TSFAE14

Subjects With Treatment-emergent Serious Adverse Events by Organ System and OCMQ (Narrow)

Output

Code
# Program Name:              tsfae14.R

# Prep Environment

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

# Define script level parameters:

# - Define output ID and file location

tblid <- "TSFAE14"
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::adaeocmq %>%
  filter(TRTEMFL == "Y" & AESER == "Y" & OCMQCLSS == "Narrow") %>%
  select(USUBJID, TRTEMFL, OCMQSOC, OCMQNAM)

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", " ", "TRT01A", "Placebo")
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 %>%
  split_rows_by(
    "OCMQSOC",
    split_label = "Organ System~[super a]",
    split_fun = trim_levels_in_group("OCMQNAM"),
    label_pos = "topleft",
    section_div = c(" "),
    nested = FALSE
  ) %>%
  summarize_row_groups(
    "OCMQSOC",
    cfun = a_freq_j,
    extra_args = append(extra_args_rr, NULL)
  ) %>%
  analyze(
    "OCMQNAM",
    afun = a_freq_j,
    extra_args = append(extra_args_rr, NULL)
  ) %>%
  append_topleft("  OCMQ (Narrow), 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 display "No data to display" text
if (nrow(adae) == 0) {
  result <- safe_prune_table(result)
}

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

if (nrow(adae) != 0) {
  result <- sort_at_path(
    result,
    c("root", "OCMQSOC"),
    scorefun = jj_complex_scorefun()
  )
  result <- sort_at_path(
    result,
    c("root", "OCMQSOC", "*", "OCMQNAM"),
    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")

TSFAE14: Subjects With Treatment-emergent Serious Adverse Events by System Organ Class and FDA Medical Query (Narrow); Safety Analysis Set (Study jjcs - core)

Active Study Agent

Risk Difference (%) (95% CI)

Organ Systema

Xanomeline High Dose

Xanomeline Low Dose

Combined

Placebo

Xanomeline High Dose vs Placebo

Xanomeline Low Dose vs Placebo

OCMQ (Narrow), n (%)

N=53

N=73

N=126

N=59

Skin and subcutaneous tissue
 disorders

34 (64.2%)

28 (38.4%)

62 (49.2%)

11 (18.6%)

45.5 (29.2, 61.8)

19.7 (4.8, 34.7)

Pruritus

24 (45.3%)

21 (28.8%)

45 (35.7%)

6 (10.2%)

35.1 (19.7, 50.6)

18.6 (5.7, 31.5)

Erythema

16 (30.2%)

14 (19.2%)

30 (23.8%)

5 (8.5%)

21.7 (7.5, 36.0)

10.7 (-0.8, 22.2)

Rash

10 (18.9%)

8 (11.0%)

18 (14.3%)

4 (6.8%)

12.1 (-0.2, 24.4)

4.2 (-5.4, 13.8)

Urticaria

1 (1.9%)

1 (1.4%)

2 (1.6%)

0

1.9 (-1.8, 5.5)

1.4 (-1.3, 4.0)

General disorders and
 administration site conditions

12 (22.6%)

16 (21.9%)

28 (22.2%)

7 (11.9%)

10.8 (-3.2, 24.7)

10.1 (-2.5, 22.6)

Local Administration Reaction

5 (9.4%)

5 (6.8%)

10 (7.9%)

4 (6.8%)

2.7 (-7.5, 12.8)

0.1 (-8.6, 8.7)

Dizziness

4 (7.5%)

4 (5.5%)

8 (6.3%)

0

7.5 (0.4, 14.7)

5.5 (0.3, 10.7)

Fatigue

4 (7.5%)

3 (4.1%)

7 (5.6%)

1 (1.7%)

5.9 (-2.0, 13.7)

2.4 (-3.2, 8.0)

Fall

1 (1.9%)

2 (2.7%)

3 (2.4%)

0

1.9 (-1.8, 5.5)

2.7 (-1.0, 6.5)

Peripheral Edema

1 (1.9%)

1 (1.4%)

2 (1.6%)

2 (3.4%)

-1.5 (-7.4, 4.4)

-2.0 (-7.4, 3.3)

Pyrexia

0

2 (2.7%)

2 (1.6%)

0

0.0 (0.0, 0.0)

2.7 (-1.0, 6.5)

Nervous system disorders

6 (11.3%)

8 (11.0%)

14 (11.1%)

2 (3.4%)

7.9 (-1.8, 17.6)

7.6 (-1.0, 16.1)

Headache

2 (3.8%)

3 (4.1%)

5 (4.0%)

1 (1.7%)

2.1 (-4.0, 8.2)

2.4 (-3.2, 8.0)

Somnolence

0

4 (5.5%)

4 (3.2%)

1 (1.7%)

-1.7 (-5.0, 1.6)

3.8 (-2.4, 10.0)

Confusional State

1 (1.9%)

1 (1.4%)

2 (1.6%)

1 (1.7%)

