AEs Related to Study Drug

Treatment-Emergent AEs Related to Study Drug by SOC and PT

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")

# Related AEs: investigator-assessed relationship of POSSIBLE or PROBABLE
adae_rel <- pharmaverseadam::adae |>
  blank_to_na() |>
  filter(SAFFL == "Y", TRTEMFL == "Y", AEREL %in% c("POSSIBLE", "PROBABLE"))

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)
n_vec <- c(arm_n, Total = N_total)

Data Preparation

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

# ── Overall row ──
any_rel_arm <- adae_rel |>
  distinct(USUBJID, TRT01A) |>
  count(TRT01A) |>
  filter(TRT01A %in% arm_levels) |>
  mutate(value = mapply(n_pct, n, arm_n[TRT01A])) |>
  select(TRT01A, value) |>
  pivot_wider(names_from = TRT01A, values_from = value)

any_rel_total <- n_distinct(adae_rel$USUBJID)

any_rel_row <- bind_cols(
  tibble(soc = "TOTAL SUBJECTS WITH A RELATED TEAE",
         pt = "TOTAL SUBJECTS WITH A RELATED TEAE", row_type = "overall"),
  any_rel_arm,
  tibble(Total = n_pct(any_rel_total, N_total))
)

# ── SOC-level ──
soc_arm <- adae_rel |>
  distinct(USUBJID, TRT01A, AEBODSYS) |>
  count(TRT01A, AEBODSYS) |>
  filter(TRT01A %in% arm_levels) |>
  mutate(value = mapply(n_pct, n, arm_n[TRT01A])) |>
  select(TRT01A, AEBODSYS, value) |>
  pivot_wider(names_from = TRT01A, values_from = value)

soc_total <- adae_rel |>
  distinct(USUBJID, AEBODSYS) |>
  count(AEBODSYS) |>
  mutate(Total = n_pct(n, N_total)) |>
  select(AEBODSYS, Total)

soc_wide <- left_join(soc_arm, soc_total, by = "AEBODSYS") |>
  mutate(soc = AEBODSYS, pt = AEBODSYS, row_type = "soc", .before = 1) |>
  select(-AEBODSYS)

# ── PT-level ──
pt_arm <- adae_rel |>
  distinct(USUBJID, TRT01A, AEBODSYS, AEDECOD) |>
  count(TRT01A, AEBODSYS, AEDECOD) |>
  filter(TRT01A %in% arm_levels) |>
  mutate(value = mapply(n_pct, n, arm_n[TRT01A])) |>
  select(TRT01A, AEBODSYS, AEDECOD, value) |>
  pivot_wider(names_from = TRT01A, values_from = value)

pt_total <- adae_rel |>
  distinct(USUBJID, AEBODSYS, AEDECOD) |>
  count(AEBODSYS, AEDECOD) |>
  mutate(Total = n_pct(n, N_total)) |>
  select(AEBODSYS, AEDECOD, Total)

pt_wide <- left_join(pt_arm, pt_total, by = c("AEBODSYS", "AEDECOD")) |>
  mutate(soc = AEBODSYS, pt = AEDECOD, row_type = "pt", .before = 1) |>
  select(-AEBODSYS, -AEDECOD)

# ── Sort and interleave ──
soc_order <- adae_rel |>
  distinct(USUBJID, AEBODSYS) |>
  count(AEBODSYS, name = "soc_n") |>
  arrange(desc(soc_n)) |> pull(AEBODSYS)

ae_rel_wide <- bind_rows(
  any_rel_row,
  bind_rows(lapply(soc_order, function(s) {
    bind_rows(
      filter(soc_wide, soc == s),
      filter(pt_wide, soc == s) |>
        left_join(
          adae_rel |> distinct(USUBJID, AEBODSYS, AEDECOD) |>
            count(AEBODSYS, AEDECOD, name = "pt_n"),
          by = c("soc" = "AEBODSYS", "pt" = "AEDECOD")
        ) |> arrange(desc(pt_n)) |> select(-pt_n)
    )
  }))
) |>
  mutate(across(where(is.character) & !c(soc, pt, row_type),
                ~ replace_na(.x, "0 (0.0)")))

