Referential Footnotes

Emily de la Rua

2024-06-20


Introduction

There is currently no formal method for adding referential footnotes to a listing object. This vignette demonstrates how referential footnotes can be added to a listing_df object via a workaround applied during pre-processing.

To learn more about how listings are constructed using the rlistings package, see the Getting Started vignette.


Referential Footnotes Workaround

When creating a listing with the rlistings package, you may want to add referential footnotes, similar to how referential footnotes can be added to rtable objects. Since there is no formal method in rlistings for applying referential footnotes to a listing_df object, we will demonstrate how a workaround can be applied to add a set of pseudo-referential footnotes to your listing.

To demonstrate, we will create a basic listing below.

We begin by loading in the rlistings package.

library(rlistings)

For this example, we will use the dummy ADAE dataset provided within the formatters package as our data frame, which consists of 48 columns of adverse event patient data, and one or more rows per patient. For the purpose of this example, we will subset the data and only use the first 30 records of the dataset.

adae <- ex_adae[1:30, ]

Now we will create a basic listing.

lsting <- as_listing(
  df = adae,
  key_cols = c("ARM", "USUBJID", "ASEQ", "ASTDY"),
  disp_cols = c("BMRKR1", "AESEV"),
)

lsting
#> Description of Planned Arm   Unique Subject Identifier   Analysis Sequence Number   Analysis Start Relative Day   Continous Level Biomarker 1   Severity/Intensity
#> ——————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————
#>         A: Drug X              AB12345-BRA-1-id-134                 1                           251                    6.46299057842479              MODERATE     
#>                                                                     2                           304                    6.46299057842479              MODERATE     
#>                                                                     3                           497                    6.46299057842479              MODERATE     
#>                                                                     4                           608                    6.46299057842479              MODERATE     
#>                                 AB12345-BRA-1-id-42                 1                           39                     2.26753940777848              MODERATE     
#>                                                                     2                           65                     2.26753940777848               SEVERE      
#>                                                                     3                           95                     2.26753940777848              MODERATE     
#>                                                                     4                           160                    2.26753940777848              MODERATE     
#>                                                                     5                           292                    2.26753940777848                MILD       
#>                                                                     6                           460                    2.26753940777848              MODERATE     
#>                                                                     7                           470                    2.26753940777848               SEVERE      
#>                                                                     8                           476                    2.26753940777848              MODERATE     
#>                                                                     9                           497                    2.26753940777848               SEVERE      
#>                                                                     10                          642                    2.26753940777848               SEVERE      
#>         B: Placebo             AB12345-BRA-1-id-236                 1                           22                     7.66300121077566               SEVERE      
#>                                                                     2                           181                    7.66300121077566               SEVERE      
#>                                                                     3                           702                    7.66300121077566               SEVERE      
#>                                 AB12345-BRA-1-id-65                 1                           145                    7.34091885189189              MODERATE     
#>                                                                     2                           191                    7.34091885189189                MILD       
#>                                                                     3                           233                    7.34091885189189               SEVERE      
#>       C: Combination           AB12345-BRA-1-id-141                 1                           259                    7.51607612428241              MODERATE     
#>                                                                     2                           303                    7.51607612428241                MILD       
#>                                                                     3                           493                    7.51607612428241                MILD       
#>                                                                     4                           600                    7.51607612428241              MODERATE     
#>                                                                     5                           635                    7.51607612428241                MILD       
#>                                                                     6                           730                    7.51607612428241               SEVERE      
#>                                AB12345-BRA-1-id-265                 1                           48                      10.323346349886              MODERATE     
#>                                                                     2                           200                     10.323346349886              MODERATE     
#>                                                                     3                           392                     10.323346349886               SEVERE      
#>                                                                     4                           403                     10.323346349886               SEVERE

For this example, we will add 4 referential footnotes.

  1. In the ARM column, for all records with ARM = "A: Drug X" and ASEQ equal to 1 or 2.
  2. In the ASTDY column, for imputed dates, where imputed dates are indicated by the ASTDTF variable.
  3. In the AESEV column, for all records with AETOXGR equal to 5.
  4. In the USUBJID column header.

