# # A tiny multi-state example # library(survival) aeq <- function(x,y) all.equal(as.vector(x), as.vector(y)) mtest <- data.frame(id= c(1, 1, 1, 2, 3, 4, 4, 4, 5, 5), t1= c(0, 4, 9, 0, 2, 0, 2, 8, 1, 3), t2= c(4, 9, 10, 5, 9, 2, 8, 9, 3, 11), st= c(1, 2, 1, 2, 3, 1, 3, 0, 2, 0)) mtest$state <- factor(mtest$st, 0:3, c("censor", "a", "b", "c")) if (FALSE) { # this graph is very useful when debugging temp <- survcheck(Surv(t1, t2, state) ~1, mtest, id=id) plot(c(0,11), c(1,5.1), type='n', xlab="Time", ylab= "Subject") with(mtest, segments(t1+.1, id, t2, id, col=as.numeric(temp$istate))) event <- subset(mtest, state!='censor') text(event$t2, event$id+.2, as.character(event$state)) } mtest <- mtest[c(1,3,2,4,5,7,6,10, 9, 8),] #not in time order mfit <- survfit(Surv(t1, t2, state) ~ 1, mtest, id=id, time0=FALSE) # True results # #time state probabilities # entry a b c entry a b c # #0 124 1 0 0 0 #1+ 1245 #2+ 1235 4 3/4 1/4 0 0 4 -> a, add 3 #3+ 123 4 5 9/16 1/4 3/16 0 5 -> b #4+ 23 14 5 6/16 7/16 3/16 0 1 -> a #5+ 3 14 5 3/16 7/16 6/16 0 2 -> b, exits #8+ 3 1 5 4 3/16 7/32 6/16 7/32 4 -> c #9+ 15 0 0 19/32 13/32 1->b, 3->c & exit # 10+ 1 5 19/64 19/64 13/32 1->a aeq(mfit$n.risk, matrix(c(4,4,3,2,1,1,0,0, 0,1,1,2,2,1,0,0, 0,0,1,1,1,1,2,1, 0,0,0,0,0,1,0,0), ncol=4)) aeq(mfit$pstate, matrix(c(24, 18, 12, 6, 6, 0, 0, 0, 8, 8, 14, 14, 7, 0, 9.5, 9.5, 0, 6, 6, 12, 12,19,9.5, 9.5, 0, 0, 0, 0, 7, 13, 13, 13)/32, ncol=4)) aeq(mfit$n.transition, matrix(c(1,0,1,0,0,0,0,0, 0,0,0,0,0,0,1,0, 0,1,0,1,0,0,0,0, 0,0,0,0,0,1,0,0, 0,0,0,0,0,1,0,0, 0,0,0,0,1,0,0,0), ncol=6)) all.equal(mfit$time, c(2, 3, 4, 5, 8, 9, 10, 11)) # Somewhat more complex. # Scramble the input data # Not everyone starts at the same time or in the same state # Case weights # tdata <- data.frame(id= c(1, 1, 1, 2, 3, 4, 4, 4, 5, 5), t1= c(0, 4, 9, 1, 2, 0, 2, 8, 1, 3), t2= c(4, 9, 10, 5, 9, 2, 8, 9, 3, 11), st= c(1, 2, 1, 2, 3, 1, 3, 0, 3, 0), i0= c(4, 1, 2, 1, 4, 4, 1, 3, 2, 3), wt= 1:10) tdata$st <- factor(tdata$st, c(0:3), labels=c("censor", "a", "b", "c")) tdata$i0 <- factor(tdata$i0, c(4, 1:3), labels=c("entry", "a", "b", "c")) if (FALSE) { #useful picture temp <- survcheck(Surv(t1, t2, st) ~1, tdata, id=id, istate=i0) plot(c(0,11), c(1,5.5), type='n', xlab="Time", ylab= "Subject") with(tdata, segments(t1+.1, id, t2, id, col=as.numeric(temp$istate))) with(subset(tdata, st!= "censor"), text(t2, id+.15, as.character(st))) with(tdata, text((t1+t2)/2, id+.25, wt)) with(subset(tdata, !duplicated(id)), text(t1, id+.15, as.character(i0))) #abline(v=c(2:5, 8:11), lty=3, col='gray') } tfun <- function(data=tdata) { reorder <- c(10, 9, 1, 2, 5, 4, 3, 7, 8, 6) new <- data[reorder,] new } # These weight vectors are in the order of tdata # w[9] is the weight for subject 5 at time 1.5, for instance # p0 is defined as all those at risk just before the first event, which in # this data set is entry:a at time 2 for id=4; id 1,2,4,5 at risk # When the functions below were written, the entry state was listed last. # Currently the entry state is first, so "[swap]" was added to the aj routines # rather than rearranging the formulas swap <- c(4,1,2,3) p0 <- function(w) c( w[1]+ w[6], w[4], w[9], 0)/ (w[1]+ w[4] + w[6] + w[9]) # aj2 = Aalen-Johansen H matrix at time 2, etc. aj2 <- function(w) { #subject 4 moves from entry to 'a' rbind(c(1, 0, 0, 0), c(0, 1, 0, 0), c(0, 0, 1, 0), c(w[6], 0, 0, w[1])/(w[1] + w[6]))[swap, swap] } aj3 <- function(w) rbind(c(1, 