library(survival) options(na.action=na.exclude) # preserve missings options(contrasts=c('contr.treatment', 'contr.poly')) #ensure constrast type aeq <- function(x,y,...) all.equal(as.vector(x), as.vector(y),...) # # Test out the results for competing risks. Survfit does this directly as just # one case of the Aalen-Johansen, but also known as 'cumulative incidence'. # # First trivial test tdata <- data.frame(time=c(1,2,2,3,3,3,5,6), status = c(0,1,0,1,0,1,0,1), event = c(1,1,2,2,1,2,3,2), grp = c(1,2,1,2,1,2,1,2), id = 1:8) old <- survfit(Surv(time, status*event, type="mstate") ~1, tdata) #old style fit <- survfit(Surv(time, factor(status*event)) ~1, tdata) # test that the old (should be depricated) form gives the same answer indx <- match("call", names(fit)) all.equal(unclass(old)[-indx], unclass(fit)[-indx]) byhand <- function() { #everyone starts in state 0 p1 <- c(1,0,0) p2 <- c(6/7, 1/7, 0) # 0-1 transition at time 2 u2 <- matrix(rep(c(1/49, -1/49, 0), each=8), ncol=3) #leverage matrix at time 2 u2[1,] <- 0 #subject 1 is not present u2[2,1:2] <- u2[2, 1:2] + c(-1/7, 1/7) p3 <- c((6/7)*(3/5), 1/7, 12/35) # 0-2 transition at time 3, 5 at risk h3 <- matrix(c(3/5, 0, 2/5, 0,1,0, 0,1,0), byrow=T, ncol=3) #hazard mat u3 <- u2 %*% h3 u3[4:8,1] <- u3[4:8,1] + p2[1]*2/25 u3[4:8,3] <- u3[4:8,3] -p2[1]*2/25 u3[4,] <- u3[4,] + c(-p2[1]/5, 0, p2[1]/5) u3[6,] <- u3[4,] p6 <- c(0, 1/7, 6/7) # 0-2 at time 6, 1 at risk h6 <- matrix(c(-1,0,1,0,1,0,0,1,0), byrow=T, ncol=3) u6 <- cbind(0, u3[,2], -u3[,2]) V <- rbind(0, colSums(u2^2), colSums(u3^2), colSums(u3^2), colSums(u6^2)) list(P=rbind(p1, p2, p3, p3, p6), u2=u2, u3=u3, u6=u6, V=V) } bfit <- byhand() aeq(fit$pstate, bfit$P) aeq(fit$n.risk[,1], c(8,7,5,2,1)) aeq(fit$n.event[,2:3], c(0,1,0,0,0, 0,0 ,2,0,1)) aeq(fit$std.err, sqrt(bfit$V)) # Check the influence directly, per row eps <- 1e-6 deltaU <- array(0, dim= c(nrow(tdata), dim(fit$pstate))) deltaC <- array(0, dim= c(nrow(tdata), dim(fit$cumhaz))) deltaA <- deltaU auc <- function(fit) { nr <- length(fit$time) rbind(fit$p0*fit$time[1], apply(diff(fit$time) * fit$pstate[-nr,], 2, cumsum)) } for (i in 1:nrow(tdata)) { twt <- rep(1, nrow(tdata)) twt[i] <- twt[i] + eps tfit <- survfit(Surv(time, factor(status*event)) ~1, tdata, id=id, weights= twt) deltaU[i,,] <- (tfit$pstate - fit$pstate)/eps # approx derivative deltaC[i,,] <- (tfit$cumhaz - fit$cumhaz)/eps deltaA[i,,] <- (auc(tfit) - auc(fit))/eps } aeq(bfit$u2, deltaU[,2,], tol=eps) aeq(bfit$u3, deltaU[,3,], tol=eps) aeq(bfit$u6, deltaU[,5,], tol=eps) sqmean <- function(x) sqrt(sum(x^2)) aeq(fit$std.chaz, apply(deltaC, 2:3, sqmean), tol=eps) aeq(fit$std.err, apply(deltaU, 2:3, sqmean), tol=eps) aeq(fit$std.auc, apply(deltaA, 