TSFAE04

Subjects With Treatment-emergent Adverse Events Leading to Permanent Discontinuation of Study Treatment by System Organ Class and Preferred Term

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Output

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# Program Name:              tsfae04.R

# Prep Environment

library(envsetup)
library(tern)
library(dplyr)
library(rtables)
library(junco)

# Define script level parameters:

# - Define output ID and file location

tblid <- "TSFAE04"
fileid <- tblid
tab_titles <- get_titles_from_file(input_path = '../../_data/', tblid)
string_map <- default_str_map

trtvar <- "TRT01A"
popfl <- "SAFFL"
combined_colspan_trt <- TRUE
risk_diff <- TRUE
rr_method <- "wald"
ctrl_grp <- "Placebo"

if (combined_colspan_trt == TRUE) {
  # Set up levels and label for the required combined columns
  add_combo <- add_combo_facet(
    "Combined",
    label = "Combined",
    levels = c("Xanomeline High Dose", "Xanomeline Low Dose")
  )

  # choose if any facets need to be removed - e.g remove the combined column for placebo
  rm_combo_from_placebo <- cond_rm_facets(
    facets = "Combined",
    ancestor_pos = NA,
    value = " ",
    split = "colspan_trt"
  )

  mysplit <- make_split_fun(post = list(add_combo, rm_combo_from_placebo))
}

# Process Data:

adsl <- pharmaverseadamjnj::adsl %>%
  filter(!!rlang::sym(popfl) == "Y") %>%
  select(STUDYID, USUBJID, all_of(trtvar), all_of(popfl))

adae <- pharmaverseadamjnj::adae %>%
  filter(TRTEMFL == "Y" & AEACN == "DRUG WITHDRAWN") %>%
  select(USUBJID, TRTEMFL, AEBODSYS, AEDECOD)

adsl$colspan_trt <- factor(
  ifelse(adsl[[trtvar]] == "Placebo", " ", "Active Study Agent"),
  levels = c("Active Study Agent", " ")
)

if (risk_diff == TRUE) {
  adsl$rrisk_header <- "Risk Difference (%) (95% CI)"
  adsl$rrisk_label <- paste(adsl[[trtvar]], paste("vs", ctrl_grp))
}

# join data together
ae <- adae %>% right_join(., adsl, by = c("USUBJID"))

colspan_trt_map <- create_colspan_map(
  adsl,
  non_active_grp = ctrl_grp,
  non_active_grp_span_lbl = " ",
  active_grp_span_lbl = "Active Study Agent",
  colspan_var = "colspan_trt",
  trt_var = trtvar
)

# Define layout and build table:

ref_path <- c("colspan_trt", " ", trtvar, ctrl_grp)
extra_args_rr <- list(
  method = rr_method,
  ref_path = ref_path,
  .stats = c("count_unique_fraction")
)


lyt <- basic_table(
  top_level_section_div = " ",
  show_colcounts = TRUE,
  colcount_format = "N=xx"
) %>%
  split_cols_by(
    "colspan_trt",
    split_fun = trim_levels_to_map(map = colspan_trt_map)
  )

if (combined_colspan_trt == TRUE) {
  lyt <- lyt %>%
    split_cols_by(trtvar, split_fun = mysplit)
} else {
  lyt <- lyt %>%
    split_cols_by(trtvar)
}

if (risk_diff == TRUE) {
  lyt <- lyt %>%
    split_cols_by("rrisk_header", nested = FALSE) %>%
    split_cols_by(
      trtvar,
      labels_var = "rrisk_label",
      split_fun = remove_split_levels("Placebo")
    )
}

lyt <- lyt %>%
  analyze(
    "TRTEMFL",
    afun = a_freq_j,
    show_labels = "hidden",
    extra_args = append(
      extra_args_rr,
      list(label = "Subjects with >=1 AE leading to discontinuation", NULL)
    )
  ) %>%
  split_rows_by(
    "AEBODSYS",
    split_label = "System Organ Class",
    split_fun = trim_levels_in_group("AEDECOD"),
    label_pos = "topleft",
    section_div = c(" "),
    nested = FALSE
  ) %>%
  summarize_row_groups(
    "AEBODSYS",
    cfun = a_freq_j,
    extra_args = append(extra_args_rr, NULL)
  ) %>%
  analyze(
    "AEDECOD",
    afun = a_freq_j,
    extra_args = append(extra_args_rr, NULL)
  ) %>%
  append_topleft("  Preferred Term, n (%)")

result <- build_table(lyt, ae, alt_counts_df = adsl)

