show.legend=FALSE)

              ## arrange both plots side by side
              ret <- gridExtra::arrangeGrob(plot1, plot2, ncol=2)
              return(ret)
          })



## ============================================================

## --------------------------------------------------
## Update a Data object
## --------------------------------------------------


##' Update method for the "Data" class
##'
##' Add new data to the \code{\linkS4class{Data}} object
##'
##' @param object the old \code{\linkS4class{Data}} object
##' @param x the dose level (one level only!)
##' @param y the DLT vector (0/1 vector), for all patients in this cohort
##' @param ID the patient IDs
##' @param newCohort logical: if TRUE (default) the new data are assigned
##' to a new cohort
##' @param \dots not used
##' @return the new \code{\linkS4class{Data}} object
##'
##' @example examples/Data-method-update-Data.R
##' @export
##' @keywords methods
setMethod("update",
          signature=
          signature(object="Data"),
          def=
          function(object,
                   x,
                   y,
                   ID=(if(length(object@ID)) max(object@ID) else 0L) + seq_along(y),
                   newCohort=TRUE,
                   ...){

              ## some checks
              stopifnot(is.scalar(x),
                        all(y %in% c(0, 1)))

              ## which grid level is the dose?
              gridLevel <- match(x, object@doseGrid)

              ## add it to the data
              if(is.na(gridLevel))
              {
                  stop("dose is not on grid")
              } else {
                  object@xLevel <- c(object@xLevel,
                                     rep(gridLevel,
                                         length(y)))
              }

              ## increment sample size
              object@nObs <- object@nObs + length(y)

              ## add dose
              object@x <- c(object@x,
                            rep(x,
                                length(y)))

              ## add DLT data
              object@y <- c(object@y, as.integer(y))

              ## add ID
              object@ID <- c(object@ID, ID)

              ## add cohort number
              if(newCohort){
                  object@cohort <- c(object@cohort,
                                     rep(max(tail(object@cohort, 1L), 0L) + 1L,
                                         length(y)))
              }else{
                  object@cohort <- c(object@cohort,
                                     rep(max(tail(object@cohort, 1L), 0L),
                                         length(y)))
              }

              ## return the object
              return(object)
          })


## --------------------------------------------------
## Update a DataParts object
## --------------------------------------------------

##' Update method for the "DataParts" class
##'
##' Add new data to the \code{\linkS4class{DataParts}} object
##'
##' @param object the old \code{\linkS4class{DataParts}} object
##' @param x the dose level (one level only!)
##' @param y the DLT vector (0/1 vector), for all patients in this cohort
##' @param ID the patient IDs
##' @param \dots not used
##' @return the new \code{\linkS4class{DataParts}} object
##'
##' @example examples/Data-method-update-DataParts.R
##' @export
##' @keywords methods
setMethod("update",
          signature=
          signature(object="DataParts"),
          def=
          function(object,
                   x,
                   y,
                   ID=(if(length(object@ID)) max(object@ID) else 0L) + seq_along(y),
                   ...){

              ## first do the usual things as for Data objects
              object <- callNextMethod(object=object, x=x, y=y, ID=ID, ...)

              ## update the part information
              object@part <- c(object@part,
                               rep(object@nextPart,
                                   length(y)))

              ## now decide which part the next cohort will belong to:
              ## only if the nextPart was 1, it can potentially be required to
              ## change it to 2 (once it is 2, it stays)
              if(object@nextPart == 1L)
              {
                  ## if there was a DLT in one of the cohorts,
                  ## or if the current dose was the highest from part 1:
                  if(any(object@y == 1L) || x == max(object@part1Ladder))
                  {
                      ## then this closes part 1 and the next cohort will
                      ## be from part 2:
                      object@nextPart <- 2L
                  }
              }

              ## return the object
              return(object)
          })

## --------------------------------------------------
## Update a DataDual object
## --------------------------------------------------

##' Update method for the "DataDual" class
##'
##' Add new data to the \code{\linkS4class{DataDual}} object
##'
##' @param object the old \code{\linkS4class{DataDual}} object
##' @param x the dose level (one level only!)
##' @param y the DLT vector (0/1 vector), for all patients in this cohort
##' @param w the biomarker vector, for all patients in this cohort
##' @param ID the patient IDs
##' @param newCohort logical: if TRUE (default) the new data are assigned 
##' to a new cohort
##' @param \dots not used
##' @return the new \code{\linkS4class{DataDual}} object
##'
##' @example examples/Data-method-update-DataDual.R
##' @export
##' @keywords methods
setMethod("update",
          signature=
          signature(object="DataDual"),
          def=
          function(object,
                   x,
                   y,
                   w,
                   newCohort=TRUE,
                   ID=(if(length(object@ID)) max(object@ID) else 0L) + seq_along(y),
                   ...){

              ## first do the usual things as for Data objects
              object <- callNextMethod(object=object, x=x, y=y, ID=ID, 
                                       newCohort=newCohort, ...)

              ## update the biomarker information
              object@w <- c(object@w,
                            w)

              ## return the object
              return(object)
          })

## -----------------------------------------------------------------------------------------
## Extracting efficacy responses for subjects without DLE observed
## ---------------------------------------------------------------------------------

##' Extracting efficacy responses for subjects without or with a DLE. This is a class where we separate
##' efficacy responses with or without a DLE. It outputs the efficacy responses and their corresponding 
##' dose levels treated at in two categories (with or without DLE)
##' 
##' @param object for data input from \code{\linkS4class{DataDual}} object
##' @param \dots unused
##' 
##' @export
##' @keywords methods
setGeneric("getEff",
           def=function(object,...){
             standardGeneric("getEff")},
           valueClass="list")

##' @rdname getEff
##' @param x todo
##' @param y todo
##' @param w todo
##' @example examples/Data-method-getEff.R
setMethod("getEff",
          signature=
            signature(object="DataDual"),
          def=
            function(object,
                     x,
                     y,
                     w,...){
              if (length(which(object@y == 1))==0){
                wNoDLE<-object@w
                wDLE<-NULL
                xNoDLE<- object@x
                xDLE<-NULL
              } else {##with observed efficacy response and DLE observed
                IndexDLE<-which(object@y==1)
                ##Take efficacy responses with no DLE observed
                wNoDLE<-object@w[-IndexDLE]
                wDLE<-object@w[IndexDLE]
                ##Take the corresponding dose levels
                xNoDLE<-object@x[-IndexDLE]
                xDLE<-object@x[IndexDLE]
              }
              ret<-list(wDLE=wDLE,xDLE=xDLE,wNoDLE=wNoDLE,xNoDLE=xNoDLE)
              return(ret)
            })

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