# # Check out the survfit routine on the simple AML data set. # The leverage validation makes use of the fact that when all # weights are 1 and there is 1 obs per subject, the IJ variance is # equal to the Greenwood. # There are 8 choices in the C code: Nelson-Aalen or Fleming-Harrington # estimate of cumulative hazard, KM or exp(cumhaz) estimate of survival, # regular or robust variance. This tries to exercise them all. library(survival) aeq <- function(x, y, ...) all.equal(as.vector(x), as.vector(y), ...) set.seed(1953) # used only to reorder the data adata <- aml adata$id <- sample(LETTERS, nrow(aml)) # labels are not in time or data order adata <- adata[sample(1:nrow(aml), nrow(aml)),] # data is unordered adata$wt <- sample((2:30)/10, nrow(aml)) # non-integer weights group <- rep("", nrow(adata)) temp <- table(adata$x) group[adata$x == "Maintained"] <- rep(letters[4:1], length=temp[1]) group[adata$x != "Maintained"] <- rep(letters[4:7], length=temp[2]) adata$group <- group adata2 <- survSplit(Surv(time, status) ~ ., adata, cut=c(10, 20, 40)) byhand <- function(time, status, weights, id) { # for a single curve utime <- sort(unique(time)) ntime <- length(utime) n <- length(time) if (missing(weights)) weights <- rep(1.0, n) if (missing(id)) id <- seq_along(time) uid <- unique(id) nid <- length(uid) id <- match(id, uid) # change it to 1:nid n.risk <- n.event <- surv <- cumhaz <- double(ntime) KM <- 1; nelson <-0; kvar <- 0; hvar<-0; U <- matrix(0, nid, 2) # the two robust influence estimates V <- matrix(0, ntime, 4) # variances usave <- array(0., dim=c(nid, 2, ntime)) estimate <- matrix(0, ntime, 2) for (i in 1:ntime) { atrisk <- (time >= utime[i]) n.risk[i] <- sum(weights[atrisk]) deaths <- (time==utime[i] & status==1) n.event[i] <- sum(weights[deaths]) haz <- n.event[i]/n.risk[i] dhaz <- (ifelse(deaths,1,0) - ifelse(atrisk, haz, 0))/n.risk[i] U[,1] <- U[,1]*(1-haz) - KM*tapply(dhaz*weights, id, sum) V[i,1] <- sum(U[,1]^2) U[,2] <- U[,2] + tapply(dhaz* weights, id, sum) #result in 'id' order V[i,2] <- sum(U[,2]^2) usave[,,i] <- U if (n.event[i] >0 ) { KM <- KM*(1-haz) nelson <- nelson + haz kvar <- kvar + n.event[i]/(n.risk[i] * (n.risk[i] - n.event[i])) hvar <- hvar + n.event[i]/(n.risk[i]^2) } V[i,3] <- kvar # var of log(S) V[i,4] <- hvar estimate[i,] <- c(KM, nelson) } dimnames(usave) <- list(uid, c("KM", "chaz"), utime) dimnames(V) <- list(time=utime, c("KM", "chaz", "Greenwood", "Aalen")) list(time=utime, n.risk=n.risk, n.event=n.event, estimate=estimate, std = sqrt(V), influence=usave) } # the byhand function can only handle one group at a time true1a <- with(subset(adata, x=="Maintained"), byhand(time, status, id=id)) true1b <- with(subset(adata, x!="Maintained"), byhand(time, status, id=id)) # The Greenwood and IJ estimates agree, except for a last point with # variance of zero. These next few lines verify the byhand() function aeq(true1a$std[,1], true1a$estimate[,1]*true1a$std[,3]) aeq(true1b$std[1:9,1], true1b$estimate[1:9,1]*true1b$std[1:9,3]) aeq(true1b$std[10,1], 0) # variance of zero for jackknife !is.finite(true1b$std[10,3]) # Inf for Greenwood temp <- with(subset(adata, x=="Maintained"), byhand(time, status, id=id, weights=rep(3,11))) aeq(temp$std[,1:2], true1a$std[,1:2]) # IJ estimates should be invariant # fit1 uses the standard formulas: NA hazard, KM survival fit1 <- survfit(Surv(time, status) ~ x, data=adata) aeq(fit1$surv, c(true1a$estimate[,1], true1b$estimate[,1])) aeq(fit1$cumhaz, c(true1a$estimate[,2], true1b$estimate[,2])) aeq(fit1$std.err, c(true1a$std[,3], true1b$std[,3])) aeq(fit1$std.chaz, c(true1a$std[,4], true1b$std[,4])) aeq(fit1$n.risk, c(true1a$n.risk, true1b$n.risk)) aeq(fit1$n.event, c(true1a$n.event, true1b$n.event)) fit1$logse # logse should be TRUE fit1b <- survfit(Surv(tstart, time, status) ~x, data=adata2, id=id) eqsurv <- function(x, y) { temp <- c("n.risk", "n.event", "n.censor", "surv", "std.err", "cumhaz", "std.chaz", "strata", "logse") if (!is.null(x$influence.surv)) temp <- c(temp, "influence.surv") if (!is.null(x$influence.chaz)) temp <- c(temp, "influence.chaz") # need unclass to avoid [.survfit all.equal(unclass(x)[temp], unclass(y)[temp]) } eqsurv(fit1, fit1b) fit1c <- survfit(Surv(tstart, time, status) ~x, data=adata2, id=id, entry=TRUE) aeq(fit1c$time[fit1c$time >0], fit1$time) aeq(fit1c$n.enter[fit1c$time==0], c(11, 12)) all(fit1c$n.enter[fit1c$time >0] ==0) # fit2 will use the IJ method fit2 <- survfit(Surv(time, status) ~ x, data=adata, id=id, influence=1) aeq(fit2$surv, c(true1a$estimate[,1], true1b$estimate[,1])) aeq(fit2$cumhaz, c(true1a$estimate[,2], true1b$estimate[,2])) aeq(fit2$std.err, c(true1a$std[,1], true1b$std[,1])) aeq(fit2$std.chaz, c(true1a$std[,2], true1b$std[,2])) aeq(fit2$n.risk, c(true1a$n.risk, true1b$n.risk)) aeq(fit2$n.event, c(true1a$n.event, true1b$n.event)) !fit2$logse # logse should be FALSE fit2b <- survfit(Surv(tstart, time, status) ~ x, data=adata2, id=id, influence=1) eqsurv(fit2, fit2b) fit2c <- survfit(Surv(tstart, time, status) ~ 1, data=adata2, id=id, subset=(x=="Maintained"), influence=1) aeq(fit2$influence.surv[[1]], fit2c$influence.surv) r2 <- resid(fit2c, times= fit2c$time, collapse=TRUE) aeq(r2, fit2c$influence.surv) fit2d <- survfit(Surv(time, factor(status)) ~ x, data=adata, id=id, influence=T) aeq(fit2d$influence[[1]][,,1], r2) r3 <- resid(fit2d, times= fit2c$time, collapse=TRUE) aeq(r3[adata$x =="Maintained",1,], r2) fit2e <- survfit(Surv(time, factor(status)) ~1, adata, id=id, influence=T, subset=(x=="Maintained")) aeq(fit2e$influence, fit2d$influence[[1]]) aeq(fit2e$influence[,,1], r2) # look at the leverage values fit3 <- survfit(Surv(time, status) ~ x, data=adata, id=id, influence=3) aeq(fit3$influence.surv[[1]], true1a$influence[,1,]) aeq(fit3$influence.surv[[2]], true1b$influence[,1,]) aeq(fit3$influence.chaz[[1]], true1a$influence[,2,]) aeq(fit3$influence.chaz[[2]], true1b$influence[,2,]) fit3b <- survfit(Surv(tstart, time, status) ~x, adata2, id=id, influence=3) eqsurv(fit3, fit3b) # compute the influence by brute force tdata <- subset(adata, x != "Maintained") eps <- 1e-8 imat1 <- imat2 <- matrix(0., 12, 10) t1 <- survfit(Surv(time, status) ~x, data=tdata) for (i in 1:12) { wtemp <- rep(1.0, 12) wtemp[i] <- 1 + eps tfit <-survfit(Surv(time, status) ~x, data=tdata, weights=wtemp) imat2[i,] <- (tfit$cumhaz - t1$cumhaz)/eps imat1[i,] <- (tfit$surv - t1$surv)/eps } aeq(imat1, true1b$influence[,1,], tol= sqrt(eps)) aeq(imat2, true1b$influence[,2,], tol= sqrt(eps)) # Repeat using the Nelson-Aalen hazard and exp(NA) for survival fit1 <- survfit(Surv(time, status) ~ x, adata, stype=2) aeq(fit1$surv, exp(-c(true1a$estimate[,2], true1b$estimate[,2]))) aeq(fit1$cumhaz, c(true1a$estimate[,2], true1b$estimate[,2])) aeq(fit1$std.err, c(true1a$std[,4], true1b$std[,4])) aeq(fit1$std.chaz, c(true1a$std[,4], true1b$std[,4])) aeq(fit1$n.risk, c(true1a$n.risk, true1b$n.risk)) fit1b <- survfit(Surv(tstart, time, status) ~x, adata2, stype=2, id=id) eqsurv(fit1, fit1b) # Nelson-Aalen + exp() surv, along with IJ variance fit2 <- survfit(Surv(time, status) ~ x, data=adata, id=id, stype=2, influence=3) aeq(fit2$surv, exp(-c(true1a$estimate[,2], true1b$estimate[,2]))) aeq(fit2$cumhaz, c(true1a$estimate[,2], true1b$estimate[,2])) aeq(fit2$std.err, c(true1a$std[,2], true1b$std[,2])) aeq(fit2$std.chaz, c(true1a$std[,2], true1b$std[,2])) aeq(fit2$n.risk, c(true1a$n.risk, true1b$n.risk)) aeq(fit2$influence.chaz[[1]], true1a$influence[,2,]) aeq(fit2$influence.chaz[[2]], true1b$influence[,2,]) aeq(fit2$influence.surv[[2]], -true1b$influence[,2,]%*% diag(fit2[2]$surv)) fit2b <- survfit(Surv(tstart, time, status) ~x, data=adata2, id=id, stype=2, influence=3) eqsurv(fit2, fit2b) # Cumulative hazard is the same for fit1 and fit2 all.equal(fit2$influence.chaz, fit2b$influence.chaz) # Weighted fits true2a <- with(subset(adata, x=="Maintained"), byhand(time, status, id=id, weights= wt)) true2b <- with(subset(adata, x!="Maintained"), byhand(time, status, id=id, weights=wt)) fit3 <- survfit(Surv(time, status) ~ x, data=adata, id=id, weights=wt, influence=TRUE) aeq(fit3$influence.surv[[1]], true2a$influence[,1,]) aeq(fit3$influence.surv[[2]], true2b$influence[,1,]) aeq(fit3$influence.chaz[[1]], true2a$influence[,2,]) aeq(fit3$influence.chaz[[2]], true2b$influence[,2,]) aeq(fit3$surv, c(true2a$estimate[,1], true2b$estimate[,1])) aeq(fit3$cumhaz, c(true2a$estimate[,2], true2b$estimate[,2])) aeq(fit3$std.err, c(true2a$std[,1], true2b$std[,1])) aeq(fit3$std.chaz, c(true2a$std[,2], true2b$std[,2])) aeq(fit3$n.risk, c(true2a$n.risk, true2b$n.risk)) aeq(fit3$n.event, c(true2a$n.event, true2b$n.event)) fit3b <- survfit(Surv(tstart, time, status) ~x, adata2, id=id, weights=wt, influence=TRUE) eqsurv(fit3, fit3b) # Different survival, same hazard fit3b <- survfit(Surv(time, status) ~ x, data=adata, id=id, weights=wt, influence=2, stype=2) temp <- c("n", "time", "cumhaz", "std.chaz", "influence.chaz", "n.risk", "n.event") aeq(unclass(fit3b)[temp], unclass(fit3)[temp]) # unclass avoids [.survfit aeq(fit3b$surv, exp(-c(true2a$estimate[,2], true2b$estimate[,2]))) aeq(fit3b$std.err, fit3b$std.chaz) aeq(fit3b$logse, FALSE) aeq(fit3b$n.risk, c(true2a$n.risk, true2b$n.risk)) aeq(fit3b$n.event, c(true2a$n.event, true2b$n.event)) # The grouped jackknife fit4 <- survfit(Surv(time, status) ~ x, data=adata, id=id, weights=wt, influence=TRUE, cluster=group) g1 <- adata$group[match(rownames(true2a$influence[,1,]), adata$id)] g2 <- adata$group[match(rownames(true2b$influence[,1,]), adata$id)] aeq(fit4$influence.surv[[1]], rowsum(true2a$influence[,1,], g1, reorder=FALSE)) aeq(fit4$influence.surv[[2]], rowsum(true2b$influence[,1,], g2, reorder=FALSE)) aeq(fit4$influence.chaz[[1]], rowsum(true2a$influence[,2,], g1, reorder=FALSE)) aeq(fit4$influence.chaz[[2]], rowsum(true2b$influence[,2,], g2, reorder=FALSE)) aeq(c(colSums(fit4$influence.surv[[1]]^2), colSums(fit4$influence.surv[[2]]^2)), fit4$std.err^2) aeq(c(colSums(fit4$influence.chaz[[1]]^2), colSums(fit4$influence.chaz[[2]]^2)), fit4$std.chaz^2) # The Fleming-Harrington is a more complex formula. Start with weights of # 1. fit5 <- survfit(Surv(time, status) ~x, adata, ctype=2) nrisk <- c(11,10,8,7, 5,4,2, 12, 11, 10, 9, 8, 6:1) chaz <- c(cumsum(1/nrisk[1:7])[c(1:4,4, 5,6,6,7,7)], cumsum(1/nrisk[8:18])[c(2,4,5,5,6:11)]) aeq(fit5$cumhaz, chaz) aeq(fit5$std.chaz, sqrt(c(cumsum(1/nrisk[1:7]^2)[c(1:4,4, 