## Remove the N=xx column headers for the risk difference columns
result <- remove_col_count(result)

# If there is no data remove top row and display "No data to display" text
if (length(adae$TRTEMFL) == 0) {
  result <- safe_prune_table(
    result,
    prune_func = remove_rows(
      removerowtext = "Subjects with >=1 AE leading to discontinuation"
    )
  )
}

# Post-Processing step to sort by descending count on chosen active treatment columns.

if (length(adae$TRTEMFL) != 0) {
  result <- sort_at_path(
    result,
    c("root", "AEBODSYS"),
    scorefun = jj_complex_scorefun()
  )
  result <- sort_at_path(
    result,
    c("root", "AEBODSYS", "*", "AEDECOD"),
    scorefun = jj_complex_scorefun()
  )
}

# Add titles and footnotes:

result <- set_titles(result, tab_titles)

# Convert to tbl file and output table

tt_to_tlgrtf(string_map = string_map, tt = result, file = fileid, orientation = "landscape")

TSFAE04: Subjects With Treatment-emergent Adverse Events Leading to Permanent Discontinuation of Study Treatment by System Organ Class and Preferred Term; Safety Analysis Set (Study jjcs - core)
	Active Study Agent				Risk Difference (%) (95% CI)
System Organ Class	Xanomeline High Dose	Xanomeline Low Dose	Combined	Placebo	Xanomeline High Dose vs Placebo	Xanomeline Low Dose vs Placebo
Preferred Term, n (%)	N=53	N=73	N=126	N=59
Subjects with ≥1 AE leading to  discontinuation	23 (43.4%)	20 (27.4%)	43 (34.1%)	18 (30.5%)	12.9 (-4.9, 30.7)	-3.1 (-18.7, 12.5)
General disorders and  administration site conditions	6 (11.3%)	8 (11.0%)	14 (11.1%)	4 (6.8%)	4.5 (-6.1, 15.2)	4.2 (-5.4, 13.8)
APPLICATION SITE PRURITUS	2 (3.8%)	4 (5.5%)	6 (4.8%)	0	3.8 (-1.4, 8.9)	5.5 (0.3, 10.7)
APPLICATION SITE IRRITATION	1 (1.9%)	3 (4.1%)	4 (3.2%)	0	1.9 (-1.8, 5.5)	4.1 (-0.4, 8.7)
APPLICATION SITE DERMATITIS	1 (1.9%)	0	1 (0.8%)	1 (1.7%)	0.2 (-4.7, 5.1)	-1.7 (-5.0, 1.6)
APPLICATION SITE ERYTHEMA	0	1 (1.4%)	1 (0.8%)	1 (1.7%)	-1.7 (-5.0, 1.6)	-0.3 (-4.6, 3.9)
ASTHENIA	0	1 (1.4%)	1 (0.8%)	0	0.0 (0.0, 0.0)	1.4 (-1.3, 4.0)
CHEST PAIN	1 (1.9%)	0	1 (0.8%)	0	1.9 (-1.8, 5.5)	0.0 (0.0, 0.0)
FATIGUE	1 (1.9%)	0	1 (0.8%)	0	1.9 (-1.8, 5.5)	0.0 (0.0, 0.0)
ULCER	0	1 (1.4%)	1 (0.8%)	0	0.0 (0.0, 0.0)	1.4 (-1.3, 4.0)
APPLICATION SITE INDURATION	0	0	0	1 (1.7%)	-1.7 (-5.0, 1.6)	-1.7 (-5.0, 1.6)
APPLICATION SITE REACTION	0	0	0	1 (1.7%)	-1.7 (-5.0, 1.6)	-1.7 (-5.0, 1.6)
