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#' Continuous time Generalized Rapid response CUSUM (CGR-CUSUM) helper - matrix
#' formulation of the problem - version 2
#'
#' @description This function calculates the value of the CGR-CUSUM using a
#' matrix formulation of the problem - this can require a lot of available RAM.
#'
#' @inheritParams cgr_cusum
#' @param data \code{data.frame} containing the following named columns:
#' \itemize{
#' \item \code{entrytime} numeric - time of entry into study,
#' \item \code{otime} numeric - time from entry until event,
#' \item \code{censorid} integer - (optional) censoring indicator (0 = right censored, 1 = observed),
#\item \code{cause} factor - cause of event - competing risks.
#' } and optionally additional covariates used for risk-adjustment.
#' @param displaypb boolean Display a progress bar?
#'
#' @return A matrix with 4 named columns:
#' \itemize{
#' \item $time time at which the value of the CGR-CUSUM was determined
#' \item $value value at corresponding time of the CGR-CUSUM
#' \item $exp_theta_t value at corresponding time of the MLE \eqn{\hat{\theta}_t}{\theta_t}
#' \item $S_nu time from which individuals contribute to the chart \eqn{S_\nu}{S_\nu}
#' }
#'
#' @importFrom utils txtProgressBar
#' @importFrom utils setTxtProgressBar
#' @importFrom parallel detectCores
#' @importFrom parallel stopCluster
#' @importFrom parallel parSapply
#' @importFrom parallel makeCluster
#' @importFrom pbapply pbmapply
#' @importFrom pbapply pbsapply
#' @importFrom pbapply pbapply
#' @importFrom parallel clusterExport
#' @importFrom pbapply pboptions
#'
#' @noRd
#' @keywords internal
#'
#' @author Daniel Gomon
#'
#'
#' @examples
#' \donttest{
#' require(survival)
#' tdat <- subset(surgerydat, hosp_num == 1)
#' tdat$otime <- tdat$entrytime + tdat$survtime
#' tcbaseh <- function(t) chaz_exp(t, lambda = 0.01)
#' varsanalysis <- c("age", "sex", "BMI")
#' exprfit <- as.formula(paste("Surv(survtime, censorid) ~" ,paste(varsanalysis, collapse='+')))
#' tcoxmod <- coxph(exprfit, data= surgerydat)
#' #Alternatively, cbaseh can be left empty when specifying coxphmod through coxph()
#' cgr2 <- cgr_helper_mat_2(data = tdat, ctimes = unique(tdat$entrytime + tdat$survtime),
#' coxphmod = tcoxmod, cbaseh = tcbaseh, displaypb = TRUE)
#' }
cgr_helper_mat_down <- function(data, ctimes, h, coxphmod, cbaseh, ncores, displaypb = FALSE, dependencies,
maxtheta){
#!
#DEVELOPMENT VERSION - DOWNWARDS CGR-CUSUM
#!
#This function consists of the following functions:
#maxoverk: calculate CGI value at specific ctime, considering only patients with entrytime S_i >= k
#maxoverj: Calculate CGR value at specific ctime by applying maxoverk on all relevant starting times (helperstimes)
#fin = apply maxoverj to all required construction times to determine the values of CGR(t) for all ctimes
#TRIPLE APPLY CONSTRUCTION.
#Lambdamat is determined using an mapply on the columns of a matrix which is structured as:
# ctime_1 ctime_2 ctime_3 ctime_4 ................ ctime_p
# i=1 ( )
# i=2 ( accumulated hazard of subject 2 at time in column )
# i=3 ( subject 3 )
# ... ( ... )
# i=p ( )
#
# Then we determine all patients which are relevant for constructing at a certain timepoint
# by indexing over the data (checking their Stimes) and determine their active
# contribution by summing over the column at the desired ctime.
# The number of failures at that timepoint is determined the same way
ctimes <- ctimes[which(ctimes >= min(data$entrytime))]
data_mat <- as.matrix(data[, c("censorid", "entrytime", "otime")])
data_mat[, "entrytime"] <- as.double(data_mat[, "entrytime"])
if (!identical(FALSE, is.unsorted(data_mat[, "entrytime"]))){
stop("'data$entrytime' must be sorted non-decreasingly and not contain NAs.")
}
#Remove R check warnings
entrytime <- NULL
if(ncores > 1){
#Create a cluster for parallel computing and error check
real_cores <- detectCores()
if(ncores > real_cores){
warning(paste0("More cores requested (", ncores ,") than detected (", real_cores,") by R. \n Proceed at own risk."))