Footnote text can be supplied either as a vector, where each element is a new footnote, or as a single string with footnotes separated by the new line (\n) character. For example, see the following list of referential footnotes:

ref_fns <- "*   ASEQ 1 or 2\n**  Analysis start date is imputed\n***  Records with ATOXGR = 5\n**** ID column"

We start with our first footnote in the ARM column for records with arm “A: Drug X” which also have analysis sequence number 1 or 2. Referential footnotes can be added to any variable by converting the variable to a factor, editing the variable values, and adding a corresponding footnote below the listing. We will add our first referential footnote in the ARM column. To ensure that levels are correctly ordered, be sure to specify the new level order when mutating your variable.

# Save variable labels for your data to add back in after mutating dataset
df_lbls <- var_labels(adae)

# Mutate variable where referential footnotes are to be added according to your conditions
# Specify order of levels with new referential footnotes added
adae <- adae %>% dplyr::mutate(
  ARM = factor(
    ifelse(ARM == "A: Drug X" & ASEQ %in% 1:2, paste0(ARM, "*"), as.character(ARM)),
    levels = c(sapply(levels(adae$ARM), paste0, c("", "*")))
  )
)

# Add data variable labels back in
var_labels(adae) <- df_lbls

# Generate listing
lsting <- as_listing(
  df = adae,
  key_cols = c("ARM", "USUBJID", "ASEQ", "ASTDY"),
  disp_cols = c("BMRKR1", "AESEV"),
)

lsting
#> Description of Planned Arm   Unique Subject Identifier   Analysis Sequence Number   Analysis Start Relative Day   Continous Level Biomarker 1   Severity/Intensity
#> ——————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————
#>         A: Drug X              AB12345-BRA-1-id-134                 3                           497                    6.46299057842479              MODERATE     
#>                                                                     4                           608                    6.46299057842479              MODERATE     
#>                                 AB12345-BRA-1-id-42                 3                           95                     2.26753940777848              MODERATE     
#>                                                                     4                           160                    2.26753940777848              MODERATE     
#>                                                                     5                           292                    2.26753940777848                MILD       
#>                                                                     6                           460                    2.26753940777848              MODERATE     
#>                                                                     7                           470                    2.26753940777848               SEVERE      
#>                                                                     8                           476                    2.26753940777848              MODERATE     
#>                                                                     9                           497                    2.26753940777848               SEVERE      
#>                                                                     10                          642                    2.26753940777848               SEVERE      
#>         A: Drug X*             AB12345-BRA-1-id-134                 1                           251                    6.46299057842479              MODERATE     
#>                                                                     2                           304                    6.46299057842479              MODERATE     
#>                                 AB12345-BRA-1-id-42                 1                           39                     2.26753940777848              MODERATE     
#>                                                                     2                           65                     2.26753940777848               SEVERE      
#>         B: Placebo             AB12345-BRA-1-id-236                 1                           22                     7.66300121077566               SEVERE      
#>                                                                     2                           181                    7.66300121077566               SEVERE      
#>                                                                     3                           702                    7.66300121077566               SEVERE      
#>                                 AB12345-BRA-1-id-65                 1                           145                    7.34091885189189              MODERATE     
#>                                                                     2                           191                    7.34091885189189                MILD       
#>                                                                     3                           233                    7.34091885189189               SEVERE      
#>       C: Combination           AB12345-BRA-1-id-141                 1                           259                    7.51607612428241              MODERATE     
#>                                                                     2                           303                    7.51607612428241                MILD       
#>                                                                     3                           493                    7.51607612428241                MILD       
#>                                                                     4                           600                    7.51607612428241              MODERATE     
#>                                                                     5                           635                    7.51607612428241                MILD       
#>                                                                     6                           730                    7.51607612428241               SEVERE      
#>                                AB12345-BRA-1-id-265                 1                           48                      10.323346349886              MODERATE     
#>                                                                     2                           200                     10.323346349886              MODERATE     
#>                                                                     3                           392                     10.323346349886               SEVERE      
#>                                                                     4                           403                     10.323346349886               SEVERE

Additional referential footnotes can be added to the data be repeating the above steps.

