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cmprsk.R
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cmprsk.R
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# Copyright (C) 2000 Robert Gray
# distributed under the terms of the GNU public license
crr <-
# function for regression modeling of subdistribution functions
# arguments:
# ftime = vector of failure/censoring times
# fstatus = vector with a unique code for each failure type and a
# separate code for censored observations
# cov1 = (nobs x ncovs) matrix of fixed covariates
# cov2 = matrix of covariates multiplied by functions of time;
# if used, often these covariates would also appear in cov1,
# to give a prop hazards effect plus a time interaction
# tf = functions of time. A function that takes a vector of times as
# an argument and returns a matrix whose jth column is the value of
# the time function corresponding to the jth column of cov2 evaluated
# at the input time vector. At time tk, the
# model includes the term cov2[,j]*tfs(tk)[,j] as a covariate.
# cengroup = vector with different values for each group with
# a distinct censoring distribution (the censoring distribution
# is estimated separately within these groups)
# failcode = code of fstatus that denotes the failure type of interest
# cencode = code of fstatus that denotes censored observations
# subset = logical vector length(ftime) indicating which cases to include
# na.action = function defining action to take for cases that have NA for
# any of ftime, fstatus, cov1, cov2 cengroup, or subset.
# gtol = iteration stops when a function of the gradient is < gtol.
# maxiter = maximum # of iterations in Newton algorithm (0 computes
# scores and var at init, but performs no iterations)
# init = initial values of regression parameters
function(ftime,fstatus,cov1,cov2,tf,cengroup,failcode=1,cencode=0,
subset,na.action=na.omit,gtol=1e-6,maxiter=10,init,variance=TRUE) {
## LS
call <- match.call()
cov1.name <- deparse(substitute(cov1))
cov1.vars <- cov2.vars <- NULL
if(!missing(cov1))
{ cov1.vars <- colnames(as.matrix(cov1)) }
cov2.name <- deparse(substitute(cov2))
if(!missing(cov2))
{ cov2.vars <- colnames(as.matrix(cov2)) }
##
d <- data.frame(ftime=ftime,fstatus=fstatus,
cengroup=if (missing(cengroup)) rep(1,length(fstatus)) else cengroup)
if (!missing(cov1)) {
cov1 <- as.matrix(cov1)
nc1 <- ncol(cov1)
d <- cbind(d,cov1)
} else {nc1 <- 0}
if (!missing(cov2)) {
cov2 <- as.matrix(cov2)
nc2 <- ncol(cov2)
d <- cbind(d,cov2)
} else {nc2 <- 0}
if (!missing(subset)) d <- d[subset,]
tmp <- nrow(d)
d <- na.action(d)
nmis <- 0
if (nrow(d) != tmp) {
nmis <- tmp-nrow(d)
cat(format(nmis),'cases omitted due to missing values\n')
}
d <- d[order(d$ftime),]
ftime <- d$ftime
cenind <- ifelse(d$fstatus==cencode,1,0)
fstatus <- ifelse(d$fstatus==failcode,1,2*(1-cenind))
ucg <- sort(unique.default(d$cengroup))
cengroup <- match(d$cengroup,ucg)
ncg <- length(ucg)
uuu <- matrix(0,nrow=ncg,ncol=length(ftime))
for (k in 1:ncg) {
u <- do.call('survfit',list(formula=Surv(ftime,cenind)~1,data=