for (a in arm_levels) {
  if (!a %in% names(ae_rel_wide)) ae_rel_wide[[a]] <- "0 (0.0)"
}

rel_ard <- ard_stack_hierarchical(
  data        = adae_rel,
  variables   = c(AEBODSYS, AEDECOD),
  by          = TRT01A,
  denominator = adsl_saf,
  id          = USUBJID,
  overall     = TRUE,
  over_variables = TRUE
) |>
  sort_ard_hierarchical(sort = "descending")

ae_rel_cards <- fr_wide_ard(
  rel_ard,
  statistic = "{n} ({p}%)",
  decimals  = c(p = 1),
  label     = c(
    "..ard_hierarchical_overall.." = "TOTAL SUBJECTS WITH A RELATED TEAE",
    AEBODSYS = "System Organ Class",
    AEDECOD  = "Preferred Term"
  )
)

arframe Pipeline

ae_rel_wide |>
  fr_table() |>
  fr_titles(
    "Table 14.3.1",
    "Treatment-Emergent Adverse Events Related to Study Drug",
    "by System Organ Class and Preferred Term",
    "Safety Population"
  ) |>
  fr_cols(
    soc      = fr_col(visible = FALSE),
    pt       = fr_col("System Organ Class\n  Preferred Term", 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 = "soc", indent_by = "pt") |>
  fr_styles(
    fr_row_style(rows = fr_rows_matches("row_type", value = "soc"), bold = TRUE),
    fr_row_style(rows = fr_rows_matches("row_type", value = "overall"), bold = TRUE)
  ) |>
  fr_footnotes(
    "Related = Investigator-assessed relationship of Possible or Probable.",
    "Subjects counted once per SOC and once per PT.",
    "Percentages based on N per treatment arm (Safety Population).",
    "SOC sorted by descending frequency; PT sorted within SOC by descending frequency."
  )