5,6,6,7,7)], cumsum(1/nrisk[8:18]^2)[c(2,4,5,5,6:11)]))) # We can compute the FH using a fake data set where each tie is spread out # over a set of fake times. # fh <- function(time, status, weights, id) { counts <- table(time, status) utime <- sort(unique(time)) tied <- counts[,2] > 1 if (missing(weights)) weights <- rep(1.0, length(time)) if (missing(id)) id <- 1:length(time) # build the expanded data set delta <- min(diff(utime))/(2*max(counts[,2])) efun <- function(x) { who <- which(time==x & status==1) ntie <- length(who) data.frame(time = rep(x - (1:ntie -1)*delta, each=ntie), id = rep(id[who], ntie), status = rep(1, ntie^2), weight = rep(weights[who]/ntie, ntie), stringsAsFactors=FALSE ) } temp <- do.call(rbind, lapply(utime[tied], efun)) notie <- (status==0 | !(time %in% utime[tied])) bfit <- byhand(time = c(time[notie], temp$time), status = c(status[notie], temp$status), id = c(id[notie], temp$id), weights = c(weights[notie], temp$weight) ) keep <- match(utime, bfit$time) # the real time points # The influence from survfit is in data order, which we have perturbed. # Fix that indx <- match(unique(id), dimnames(bfit$influence)[[1]]) list(time=bfit$time[keep], n.risk=bfit$n.risk[keep - pmax(0, counts[,2]-1)], n.event = bfit$n.event[keep]* counts[,2], estimate=bfit$estimate[keep,], std = bfit$std[keep,], influence=bfit$influence[indx,,keep]) } # Case weights true6a <- with(subset(adata, x=="Maintained"), fh(time, status, wt, id)) true6b <- with(subset(adata, x!="Maintained"), fh(time, status, wt, id)) fit6 <- survfit(Surv(time, status) ~ x, weights=wt, data=adata, stype=2, ctype=2, robust=FALSE) aeq(fit6$cumhaz, c(true6a$estimate[,2], true6b$estimate[,2])) aeq(fit6$surv, exp(-c(true6a$estimate[,2], true6b$estimate[,2]))) aeq(fit6$std.chaz, c(true6a$std[,4], true6b$std[,4])) aeq(fit6$n.risk, c(true6a$n.risk, true6b$n.risk)) aeq(fit6$n.event, c(true6a$n.event, true6b$n.event)) # Robust variance fit7 <- survfit(Surv(time, status) ~ x, weights=wt, data=adata, stype=2,ctype=2, id=id, influence=2, robust=TRUE) aeq(fit7$cumhaz, c(true6a$estimate[,2], true6b$estimate[,2])) aeq(fit7$surv, exp(-c(true6a$estimate[,2], true6b$estimate[,2]))) aeq(fit7$std.chaz, c(true6a$std[,2], true6b$std[,2])) aeq(fit7$n.risk, c(true6a$n.risk, true6b$n.risk)) aeq(fit7$n.event, c(true6a$n.event, true6b$n.event)) aeq(fit7$influence.chaz[[1]], true6a$influence[,2,]) aeq(fit7$influence.chaz[[2]], true6b$influence[,2,]) # compute the influence by brute force tdata <- subset(adata, x != "Maintained") eps <- 1e-8 imat <- matrix(0., 12, 10) t1 <- survfit(Surv(time, status) ~x, data=tdata, ctype=2, weights=wt) for (i in 1:12) { wtemp <- tdata$wt wtemp[i] <- wtemp[i] + eps tfit <-survfit(Surv(time, status) ~x, data=tdata, ctype=2, weights=wtemp) imat[i,] <- tdata$wt[i] * (tfit$cumhaz - t1$cumhaz)/eps } aeq(fit7$influence.chaz[[2]], imat, tol=sqrt(eps)) # # verify that the times and scale arguments work as expected. They # are in the summary and print.survfit functions. # s1 <- summary(fit1, scale=1) s2 <- summary(fit1, scale=2) aeq(s1$time/2, s2$time) #times change aeq(s1$surv, s2$surv) tscale <- rep(c(1,1,1,1, 2,2,2,2,2), each=2) aeq(s1$table, s2$table *tscale) s3 <- summary(fit1, scale=1, times=c(9, 18, 23, 33, 34)) s4 <- summary(fit1, scale=2, times=c(9, 18, 23, 33, 34)) aeq(s3$time, s4$time*2) aeq(s3$surv, s4$surv) print(fit1, rmean='common') print(fit1, rmean='common', scale=2)