For example, we can add the second referential footnote to the ASTDY column for imputed analysis start days. We use dummy variable ASTDTF to indicate imputed analysis start dates. When adding referential footnotes to numeric variables, the variables must be converted to factors.

set.seed(1)

# Save variable labels for your data to add back in after mutating dataset
df_lbls <- var_labels(adae)

# Mutate variable where referential footnotes are to be added according to your conditions
# Specify order of levels with new referential footnotes added
adae <- adae %>%
  dplyr::mutate(ASTDTF = sample(c("Y", NA), nrow(.), replace = TRUE, prob = c(0.25, 0.75))) %>%
  dplyr::mutate(ASTDY = factor(
    ifelse(!is.na(ASTDTF), paste0(as.character(ASTDY), "**"), as.character(ASTDY)),
    levels = c(sapply(sort(unique(adae$ASTDY)), paste0, c("", "**")))
  )) %>%
  dplyr::select(-ASTDTF)

# Add data variable labels back in
var_labels(adae) <- df_lbls

# Generate listing
lsting <- as_listing(
  df = adae,
  key_cols = c("ARM", "USUBJID", "ASEQ", "ASTDY"),
  disp_cols = c("BMRKR1", "AESEV"),
)

lsting
#> Description of Planned Arm   Unique Subject Identifier   Analysis Sequence Number   Analysis Start Relative Day   Continous Level Biomarker 1   Severity/Intensity
#> ——————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————
#>         A: Drug X              AB12345-BRA-1-id-134                 3                           497                    6.46299057842479              MODERATE     
#>                                                                     4                          608**                   6.46299057842479              MODERATE     
#>                                 AB12345-BRA-1-id-42                 3                          95**                    2.26753940777848              MODERATE     
#>                                                                     4                          160**                   2.26753940777848              MODERATE     
#>                                                                     5                           292                    2.26753940777848                MILD       
#>                                                                     6                           460                    2.26753940777848              MODERATE     
#>                                                                     7                           470                    2.26753940777848               SEVERE      
#>                                                                     8                           476                    2.26753940777848              MODERATE     
#>                                                                     9                           497                    2.26753940777848               SEVERE      
#>                                                                     10                          642                    2.26753940777848               SEVERE      
#>         A: Drug X*             AB12345-BRA-1-id-134                 1                           251                    6.46299057842479              MODERATE     
#>                                                                     2                           304                    6.46299057842479              MODERATE     
#>                                 AB12345-BRA-1-id-42                 1                          39**                    2.26753940777848              MODERATE     
#>                                                                     2                           65                     2.26753940777848               SEVERE      
#>         B: Placebo             AB12345-BRA-1-id-236                 1                           22                     7.66300121077566               SEVERE      
#>                                                                     2                           181                    7.66300121077566               SEVERE      
#>                                                                     3                           702                    7.66300121077566               SEVERE      
#>                                 AB12345-BRA-1-id-65                 1                           145                    7.34091885189189              MODERATE     
#>                                                                     2                          191**                   7.34091885189189                MILD       
#>                                                                     3                           233                    7.34091885189189               SEVERE      
#>       C: Combination           AB12345-BRA-1-id-141                 1                           259                    7.51607612428241              MODERATE     
#>                                                                     2                          303**                   7.51607612428241                MILD       
#>                                                                     3                          493**                   7.51607612428241                MILD       
#>                                                                     4                           600                    7.51607612428241              MODERATE     
#>                                                                     5                           635                    7.51607612428241                MILD       
#>                                                                     6                           730                    7.51607612428241               SEVERE      
#>                                AB12345-BRA-1-id-265                 1                           48                      10.323346349886              MODERATE     
#>                                                                     2                          200**                    10.323346349886              MODERATE     
#>                                                                     3                           392                     10.323346349886               SEVERE      
#>                                                                     4                           403                     10.323346349886               SEVERE

Next we can add our third referential footnote to the AESEV column for records with analysis toxicity grade 5.

# Save variable labels for your data to add back in after mutating dataset
df_lbls <- var_labels(adae)

# Mutate variable where referential footnotes are to be added according to your conditions
# Specify order of levels with new referential footnotes added
adae <- adae %>% dplyr::mutate(
  AESEV = factor(
    ifelse(AETOXGR == 5, paste0(AESEV, "***"), as.character(AESEV)),
    levels = c(sapply(levels(adae$AESEV), paste0, c("", "***")))
  )
)