0.2 (-4.7, 5.1)

-0.3 (-4.6, 3.9)

Stroke and TIA

0

2 (2.7%)

2 (1.6%)

0

0.0 (0.0, 0.0)

2.7 (-1.0, 6.5)

Paresthesia

1 (1.9%)

0

1 (0.8%)

0

1.9 (-1.8, 5.5)

0.0 (0.0, 0.0)

Seizure

1 (1.9%)

0

1 (0.8%)

0

1.9 (-1.8, 5.5)

0.0 (0.0, 0.0)

Syncope

1 (1.9%)

0

1 (0.8%)

0

1.9 (-1.8, 5.5)

0.0 (0.0, 0.0)

Cardiac disorders

6 (11.3%)

7 (9.6%)

13 (10.3%)

5 (8.5%)

2.8 (-8.3, 13.9)

1.1 (-8.7, 10.9)

Arrhythmia

4 (7.5%)

5 (6.8%)

9 (7.1%)

3 (5.1%)

2.5 (-6.6, 11.5)

1.8 (-6.3, 9.8)

Acute Coronary Syndrome

2 (3.8%)

1 (1.4%)

3 (2.4%)

2 (3.4%)

0.4 (-6.5, 7.3)

-2.0 (-7.4, 3.3)

Myocardial Infarction

2 (3.8%)

1 (1.4%)

3 (2.4%)

2 (3.4%)

0.4 (-6.5, 7.3)

-2.0 (-7.4, 3.3)

Myocardial Ischemia

2 (3.8%)

1 (1.4%)

3 (2.4%)

2 (3.4%)

0.4 (-6.5, 7.3)

-2.0 (-7.4, 3.3)

Cardiac Conduction
 Disturbance

0

2 (2.7%)

2 (1.6%)

2 (3.4%)

-3.4 (-8.0, 1.2)

-0.7 (-6.6, 5.3)

Tachycardia

0

0

0

1 (1.7%)

-1.7 (-5.0, 1.6)

-1.7 (-5.0, 1.6)

Gastrointestinal disorders

8 (15.1%)

4 (5.5%)

12 (9.5%)

3 (5.1%)

10.0 (-1.1, 21.2)

0.4 (-7.3, 8.1)

Diarrhea

2 (3.8%)

2 (2.7%)

4 (3.2%)

1 (1.7%)

2.1 (-4.0, 8.2)

1.0 (-3.9, 6.0)

Abdominal Pain

2 (3.8%)

1 (1.4%)

3 (2.4%)

1 (1.7%)

2.1 (-4.0, 8.2)

-0.3 (-4.6, 3.9)

Vomiting

3 (5.7%)

0

3 (2.4%)

0

5.7 (-0.6, 11.9)

0.0 (0.0, 0.0)

Nausea

2 (3.8%)

0

2 (1.6%)

0

3.8 (-1.4, 8.9)

0.0 (0.0, 0.0)

Dyspepsia

0

1 (1.4%)

1 (0.8%)

1 (1.7%)

-1.7 (-5.0, 1.6)

-0.3 (-4.6, 3.9)

Constipation

0

0

0

1 (1.7%)

-1.7 (-5.0, 1.6)

-1.7 (-5.0, 1.6)

Infections and infestations

5 (9.4%)

5 (6.8%)

10 (7.9%)

7 (11.9%)

-2.4 (-13.8, 9.0)

-5.0 (-15.1, 5.1)

Nasopharyngitis

4 (7.5%)

3 (4.1%)

7 (5.6%)

5 (8.5%)

-0.9 (-11.0, 9.1)

-4.4 (-12.8, 4.1)

Bacterial Infection

1 (1.9%)

1 (1.4%)

2 (1.6%)

1 (1.7%)

0.2 (-4.7, 5.1)

-0.3 (-4.6, 3.9)

Pneumonia

0

1 (1.4%)

1 (0.8%)

0

0.0 (0.0, 0.0)

1.4 (-1.3, 4.0)

Viral Infection

1 (1.9%)

0

1 (0.8%)

1 (1.7%)

0.2 (-4.7, 5.1)

-1.7 (-5.0, 1.6)

Vascular disorders

3 (5.7%)

6 (8.2%)

9 (7.1%)

3 (5.1%)

0.6 (-7.8, 8.9)

3.1 (-5.3, 11.6)

Thrombosis

2 (3.8%)

3 (4.1%)

5 (4.0%)

2 (3.4%)

0.4 (-6.5, 7.3)

0.7 (-5.8, 7.2)

Thrombosis Arterial

2 (3.8%)

3 (4.1%)

5 (4.0%)

2 (3.4%)

0.4 (-6.5, 7.3)

0.7 (-5.8, 7.2)

Hemorrhage

1 (1.9%)

3 (4.1%)

4 (3.2%)

1 (1.7%)

0.2 (-4.7, 5.1)

2.4 (-3.2, 8.0)

Hypotension

0

0

0

2 (3.4%)

