Deaths, Safety Population, Pooled Analysis (or Trial X)
FDA Table 08
table
FDA
safety
deaths
FDA IG Shell
Programming Notes
Background and Instructions
The clinical reviewer should be aware that sometimes not all deaths are captured in the submitted datasets. All deaths included in submitted datasets (e.g., death details and AE datasets) should be included in this table without regard to the investigator or applicant’s judgment about causality. The clinical reviewer should ensure that all deaths that occurred during the trial, including those reported from other sources (e.g., case narratives) are discussed in the review. In general, deaths should be assessed using an on-study analysis as there is likely some latency to the observance of death after a serious AE.
Customization
After analyzing the initial presentation of Table 8: Deaths, consider requesting a KM plot for deaths (if numerous). Consider requesting a similar table that displays results by individual trials or studies of large size, for populations at high risk, or for trials or studies that include many deaths.
Output
Code
# FDA TABLE 08 ---------------------------------------------------------------
# Self-contained template. Run top-to-bottom to build the objects below.
# Used by tests via run_template() and published in the catalog.
library(dplyr)
library(cards)
library(gtsummary)
adsl <- pharmaverseadam::adsl
adae <- pharmaverseadam::adae
# Pre-processing --------------------------------------------
adsl <- adsl |>
filter(SAFFL == "Y") # safety population
data <- adae |>
filter(
# safety population
SAFFL == "Y",
# deaths
DTHFL == "Y"
)
tbl_dthcaus <- data |>
tbl_hierarchical(
variables = DTHCAUS,
id = USUBJID,
by = TRT01A,
denominator = adsl,
overall_row = TRUE,
label = list("..ard_hierarchical_overall.." = "Death details", DTHCAUS = "**Deaths**")
) |>
sort_hierarchical() |>
modify_indent(columns = label, rows = variable == "DTHCAUS", indent = 4L)
tbl_aesdth <- data |>
filter(AESDTH == "Y") |>
tbl_hierarchical(
variables = AEDECOD,
id = USUBJID,
by = TRT01A,
denominator = adsl,
overall_row = TRUE,
label = list("..ard_hierarchical_overall.." = "Adverse events with an outcome of death", AEDECOD = "**Deaths**")
) |>
sort_hierarchical() |>
modify_indent(columns = label, rows = variable == "AEDECOD", indent = 4L)
tbl <- tbl_stack(list(tbl_dthcaus, tbl_aesdth))
ard <- gtsummary::gather_ard(tbl)| ****Deaths**** |
Placebo N = 861 |
Xanomeline Low Dose N = 961 |
|---|---|---|
| Death details | 2 (2.3%) | 1 (1.0%) |
| COMPLETED SUICIDE | 1 (1.2%) | 0 (0%) |
| MYOCARDIAL INFARCTION | 1 (1.2%) | 0 (0%) |
| SUDDEN DEATH | 0 (0%) | 1 (1.0%) |
| Adverse events with an outcome of death | 2 (2.3%) | 1 (1.0%) |
| COMPLETED SUICIDE | 1 (1.2%) | 0 (0%) |
| MYOCARDIAL INFARCTION | 1 (1.2%) | 0 (0%) |
| SUDDEN DEATH | 0 (0%) | 1 (1.0%) |
| 1 n (%) | ||
[[1]]
[[1]]$tbl_hierarchical
# An ARD data frame: 33 × 13
group1 group1_level variable variable_level context stat_name stat_label stat stat_fmt fmt_fun warning error gts_column
<chr> <list> <chr> <list> <chr> <chr> <chr> <list> <list> <list> <list> <list> <chr>
1 <NA> <NULL> TRT01A Placebo tabulate n n 86 86 0 <NULL> <NULL> stat_1
2 <NA> <NULL> TRT01A Placebo tabulate N N 254 254 0 <NULL> <NULL> stat_1
