################################################################################
# FIGURE    : f_vitals_change  (Multiple Ascending Dose)
# TITLE     : Mean (+/-SE) Change from Baseline in Vital Signs by Dosing Day/Visit
# POPULATION: Safety Population (SAFFL == "Y"), post-baseline
# INPUT     : ADVS (PARAMCD in SYSBP, DIABP, PULSE, TEMP, RESP)
# NOTE      : PSEUDOCODE. Mean change from baseline (CHG) with +/-1 SE error bars
#             over scheduled post-baseline visits spanning the repeat-dosing
#             period, one line per dose cohort, faceted by parameter. MAD =
#             parallel dose cohorts; between-cohort comparison, colour =
#             dv$trtvar (TRT01A = dose level; placebo pooled). The multi-day
#             visit axis surfaces any drift in vitals over repeated dosing.
################################################################################
source("../00_setup_helpers.R")
env <- setup(study = "CP-101", adam = "/data/adam", out = "/data/tfl")
dv  <- design_vars("MAD")

## post-baseline analysis records (CHG defined); scheduled timepoints only
vs <- adam$advs %>%
  filter(SAFFL == "Y", ANL01FL == "Y", !is.na(CHG),
         PARAMCD %in% c("SYSBP","DIABP","PULSE","TEMP","RESP")) %>%
  mutate(trt    = .data[[dv$trtvar]],            # dose-level cohort (placebo pooled)
         PARAM  = factor(PARAM),
         AVISIT = factor(AVISIT, levels = unique(AVISIT[order(AVISITN)])))

## mean +/- SE of change by cohort x param x visit
sumdat <- vs %>%
  group_by(PARAM, AVISIT, AVISITN, trt) %>%
  summarise(n    = sum(!is.na(CHG)),
            mean = mean(CHG, na.rm = TRUE),
            se   = sd(CHG, na.rm = TRUE) / sqrt(n),
            .groups = "drop") %>%
  mutate(lo = mean - se, hi = mean + se)

ttl <- tfl_titles(num = "14.3.7.2", type = "Figure",
   text = "Mean (+/-SE) Change from Baseline in Vital Signs by Dosing Day/Visit",
   pop  = "Safety Population",
   foot = paste("Points = dose-cohort mean change from baseline; error bars = +/-1 SE.",
                "Baseline = last value prior to first dose (Day 1). Dashed line = no",
                "change. Visit axis spans the repeat-dosing period (placebo pooled)."))

pd <- position_dodge(width = 0.3)
p <- ggplot(sumdat, aes(x = AVISIT, y = mean, colour = trt, group = trt)) +
  geom_hline(yintercept = 0, linetype = "dashed") +
  geom_errorbar(aes(ymin = lo, ymax = hi), width = 0.2, position = pd) +
  geom_line(position = pd) +
  geom_point(size = 2, position = pd) +
  facet_wrap(~ PARAM, scales = "free_y") +
  labs(x = "Dosing day / visit", y = "Mean change from baseline (+/-SE)",
       colour = "Dose cohort", title = ttl$titles[3], caption = ttl$footnotes[1]) +
  theme_bw() +
  theme(legend.position = "bottom",
        axis.text.x = element_text(angle = 45, hjust = 1))
# ggsave(file.path(env$out, "f_vitals_change.png"), p, width = 10, height = 7, dpi = 300)
print(p)