data.frame(ftime,cenind,cengroup),subset=cengroup==k))
### note: want censring dist km at ftime-
# changed 9-30-2019 for events at 0
# u <- approx(c(0,u$time,max(u$time)*(1+10*.Machine$double.eps)),c(1,u$surv,
# 0),xout=ftime*(1-100*.Machine$double.eps),method='constant',f=0,rule=2)
u <- approx(c(min(0,u$time)-10*.Machine$double.eps,c(u$time,max(u$time)*(1+10*.Machine$double.eps))),c(1,u$surv,
0),xout=ftime*(1-100*.Machine$double.eps),method='constant',f=0,rule=2)
uuu[k,1:length(u$y)] <- u$y
# u <- summary(u,times=sort(ftime*(1-.Machine$double.eps)))
# uuu[k,1:length(u$surv)] <- u$surv
}
uft <- sort(unique(ftime[fstatus==1]))
ndf <- length(uft)
if (nc2 == 0) {
cov1 <- as.matrix(d[,(1:nc1)+3])
np <- nc1
npt <- 0
cov2 <- 0
tfs <- 0
} else if (nc1 == 0) {
cov2 <- as.matrix(d[,(1:nc2)+3+nc1])
npt <- np <- nc2
cov1 <- 0
tfs <- tf(uft)
} else {
cov1 <- as.matrix(d[,(1:nc1)+3])
cov2 <- as.matrix(d[,(1:nc2)+3+nc1])
npt <- nc2
np <- nc1+nc2
tfs <- tf(uft)
}
### start of nr
if (missing(init)) b <- rep(0,np)
else b <- init
stepf <- .5
for (ll in 0:maxiter) {
z <- .Fortran('crrfsv',as.double(ftime),as.integer(fstatus),
as.integer(length(ftime)),as.double(cov1),as.integer(np-npt),
as.integer(np),as.double(cov2),as.integer(npt),
as.double(tfs),as.integer(ndf),as.double(uuu),
as.integer(ncg),as.integer(cengroup),as.double(b),
double(1),double(np),double(np*np),double(np),double(np),
double(np*np),PACKAGE = "cmprsk")[15:17]
if (max(abs(z[[2]])*pmax(abs(b),1)) < max(abs(z[[1]]),1)*gtol) {
converge <- TRUE
break
}
if (ll==maxiter) {
converge <- FALSE
break
}
h <- z[[3]]
dim(h) <- c(np,np)
### better to guarantee a pd factorization, but
### matrix should be pd except in rare circumstances
sc <- -solve(h,z[[2]])
bn <- b+sc
fbn <- .Fortran('crrf',as.double(ftime),as.integer(fstatus),
as.integer(length(ftime)),as.double(cov1),as.integer(np-npt),
as.integer(np),as.double(cov2),as.integer(npt),
as.double(tfs),as.integer(ndf),as.double(uuu),
as.integer(ncg),as.integer(cengroup),as.double(bn),
double(1),double(np),PACKAGE = "cmprsk")[[15]]
# backtracking loop
i <- 0
while (is.na(fbn) || fbn>z[[1]]+(1e-4)*sum(sc*z[[2]])) {
i <- i+1
sc <- sc*stepf
bn <- b+sc
fbn <- .Fortran('crrf',as.double(ftime),as.integer(fstatus),
as.integer(length(ftime)),as.double(cov1),as.integer(np-npt),
as.integer(np),as.double(cov2),as.integer(npt),
as.double(tfs),as.integer(ndf),as.double(uuu),
as.integer(ncg),as.integer(cengroup),as.double(bn),
double(1),double(np),PACKAGE = "cmprsk")[[15]]
if (i>20) break
}
if (i>20) {
converge <- FALSE
break
}
b <- c(bn)
}
if (variance) {
v <- .Fortran('crrvv',as.double(ftime),as.integer(fstatus),
as.integer(length(ftime)),as.double(cov1),as.integer(np-npt),
as.integer(np),as.double(cov2),as.integer(npt),
as.double(tfs),as.integer(ndf),as.double(uuu),
as.integer(ncg),as.integer(cengroup),as.double(b),
double(np*np),double(np*np),double(np*np),
double(length(ftime)*(np+1)),double(np),double(np*ncg),
double(2*np),double(ncg*np),
integer(ncg),double(ncg*np),double(ncg),