}
cl <- makeCluster(ncores)
} else{
cl <- NULL
}
#Calculate Lambda_i for a single person at times - can be applied to matrix columns
Lambdafun_noparallel <- function(entrytime, otime, times, cbaseh){
lamval <- sapply(times, FUN = function(x) {
if(x >= entrytime){
cbaseh(min(x, otime) - entrytime)
} else{0}
})
}
#Same as lamdafun_noparallel, but can be applied to matrix rows using apply
Lambdafun <- function(y, times, cbaseh){
lamval <- sapply(times, FUN = function(x) {
if(x >= y[1]){
cbaseh(min(x, y[2]) - y[1])
} else{0}
})
}
#---------NEW FCT BODY-------------
#Calculate subject specific failure risk (exp(\beta Z))
riskdat <- calc_risk(data, coxphmod)
#ctimes are already pre-sorted in cgrcusum
#Create matrix containing Lambda_i(t) per patient. Rows represent patient i
if(displaypb){
message("Step 1/2: Determining hazard contributions.")
pboptions(type = "timer")
} else{
pboptions(type = "none")
}
#MULTI-CORE:
#Provide dependencies to cluster (such as functions required for clusters)
if(!missing(dependencies)){
clusterExport(cl,dependencies, envir=environment())
}
#Create matrix containing Lambda_i(t) per patient. Rows represent subject i, columns represent ctimes
#the columns are exactly ctimes
#tryCatch: if MULTI-CORE doesn't work, go back to SINGLE-CORE
lambdamat <- tryCatch({t(pbapply(X = data[, c("entrytime", "otime")], MARGIN = 1,
FUN = Lambdafun, times = ctimes, cbaseh = cbaseh, cl = cl))},
error = function(cond){
asd <- cond
message(cond)
message(paste0("\nPlease specify above missing functions/variables as a list to cgr_cusum under"
," the argument 'dependencies'"))
message("\nStep 1/2 will continue WITHOUT PARALLELIZATION - MAY BE SLOW!")
t(pbmapply(FUN = Lambdafun_noparallel, entrytime = data$entrytime,
otime = data$otime, MoreArgs = list( times = ctimes, cbaseh = cbaseh)))
}
)
#Risk-adjust the cumulative intensity calculated at times
lambdamat <- lambdamat * as.vector(riskdat)
#Determine times from which to construct the CGR
helperstimes <- as.double(sort(unique(data$entrytime)))
#helperfailtimes are not used in lower sided CGR-CUSUMS, because any
#contribution to Lambda(t) will drift the chart downwards... :(
#helperfailtimes <- numeric(length(helperstimes))
#Determine failure times, as we only have to use helperstimes with failure times
#smaller than the construction time.
#for(i in seq_along(helperstimes)){
# failtemptime <- min(subset(data, entrytime == helperstimes[i])$otime)
# helperfailtimes[i] <- failtemptime
# if(failtemptime == helperstimes[i]){
# if(i > 1){
# helperfailtimes[i-1] <- failtemptime
# }
# }
# }
#Function used for maximizing over starting points (patients with starting time >= k)
maxoverk <- function(helperstime, ctime, ctimes, data, lambdamat, maxtheta){
#Determine part of data that is active at required times
#This code works because data is sorted according to entrytime and then otime
#We use findInterval instead of match or which because it's faster
#Important: findInterval requires DOUBLE inputs. all inputs have been
#coerced to doubles beforehand.
lower <- binary_search(data[, "entrytime"], helperstime, index = TRUE)
upper <- nrow(data) - binary_search(rev(-1*data[, "entrytime"]), (-1*ctime), index = TRUE) +1
#lower <- .Internal(findInterval(data[, "entrytime"], helperstime, rightmost.closed = FALSE,
# all.inside = FALSE, left.open = TRUE)) + 1
#upper <- .Internal(findInterval(data[, "entrytime"], ctime, rightmost.closed = FALSE,
# all.inside = FALSE, left.open = FALSE))
matsub <- lower:upper
#The cumulative intensity at that time is the column sum of the specified ctime
AT <- sum(lambdamat[matsub, match(ctime, ctimes)])
#Determine amount of failures at ctime.
tmat <- data[matsub, , drop = FALSE]
NDT <- sum(tmat[, "censorid"] == 1 & tmat[, "otime"] <= ctime)
NDT_current <- sum(tmat[, "censorid"] == 1 & tmat[, "otime"] == ctime)
#Determine MLE of theta
thetat <- log(NDT/AT)
thetat_down <- log((NDT-NDT_current)/AT)
if (is.finite(thetat)){
thetat <- max(min(0, thetat), -abs(maxtheta))
} else {thetat <- 0}
if (is.finite(thetat_down)){
thetat_down <- max(min(0, thetat_down), -abs(maxtheta))
} else {thetat_down <- 0}
#Determine value of CGI-CUSUM using only patients with S_i > helperstimes[i]
CGIvalue <- - thetat * NDT + (exp(thetat)- 1) * AT
CGI_down <- - thetat_down * (NDT - NDT_current) + (exp(thetat_down)- 1) * AT
#Return both the value of CGI and the MLE (to be used later)
return(c(CGI_down, CGIvalue, thetat_down, thetat))
}
#Function to calculate CGR value at one ctime by ways of maximizing over all CGI(t) values.
