Admiral Adae

library(admiral)
library(dplyr)
library(lubridate)
library(pharmaversesdtm)

# Load SDTM domains
ae   <- pharmaversesdtm::ae
adsl <- adsl  # assumed derived upstream; replace with path/load as needed
# mh <- pharmaversesdtm::mh  # uncomment if pre-existing condition flag in scope

# Remove DOMAIN from AE to avoid variable conflicts in merges
ae <- ae |> select(-DOMAIN)

# Confirm AE has at least one record
stopifnot(nrow(ae) > 0)

adae <- ae

# REVIEW: Confirm which ADSL variables are required per the ADAE spec.
#   The list below covers the minimum set for TEAE flag derivation and treatment
#   labelling. Extend with population flags and other ADSL variables as needed.
adsl_vars <- exprs(
  STUDYID, USUBJID,
  TRTSDT, TRTEDT, TRTSDTM,
  TRT01P, TRT01PN, TRT01A, TRT01AN,
  SAFFL, ITTFL
)

adae <- adae |>
  derive_vars_merged(
    dataset_add = adsl |> select(!!!adsl_vars),
    by_vars     = exprs(STUDYID, USUBJID)
  )

adae <- adae |>
  derive_vars_dt(
    dtc             = AESTDTC,
    new_vars_prefix = "AST",
    date_imputation = "first",
    flag_imputation = "auto"
  ) |>
  derive_vars_dt(
    dtc             = AEENDTC,
    new_vars_prefix = "AEN",
    date_imputation = "last",
    flag_imputation = "auto"
  )

adae <- adae |>
  derive_vars_dy(
    reference_date = TRTSDT,
    source_vars    = exprs(ASTDT, AENDT)
  )

# REVIEW: end_window is protocol-specific. Common values are 30 days post-last
#   dose for SAEs and 7 days for non-serious AEs, but always confirm from the
#   SAP. If the protocol does not specify a post-treatment window, set end_window
#   to 0 to include only AEs on or before the last dose date.
#   The ignore_time_for_trt_end argument should be TRUE if TRTEDTM is not
#   reliable for all subjects — confirm with the data manager.
adae <- adae |>
  derive_var_trtemfl(
    new_var                    = TRTEMFL,
    start_date                 = ASTDT,
    end_date                   = AENDT,
    trt_start_date             = TRTSDT,
    trt_end_date               = TRTEDT,
    end_window                 = 30,        # PLACEHOLDER — confirm from SAP
    ignore_time_for_trt_end    = TRUE
  )

adae <- adae |>
  mutate(
    # AESEV: severity — use decoded AESEV directly from AE; no transformation required
    AESEV = AESEV,
    # AESEVN: optional numeric mapping for sorting
    # REVIEW: Confirm severity ordering and numeric mapping against the ADaM spec.
    AESEVN = case_when(
      AESEV == "MILD"     ~ 1L,
      AESEV == "MODERATE" ~ 2L,
      AESEV == "SEVERE"   ~ 3L
    )
  )

# AETOXGR: CTCAE numeric grade — carry through from AE if grading was collected
# Uncomment if in scope per ADaM spec:
# adae <- adae |>
#   mutate(AETOXGR = AETOXGR)

adae <- adae |>
  mutate(
    # AESER: serious AE flag — "Y" or NA only; never "N" per CDISC convention
    AESER = if_else(AESER == "Y", "Y", NA_character_),
    # AESDTH: AE resulted in death — "Y" or NA
    AESDTH = if_else(AESDTH == "Y", "Y", NA_character_),
    # AEOUT: outcome — verify CDISC CT values in spec
    # REVIEW: Confirm AEOUT coded values align with the CDISC AE outcome codelist
    #   (RECOVER, NOT RECOVERED/NOT RESOLVED, RECOVERING/RESOLVING, etc.)
    AEOUT = AEOUT
  )

adae <- adae |>
  mutate(
    # AEREL: relationship to study treatment — usually "RELATED" / "NOT RELATED"
    # REVIEW: Some studies use "POSSIBLE", "PROBABLE" — confirm CT per spec.
    AEREL = AEREL,
    # AERELN: numeric causality code for sorting/analysis if required by spec
    AERELN = case_when(
      AEREL == "NOT RELATED" ~ 1L,
      AEREL == "RELATED"     ~ 2L
    ),
    # AERELNST: causality to non-study treatment if applicable
    # Uncomment if in scope: AERELNST = AERELNST
    #
    # AEACN: action taken with study treatment
    AEACN = AEACN
  )

# PREFL: pre-existing condition flag from MH
# REVIEW: The matching logic below uses AEDECOD = MHDECOD. Confirm the
#   match strategy with the medical reviewer — some specs require AEBODSYS
#   matching or a more specific term hierarchy.
# Requires: mh <- pharmaversesdtm::mh |> select(-DOMAIN)
#
# mh_terms <- mh |>
#   filter(MHSTAT != "HISTORY OF") |>   # REVIEW: filter condition is study-specific
#   distinct(STUDYID, USUBJID, MHDECOD)
#
# adae <- adae |>
#   derive_var_merged_exist_flag(
#     dataset_add   = mh_terms,
#     by_vars       = exprs(STUDYID, USUBJID, AEDECOD = MHDECOD),
#     new_var       = PREFL,
#     condition     = TRUE,
#     true_value    = "Y",
#     false_value   = NA_character_,
#     missing_value = NA_character_
#   )

# AMAXSEVFL: flag for the most severe AE per subject within TRTEMFL == "Y"
# REVIEW: Confirm whether worst-severity flag applies to TEAE only or all AEs.
adae <- adae |>
  restrict_derivation(
    derivation = derive_var_extreme_flag,
    args = params(
      by_vars   = exprs(STUDYID, USUBJID),
      order     = exprs(desc(AESEVN), ASTDT, AESEQ),
      new_var   = AMAXSEVFL,
      mode      = "first"
    ),
    filter = TRTEMFL == "Y"
  )

# SMQ / grouping flags via derive_vars_query()
# REVIEW: SMQ membership lists are sponsor-defined; confirm the query dataset
#   structure and variable names against the ADaM ADAE spec and MedDRA version.
# Requires: queries_smq — a data frame in admiral query format
#   (see admiral::queries_mednav for structure reference)
#
# adae <- adae |>
#   derive_vars_query(
#     dataset_queries = queries_smq
#   )