3 <NA> <NULL> TRT01A Placebo tabulate p % 0.339 33.9 <fn> <NULL> <NULL> stat_1
4 <NA> <NULL> TRT01A Xanomeline High Dose tabulate n n 72 72 0 <NULL> <NULL> stat_2
5 <NA> <NULL> TRT01A Xanomeline High Dose tabulate N N 254 254 0 <NULL> <NULL> stat_2
6 <NA> <NULL> TRT01A Xanomeline High Dose tabulate p % 0.283 28.3 <fn> <NULL> <NULL> stat_2
7 <NA> <NULL> TRT01A Xanomeline Low Dose tabulate n n 96 96 0 <NULL> <NULL> stat_3
8 <NA> <NULL> TRT01A Xanomeline Low Dose tabulate N N 254 254 0 <NULL> <NULL> stat_3
9 <NA> <NULL> TRT01A Xanomeline Low Dose tabulate p % 0.378 37.8 <fn> <NULL> <NULL> stat_3
10 TRT01A Placebo ..ard_hierarchical_overall.. TRUE hierarchical n n 2 2 <fn> <NULL> <NULL> stat_1
11 TRT01A Placebo ..ard_hierarchical_overall.. TRUE hierarchical N N 86 86 <fn> <NULL> <NULL> stat_1
12 TRT01A Placebo ..ard_hierarchical_overall.. TRUE hierarchical p % 0.0233 2.3 <fn> <NULL> <NULL> stat_1
13 TRT01A Xanomeline Low Dose ..ard_hierarchical_overall.. TRUE hierarchical n n 1 1 <fn> <NULL> <NULL> stat_2
14 TRT01A Xanomeline Low Dose ..ard_hierarchical_overall.. TRUE hierarchical N N 96 96 <fn> <NULL> <NULL> stat_2
15 TRT01A Xanomeline Low Dose ..ard_hierarchical_overall.. TRUE hierarchical p % 0.0104 1.0 <fn> <NULL> <NULL> stat_2
16 TRT01A Placebo DTHCAUS COMPLETED SUICIDE hierarchical n n 1 1 <fn> <NULL> <NULL> stat_1
17 TRT01A Placebo DTHCAUS COMPLETED SUICIDE hierarchical N N 86 86 <fn> <NULL> <NULL> stat_1
18 TRT01A Placebo DTHCAUS COMPLETED SUICIDE hierarchical p % 0.0116 1.2 <fn> <NULL> <NULL> stat_1
19 TRT01A Xanomeline Low Dose DTHCAUS COMPLETED SUICIDE hierarchical n n 0 0 <fn> <NULL> <NULL> stat_2
20 TRT01A Xanomeline Low Dose DTHCAUS COMPLETED SUICIDE hierarchical N N 96 96 <fn> <NULL> <NULL> stat_2
21 TRT01A Xanomeline Low Dose DTHCAUS COMPLETED SUICIDE hierarchical p % 0 0 <fn> <NULL> <NULL> stat_2
22 TRT01A Placebo DTHCAUS MYOCARDIAL INFARCTION hierarchical n n 1 1 <fn> <NULL> <NULL> stat_1
23 TRT01A Placebo DTHCAUS MYOCARDIAL INFARCTION hierarchical N N 86 86 <fn> <NULL> <NULL> stat_1
24 TRT01A Placebo DTHCAUS MYOCARDIAL INFARCTION hierarchical p % 0.0116 1.2 <fn> <NULL> <NULL> stat_1
25 TRT01A Xanomeline Low Dose DTHCAUS MYOCARDIAL INFARCTION hierarchical n n 0 0 <fn> <NULL> <NULL> stat_2
26 TRT01A Xanomeline Low Dose DTHCAUS MYOCARDIAL INFARCTION hierarchical N N 96 96 <fn> <NULL> <NULL> stat_2
27 TRT01A Xanomeline Low Dose DTHCAUS MYOCARDIAL INFARCTION hierarchical p % 0 0 <fn> <NULL> <NULL> stat_2
28 TRT01A Placebo DTHCAUS SUDDEN DEATH hierarchical n n 0 0 <fn> <NULL> <NULL> stat_1
29 TRT01A Placebo DTHCAUS SUDDEN DEATH hierarchical N N 86 86 <fn> <NULL> <NULL> stat_1
30 TRT01A Placebo DTHCAUS SUDDEN DEATH hierarchical p % 0 0 <fn> <NULL> <NULL> stat_1
31 TRT01A Xanomeline Low Dose DTHCAUS SUDDEN DEATH hierarchical n n 1 1 <fn> <NULL> <NULL> stat_2
32 TRT01A Xanomeline Low Dose DTHCAUS SUDDEN DEATH hierarchical N N 96 96 <fn> <NULL> <NULL> stat_2
33 TRT01A Xanomeline Low Dose DTHCAUS SUDDEN DEATH hierarchical p % 0.0104 1.0 <fn> <NULL> <NULL> stat_2
[[2]]
[[2]]$tbl_hierarchical
# An ARD data frame: 33 × 13
group1 group1_level variable variable_level context stat_name stat_label stat stat_fmt fmt_fun warning error gts_column