Rendered Table

Table 14.3.1

Treatment-Emergent Adverse Events Related to Study Drug

by System Organ Class and Preferred Term

Safety Population

System Organ Class Preferred Term	Placebo (N=86)	Xanomeline High Dose (N=72)	Xanomeline Low Dose (N=96)	Total (N=254)
TOTAL SUBJECTS WITH A RELATED TEAE	43 (50.0)	64 (88.9)	77 (80.2)	184 (72.4)
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS	18 (20.9)	33 (45.8)	45 (46.9)	96 (37.8)
APPLICATION SITE PRURITUS	6 ( 7.0)	21 (29.2)	23 (24.0)	50 (19.7)
APPLICATION SITE ERYTHEMA	3 ( 3.5)	14 (19.4)	13 (13.5)	30 (11.8)
APPLICATION SITE DERMATITIS	5 ( 5.8)	7 ( 9.7)	9 ( 9.4)	21 ( 8.3)
APPLICATION SITE IRRITATION	3 ( 3.5)	9 (12.5)	9 ( 9.4)	21 ( 8.3)
APPLICATION SITE VESICLES	1 ( 1.2)	5 ( 6.9)	5 ( 5.2)	11 ( 4.3)
FATIGUE	1 ( 1.2)	4 ( 5.6)	2 ( 2.1)	7 ( 2.8)
APPLICATION SITE SWELLING	0	2 ( 2.8)	1 ( 1.0)	3 ( 1.2)
APPLICATION SITE URTICARIA	0	1 ( 1.4)	2 ( 2.1)	3 ( 1.2)
APPLICATION SITE REACTION	1 ( 1.2)	1 ( 1.4)	0	2 ( 0.8)
CHILLS	1 ( 1.2)	0	1 ( 1.0)	2 ( 0.8)
APPLICATION SITE PAIN	0	2 ( 2.8)	0	2 ( 0.8)
APPLICATION SITE PERSPIRATION	0	2 ( 2.8)	0	2 ( 0.8)
MALAISE	0	1 ( 1.4)	1 ( 1.0)	2 ( 0.8)
PAIN	0	1 ( 1.4)	1 ( 1.0)	2 ( 0.8)
OEDEMA	0	0	2 ( 2.1)	2 ( 0.8)
APPLICATION SITE INDURATION	1 ( 1.2)	0	0	1 ( 0.4)
ASTHENIA	1 ( 1.2)	0	0	1 ( 0.4)
APPLICATION SITE DISCHARGE	0	1 ( 1.4)	0	1 ( 0.4)
FEELING ABNORMAL	0	1 ( 1.4)	0	1 ( 0.4)
OEDEMA PERIPHERAL	0	1 ( 1.4)	0	1 ( 0.4)
APPLICATION SITE BLEEDING	0	0	1 ( 1.0)	1 ( 0.4)
APPLICATION SITE DESQUAMATION	0	0	1 ( 1.0)	1 ( 0.4)
APPLICATION SITE DISCOLOURATION	0	0	1 ( 1.0)	1 ( 0.4)
APPLICATION SITE WARMTH	0	0	1 ( 1.0)	1 ( 0.4)
CHEST DISCOMFORT	0	0	1 ( 1.0)	1 ( 0.4)
SKIN AND SUBCUTANEOUS TISSUE DISORDERS	16 (18.6)	38 (52.8)	37 (38.5)	91 (35.8)
PRURITUS	7 ( 8.1)	25 (34.7)	20 (20.8)	52 (20.5)
ERYTHEMA	8 ( 9.3)	14 (19.4)	13 (13.5)	35 (13.8)
RASH	3 ( 3.5)	6 ( 8.3)	11 (11.5)	20 ( 7.9)
HYPERHIDROSIS	1 ( 1.2)	8 (11.1)	4 ( 4.2)	13 ( 5.1)
SKIN IRRITATION	2 ( 2.3)	5 ( 6.9)	6 ( 6.2)	13 ( 5.1)
BLISTER	0	1 ( 1.4)	5 ( 5.2)	6 ( 2.4)
RASH PRURITIC	0	2 ( 2.8)	1 ( 1.0)	3 ( 1.2)
PRURITUS GENERALISED	0	1 ( 1.4)	1 ( 1.0)	2 ( 0.8)
URTICARIA	0	1 ( 1.4)	1 ( 1.0)	2 ( 0.8)
COLD SWEAT	1 ( 1.2)	0	0	1 ( 0.4)
SKIN ULCER	1 ( 1.2)	0	0	1 ( 0.4)
RASH MACULO-PAPULAR	0	1 ( 1.4)	0	1 ( 0.4)