2:3, sqmean), tol=eps) # Times purposely has values that are before the start, exact, intermediate # and after the end of the observed times sfit <- summary(fit, times=c(0, 1, 3.5, 6, 7), extend=TRUE) aeq(sfit$pstate, rbind(c(1,0,0), bfit$P[c(1,3,5,5),])) aeq(sfit$n.risk[,1], c(8,8, 2, 1, 0)) aeq(sfit$n.event, matrix(c(0,0,0,0,0, 0,0,1,0,0, 0,0,2,1,0), ncol=3)) # # For this we need the competing risks MGUS data set, first # event # tdata <- mgus1[mgus1$enum==1,] # Ensure the old-style call using "etype" works (backwards compatability) fit1 <- survfit(Surv(stop, status) ~ 1, etype=event, tdata) fit1b <-survfit(Surv(stop, event) ~1, tdata) indx <- match("call", names(fit1)) all.equal(unclass(fit1)[-indx], unclass(fit1b)[-indx]) # Now get the overall survival, and the hazard for progression fit2 <- survfit(Surv(stop, status) ~1, tdata) #overall to "first bad thing" fit3 <- survfit(Surv(stop, status*(event=='pcm')) ~1, tdata, type='fleming') fit4 <- survfit(Surv(stop, status*(event=='death')) ~1, tdata, type='fleming') aeq(fit1$n.risk[,1], fit2$n.risk) aeq(rowSums(fit1$n.event), fit2$n.event) # Classic CI formula # integral [hazard(t) S(t-0) dt], where S= "survival to first event" haz1 <- diff(c(0, -log(fit3$surv))) #Aalen hazard estimate for progression haz2 <- diff(c(0, -log(fit4$surv))) #Aalen estimate for death tsurv <- c(1, fit2$surv[-length(fit2$surv)]) #lagged survival ci1 <- cumsum(haz1 *tsurv) ci2 <- cumsum(haz2 *tsurv) aeq(cbind(ci1, ci2), fit1$pstate[,2:3]) # # Now, make sure that it works for subgroups # fit1 <- survfit(Surv(stop, event) ~ sex, tdata) fit2 <- survfit(Surv(stop, event) ~ 1, tdata, subset=(sex=='female')) fit3 <- survfit(Surv(stop, event) ~ 1, tdata, subset=(sex=='male')) aeq(fit2$pstate, fit1$pstate[1:fit1$strata[1],]) aeq(fit2$std, fit1$std[1:fit1$strata[1],]) aeq(fit3$pstate, fit1$pstate[-(1:fit1$strata[1]),]) # A second test of cumulative incidence # compare results to Bob Gray's functions # The file gray1 is the result of # library(cmprsk) # tstat <- ifelse(tdata$status==0, 0, 1+ (tdata$event=='death')) # gray1 <- cuminc(tdata$stop, tstat) load("gray1.rda") fit2 <- survfit(Surv(stop, event) ~ 1, tdata) if (FALSE) { # lines of the two graphs should overlay plot(gray1[[1]]$time, gray1[[1]]$est, type='l', ylim=range(c(gray1[[1]]$est, gray1[[2]]$est)), xlab="Time") lines(gray1[[2]]$time, gray1[[2]]$est, lty=2) matlines(fit2$time, fit2$pstate, col=2, lty=1:2, type='s') } # To formally match these is a bit of a nuisance. # The cuminc function returns a full step function, and survfit only # the bottoms of the steps. temp1 <- tapply(gray1[[1]]$est, gray1[[1]]$time, max)[-1] #toss time 0 indx1 <- match(names(temp1), fit2$time) aeq(temp1, fit2$pstate[indx1,2])