0, 0, 0), c(0, 0, 1, 0), # 5 moves from b to c c(0, 0, 1, 0), c(0, 0, 0, 1))[swap,swap] aj4 <- function(w) { # subject 1 moves from entry to a rbind(c(1, 0, 0, 0), c(0, 1, 0, 0), c(0, 0, 1, 0), c(w[1], 0, 0, w[5])/(w[1] + w[5])) [swap, swap] } aj5 <- function(w) { # subject 2 from a to b rbind(c(w[2]+w[7], w[4], 0, 0)/(w[2]+ w[4] + w[7]), c(0, 1, 0, 0), c(0, 0, 1, 0), c(0, 0, 0, 1))[swap, swap] } aj8 <- function(w) rbind(c(w[2], 0, w[7], 0)/(w[2]+ w[7]), # 4 a to c c(0, 1, 0, 0), c(0, 0, 1, 0), c(0, 0, 0, 1))[swap, swap] aj9 <- function(w) rbind(c(0, 1, 0, 0), # 1 a to b c(0, 1, 0, 0), c(0, 0, 1, 0), c(0, 0, 1 ,0)) [swap, swap] # 3 entry to c aj10 <- function(w)rbind(c(1, 0, 0, 0), c(1, 0, 0, 0), #1 b to a c(0, 0, 1, 0), c(0, 0, 0, 1))[swap, swap] #time state # a b c entry # #1 2 5 14 initial distribution #2 24 5 1 4 -> a, add 3 #3 24 5 13 5 from b to c #4 124 5 3 1 -> a #5 14 5 3 2 -> b, exits #8 1 45 3 4 -> c #9 1 45 1->b, 3->c & exit #10 1 45 1->a # P is a product of matrices dopstate <- function(w) { p1 <- p0(w) p2 <- p1 %*% aj2(w) p3 <- p2 %*% aj3(w) p4 <- p3 %*% aj4(w) p5 <- p4 %*% aj5(w) p8 <- p5 %*% aj8(w) p9 <- p8 %*% aj9(w) p10<- p9 %*% aj10(w) rbind(p2, p3, p4, p5, p8, p9, p10, p10) } # Check the pstate estimate w1 <- rep(1,10) mtest2 <- tfun(tdata) # scrambled order mfit2 <- survfit(Surv(t1, t2, st) ~ 1, tdata, id=id, istate=i0, time0=FALSE) # ordered aeq(mfit2$pstate, dopstate(w1)) aeq(mfit2$p0, p0(w1)) mfit2b <- survfit(Surv(t1, t2, st) ~ 1, mtest2, id=id, istate=i0, time0=FALSE) aeq(mfit2b$pstate, dopstate(w1)) aeq(mfit2b$p0, p0(w1)) mfit2b$call <- mfit2$call <- NULL all.equal(mfit2b, mfit2) aeq(mfit2$transitions, c(2,0,1,0, 0,2,0,0, 1,1,1,0, 0,0,0,2)) # Now the harder one, where subjects change weights mfit3 <- survfit(Surv(t1, t2, st) ~ 1, tdata, id=id, istate=i0, weights=wt, influence=TRUE, time0=FALSE) aeq(mfit3$p0, p0(1:10)) aeq(mfit3$pstate, dopstate(1:10)) # The derivative of a matrix product AB is (dA)B + A(dB) where dA is the # elementwise derivative of A and etc for B. # dp0 creates the derivatives of p0 with respect to each subject, a 5 by 4 # matrix # All the functions below are hand coded for a weight vector that is in # exactly the same order as the rows of mtest. # Since p0 = (w[1]+ w[6], w[4], w[9], 0)/ (w[1]+ w[4] + w[6] + w[9]) # and subject id is 1,1,1, 2, 3, 4,4,4, 5,5 # we get the derivative below # dp0 <- function(w) { # influence just before the first event p <- p0(w) w0 <- w[c(1,4,6,9)] # the 4 obs at the start, subjects 1, 2, 4, 5 rbind(c(1,0, 0, 0) - p, # subject 1 affects p[entry] c(0,1, 0, 0) - p, # subject 2 affects p[a] 0, # subject 3 affects none c(1, 0, 0, 0) - p, # subject 4 affect p[entry] c(0, 0, 1, 0) - p)/ # subject 5 affects p[b] sum(w0) } dp2 <- function(w) { h2 <- aj2(w) # H matrix at time 2 part1 <- dp0(w) %*% h2 # 1 and 4 in entry, obs 4 moves from entry to a mult <- p0(w)[1]/(w[1] + w[6]) #p(t-) / weights in state part2 <- rbind((c(1,0,0,0)- h2[1,]) * mult, 0, 0, (c(0,1,0,0) - h2[1,]) * mult, 0) part1 + part2 } dp3 <- function(w) { dp2(w) %*% aj3(w) } dp4 <- function(w) { h4 <- aj4(w) # H matrix at time 4 part1 <- dp3(w) %*% h4 # subjects 1 and 3 in state entry (obs 1 and 5) 1 moves to a mult <- dopstate(w)[2,1]/ (w[1] + w[5]) # p_1(time 4-0) / wt part2 <- rbind((c(0,1,0,0)- h4[1,]) * mult, 0, (c(1,0,0,0)- h4[1,]) * mult, 0, 0) part1 + part2 } dp5 <- function(w) { h5 <- aj5(w) # H matrix at time 5 part1 <- dp4(w) %*% h5 # subjects 124 in state a (obs 2,4,7), 2 goes to b mult <- dopstate(w)[3,2]/ (w[2] + w[4] + w[7]) part2 <- rbind((c(0,1,0,0)- h5[2,]) * mult, (c(0,0,1,0)- h5[2,]) * mult, 0, (c(0,1,0,0)- h5[2,]) * mult, 0) part1 + part2 } dp8 <- function(w) { h8 <- aj8(w) # H matrix at time 8 part1 <- dp5(w) %*% h8 # subjects 14 in state a (obs 2 &7), 4 goes to c mult <- dopstate(w)[4, 2]/ (w[2] + w[7]) part2 <- rbind((c(0,1,0,0)- h8[2,]) * mult, 0, 0, (c(0,0,0,1)- h8[2,]) * mult, 0) part1 + part2 } dp9 <- function(w) dp8(w) %*% aj9(w) dp10<- function(w) dp9(w) %*% aj10(w) # # Feb 4 2024: discovered that the variance computation above is incorrect. # Let U = influence for phat, with one row per observation in the data # The weighted per subject influence is Z(t)= BDU(t) where # B= rbind(c(1,1,1,0,0,0,0,0,0,0), # c(0,0,0,1,0,0,0,0,0,0), # c(0,0,0,0,1,0,0,0,0,0), # c(0,0,0,0,0,1,1,1,0,0), # c(0,0,0,0,0,0,0,0,1,1)) # and D= diag(1:10) # which can be summarized as "weight each row, then add over subjects". # The variance at time t is the column sums of Z^2(t) (elementwise squares) # # The code above for dp0, dp2, etc returns BU, which matches the computation of # the influence in survfitci.c. If the weight for a given subject is constant # over time, then BDU= WBU where W is the diagonal matrix of per-subject # weights: survfitci.c implicitly made this assumption, and was correct # in this case. It returned U as the influence, which matches dp0 etc. # # survfitci.c has been replaced by survfitaj.c, which uses the careful # derivations in the methods vignette, and returns BDU. # The checks below have been changed to a case with constant weights per # subject. R code to test for general weights is in mstate2.R # w1 <- tdata$id mfit4 <- survfit(Surv(t1, t2, st) ~1, tdata, id=id, weights=id, istate=i0, influence=TRUE, time0= FALSE) aeq(mfit4$influence[,1,], 1:5*dp2(w1)) #time 2 aeq(mfit4$influence[,2,], 1:5*dp3(w1)) aeq(mfit4$influence[,3,], 1:5*dp4(w1)) aeq(mfit4$influence[,4,], 1:5*dp5(w1)) aeq(mfit4$influence[,5,], 1:5*dp8(w1)) # time 8 aeq(mfit4$influence[,6,], 1:5* dp9(w1)) aeq(mfit4$influence[,7,], 1:5* dp10(w1)) aeq(mfit4$influence[,8,], 1:5* dp10(w1)) # no changes at time 11 ssq <- function(x) sqrt(sum(x^2)) temp2 <- apply(mfit4$influence.pstate, 2:3, ssq) aeq(temp2, mfit4$std.err) if (FALSE) { # old test, survfitci returned the time 0 influence as well w1 <- 1:10 aeq(mfit3$influence[,1,], dp0(w1)) aeq(mfit3$influence[,2,], dp2(w1)) aeq(mfit3$influence[,3,], dp3(w1)) aeq(mfit3$influence[,4,], dp4(w1)) aeq(mfit3$influence[,5,], dp5(w1)) aeq(mfit3$influence[,6,], dp8(w1)) aeq(mfit3$influence[,7,], dp9(w1)) aeq(mfit3$influence[,8,], dp10(w1)) aeq(mfit3$influence[,9,], dp10(w1)) # no changes at time 11 } # end of if (FALSE) # The cumulative hazard at each time point is remapped from a matrix # into a vector (in survfit) # First check out the names nstate <- length(mfit4$states) temp <- matrix(0, nstate, nstate) indx1 <- match(rownames(mfit4$transitions), mfit4$states) indx2 <- match(colnames(mfit4$transitions), mfit4$states, nomatch=0) temp[indx1, indx2] <- mfit4$transitions[, indx2>0] # temp is an nstate by nstate version of the transitions matrix from <- row(temp)[temp>0] to <- col(temp)[temp>0] all.equal(colnames(mfit4$cumhaz), paste(from, to, sep='.')) # check the cumulative hazard temp <- mfit4$n.risk[,from] hazard <- mfit4$n.transition/ifelse(temp==0, 1, temp) aeq(apply(hazard, 2, cumsum), mfit4$cumhaz)