Extent of Exposure

Study Drug Exposure Summary

Setup

See Prerequisites for installation instructions.

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

adex_saf <- pharmaverseadam::adex |>
  blank_to_na() |>
  filter(
    SAFFL  == "Y",
    TRT01A != "Screen Failure",
    PARAMCD %in% c("TDURD", "TDOSE", "AVDDSE")
  )

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

# N per arm from TDURD (one row per subject)
arm_n <- adex_saf |>
  filter(PARAMCD == "TDURD") |>
  count(TRT01A) |>
  pull(n, name = TRT01A)
arm_n <- arm_n[arm_levels]

Data Preparation

param_labels <- c(
  TDURD  = "Total Duration (days)",
  TDOSE  = "Total Dose (mg)",
  AVDDSE = "Average Daily Dose (mg)"
)

# ── Continuous stats per PARAMCD × TRT01A ──
cont_stats <- adex_saf |>
  group_by(PARAMCD, TRT01A) |>
  summarise(
    N      = as.character(n()),
    Mean   = sprintf("%.1f", mean(AVAL, na.rm = TRUE)),
    SD     = sprintf("%.2f", sd(AVAL, na.rm = TRUE)),
    Median = sprintf("%.1f", median(AVAL, na.rm = TRUE)),
    Min    = sprintf("%.1f", min(AVAL, na.rm = TRUE)),
    Max    = sprintf("%.1f", max(AVAL, na.rm = TRUE)),
    .groups = "drop"
  ) |>
  pivot_longer(c(N, Mean, SD, Median, Min, Max),
               names_to = "stat_label", values_to = "value") |>
  pivot_wider(names_from = TRT01A, values_from = value) |>
  mutate(
    variable = unname(param_labels[PARAMCD]),
    .before  = 1
  ) |>
  select(-PARAMCD)

# ── Duration category rows (derived from TDURD) ──
tdurd_data <- adex_saf |> filter(PARAMCD == "TDURD")

dur_thresholds <- c(
  "\u22651 day"   = 1,
  "\u226530 days" = 30,
  "\u226560 days" = 60,
  "\u226590 days" = 90,
  "\u2265180 days" = 180
)

dur_rows <- lapply(names(dur_thresholds), function(lbl) {
  thresh <- dur_thresholds[[lbl]]
  by_arm <- tdurd_data |>
    group_by(TRT01A) |>
    summarise(
      n   = sum(AVAL >= thresh, na.rm = TRUE),
      N   = n(),
      pct = sprintf("%d (%.1f)", n, n / N * 100),
      .groups = "drop"
    ) |>
    select(TRT01A, pct) |>
    pivot_wider(names_from = TRT01A, values_from = pct)

  by_arm |>
    mutate(
      variable   = "Duration Categories, n (%)",
      stat_label = lbl,
      .before    = 1
    )
})

dur_wide <- bind_rows(dur_rows)

# ── Combine all rows ──
# Order: TDURD stats, TDOSE stats, AVDDSE stats, duration categories
param_order <- c("Total Duration (days)", "Total Dose (mg)", "Average Daily Dose (mg)",
                 "Duration Categories, n (%)")

exposure_wide <- bind_rows(cont_stats, dur_wide) |>
  mutate(
    variable = factor(variable, levels = param_order),
    stat_label = factor(stat_label, levels = c("N", "Mean", "SD", "Median", "Min", "Max",
                                                names(dur_thresholds)))
  ) |>
  arrange(variable, stat_label) |>
  mutate(
    variable   = as.character(variable),
    stat_label = as.character(stat_label)
  ) |>
  mutate(across(all_of(arm_levels), ~ replace_na(.x, "")))
# ── Continuous stats via cards ──
# .by = c("TRT01A", "PARAMCD"): TRT01A becomes arm columns, PARAMCD is preserved
# as an extra group column in fr_wide_ard output alongside variable/stat_label.
ex_ard <- ard_stack(
  data = adex_saf,
  .by  = c("TRT01A", "PARAMCD"),
  ard_continuous(
    variables  = "AVAL",
    statistic  = ~ continuous_summary_fns(c("N", "mean", "sd", "median", "min", "max"))
  ),
  .overall = FALSE
) |>
  filter(variable == "AVAL")

param_labels <- c(
  TDURD  = "Total Duration (days)",
  TDOSE  = "Total Dose (mg)",
  AVDDSE = "Average Daily Dose (mg)"
)

exposure_cards <- fr_wide_ard(
  ex_ard,
  statistic = list(
    continuous = c(
      "N"      = "{N}",
      "Mean"   = "{mean}",
      "SD"     = "{sd}",
      "Median" = "{median}",
      "Min"    = "{min}",
      "Max"    = "{max}"
    )
  ),
  decimals = c(mean = 1, sd = 2, median = 1, min = 1, max = 1),
  column  = "TRT01A"
) |>
  mutate(variable = unname(param_labels[PARAMCD])) |>
  select(-PARAMCD) |>
  mutate(across(where(is.factor), as.character))

arframe Pipeline

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

exposure_wide |>
  fr_table() |>
  fr_titles(
    "Extent of Exposure",
    "Study Drug Exposure Summary",
    "Safety Population"
  ) |>
  fr_cols(
    variable   = fr_col(visible = FALSE),
    stat_label = fr_col("", width = 2.2),
    !!!setNames(
      lapply(arm_levels, function(a) fr_col(a, align = "decimal")),
      arm_levels
    ),
    .n = arm_n
  ) |>
  fr_header(bold = TRUE, align = "center") |>
  fr_rows(
    group_by    = list(cols = "variable", label = "stat_label"),
    blank_after = "variable",
    group_style = list(bold = TRUE)
  ) |>
  fr_footnotes(
    "Safety Population: subjects who received at least one dose of study drug.",
    "Duration categories are based on Total Duration (TDURD). Percentages based on N per treatment group.",
    "SD = Standard Deviation."
  )

Rendered Table

Extent of Exposure
Study Drug Exposure Summary
Safety Population
Placebo
(N=86)		Xanomeline High Dose
(N=72)		Xanomeline Low Dose
(N=96)
Total Duration (days)
N86 72 96
Mean147.8 112.2 85.9
SD 62.13 65.52 70.66
Median182.0 96.5 62.5
Min 0.0 15.0 0.0
Max210.0 200.0 212.0
Total Dose (mg)
N86 72 96
Mean 0.0 8341.5 4638.9
SD 0.00 5182.95 3815.61
Median 0.0 7114.5 3375.0
Min 0.0 810.0 0.0
Max 0.0 15417.0 11448.0
Average Daily Dose (mg)
N86 72 96
Mean 0.0 72.9 54.0
SD 0.00 9.68 0.00
Median 0.0 75.9 54.0
Min 0.0 4.4 54.0
Max 0.0 78.6 54.0
Duration Categories, n (%)
≥1 day85 (98.8)72 (100.0)95 (99.0)
≥30 days78 (90.7)67 ( 93.1)65 (67.7)
≥60 days71 (82.6)49 ( 68.1)51 (53.1)
≥90 days67 (77.9)38 ( 52.8)40 (41.7)
≥180 days55 (64.0)26 ( 36.1)25 (26.0)
Safety Population: subjects who received at least one dose of study drug.
Duration categories are based on Total Duration (TDURD). Percentages based on N per treatment group.
SD = Standard Deviation.
/opt/quarto/share/rmd/rmd.R 01APR2026 09:53:08