t_on = 56, t_off = 84,

fluid = 3.0, k_rate = 40, thi = 100, dex = 150,

end = T_END, delta = 0.25) {

base_par <- par

p1 <- mod %>% param(base_par) %>%

param(IV_FLUID = 0, IV_K_RATE = 0, IV_THI = 0, IV_DEX_G = 0)

seg1 <- p1 %>% mrgsim(events = if (is.null(ev)) NULL else ev,

start = T_START, end = t_on, delta = delta)

y1 <- unlist(tail(as.data.frame(seg1)[, names(init(mod))], 1))

p2 <- mod %>% param(base_par) %>%

param(IV_FLUID = fluid, IV_K_RATE = k_rate, IV_THI = thi, IV_DEX_G = dex) %>%

init(as.list(y1))

seg2 <- p2 %>% mrgsim(events = if (is.null(ev)) NULL else ev,

start = t_on, end = t_off, delta = delta)

y2 <- unlist(tail(as.data.frame(seg2)[, names(init(mod))], 1))

p3 <- mod %>% param(base_par) %>%

param(IV_FLUID = 0, IV_K_RATE = 0, IV_THI = 0, IV_DEX_G = 0) %>%

init(as.list(y2))

seg3 <- p3 %>% mrgsim(events = if (is.null(ev)) NULL else ev,

start = t_off, end = end, delta = delta)

bind_rows(as.data.frame(seg1), as.data.frame(seg2), as.data.frame(seg3)) %>%

distinct(time, .keep_all = TRUE) %>% arrange(time)

m <- mod

if (length(sc$par)) m <- m %>% param(sc$par)

out <- m %>% mrgsim(events = sc$ev, start = T_START, end = end, delta = delta)

as.data.frame(out) %>% mutate(scenario = sc$name)

g <- function(nm, t) {

s <- sims[sims$scenario == nm, ]

s$PUQE[which.min(abs(s$time - t))]

}

(g(arm, TR + day) - g(arm, TR)) - (g(ref, TR + day) - g(ref, TR))

1.08, 1.18, 1.30),

days = c(2, 4, 7, 14)) {

res <- lapply(sens, function(s) {

a <- run_scenario(list(name = "arm", par = list(SENS = s), ev = arm_ev),

end = TR + 22)

p <- run_scenario(list(name = "pbo", par = list(SENS = s), ev = NULL),

end = TR + 22)

gp <- function(df, t) df$PUQE[which.min(abs(df$time - t))]

sapply(days, function(d)

(gp(a, TR + d) - gp(a, TR)) - (gp(p, TR + d) - gp(p, TR)))

})

setNames(rowMeans(do.call(cbind, res)), paste0("day", days))