OEDEMA PERIPHERAL	0	0	0	1 (1.7%)	-1.7 (-5.0, 1.6)	-1.7 (-5.0, 1.6)
Skin and subcutaneous tissue  disorders	7 (13.2%)	3 (4.1%)	10 (7.9%)	5 (8.5%)	4.7 (-6.8, 16.3)	-4.4 (-12.8, 4.1)
PRURITUS	2 (3.8%)	1 (1.4%)	3 (2.4%)	0	3.8 (-1.4, 8.9)	1.4 (-1.3, 4.0)
ERYTHEMA	2 (3.8%)	0	2 (1.6%)	1 (1.7%)	2.1 (-4.0, 8.2)	-1.7 (-5.0, 1.6)
RASH	2 (3.8%)	0	2 (1.6%)	1 (1.7%)	2.1 (-4.0, 8.2)	-1.7 (-5.0, 1.6)
SKIN IRRITATION	1 (1.9%)	1 (1.4%)	2 (1.6%)	1 (1.7%)	0.2 (-4.7, 5.1)	-0.3 (-4.6, 3.9)
BLISTER	0	1 (1.4%)	1 (0.8%)	0	0.0 (0.0, 0.0)	1.4 (-1.3, 4.0)
RASH PRURITIC	1 (1.9%)	0	1 (0.8%)	0	1.9 (-1.8, 5.5)	0.0 (0.0, 0.0)
DRUG ERUPTION	0	0	0	1 (1.7%)	-1.7 (-5.0, 1.6)	-1.7 (-5.0, 1.6)
HYPERHIDROSIS	0	0	0	1 (1.7%)	-1.7 (-5.0, 1.6)	-1.7 (-5.0, 1.6)
Nervous system disorders	4 (7.5%)	4 (5.5%)	8 (6.3%)	1 (1.7%)	5.9 (-2.0, 13.7)	3.8 (-2.4, 10.0)
DIZZINESS	1 (1.9%)	3 (4.1%)	4 (3.2%)	0	1.9 (-1.8, 5.5)	4.1 (-0.4, 8.7)
HEADACHE	2 (3.8%)	0	2 (1.6%)	0	3.8 (-1.4, 8.9)	0.0 (0.0, 0.0)
SYNCOPE	1 (1.9%)	1 (1.4%)	2 (1.6%)	0	1.9 (-1.8, 5.5)	1.4 (-1.3, 4.0)
PARKINSON'S DISEASE	0	0	0	1 (1.7%)	-1.7 (-5.0, 1.6)	-1.7 (-5.0, 1.6)
Respiratory, thoracic and  mediastinal disorders	2 (3.8%)	2 (2.7%)	4 (3.2%)	1 (1.7%)	2.1 (-4.0, 8.2)	1.0 (-3.9, 6.0)
ALLERGIC GRANULOMATOUS  ANGIITIS	1 (1.9%)	0	1 (0.8%)	0	1.9 (-1.8, 5.5)	0.0 (0.0, 0.0)
DYSPHONIA	0	1 (1.4%)	1 (0.8%)	0	0.0 (0.0, 0.0)	1.4 (-1.3, 4.0)
DYSPNOEA	0	1 (1.4%)	1 (0.8%)	0	0.0 (0.0, 0.0)	1.4 (-1.3, 4.0)
NASAL CONGESTION	1 (1.9%)	0	1 (0.8%)	0	1.9 (-1.8, 5.5)	0.0 (0.0, 0.0)
RESPIRATORY TRACT  CONGESTION	1 (1.9%)	0	1 (0.8%)	0	1.9 (-1.8, 5.5)	0.0 (0.0, 0.0)
POSTNASAL DRIP	0	0	0	1 (1.7%)	-1.7 (-5.0, 1.6)	-1.7 (-5.0, 1.6)
Gastrointestinal disorders	1 (1.9%)	2 (2.7%)	3 (2.4%)	2 (3.4%)	-1.5 (-7.4, 4.4)	-0.7 (-6.6, 5.3)
DIARRHOEA	0	2 (2.7%)	2 (1.6%)	1 (1.7%)	-1.7 (-5.0, 1.6)	1.0 (-3.9, 6.0)
SALIVARY HYPERSECRETION	1 (1.9%)	0	1 (0.8%)	0	1.9 (-1.8, 5.5)	0.0 (0.0, 0.0)
VOMITING	0	1 (1.4%)	1 (0.8%)	0	0.0 (0.0, 0.0)	1.4 (-1.3, 4.0)
HIATUS HERNIA	0	0	0	1 (1.7%)	-1.7 (-5.0, 1.6)	-1.7 (-5.0, 1.6)
Infections and infestations	2 (3.8%)	1 (1.4%)	3 (2.4%)	5 (8.5%)	-4.7 (-13.5, 4.1)	-7.1 (-14.7, 0.5)
NASOPHARYNGITIS	1 (1.9%)	1 (1.4%)	2 (1.6%)	1 (1.7%)	0.2 (-4.7, 5.1)	-0.3 (-4.6, 3.9)
UPPER RESPIRATORY TRACT  INFECTION	1 (1.9%)	0	1 (0.8%)	2 (3.4%)	-1.5 (-7.4, 4.4)	-3.4 (-8.0, 1.2)