PACKAGE = "cmprsk")[15:16]
dim(v[[2]]) <- dim(v[[1]]) <- c(np,np)
h0 <- v[[1]]
h <- solve(v[[1]])
v <- h %*% v[[2]] %*% t(h)
r <- .Fortran('crrsr',as.double(ftime),as.integer(fstatus),
as.integer(length(ftime)),as.double(cov1),as.integer(np-npt),
as.integer(np),as.double(cov2),as.integer(npt),
as.double(tfs),as.integer(ndf),as.double(uuu),
as.integer(ncg),as.integer(cengroup),as.double(b),
double(ndf*np),double(np),double(np),PACKAGE = "cmprsk")[[15]]
r <- t(matrix(r,nrow=np))
##
} else {
v <- h <- h0 <- matrix(NA,np,np)
r <- NULL
# bj <- NULL
}
nobs <- length(ftime)
b0 <- rep(0,length(b))
fb0 <- .Fortran('crrf',as.double(ftime),as.integer(fstatus),
as.integer(length(ftime)),as.double(cov1),as.integer(np-npt),
as.integer(np),as.double(cov2),as.integer(npt),
as.double(tfs),as.integer(ndf),as.double(uuu),
as.integer(ncg),as.integer(cengroup),as.double(b0),
double(1),double(np),PACKAGE = "cmprsk")[[15]]
bj <- .Fortran('crrfit',as.double(ftime),as.integer(fstatus),
as.integer(length(ftime)),as.double(cov1),as.integer(np-npt),
as.integer(np),as.double(cov2),as.integer(npt),
as.double(tfs),as.integer(ndf),as.double(uuu),
as.integer(ncg),as.integer(cengroup),as.double(b),
double(ndf),double(np),PACKAGE = "cmprsk")[[15]]
if (nc1>0) {
x1 <- paste(cov1.name, 1:nc1, sep="")
if(is.null(cov1.vars)) cov1.vars <- x1
else cov1.vars <- ifelse(cov1.vars=="",x1,cov1.vars)
}
if(nc2 > 0) {
x1 <- paste(cov2.name, 1:nc2, sep="")
if (is.null(cov2.vars)) cov2.vars <- x1
else cov2.vars <- ifelse(cov2.vars=="",x1,cov2.vars)
x1 <- paste('tf',1:nc2,sep='')
x2 <- colnames(tfs)
if (!is.null(x2)) x1 <- ifelse(x2=="",x1,x2)
cov2.vars <- paste(cov2.vars, x1, sep="*")
}
names(b) <- c(cov1.vars, cov2.vars)
##
z <- list(coef=b,loglik=-z[[1]],score=-z[[2]],inf=h0,
var=v,res=r,uftime=uft,bfitj=bj,
tfs=as.matrix(tfs),converged=converge,call = call, n = nobs,
n.missing = nmis, loglik.null = -fb0,invinf=h)
class(z) <- 'crr'
z
}
"summary.crr" <- function(object, conf.int = 0.95, digits = max(options()$digits - 5, 2), ...)
{
beta <- object$coef
se <- sqrt(diag(object$var))
out <- list(call = object$call, converged = object$converged,
n = object$n, n.missing = object$n.missing,
loglik = object$loglik)
tmp <- cbind(beta, exp(beta), se, beta/se,
signif(2 * (1 - pnorm(abs(beta)/se)), digits))
dimnames(tmp) <- list(names(beta), c("coef", "exp(coef)",
"se(coef)", "z", "p-value"))
out$coef <- tmp
if(conf.int)
{ a <- (1 - conf.int)/2
a <- c(a, 1 - a)
z <- qnorm(a)
tmp <- cbind(exp(beta), exp(-beta),
exp(beta + z[1] * se), exp(beta + z[2] * se))
dimnames(tmp) <- list(names(beta), c("exp(coef)", "exp(-coef)",
paste(format(100*a, trim = TRUE,
scientific = FALSE,
digits = 3), "%", sep="")))
out$conf.int <- tmp
}
df <- length(beta)
logtest <- -2 * (object$loglik.null - object$loglik)
out$logtest <- c(test = logtest, df = df)
# out$rsq <- c(rsq = 1 - exp(-logtest/object$n),
# maxrsq = 1 - exp(2 * object$loglik.null/object$n))
class(out) <- "summary.crr"
out
}
"print.summary.crr" <- function (x, digits = max(options()$digits - 4, 3), ...)
