Concomitant Medications

Summary of Concomitant Medications by ATC Class and Medication Name

Setup

See Prerequisites for installation instructions.

library(arframe)
library(pharmaverseadam)
library(dplyr, warn.conflicts = FALSE)
library(tidyr)
library(cards)

adsl_saf <- pharmaverseadam::adsl |>
  blank_to_na() |>
  filter(SAFFL == "Y", TRT01A != "Screen Failure")

# adcm: on-treatment concomitant medications (ANL01FL = "Y")
adcm_ont <- pharmaverseadam::adcm |>
  blank_to_na() |>
  filter(ONTRTFL == "Y", TRT01A != "Screen Failure") |>
  mutate(
    CMCLAS  = if_else(is.na(CMCLAS), "UNCODED", toupper(CMCLAS)),
    CMDECOD = if_else(is.na(CMDECOD), CMTRT, CMDECOD),
    CMDECOD = toupper(CMDECOD)
  )

arm_levels <- c("Placebo", "Xanomeline Low Dose", "Xanomeline High Dose")

arm_n <- adsl_saf |>
  filter(TRT01A %in% arm_levels) |>
  count(TRT01A) |>
  pull(n, name = TRT01A)
arm_n <- arm_n[arm_levels]

N_total <- nrow(adsl_saf)

Data Preparation

n_pct <- function(n, denom) sprintf("%d (%.1f)", n, n / denom * 100)

# ── ATC class level ──
atc_arm <- adcm_ont |>
  distinct(USUBJID, TRT01A, CMCLAS) |>
  count(TRT01A, CMCLAS) |>
  filter(TRT01A %in% arm_levels) |>
  mutate(value = mapply(n_pct, n, arm_n[TRT01A])) |>
  select(TRT01A, CMCLAS, value) |>
  pivot_wider(names_from = TRT01A, values_from = value)

atc_total <- adcm_ont |>
  distinct(USUBJID, CMCLAS) |>
  count(CMCLAS) |>
  mutate(Total = n_pct(n, N_total)) |>
  select(CMCLAS, Total)

atc_wide <- left_join(atc_arm, atc_total, by = "CMCLAS") |>
  mutate(
    atc_class = CMCLAS,
    med_name  = CMCLAS,
    row_type  = "atc",
    .before   = 1
  ) |>
  select(-CMCLAS)

# ── Medication name level ──
med_arm <- adcm_ont |>
  distinct(USUBJID, TRT01A, CMCLAS, CMDECOD) |>
  count(TRT01A, CMCLAS, CMDECOD) |>
  filter(TRT01A %in% arm_levels) |>
  mutate(value = mapply(n_pct, n, arm_n[TRT01A])) |>
  select(TRT01A, CMCLAS, CMDECOD, value) |>
  pivot_wider(names_from = TRT01A, values_from = value)

med_total <- adcm_ont |>
  distinct(USUBJID, CMCLAS, CMDECOD) |>
  count(CMCLAS, CMDECOD) |>
  mutate(Total = n_pct(n, N_total)) |>
  select(CMCLAS, CMDECOD, Total)

med_wide <- left_join(med_arm, med_total, by = c("CMCLAS", "CMDECOD")) |>
  mutate(
    atc_class = CMCLAS,
    med_name  = CMDECOD,
    row_type  = "med",
    .before   = 1
  ) |>
  select(-CMCLAS, -CMDECOD)

# ── Sort: ATC class descending by subject count, meds descending within class ──
atc_order <- adcm_ont |>
  distinct(USUBJID, CMCLAS) |>
  count(CMCLAS, name = "n") |>
  arrange(desc(n)) |>
  pull(CMCLAS)

med_sorted <- adcm_ont |>
  distinct(USUBJID, CMCLAS, CMDECOD) |>
  count(CMCLAS, CMDECOD, name = "n") |>
  arrange(match(CMCLAS, atc_order), desc(n)) |>
  select(atc_class = CMCLAS, med_name = CMDECOD)

med_wide <- med_sorted |> left_join(med_wide, by = c("atc_class", "med_name"))

# ── Interleave ATC header rows + medication rows ──
cm_wide <- bind_rows(
  lapply(atc_order, function(a) {
    bind_rows(
      filter(atc_wide, atc_class == a),
      filter(med_wide, atc_class == a)
    )
  })
) |>
  mutate(across(all_of(c(arm_levels, "Total")), ~ replace_na(.x, "0 (0.0)")))

n_vec <- c(arm_n, Total = N_total)

cm_ard <- ard_stack_hierarchical(
  data        = adcm_ont |> filter(TRT01A %in% arm_levels),
  variables   = c(CMCLAS, CMDECOD),
  by          = TRT01A,
  denominator = adsl_saf,
  id          = USUBJID,
  overall     = TRUE
) |>
  sort_ard_hierarchical(sort = "descending")

# Note: cards output uses soc/pt column names vs dplyr's atc_class/med_name
cm_cards <- fr_wide_ard(
  cm_ard,
  statistic = "{n} ({p}%)",
  decimals  = c(p = 1),
  label     = c(
    CMCLAS  = "ATC Class",
    CMDECOD = "Medication Name"
  )
)

arframe Pipeline

The rendered table below uses the dplyr data prep (cm_wide). The cards tab produces an equivalent cm_cards — swap it in to use the cards path instead.