<chr> <list> <chr> <list> <chr> <chr> <chr> <list> <list> <list> <list> <list> <chr>
1 <NA> <NULL> TRT01A Placebo tabulate n n 86 86 0 <NULL> <NULL> stat_1
2 <NA> <NULL> TRT01A Placebo tabulate N N 254 254 0 <NULL> <NULL> stat_1
3 <NA> <NULL> TRT01A Placebo tabulate p % 0.339 33.9 <fn> <NULL> <NULL> stat_1
4 <NA> <NULL> TRT01A Xanomeline High Dose tabulate n n 72 72 0 <NULL> <NULL> stat_2
5 <NA> <NULL> TRT01A Xanomeline High Dose tabulate N N 254 254 0 <NULL> <NULL> stat_2
6 <NA> <NULL> TRT01A Xanomeline High Dose tabulate p % 0.283 28.3 <fn> <NULL> <NULL> stat_2
7 <NA> <NULL> TRT01A Xanomeline Low Dose tabulate n n 96 96 0 <NULL> <NULL> stat_3
8 <NA> <NULL> TRT01A Xanomeline Low Dose tabulate N N 254 254 0 <NULL> <NULL> stat_3
9 <NA> <NULL> TRT01A Xanomeline Low Dose tabulate p % 0.378 37.8 <fn> <NULL> <NULL> stat_3
10 TRT01A Placebo ..ard_hierarchical_overall.. TRUE hierarchical n n 2 2 <fn> <NULL> <NULL> stat_1
11 TRT01A Placebo ..ard_hierarchical_overall.. TRUE hierarchical N N 86 86 <fn> <NULL> <NULL> stat_1
12 TRT01A Placebo ..ard_hierarchical_overall.. TRUE hierarchical p % 0.0233 2.3 <fn> <NULL> <NULL> stat_1
13 TRT01A Xanomeline Low Dose ..ard_hierarchical_overall.. TRUE hierarchical n n 1 1 <fn> <NULL> <NULL> stat_2
14 TRT01A Xanomeline Low Dose ..ard_hierarchical_overall.. TRUE hierarchical N N 96 96 <fn> <NULL> <NULL> stat_2
15 TRT01A Xanomeline Low Dose ..ard_hierarchical_overall.. TRUE hierarchical p % 0.0104 1.0 <fn> <NULL> <NULL> stat_2
16 TRT01A Placebo AEDECOD COMPLETED SUICIDE hierarchical n n 1 1 <fn> <NULL> <NULL> stat_1
17 TRT01A Placebo AEDECOD COMPLETED SUICIDE hierarchical N N 86 86 <fn> <NULL> <NULL> stat_1
18 TRT01A Placebo AEDECOD COMPLETED SUICIDE hierarchical p % 0.0116 1.2 <fn> <NULL> <NULL> stat_1
19 TRT01A Xanomeline Low Dose AEDECOD COMPLETED SUICIDE hierarchical n n 0 0 <fn> <NULL> <NULL> stat_2
20 TRT01A Xanomeline Low Dose AEDECOD COMPLETED SUICIDE hierarchical N N 96 96 <fn> <NULL> <NULL> stat_2
21 TRT01A Xanomeline Low Dose AEDECOD COMPLETED SUICIDE hierarchical p % 0 0 <fn> <NULL> <NULL> stat_2
22 TRT01A Placebo AEDECOD MYOCARDIAL INFARCTION hierarchical n n 1 1 <fn> <NULL> <NULL> stat_1
23 TRT01A Placebo AEDECOD MYOCARDIAL INFARCTION hierarchical N N 86 86 <fn> <NULL> <NULL> stat_1
24 TRT01A Placebo AEDECOD MYOCARDIAL INFARCTION hierarchical p % 0.0116 1.2 <fn> <NULL> <NULL> stat_1
25 TRT01A Xanomeline Low Dose AEDECOD MYOCARDIAL INFARCTION hierarchical n n 0 0 <fn> <NULL> <NULL> stat_2
26 TRT01A Xanomeline Low Dose AEDECOD MYOCARDIAL INFARCTION hierarchical N N 96 96 <fn> <NULL> <NULL> stat_2
27 TRT01A Xanomeline Low Dose AEDECOD MYOCARDIAL INFARCTION hierarchical p % 0 0 <fn> <NULL> <NULL> stat_2
28 TRT01A Placebo AEDECOD SUDDEN DEATH hierarchical n n 0 0 <fn> <NULL> <NULL> stat_1
29 TRT01A Placebo AEDECOD SUDDEN DEATH hierarchical N N 86 86 <fn> <NULL> <NULL> stat_1
30 TRT01A Placebo AEDECOD SUDDEN DEATH hierarchical p % 0 0 <fn> <NULL> <NULL> stat_1
31 TRT01A Xanomeline Low Dose AEDECOD SUDDEN DEATH hierarchical n n 1 1 <fn> <NULL> <NULL> stat_2
32 TRT01A Xanomeline Low Dose AEDECOD SUDDEN DEATH hierarchical N N 96 96 <fn> <NULL> <NULL> stat_2
33 TRT01A Xanomeline Low Dose AEDECOD SUDDEN DEATH hierarchical p % 0.0104 1.0 <fn> <NULL> <NULL> stat_2