{
cat("Competing Risks Regression\n\n")
if(!is.null(x$call))
{ cat("Call:\n")
dput(x$call)
cat("\n")
}
if(!x$converged)
{ cat("crr converged:", x$converged, "\n")
return()
}
savedig <- options(digits = digits)
on.exit(options(savedig))
print(x$coef)
cat("\n")
print(x$conf.int)
cat("\n")
cat("Num. cases =", x$n)
if(x$n.missing > 0)
cat(" (", x$n.missing, " cases omitted due to missing values)", sep="")
cat("\n")
# cat("Rsquare =", format(round(x$rsq["rsq"], 3)), " (max possible =",
# format(round(x$rsq["maxrsq"], 3)), ")\n")
cat("Pseudo Log-likelihood =", x$loglik, "\n")
cat("Pseudo likelihood ratio test = ", format(round(x$logtest["test"], 2)),
" on ", x$logtest["df"], " df,", "\n", sep = "")
# " p-value = ", format(x$logtest["pvalue"]), "\n", sep = "")
invisible()
}
predict.crr <-
# for a crr object x, estimates subdistributions at covariate
# combinations given by rows of cov1 and cov2. The terms in cov1
# cov2 must correspond exactly to the corresponding call to crr.
function(object,cov1,cov2,...) {
if (is.null(object$bfitj)) stop('predict requires variance=TRUE in crr')
np <- length(object$coef)
if (length(object$tfs)<=1) {
if (length(object$coef)==length(cov1)) lhat <- cumsum(exp(sum(cov1*object$coef))*object$bfitj)
else {
cov1 <- as.matrix(cov1)
lhat <- matrix(0,nrow=length(object$uftime),ncol=nrow(cov1))
for (j in 1:nrow(cov1)) lhat[,j] <- cumsum(exp(sum(cov1[j,]*object$coef))*object$bfitj)
}
} else {
if (length(object$coef)==ncol(as.matrix(object$tfs))) {
if (length(object$coef)==length(cov2))
lhat <- cumsum(exp(object$tfs %*% c(cov2*object$coef))*object$bfitj)
else {
cov2 <- as.matrix(cov2)
lhat <- matrix(0,nrow=length(object$uftime),ncol=nrow(cov1))
for (j in 1:nrow(cov2)) lhat[,j] <-
cumsum(exp(object$tfs %*% c(cov2[j,]*object$coef))*object$bfitj)
}
} else {
if (length(object$coef)==length(cov1)+length(cov2))
lhat <- cumsum(exp(sum(cov1*object$coef[1:length(cov1)])+object$tfs %*%
c(cov2*object$coef[(np-length(cov2)+1):np]))*object$bfitj)
else {
cov1 <- as.matrix(cov1)
cov2 <- as.matrix(cov2)
lhat <- matrix(0,nrow=length(object$uftime),ncol=nrow(cov1))
for (j in 1:nrow(cov1)) lhat[,j] <-
cumsum(exp(sum(cov1[j,]*object$coef[1:ncol(cov1)])+object$tfs %*%
c(cov2[j,]*object$coef[(np-ncol(cov2)+1):np]))*object$bfitj)
}
}
}
lhat <- cbind(object$uftime,1-exp(-lhat))
class(lhat) <- 'predict.crr'
lhat
}
plot.predict.crr <-
# plots estimated subdistributions from predict.crr
function(x,lty=1:(ncol(x)-1),color=1,ylim=c(0,max(x[,-1])),xmin=0,xmax=max(x[,1]),...) {
if (length(lty)<ncol(x)-1) lty <- rep(lty[1],ncol(x)-1)
if (length(color)<ncol(x)-1) color <- rep(color[1],ncol(x)-1)
if (xmax<max(x[,1])) x <- x[x[,1]<xmax,]
times <- c(xmin,rep(x[,1],rep(2,nrow(x))),xmax)
plot(c(xmin,xmax),ylim,type='n',...)
for (j in 2:ncol(x)) lines(times,c(0,0,rep(x[,j],rep(2,nrow(x)))),lty=lty[j-1],col=color[j-1])
}
print.crr <-
# prints a summary of the crr fit x
function(x,...) {
cat('convergence: ',x$converged,'\n')
cat('coefficients:\n')
print(signif(x$coef,4),...)
v <- sqrt(diag(x$var))
cat('standard errors:\n')
print(signif(v,4),...)
v <- 2*(1-pnorm(abs(x$coef)/v))
cat('two-sided p-values:\n')
print(signif(v,2),...)
