library(survival) aeq <- function(x, y, ...) all.equal(as.vector(x), as.vector(y), ...) # Check that a multi-state model, correctly set up, gives the same # solution as a time-dependent covariate. # This is a stronger test than mstrata: there the covariate which was mapped # into a state was constant, here it is time-dependent. # # First build the TD data set from pbcseq, with a categorical bilirubin pbc1 <- pbcseq pbc1$bili4 <- cut(pbc1$bili, c(0,1, 2,4, 100), c("normal", "1-2x", "2-4x", ">4")) ptemp <- subset(pbc1, !duplicated(id)) # first row of each pbc2 <- tmerge(ptemp[, c("id", "age", "sex")], ptemp, id, death= event(futime, status==2)) pbc2 <- tmerge(pbc2, pbc1, id=id, bili = tdc(day, bili), bili4 = tdc(day, bili4), bstat = event(day, as.numeric(bili4))) btemp <- with(pbc2, ifelse(death, 5, bstat)) # a row with the same starting and ending bili4 level is not an event b2 <- ifelse(((as.numeric(pbc2$bili4)) == btemp), 0, btemp) pbc2$bstat <- factor(b2, 0:5, c("censor", "normal", "1-2x", "2-4x", ">4", "death")) check1 <- survcheck(Surv(tstart, tstop, bstat) ~ 1, istate= bili4, id = id, data=pbc2) check1$transitions all.equal(as.character(pbc2$bili4), as.character(check1$istate)) # the above verifies that I created the data set correctly # Standard coxph fit with a time dependent bili4 variable. fit1 <- coxph(Surv(tstart, tstop, death) ~ age + bili4, pbc2) # An additive multi-state fit, where bili4 is a state # The three forms below should all give identical models fit2 <- coxph(list(Surv(tstart, tstop, bstat) ~ 1, c(1:4):5 ~ age / common + shared), id= id, istate=bili4, data=pbc2) fit2b <- coxph(list(Surv(tstart, tstop, bstat) ~ 1, 1:5 + 2:5 + 3:5 + 4:5 ~ age / common + shared), id= id, istate=bili4, data=pbc2) fit2c <- coxph(list(Surv(tstart, tstop, bstat) ~ 1, 0:5 ~ age / common + shared), id= id, istate=bili4, data=pbc2) # Make sure the names are correct and the coefficients match aeq(coef(fit1), coef(fit2)) aeq(names(coef(fit2)), c("age", "ph(2:5/1:5)", "ph(3:5/1:5)", "ph(4:5/1:5)")) all.equal(coef(fit2), coef(fit2b)) all.equal(coef(fit2), coef(fit2c)) # Now a model with a separate age effect for each bilirubin group fit3 <- coxph(Surv(tstart, tstop, death) ~ age*bili4, pbc2) fit3b <- coxph(Surv(tstart, tstop, death) ~ bili4/age, pbc2) fit4 <- coxph(list(Surv(tstart, tstop, bstat) ~ 1, c(1:4):5 ~ age / shared), id= id, istate=bili4, data=pbc2) all.equal(fit3$loglik, fit3b$loglik) all.equal(fit3$loglik, fit4$loglik) # The coefficients are quite different due to different codings for dummy vars # Unpack the interaction, first 4 coefs will be the age effect within each # bilirubin group temp <- c(coef(fit3)[1] + c(0, coef(fit3)[5:7]), coef(fit3)[2:4]) names(temp)[1:4] <- c("age1", "age2", "age3", "age4") aeq(temp, coef(fit3b)[c(4:7, 1:3)]) aeq(temp, coef(fit4)) # Third, a model with separate baseline hazards for each bili group fit5 <- coxph(Surv(tstart, tstop, death) ~ strata(bili4)/age, pbc2, cluster=id) fit6 <- coxph(list(Surv(tstart, tstop, bstat) ~ 1, 0:5 ~ age), id=id, istate=bili4, pbc2) aeq(coef(fit5), coef(fit6)) aeq(fit5$var, fit6$var) aeq(fit5$naive.var, fit6$naive.var)