# Add data variable labels back in
var_labels(adae) <- df_lbls

# Generate listing
lsting <- as_listing(
  df = adae,
  key_cols = c("ARM", "USUBJID", "ASEQ", "ASTDY"),
  disp_cols = c("BMRKR1", "AESEV"),
)

lsting
#> Description of Planned Arm   Unique Subject Identifier   Analysis Sequence Number   Analysis Start Relative Day   Continous Level Biomarker 1   Severity/Intensity
#> ——————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————
#>         A: Drug X              AB12345-BRA-1-id-134                 3                           497                    6.46299057842479              MODERATE     
#>                                                                     4                          608**                   6.46299057842479              MODERATE     
#>                                 AB12345-BRA-1-id-42                 3                          95**                    2.26753940777848              MODERATE     
#>                                                                     4                          160**                   2.26753940777848              MODERATE     
#>                                                                     5                           292                    2.26753940777848                MILD       
#>                                                                     6                           460                    2.26753940777848              MODERATE     
#>                                                                     7                           470                    2.26753940777848             SEVERE***     
#>                                                                     8                           476                    2.26753940777848              MODERATE     
#>                                                                     9                           497                    2.26753940777848               SEVERE      
#>                                                                     10                          642                    2.26753940777848             SEVERE***     
#>         A: Drug X*             AB12345-BRA-1-id-134                 1                           251                    6.46299057842479              MODERATE     
#>                                                                     2                           304                    6.46299057842479              MODERATE     
#>                                 AB12345-BRA-1-id-42                 1                          39**                    2.26753940777848              MODERATE     
#>                                                                     2                           65                     2.26753940777848             SEVERE***     
#>         B: Placebo             AB12345-BRA-1-id-236                 1                           22                     7.66300121077566             SEVERE***     
#>                                                                     2                           181                    7.66300121077566             SEVERE***     
#>                                                                     3                           702                    7.66300121077566             SEVERE***     
#>                                 AB12345-BRA-1-id-65                 1                           145                    7.34091885189189              MODERATE     
#>                                                                     2                          191**                   7.34091885189189                MILD       
#>                                                                     3                           233                    7.34091885189189             SEVERE***     
#>       C: Combination           AB12345-BRA-1-id-141                 1                           259                    7.51607612428241              MODERATE     
#>                                                                     2                          303**                   7.51607612428241                MILD       
#>                                                                     3                          493**                   7.51607612428241                MILD       
#>                                                                     4                           600                    7.51607612428241              MODERATE     
#>                                                                     5                           635                    7.51607612428241                MILD       
#>                                                                     6                           730                    7.51607612428241             SEVERE***     
#>                                AB12345-BRA-1-id-265                 1                           48                      10.323346349886              MODERATE     
#>                                                                     2                          200**                    10.323346349886              MODERATE     
#>                                                                     3                           392                     10.323346349886             SEVERE***     
#>                                                                     4                           403                     10.323346349886               SEVERE

Referential footnotes can also be added to column header labels. Suppose we want to add our fourth referential footnote to the USUBJID column label. We can do so by editing the USUBJID variable label and adding the footnote text as follows:

# Modify data variable label
adae <- adae %>% var_relabel(
  USUBJID = paste0(var_labels(adae)[["USUBJID"]], "****")
)

# Generate listing
lsting <- as_listing(
  df = adae,
  key_cols = c("ARM", "USUBJID", "ASTDY", "ASEQ"),
  disp_cols = c("BMRKR1", "AESEV")
)

lsting
#> Description of Planned Arm   Unique Subject Identifier****   Analysis Start Relative Day   Analysis Sequence Number   Continous Level Biomarker 1   Severity/Intensity
#> ——————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————
#>         A: Drug X                AB12345-BRA-1-id-134                    497                          3                    6.46299057842479              MODERATE     
#>                                                                         608**                         4                    6.46299057842479              MODERATE     
#>                                   AB12345-BRA-1-id-42                   95**                          3                    2.26753940777848              MODERATE     
#>                                                                         160**                         4                    2.26753940777848              MODERATE     
#>                                                                          292                          5                    2.26753940777848                MILD       
#>                                                                          460                          6                    2.26753940777848              MODERATE     
#>                                                                          470                          7                    2.26753940777848             SEVERE***     
#>                                                                          476                          8                    2.26753940777848              MODERATE     
#>                                                                          497                          9                    2.26753940777848               SEVERE      
#>                                                                          642                          10                   2.26753940777848             SEVERE***     
#>         A: Drug X*               AB12345-BRA-1-id-134                    251                          1                    6.46299057842479              MODERATE     
#>                                                                          304                          2                    6.46299057842479              MODERATE     
#>                                   AB12345-BRA-1-id-42                   39**                          1                    2.26753940777848              MODERATE     
#>                                                                          65                           2                    2.26753940777848             SEVERE***     
#>         B: Placebo               AB12345-BRA-1-id-236                    22                           1                    7.66300121077566             SEVERE***     
#>                                                                          181                          2                    7.66300121077566             SEVERE***     
#>                                                                          702                          3                    7.66300121077566             SEVERE***     
#>                                   AB12345-BRA-1-id-65                    145                          1                    7.34091885189189              MODERATE     
#>                                                                         191**                         2                    7.34091885189189                MILD       
#>                                                                          233                          3                    7.34091885189189             SEVERE***     
#>       C: Combination             AB12345-BRA-1-id-141                    259                          1                    7.51607612428241              MODERATE     
#>                                                                         303**                         2                    7.51607612428241                MILD       
#>                                                                         493**                         3                    7.51607612428241                MILD       
#>                                                                          600                          4                    7.51607612428241              MODERATE     
#>                                                                          635                          5                    7.51607612428241                MILD       
#>                                                                          730                          6                    7.51607612428241             SEVERE***     
#>                                  AB12345-BRA-1-id-265                    48                           1                     10.323346349886              MODERATE     
#>                                                                         200**                         2                     10.323346349886              MODERATE     
#>                                                                          392                          3                     10.323346349886             SEVERE***     
#>                                                                          403                          4                     10.323346349886               SEVERE