invisible()
}
cuminc <- function(ftime,fstatus,group,strata,rho=0,cencode=0,subset,na.action=na.omit) {
# ftime=failure times, fstatus=variable which indicates the type
# of failure (and cens), group is the group variable, strata=
# strata variables for the tests (omit if none), rho is the
# power of the weight function used in the tests, cencode is the value
# of fstatus which indicates that a time is censored (default is 0)
# subset = logical vector length(ftime) indicating which cases to include
# na.action = function defining action to take for cases that have NA for
# any of ftime, fstatus, group, strata, or subset.
# output is a list giving the estmated cuminc
# functions (times, function values, variances) for each group, and
# a component
# values of the test statistics for comparing each cause among the
# groups. the tests are stratified (if strata specified).
# check lengths, and status of group and strata
d <- data.frame(time=ftime,cause=fstatus,
group=as.factor(if (missing(group)) rep(1,length(ftime)) else group),
strata=as.factor(if (missing(strata)) rep(1,length(ftime)) else strata))
if (!missing(subset)) d <- d[subset,]
tmp <- nrow(d)
d <- na.action(d)
if (nrow(d) != tmp) cat(format(tmp-nrow(d)),'cases omitted due to missing values\n')
no <- nrow(d)
cg <- " "
nst <- length(levels(d$strata))
d <- d[order(d$time),]
ugg <- table(d$group)
d$group <- factor(d$group,names(ugg)[ugg>0])
ugg <- levels(d$group)
censind <- ifelse(d$cause==cencode,0,1)
if (is.factor(d$cause)) {
uc <- table(d$cause[censind==1])
uclab <- names(uc)[uc>0]
} else {
uclab <- sort(unique(d$cause[censind==1])) # as.numeric(names(uc)[uc>0])
}
nc <- length(uclab)
ng <- length(ugg)
if (ng>1) {
ng1 <- ng-1
ng2 <- ng*ng1/2
v <- matrix(0,nrow=ng1,ncol=ng1)
storage.mode(v) <- "double"
vt <- double(ng2)
s <- double(ng1)
}
pf <- vector("list",ng*nc)
stat <- double(nc)
l <- 0
for (ii in 1:nc) {
causeind <- ifelse(d$cause==uclab[ii],1,0)
for (jj in 1:length(ugg)) {
cg <- c(cg,paste(ugg[jj],uclab[ii]))
l <- l+1
cgind <- d$group==ugg[jj]
ncg <- length(cgind[cgind])
n2 <- length(unique(d$time[cgind & causeind==1]))
n2 <- 2*n2+2
tmp <- double(n2)
z <- .Fortran("cinc",as.double(d$time[cgind]),as.integer(censind[cgind]),
as.integer(causeind[cgind]),as.integer(ncg),
x=tmp,f=tmp,v=tmp,PACKAGE = "cmprsk")
pf[[l]] <- list(time=z$x,est=z$f,var=z$v)
}
if (ng>1) {
causeind <- 2*censind-causeind
z2 <- .Fortran("crstm",as.double(d$time),as.integer(causeind),
as.integer(d$group),as.integer(d$strata),as.integer(no),
as.double(rho),as.integer(nst),as.integer(ng),s,v,
as.double(d$time),as.integer(causeind),as.integer(d$group),
vt,s,vt,double((4+3*ng)*ng),integer(4*ng),PACKAGE = "cmprsk")
stat[ii] <- -1
a <- qr(z2[[10]])
if (a$rank==ncol(a$qr)) {
b <- diag(dim(a$qr)[1])
stat[ii] <- z2[[9]]%*%qr.coef(a,b)%*%z2[[9]]
}
}
}
names(pf) <- cg[2:length(cg)]
if (ng>1) {
names(stat) <- uclab
stat <- list(Tests=cbind(stat=stat,pv=1-pchisq(stat,ng-1),df=rep(ng-1,length(stat))))
pf <- c(pf,stat)
}
attr(pf, "class") <- "cuminc"
pf
}
print.cuminc <- function(x,ntp=4,maxtime,...) {
if (!is.null(x$Tests)) {
cat('Tests:\n')
print(x$Tests)
nc <- length(x)-1
} else {
nc <- length(x)
}
if (missing(maxtime)) {
maxtime <- 0
for (i in 1:nc) maxtime <- max(maxtime,x[[i]]$time)
}
tp <- pretty(c(0,maxtime),ntp+1)
cat('Estimates and Variances:\n')
print(timepoints(x,tp[-c(1,length(tp))]),...)
