library(dplyr, warn.conflicts = FALSE) library(survival) library(geepack) test_that("tsegest: logistic g-estimation", { sim1 <- tsegestsim( n = 500, allocation1 = 2, allocation2 = 1, pbprog = 0.5, trtlghr = -0.5, bprogsl = 0.3, shape1 = 1.8, scale1 = 0.000025, shape2 = 1.7, scale2 = 0.000015, pmix = 0.5, admin = 5000, pcatnotrtbprog = 0.5, pcattrtbprog = 0.25, pcatnotrt = 0.2, pcattrt = 0.1, catmult = 0.5, tdxo = 1, ppoor = 0.1, pgood = 0.04, ppoormet = 0.4, pgoodmet = 0.2, xomult = 1.4188308, milestone = 546, swtrt_control_only = TRUE, outputRawDataset = 1, seed = 2000) fit1 <- tsegest( data = sim1$paneldata, id = "id", tstart = "tstart", tstop = "tstop", event = "died", treat = "trtrand", censor_time = "censor_time", pd = "progressed", pd_time = "timePFSobs", swtrt = "xo", swtrt_time = "xotime", swtrt_time_upper = "xotime_upper", base_cov = "bprog", conf_cov = "bprog*catlag", low_psi = -3, hi_psi = 3, strata_main_effect_only = TRUE, recensor = TRUE, admin_recensor_only = FALSE, swtrt_control_only = TRUE, alpha = 0.05, ties = "efron", tol = 1.0e-6, boot = FALSE) # last observation within each subject data1 <- sim1$paneldata %>% group_by(id) %>% slice(n()) %>% mutate(os = died, ostime = tstop) %>% select(id, trtrand, progressed, timePFSobs, os, ostime, censor_time, xo, xotime, bprog) # post progression data up to switching data2 <- sim1$paneldata %>% filter(trtrand == 0 & progressed == 1 & tstop >= timePFSobs & ((xo == 0 & tstop <= xotime_upper) | (xo == 1 & tstop <= xotime))) # re-baseline data3a <- data2 %>% left_join(data1 %>% select(id, os, ostime), by = "id") %>% group_by(id) %>% slice(1) %>% mutate(ostime = ostime - timePFSobs, censor_time = censor_time - timePFSobs, xotime = xotime - timePFSobs) %>% ungroup() # setup treatment switching indicators data3b <- data2 %>% left_join(data1 %>% select(id, os, ostime), by = "id") %>% mutate(y = ifelse(xo == 1 & tstop == xotime, 1, 0)) g <- function(psi, target) { data4a <- data3a %>% mutate(u = ifelse(xo==1, xotime + (ostime-xotime)*exp(psi), ostime), c = pmin(censor_time, censor_time*exp(psi)), time_ts = pmin(u, c), event_ts = os*(u <= c)) fit_cox <- coxph(Surv(time_ts, event_ts) ~ 1, data = data4a) resid <- residuals(fit_cox) data4b <- data3b %>% left_join(data4a %>% mutate(resid = resid) %>% select(id, resid), by = "id") fit_lgs <- geeglm(y ~ resid + bprog*catlag, family = binomial, data = data4b, id = id) z_lgs <- coefficients(fit_lgs)/sqrt(diag(vcov(fit_lgs))) as.numeric(z_lgs["resid"]) - target } psi <- uniroot(g, c(-3, 3), 0, tol = 1.0e-6)$root data4 <- data1 %>% filter(trtrand == 0) %>% mutate(u = ifelse(xo==1, xotime + (ostime-xotime)*exp(psi), ostime), c = pmin(censor_time, censor_time*exp(psi)), time_ts = pmin(u, c), event_ts = os*(u <= c)) %>% select(id, time_ts, event_ts, trtrand, bprog) %>% bind_rows(data1 %>% filter(trtrand == 1) %>% mutate(time_ts = ostime, event_ts = os) %>% select(id, time_ts, event_ts, trtrand, bprog)) fit <- coxph(Surv(time_ts, event_ts) ~ trtrand + bprog, data = data4, ties = "efron") hr1 <- exp(as.numeric(c(fit$coefficients[1], confint(fit)[1,]))) expect_equal(hr1, c(fit1$hr, fit1$hr_CI)) })