Finally, we add in the referential footnote text below the listing as follows.

# Generate listing
lsting <- as_listing(
  df = adae,
  key_cols = c("ARM", "USUBJID", "ASTDY", "ASEQ"),
  disp_cols = c("BMRKR1", "AESEV")
)

main_footer(lsting) <- c(main_footer(lsting), ref_fns)

lsting
#> Description of Planned Arm   Unique Subject Identifier****   Analysis Start Relative Day   Analysis Sequence Number   Continous Level Biomarker 1   Severity/Intensity
#> ——————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————
#>         A: Drug X                AB12345-BRA-1-id-134                    497                          3                    6.46299057842479              MODERATE     
#>                                                                         608**                         4                    6.46299057842479              MODERATE     
#>                                   AB12345-BRA-1-id-42                   95**                          3                    2.26753940777848              MODERATE     
#>                                                                         160**                         4                    2.26753940777848              MODERATE     
#>                                                                          292                          5                    2.26753940777848                MILD       
#>                                                                          460                          6                    2.26753940777848              MODERATE     
#>                                                                          470                          7                    2.26753940777848             SEVERE***     
#>                                                                          476                          8                    2.26753940777848              MODERATE     
#>                                                                          497                          9                    2.26753940777848               SEVERE      
#>                                                                          642                          10                   2.26753940777848             SEVERE***     
#>         A: Drug X*               AB12345-BRA-1-id-134                    251                          1                    6.46299057842479              MODERATE     
#>                                                                          304                          2                    6.46299057842479              MODERATE     
#>                                   AB12345-BRA-1-id-42                   39**                          1                    2.26753940777848              MODERATE     
#>                                                                          65                           2                    2.26753940777848             SEVERE***     
#>         B: Placebo               AB12345-BRA-1-id-236                    22                           1                    7.66300121077566             SEVERE***     
#>                                                                          181                          2                    7.66300121077566             SEVERE***     
#>                                                                          702                          3                    7.66300121077566             SEVERE***     
#>                                   AB12345-BRA-1-id-65                    145                          1                    7.34091885189189              MODERATE     
#>                                                                         191**                         2                    7.34091885189189                MILD       
#>                                                                          233                          3                    7.34091885189189             SEVERE***     
#>       C: Combination             AB12345-BRA-1-id-141                    259                          1                    7.51607612428241              MODERATE     
#>                                                                         303**                         2                    7.51607612428241                MILD       
#>                                                                         493**                         3                    7.51607612428241                MILD       
#>                                                                          600                          4                    7.51607612428241              MODERATE     
#>                                                                          635                          5                    7.51607612428241                MILD       
#>                                                                          730                          6                    7.51607612428241             SEVERE***     
#>                                  AB12345-BRA-1-id-265                    48                           1                     10.323346349886              MODERATE     
#>                                                                         200**                         2                     10.323346349886              MODERATE     
#>                                                                          392                          3                     10.323346349886             SEVERE***     
#>                                                                          403                          4                     10.323346349886               SEVERE      
#> ——————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————
#> 
#> *   ASEQ 1 or 2
#> **  Analysis start date is imputed
#> ***  Records with ATOXGR = 5
#> **** ID column

Now our listing is complete, with all four referential footnotes denoted within the listing and described in the footnotes section below.


Summary

In this vignette, you have learned how a pre-processing workaround can be applied to add referential footnotes to listings.

For more information please explore the rlistings website.