DERMATITIS CONTACT	0	0	1 ( 1.0)	1 ( 0.4)
RASH ERYTHEMATOUS	0	0	1 ( 1.0)	1 ( 0.4)
SKIN EXFOLIATION	0	0	1 ( 1.0)	1 ( 0.4)
NERVOUS SYSTEM DISORDERS	4 ( 4.7)	13 (18.1)	14 (14.6)	31 (12.2)
DIZZINESS	2 ( 2.3)	5 ( 6.9)	7 ( 7.3)	14 ( 5.5)
SYNCOPE	0	2 ( 2.8)	5 ( 5.2)	7 ( 2.8)
HEADACHE	1 ( 1.2)	1 ( 1.4)	1 ( 1.0)	3 ( 1.2)
BURNING SENSATION	0	2 ( 2.8)	0	2 ( 0.8)
LETHARGY	0	1 ( 1.4)	1 ( 1.0)	2 ( 0.8)
SOMNOLENCE	1 ( 1.2)	0	0	1 ( 0.4)
HYPERSOMNIA	0	1 ( 1.4)	0	1 ( 0.4)
PAROSMIA	0	1 ( 1.4)	0	1 ( 0.4)
SYNCOPE VASOVAGAL	0	1 ( 1.4)	0	1 ( 0.4)
BALANCE DISORDER	0	0	1 ( 1.0)	1 ( 0.4)
COMPLEX PARTIAL SEIZURES	0	0	1 ( 1.0)	1 ( 0.4)
COORDINATION ABNORMAL	0	0	1 ( 1.0)	1 ( 0.4)
PARAESTHESIA ORAL	0	0	1 ( 1.0)	1 ( 0.4)
STUPOR	0	0	1 ( 1.0)	1 ( 0.4)
TRANSIENT ISCHAEMIC ATTACK	0	0	1 ( 1.0)	1 ( 0.4)
GASTROINTESTINAL DISORDERS	4 ( 4.7)	9 (12.5)	8 ( 8.3)	21 ( 8.3)
DIARRHOEA	3 ( 3.5)	1 ( 1.4)	3 ( 3.1)	7 ( 2.8)
NAUSEA	0	3 ( 4.2)	3 ( 3.1)	6 ( 2.4)
VOMITING	0	2 ( 2.8)	3 ( 3.1)	5 ( 2.0)
SALIVARY HYPERSECRETION	0	3 ( 4.2)	0	3 ( 1.2)
DYSPEPSIA	1 ( 1.2)	0	1 ( 1.0)	2 ( 0.8)
ABDOMINAL PAIN	0	1 ( 1.4)	1 ( 1.0)	2 ( 0.8)
GASTROOESOPHAGEAL REFLUX DISEASE	1 ( 1.2)	0	0	1 ( 0.4)
STOMACH DISCOMFORT	0	1 ( 1.4)	0	1 ( 0.4)
CARDIAC DISORDERS	6 ( 7.0)	3 ( 4.2)	8 ( 8.3)	17 ( 6.7)
MYOCARDIAL INFARCTION	2 ( 2.3)	1 ( 1.4)	1 ( 1.0)	4 ( 1.6)
SINUS BRADYCARDIA	2 ( 2.3)	0	2 ( 2.1)	4 ( 1.6)
ATRIAL FIBRILLATION	1 ( 1.2)	1 ( 1.4)	1 ( 1.0)	3 ( 1.2)
SUPRAVENTRICULAR EXTRASYSTOLES	0	1 ( 1.4)	1 ( 1.0)	2 ( 0.8)
ATRIOVENTRICULAR BLOCK FIRST DEGREE	1 ( 1.2)	0	0	1 ( 0.4)
ATRIOVENTRICULAR BLOCK SECOND DEGREE	1 ( 1.2)	0	0	1 ( 0.4)
BRADYCARDIA	1 ( 1.2)	0	0	1 ( 0.4)
CARDIAC FAILURE CONGESTIVE	1 ( 1.2)	0	0	1 ( 0.4)
SINUS ARRHYTHMIA	1 ( 1.2)	0	0	1 ( 0.4)
ATRIAL FLUTTER	0	0	1 ( 1.0)	1 ( 0.4)
BUNDLE BRANCH BLOCK RIGHT	0	0	1 ( 1.0)	1 ( 0.4)
PALPITATIONS	0	0	1 ( 1.0)	1 ( 0.4)
VENTRICULAR EXTRASYSTOLES	0	0	1 ( 1.0)	1 ( 0.4)
WOLFF-PARKINSON-WHITE SYNDROME	0	0	1 ( 1.0)	1 ( 0.4)
PSYCHIATRIC DISORDERS	2 ( 2.3)	5 ( 6.9)	9 ( 9.4)	16 ( 6.3)
CONFUSIONAL STATE	1 ( 1.2)	0	2 ( 2.1)	3 ( 1.2)
ANXIETY	0	0	3 ( 3.1)	3 ( 1.2)
IRRITABILITY	1 ( 1.2)	0	1 ( 1.0)	2 ( 0.8)
INSOMNIA	0	2 ( 2.8)	0	2 ( 0.8)
AGITATION	0	0	2 ( 2.1)	2 ( 0.8)
DELIRIUM	0	1 ( 1.4)	0	1 ( 0.4)