#Achieved by applying the maxoverk function and determining maxima.
maxoverj <- function(y){
#don't use helperfailtimes in downward CUSUM
#a <- sapply(helperstimes[which(helperstimes <= y & helperfailtimes <= y)], function(x) maxoverk(helperstime = x, ctime = y, ctimes = ctimes, data = data, lambdamat = lambdamat))
#We first apply the maxoverk function to determine CGI values
#starting from all relevant helper S_i times (patient entry times)
#We only need to calculate the CGI value when the the starting time of patients
a <- sapply(helperstimes[which(helperstimes <= y)],
function(x) maxoverk(helperstime = x, ctime = y, ctimes = ctimes,
data = data_mat,
lambdamat = lambdamat, maxtheta = maxtheta))
#If there are no values to be calculated, return trivial values
if(length(a) == 0){
#Returns empty values if nothing to calculate
return(c(0,0,0,0,1,1))
}else{
#First row is value of chart, second row associated value of theta
#Third row is value of chart without current failures
#Determine which entry is the smallest (largest CGI value)
tidmin <- which.min(a[1,])
#Determine which entry is the smallest when considering failure again
tidmax <- which.min(a[2,])
#Determine the corresponding value of CGI(t)
atemp <- a[,tidmin]
atemp_up <- a[,tidmax]
#Returns c(chartval, thetaval) at maximum of CGI(t)
#More specific: CGI_down, CGI_up, theta_down, theta_up, idx_down, idx_up (see maxoverk)
return(c(atemp[1], atemp_up[2], atemp[3], atemp_up[4], tidmin, tidmax))
}
}
maxoverj_h <- function(y, h){
#We first apply the maxoverk function to determine CGI values
#starting from all relevant helper S_i times (patient entry times)
#We only need to calculate the CGI value when the the starting time of patients
#is before our construction time
#For when I fix helperfailtimes problem.
#a <- sapply(helperstimes[which(helperstimes <= y & helperfailtimes <= y)], function(x) maxoverk(helperstime = x, ctime = y, ctimes = ctimes, data = data, lambdamat = lambdamat))
a <- sapply(helperstimes[which(helperstimes <= y)],
function(x) maxoverk(helperstime = x, ctime = y, ctimes = ctimes,
data = data_mat,
lambdamat = lambdamat, maxtheta = maxtheta))
if(length(a) == 0){
#Returns empty values if nothing to calculate
return(c(0,0,0,0,1,1))
}else{
#First row is value of chart, second row associated value of theta
#Determine which entry is the largest (largest CGI value)
tidmin <- which.min(a[1,])
tidmax <- which.min(a[2,])
#Determine the corresponding value of CGI(t)
atemp <- a[,tidmin]
atemp_up <- a[,tidmax]
if(abs(atemp[1]) >= abs(h)){
hcheck <<- TRUE
stopind <<- TRUE
stopctime <<- match(y, ctimes)
}
#Returns c(chartval, thetaval) at maximum of CGI(t)
#More specific: CGI_down, CGI_up, theta_down, theta_up, idx_down, idx_up (see maxoverk)
return(c(atemp[1], atemp_up[2], atemp[3], atemp_up[4], tidmin, tidmax))
}
}
#hcheck used to check whether value of CGR has surpassed control limit
hcheck <- FALSE
stopind <- FALSE
stopctime <- NA
#Calculate maxoverk for every construction time ctimes
#If progress bar, then pbsapply (with possible multi-core)
if(displaypb){
message("Step 2/2: Determining chart values.")
}
if(!missing(h)){
#Calculate maxoverk for every construction time ctimes by applying maxoverj on all ctimes.
if(ncores > 1){
stopCluster(cl)
cl <- NULL
}
fin <- pbsapply(ctimes, function(x){ if(isFALSE(hcheck)){ maxoverj_h(x, h = h)} else{return(c(0,0,0,0,1,1))}}, cl = cl)
} else{
fin <- pbsapply(ctimes, maxoverj, cl = cl)
if(ncores > 1){
stopCluster(cl)
}
}
Gt <- t(fin)
if(!is.na(stopctime)){
Gt <- Gt[1:stopctime,]
}
Gt[,3] <- exp(Gt[,3])
Gt[,4] <- exp(Gt[,4])
Gt[,5] <- helperstimes[Gt[,5]]
Gt[,6] <- helperstimes[Gt[,6]]
if(!is.na(stopctime)){
Gt <- cbind(ctimes[1:stopctime], Gt)
} else{
Gt <- cbind(ctimes, Gt)
}
Gt <- unname(Gt)
#Initiate final matrix
Gt_final <- matrix(c(min(ctimes, min(data$entrytime)), 0, 1, 0), ncol = 4)
for(l in 1:nrow(Gt)){
if(Gt[l, 2] == Gt[l,3]){
Gt_final <- rbind(Gt_final, Gt[l, c(1, 2, 4, 6)])
} else{
Gt_final <- rbind(Gt_final, Gt[l, c(1, 2, 4, 6)])
Gt_final <- rbind(Gt_final, Gt[l, c(1, 3, 5, 7)])
}
}
Gt_final <- as.data.frame(Gt_final)
colnames(Gt_final) <- c("time", "value", "exp_theta_t", "S_nu")
#return list of relevant values
return(Gt_final)
}
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