invisible()
}
timepoints <- function(w,times) {
# w=list (see cuminc or km), times= times you want estimates for.
# output is a list with components est giving the estimates, var giving
# the variances,
if (!is.null(w$Tests)) w <- w[names(w) != 'Tests']
ng <- length(w)
times <- sort(unique(times))
nt <- length(times)
storage.mode(times) <- "double"
storage.mode(nt) <- "integer"
ind <- matrix(0,ncol=nt,nrow=ng)
oute <- matrix(NA,ncol=nt,nrow=ng)
outv <- oute
storage.mode(ind) <- "integer"
slct <- rep(TRUE,ng)
for (i in 1:ng) {
if (is.null((w[[i]])$est)) { slct[i] <- FALSE} else {
z <- .Fortran("tpoi",as.double(w[[i]][[1]]),
as.integer(length(w[[i]][[1]])),ind[i,],times,nt,PACKAGE = "cmprsk")
ind[i,] <- z[[3]]
oute[i,ind[i,]>0] <- w[[i]][[2]][z[[3]]]
if (length(w[[i]])>2) outv[i,ind[i,]>0] <- w[[i]][[3]][z[[3]]]
}
}
dimnames(oute) <- list(names(w)[1:ng],as.character(times))
dimnames(outv) <- dimnames(oute)
list(est=oute[slct,,drop=FALSE],var=outv[slct,,drop=FALSE])
}
plot.cuminc <- function(x,main=" ",curvlab,ylim=c(0,1),xlim,wh=2,xlab="Years",
ylab="Probability",lty=1:length(x),color=1,lwd = par('lwd'),...) {
# x is a list containing curves to be plotted. Each component of
# x is a list with the first component containing the x values
# and the second component the y values. main = main title in the plot
# curvlab=curve labels (vector), wh=where curve labels are plotted
# 1=lower left 2=upper left 3=upper right 4=lower right
if (!is.null(x$Tests)) x <- x[names(x) != 'Tests']
nc <- length(x)
if (length(lty) < nc) lty <- rep(lty[1],nc) else lty <- lty[1:nc]
if (length(lwd) < nc) lwd <- rep(lwd[1],nc) else lwd <- lwd[1:nc]
if (length(color) < nc) color <- rep(color[1],nc) else color <- color[1:nc]
if (missing(curvlab)) {
if (mode(names(x))=="NULL") {
curvlab <- as.character(1:nc) }
else curvlab <- names(x)[1:nc]
}
if (missing(xlim)) {
xmax <- 0
for (i in 1:nc) {
xmax <- max(c(xmax,x[[i]][[1]]))
}
xlim <- c(0,xmax)
}
plot(x[[1]][[1]],x[[1]][[2]],type="n",ylim=ylim,xlim=xlim,
main=main,xlab=xlab,ylab=ylab,bty="l",...)
if (length(wh) != 2) {
wh <- c(xlim[1],ylim[2])
}
u <- list(...)
if (length(u)>0) {
i <- pmatch(names(u),names(formals(legend)),0)
do.call('legend',c(list(x=wh[1],y=wh[2],legend=curvlab,col=color,lty=lty,lwd=lwd,bty="n",bg=-999999),u[i>0]))
} else {
do.call('legend',list(x=wh[1],y=wh[2],legend=curvlab,col=color,lty=lty,lwd=lwd,bty="n",bg=-999999))
}
# legend(wh[1],wh[2],legend=curvlab,col=color,lty=lty,bty="n",bg=-999999,...)
for (i in 1:nc) {
lines(x[[i]][[1]],x[[i]][[2]],lty=lty[i],col=color[i],lwd=lwd[i],...)
}
}
"[.cuminc" <- function(x,i,...) {
x <- NextMethod("[")
class(x) <- 'cuminc'
x
}