-3.4 (-8.0, 1.2)

-3.4 (-8.0, 1.2)

Psychiatric disorders

1 (1.9%)

4 (5.5%)

5 (4.0%)

4 (6.8%)

-4.9 (-12.3, 2.5)

-1.3 (-9.6, 7.0)

Study Agent Abuse Potential

0

3 (4.1%)

3 (2.4%)

1 (1.7%)

-1.7 (-5.0, 1.6)

2.4 (-3.2, 8.0)

Anxiety

0

1 (1.4%)

1 (0.8%)

0

0.0 (0.0, 0.0)

1.4 (-1.3, 4.0)

Insomnia

1 (1.9%)

0

1 (0.8%)

1 (1.7%)

0.2 (-4.7, 5.1)

-1.7 (-5.0, 1.6)

Irritability

0

0

0

1 (1.7%)

-1.7 (-5.0, 1.6)

-1.7 (-5.0, 1.6)

Psychosis

0

0

0

1 (1.7%)

-1.7 (-5.0, 1.6)

-1.7 (-5.0, 1.6)

Musculoskeletal and connective
 tissue disorders

4 (7.5%)

0

4 (3.2%)

1 (1.7%)

5.9 (-2.0, 13.7)

-1.7 (-5.0, 1.6)

Back Pain

3 (5.7%)

0

3 (2.4%)

0

5.7 (-0.6, 11.9)

0.0 (0.0, 0.0)

Arthralgia

1 (1.9%)

0

1 (0.8%)

0

1.9 (-1.8, 5.5)

0.0 (0.0, 0.0)

Fracture

1 (1.9%)

0

1 (0.8%)

1 (1.7%)

0.2 (-4.7, 5.1)

-1.7 (-5.0, 1.6)

Osteoporosis

0

0

0

1 (1.7%)

-1.7 (-5.0, 1.6)

-1.7 (-5.0, 1.6)

Respiratory, thoracic and
 mediastinal disorders

3 (5.7%)

1 (1.4%)

4 (3.2%)

0

5.7 (-0.6, 11.9)

1.4 (-1.3, 4.0)

Cough

3 (5.7%)

1 (1.4%)

4 (3.2%)

0

5.7 (-0.6, 11.9)

1.4 (-1.3, 4.0)

Reproductive system and
 breast disorders

3 (5.7%)

0

3 (2.4%)

1 (1.7%)

4.0 (-3.1, 11.0)

-1.7 (-5.0, 1.6)

Sexual Dysfunction

2 (3.8%)

0

2 (1.6%)

1 (1.7%)

2.1 (-4.0, 8.2)

-1.7 (-5.0, 1.6)

Abnormal Uterine Bleeding

1 (1.9%)

0

1 (0.8%)

0

1.9 (-1.8, 5.5)

0.0 (0.0, 0.0)

Erectile Dysfunction

1 (1.9%)

0

1 (0.8%)

1 (1.7%)

0.2 (-4.7, 5.1)

-1.7 (-5.0, 1.6)

Excessive Menstrual Bleeding

1 (1.9%)

0

1 (0.8%)

0

1.9 (-1.8, 5.5)

0.0 (0.0, 0.0)

Ear and labyrinth disorders

0

1 (1.4%)

1 (0.8%)

0

0.0 (0.0, 0.0)

1.4 (-1.3, 4.0)

Vertigo

0

1 (1.4%)

1 (0.8%)

0

0.0 (0.0, 0.0)

1.4 (-1.3, 4.0)

Endocrine disorders

1 (1.9%)

0

1 (0.8%)

0

1.9 (-1.8, 5.5)

0.0 (0.0, 0.0)

Hyperglycemia

1 (1.9%)

0

1 (0.8%)

0

1.9 (-1.8, 5.5)

0.0 (0.0, 0.0)

Metabolism and nutrition
 disorders

1 (1.9%)

0

1 (0.8%)

0

1.9 (-1.8, 5.5)

0.0 (0.0, 0.0)

Lipid Disorder

1 (1.9%)

0

1 (0.8%)

0

1.9 (-1.8, 5.5)

0.0 (0.0, 0.0)

Immune system disorders

0

0

0

1 (1.7%)

-1.7 (-5.0, 1.6)

-1.7 (-5.0, 1.6)

Hypersensitivity

0

0

0

1 (1.7%)

-1.7 (-5.0, 1.6)

-1.7 (-5.0, 1.6)

Renal and urinary disorders

0

0

0

1 (1.7%)

-1.7 (-5.0, 1.6)

-1.7 (-5.0, 1.6)

Renal & Urinary Tract
 Infection

0

0

0

1 (1.7%)

-1.7 (-5.0, 1.6)

-1.7 (-5.0, 1.6)

Key: FMQ=FDA Medical Query

a Each FMQ is aligned to a single system organ class based on clinical judgment, as defined by FDA. However, some FMQs may contain preferred terms from more than one system organ class.

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