HALLUCINATION, VISUAL	0	1 ( 1.4)	0	1 ( 0.4)
LIBIDO DECREASED	0	1 ( 1.4)	0	1 ( 0.4)
LISTLESS	0	1 ( 1.4)	0	1 ( 0.4)
DEPRESSED MOOD	0	0	1 ( 1.0)	1 ( 0.4)
RESTLESSNESS	0	0	1 ( 1.0)	1 ( 0.4)
INVESTIGATIONS	4 ( 4.7)	1 ( 1.4)	2 ( 2.1)	7 ( 2.8)
ELECTROCARDIOGRAM ST SEGMENT DEPRESSION	1 ( 1.2)	0	1 ( 1.0)	2 ( 0.8)
BLOOD CREATINE PHOSPHOKINASE INCREASED	1 ( 1.2)	0	0	1 ( 0.4)
HEART RATE INCREASED	1 ( 1.2)	0	0	1 ( 0.4)
HEART RATE IRREGULAR	1 ( 1.2)	0	0	1 ( 0.4)
ELECTROCARDIOGRAM T WAVE INVERSION	0	1 ( 1.4)	0	1 ( 0.4)
BODY TEMPERATURE INCREASED	0	0	1 ( 1.0)	1 ( 0.4)
METABOLISM AND NUTRITION DISORDERS	3 ( 3.5)	1 ( 1.4)	0	4 ( 1.6)
DECREASED APPETITE	1 ( 1.2)	1 ( 1.4)	0	2 ( 0.8)
FOOD CRAVING	1 ( 1.2)	0	0	1 ( 0.4)
INCREASED APPETITE	1 ( 1.2)	0	0	1 ( 0.4)
VASCULAR DISORDERS	1 ( 1.2)	1 ( 1.4)	2 ( 2.1)	4 ( 1.6)
HYPOTENSION	1 ( 1.2)	0	1 ( 1.0)	2 ( 0.8)
ORTHOSTATIC HYPOTENSION	1 ( 1.2)	0	0	1 ( 0.4)
WOUND HAEMORRHAGE	0	1 ( 1.4)	0	1 ( 0.4)
HYPERTENSION	0	0	1 ( 1.0)	1 ( 0.4)
INJURY, POISONING AND PROCEDURAL COMPLICATIONS	0	1 ( 1.4)	2 ( 2.1)	3 ( 1.2)
EXCORIATION	0	1 ( 1.4)	0	1 ( 0.4)
FALL	0	0	1 ( 1.0)	1 ( 0.4)
SKIN LACERATION	0	0	1 ( 1.0)	1 ( 0.4)
WOUND	0	0	1 ( 1.0)	1 ( 0.4)
EAR AND LABYRINTH DISORDERS	0	1 ( 1.4)	1 ( 1.0)	2 ( 0.8)
VERTIGO	0	1 ( 1.4)	1 ( 1.0)	2 ( 0.8)
EYE DISORDERS	0	1 ( 1.4)	1 ( 1.0)	2 ( 0.8)
VISION BLURRED	0	1 ( 1.4)	1 ( 1.0)	2 ( 0.8)
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS	1 ( 1.2)	1 ( 1.4)	0	2 ( 0.8)
SHOULDER PAIN	1 ( 1.2)	0	0	1 ( 0.4)
MYALGIA	0	1 ( 1.4)	0	1 ( 0.4)
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS	2 ( 2.3)	0	0	2 ( 0.8)
DYSPNOEA	1 ( 1.2)	0	0	1 ( 0.4)
EMPHYSEMA	1 ( 1.2)	0	0	1 ( 0.4)
CONGENITAL, FAMILIAL AND GENETIC DISORDERS	0	0	1 ( 1.0)	1 ( 0.4)
VENTRICULAR SEPTAL DEFECT	0	0	1 ( 1.0)	1 ( 0.4)
RENAL AND URINARY DISORDERS	0	1 ( 1.4)	0	1 ( 0.4)
MICTURITION URGENCY	0	1 ( 1.4)	0	1 ( 0.4)
REPRODUCTIVE SYSTEM AND BREAST DISORDERS	1 ( 1.2)	0	0	1 ( 0.4)
PELVIC PAIN	1 ( 1.2)	0	0	1 ( 0.4)

Related = Investigator-assessed relationship of Possible or Probable.

Subjects counted once per SOC and once per PT.

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

SOC sorted by descending frequency; PT sorted within SOC by descending frequency.

/opt/quarto/share/rmd/rmd.R 01APR2026 09:52:16