LOCALISED INFECTION	0	0	0	1 (1.7%)	-1.7 (-5.0, 1.6)	-1.7 (-5.0, 1.6)
URINARY TRACT INFECTION	0	0	0	1 (1.7%)	-1.7 (-5.0, 1.6)	-1.7 (-5.0, 1.6)
Cardiac disorders	1 (1.9%)	1 (1.4%)	2 (1.6%)	0	1.9 (-1.8, 5.5)	1.4 (-1.3, 4.0)
MYOCARDIAL INFARCTION	1 (1.9%)	0	1 (0.8%)	0	1.9 (-1.8, 5.5)	0.0 (0.0, 0.0)
PALPITATIONS	0	1 (1.4%)	1 (0.8%)	0	0.0 (0.0, 0.0)	1.4 (-1.3, 4.0)
Injury, poisoning and  procedural complications	1 (1.9%)	1 (1.4%)	2 (1.6%)	0	1.9 (-1.8, 5.5)	1.4 (-1.3, 4.0)
CONTUSION	1 (1.9%)	1 (1.4%)	2 (1.6%)	0	1.9 (-1.8, 5.5)	1.4 (-1.3, 4.0)
Psychiatric disorders	2 (3.8%)	0	2 (1.6%)	1 (1.7%)	2.1 (-4.0, 8.2)	-1.7 (-5.0, 1.6)
DELIRIUM	1 (1.9%)	0	1 (0.8%)	0	1.9 (-1.8, 5.5)	0.0 (0.0, 0.0)
LISTLESS	1 (1.9%)	0	1 (0.8%)	0	1.9 (-1.8, 5.5)	0.0 (0.0, 0.0)
DISORIENTATION	0	0	0	1 (1.7%)	-1.7 (-5.0, 1.6)	-1.7 (-5.0, 1.6)
Investigations	0	1 (1.4%)	1 (0.8%)	3 (5.1%)	-5.1 (-10.7, 0.5)	-3.7 (-9.9, 2.5)
WEIGHT DECREASED	0	1 (1.4%)	1 (0.8%)	0	0.0 (0.0, 0.0)	1.4 (-1.3, 4.0)
BLOOD CREATINE  PHOSPHOKINASE INCREASED	0	0	0	1 (1.7%)	-1.7 (-5.0, 1.6)	-1.7 (-5.0, 1.6)
CYSTOSCOPY	0	0	0	1 (1.7%)	-1.7 (-5.0, 1.6)	-1.7 (-5.0, 1.6)
ELECTROCARDIOGRAM T WAVE  AMPLITUDE DECREASED	0	0	0	1 (1.7%)	-1.7 (-5.0, 1.6)	-1.7 (-5.0, 1.6)
Renal and urinary disorders	0	1 (1.4%)	1 (0.8%)	0	0.0 (0.0, 0.0)	1.4 (-1.3, 4.0)
INCONTINENCE	0	1 (1.4%)	1 (0.8%)	0	0.0 (0.0, 0.0)	1.4 (-1.3, 4.0)
Vascular disorders	1 (1.9%)	0	1 (0.8%)	0	1.9 (-1.8, 5.5)	0.0 (0.0, 0.0)
WOUND HAEMORRHAGE	1 (1.9%)	0	1 (0.8%)	0	1.9 (-1.8, 5.5)	0.0 (0.0, 0.0)
Eye disorders	0	0	0	1 (1.7%)	-1.7 (-5.0, 1.6)	-1.7 (-5.0, 1.6)
EYE PRURITUS	0	0	0	1 (1.7%)	-1.7 (-5.0, 1.6)	-1.7 (-5.0, 1.6)
Metabolism and nutrition  disorders	0	0	0	1 (1.7%)	-1.7 (-5.0, 1.6)	-1.7 (-5.0, 1.6)
DECREASED APPETITE	0	0	0	1 (1.7%)	-1.7 (-5.0, 1.6)	-1.7 (-5.0, 1.6)
Musculoskeletal and connective  tissue disorders	0	0	0	1 (1.7%)	-1.7 (-5.0, 1.6)	-1.7 (-5.0, 1.6)
SHOULDER PAIN	0	0	0	1 (1.7%)	-1.7 (-5.0, 1.6)	-1.7 (-5.0, 1.6)
Surgical and medical  procedures	0	0	0	1 (1.7%)	-1.7 (-5.0, 1.6)	-1.7 (-5.0, 1.6)
CATARACT OPERATION	0	0	0	1 (1.7%)	-1.7 (-5.0, 1.6)	-1.7 (-5.0, 1.6)
Note: Subjects are counted only once for any given event, regardless of the number of times they actually experienced the event.
Note: Adverse events are coded using MedDRA version 26.0.

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