################################################################################
# TABLE     : t_ae_sae_death_withdrawal  (Single Ascending Dose)
# TITLE     : Serious Adverse Events, Deaths, and Adverse Events Leading to
#             Study Drug Discontinuation by SOC and Preferred Term, by Dose Level
# POPULATION: Safety Population (SAFFL == "Y")
# INPUT     : ADAE (TRTEMFL == "Y")
# NOTE      : PSEUDOCODE. Three stacked panels (SAEs / Deaths / Discontinuations).
#             Counts = PARTICIPANTS (n_distinct USUBJID), NOT event rows. n (%) per
#             dose level; % denominator = SAFFL N per dose level. SAD: column =
#             dose level (dv$trtvar = TRT01A), ordered low->high (TRT01AN),
#             placebo often pooled. Fatal = AESDTH=="Y"; discontinuation =
#             AEACN=="DRUG WITHDRAWN". After a single dose, discontinuation is
#             typically rare but is retained for completeness / DLT context.
################################################################################
source("../00_setup_helpers.R")
env <- setup(study = "CP-101", adam = "/data/adam", out = "/data/tfl")
dv  <- design_vars("SAD")                       # trtvar = TRT01A

denom <- bign(adam$adsl, trtvar = dv$trtvar, popfl = "SAFFL")

## ascending-dose column order (+ optional placebo pooling) for rendering
dose_key <- adam$adsl %>% filter(SAFFL == "Y") %>%
  distinct(trt = .data[[dv$trtvar]], dosen = .data[[dv$trtnvar]]) %>%
  mutate(is_pbo = grepl("PLACEBO|PBO", toupper(trt)),
         dose_ord = if_else(is_pbo, -Inf, dosen))

adae <- adam$adae %>% filter(SAFFL == "Y", TRTEMFL == "Y")

## --- generic panel builder: Any -> SOC -> indented PT (distinct participants) ---
## Each panel is the same SOC/PT skeleton restricted by a category predicate.
build_panel <- function(df, where, anylabel, panel) {
  sub <- df %>% filter(!!where)

  any_row <- sub %>% group_by(trt = .data[[dv$trtvar]]) %>%
    summarise(nsubj = n_distinct(USUBJID), .groups = "drop") %>%
    mutate(AESOC = NA_character_, AEDECOD = NA_character_, level = 0L, term = anylabel)

  soc <- aecount(sub, trtvar = dv$trtvar, where = where, byvars = "AESOC") %>%
    mutate(level = 1L, term = AESOC)

  socpt <- aecount(sub, trtvar = dv$trtvar, where = where,
                   byvars = c("AESOC","AEDECOD")) %>%
    mutate(level = 2L, term = paste0("   ", AEDECOD))

  soc_ord <- soc   %>% group_by(AESOC)          %>% summarise(socn = sum(nsubj), .groups = "drop")
  pt_ord  <- socpt %>% group_by(AESOC, AEDECOD) %>% summarise(ptn  = sum(nsubj), .groups = "drop")

  bind_rows(any_row, soc, socpt) %>%
    left_join(soc_ord, by = "AESOC") %>%
    left_join(pt_ord,  by = c("AESOC","AEDECOD")) %>%
    arrange(desc(socn), AESOC, level, desc(ptn)) %>%
    mutate(panel = panel, panel_ord = match(panel, c(
      "Serious Adverse Events",
      "Adverse Events with Fatal Outcome",
      "Adverse Events Leading to Study Drug Discontinuation")))
}

## --- three panels ----------------------------------------------------------
panels <- bind_rows(
  build_panel(adae, quote(AESER == "Y"),
              "Participants with any SAE", "Serious Adverse Events"),
  build_panel(adae, quote(AESDTH == "Y"),
              "Participants with any AE with fatal outcome", "Adverse Events with Fatal Outcome"),
  build_panel(adae, quote(AEACN == "DRUG WITHDRAWN"),
              "Participants with any AE leading to discontinuation",
              "Adverse Events Leading to Study Drug Discontinuation")
)

## --- attach denominators -> n (%), to wide per dose level ------------------
rep <- panels %>%
  left_join(denom, by = "trt") %>%
  mutate(value = n_pct(nsubj, N)) %>%
  arrange(panel_ord, desc(socn), AESOC, level, desc(ptn)) %>%
  select(panel, panel_ord, term, level, trt, value) %>%
  pivot_wider(names_from = trt, values_from = value)
## NB: dose columns re-ordered low->high via dose_key$dose_ord at render.

ttl <- tfl_titles(
  num  = "14.3.1.4",
  type = "Table",
  text = "Serious Adverse Events, Deaths, and AEs Leading to Discontinuation by SOC and Preferred Term, by Dose Level",
  pop  = "Safety Population",
  foot = paste("SAD: each column = single ascending dose level (TRT01A), ordered",
               "low to high; placebo may be pooled. SAE = AESER==Y; fatal =",
               "AESDTH==Y; discontinuation = AEACN==DRUG WITHDRAWN. Treatment-",
               "emergent only (TRTEMFL=Y). A participant is counted once at each level",
               "within a panel. % = participants / N in dose level. {meddra}."))

## rtables: split_rows_by(panel) outermost; split_cols_by(dv$trtvar) (ascending
## dose); within each panel, SOC bold, PT indented.
print(rep)