cm_wide |>
  fr_table() |>
  fr_titles(
    "Table 14.5.1",
    "Summary of Concomitant Medications by ATC Class and Medication Name",
    "Safety Population \u2014 On-Treatment Period"
  ) |>
  fr_cols(
    atc_class = fr_col(visible = FALSE),
    med_name  = fr_col("ATC Class\n  Medication Name", width = 3.5),
    row_type  = fr_col(visible = FALSE),
    !!!setNames(
      lapply(arm_levels, function(a) fr_col(a, align = "decimal")),
      arm_levels
    ),
    Total = fr_col("Total", align = "decimal"),
    .n = n_vec
  ) |>
  fr_header(bold = TRUE, align = "center") |>
  fr_rows(
    group_by  = "atc_class",
    indent_by = "med_name"
  ) |>
  fr_styles(
    fr_row_style(rows = fr_rows_matches("row_type", value = "atc"), bold = TRUE)
  ) |>
  fr_footnotes(
    "Concomitant medications are those with ONTRTFL = 'Y'.",
    "Subjects are counted once per ATC class and once per medication name.",
    "Percentages based on N per treatment arm (Safety Population).",
    "ATC class rows sorted by descending subject frequency; medications sorted within class by descending frequency.",
    "Medication names from CMDECOD (WHO Drug coded); ATC class from CMCLAS."
  )

Rendered Table

Table 14.5.1

Summary of Concomitant Medications by ATC Class and Medication Name

Safety Population — On-Treatment Period

ATC Class Medication Name	Placebo (N=86)	Xanomeline High Dose (N=72)	Xanomeline Low Dose (N=96)	Total (N=254)
UNCODED	49 (57.0)	46 (63.9)	54 (56.2)	149 (58.7)
UNCODED	49 (57.0)	46 (63.9)	54 (56.2)	149 (58.7)
SYSTEMIC HORMONAL PREPARATIONS, EXCL.	2 ( 2.3)	8 (11.1)	13 (13.5)	23 ( 9.1)
HYDROCORTISONE	2 ( 2.3)	8 (11.1)	13 (13.5)	23 ( 9.1)
CARDIOVASCULAR SYSTEM	3 ( 3.5)	3 ( 4.2)	3 ( 3.1)	9 ( 3.5)
AMLODIPINE	3 ( 3.5)	0	0	3 ( 1.2)
DOXAZOSIN MESILATE	0	1 ( 1.4)	1 ( 1.0)	2 ( 0.8)
DIGOXIN	0	0	1 ( 1.0)	1 ( 0.4)
DILTIAZEM HYDROCHLORIDE	0	1 ( 1.4)	0	1 ( 0.4)
FUROSEMIDE	0	1 ( 1.4)	0	1 ( 0.4)
LOSARTAN POTASSIUM	0	0	1 ( 1.0)	1 ( 0.4)
ALIMENTARY TRACT AND METABOLISM	2 ( 2.3)	2 ( 2.8)	2 ( 2.1)	6 ( 2.4)
ALGELDRATE	1 ( 1.2)	2 ( 2.8)	0	3 ( 1.2)
LOPERAMIDE HYDROCHLORIDE	1 ( 1.2)	0	1 ( 1.0)	2 ( 0.8)
CIMETIDINE	0	0	1 ( 1.0)	1 ( 0.4)
NIZATIDINE	0	0	1 ( 1.0)	1 ( 0.4)
NERVOUS SYSTEM	2 ( 2.3)	1 ( 1.4)	1 ( 1.0)	4 ( 1.6)
ACETYLSALICYLIC ACID	2 ( 2.3)	1 ( 1.4)	1 ( 1.0)	4 ( 1.6)
RESPIRATORY SYSTEM	1 ( 1.2)	1 ( 1.4)	1 ( 1.0)	3 ( 1.2)
BUDESONIDE	0	1 ( 1.4)	0	1 ( 0.4)
GUAIFENESIN	1 ( 1.2)	0	0	1 ( 0.4)
SALBUTAMOL SULFATE	0	0	1 ( 1.0)	1 ( 0.4)
ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS	0	0	1 ( 1.0)	1 ( 0.4)
LEUPRORELIN ACETATE	0	0	1 ( 1.0)	1 ( 0.4)
GENITO URINARY SYSTEM AND SEX HORMONES	0	1 ( 1.4)	0	1 ( 0.4)
ESTROGENS CONJUGATED	0	1 ( 1.4)	0	1 ( 0.4)

Concomitant medications are those with ONTRTFL = 'Y'.

Subjects are counted once per ATC class and once per medication name.

Percentages based on N per treatment arm (Safety Population).

ATC class rows sorted by descending subject frequency; medications sorted within class by descending frequency.

Medication names from CMDECOD (WHO Drug coded); ATC class from CMCLAS.

/opt/quarto/share/rmd/rmd.R 01APR2026 09:52:38