Generic Functions

In admiral: ADaM in R Asset Library

knitr::opts_chunk$set(
  collapse = TRUE,
  comment = "#>"
)
library(admiraldev)

Introduction

This vignette explains some of the {admiral} generic functions, which we believe are able to be re-used to sometimes save users having to create so many of their own functions for study-specific analysis derivations. These re-usable functions give the users great flexibility, but the challenge is knowing which to use when. So this vignette is intended to help understand the differences between each, thus improving the findability of the function needed for each task.

The focus will be on the following different sets of generic functions:

• merged functions
• joined functions
• extreme functions

In each section below, we will show examples of different functions that belong to each of these sets, but we don't list out each and every function offered. Users should refer to the Reference page and search for example "merged" to see the full list of functions offered for this respective set, with more examples shown within each function page.

Required Packages

The examples in this vignette require the following packages.

For example purpose, the SDTM datasets from {pharmaversesdtm} are used.

library(admiral)
library(pharmaversesdtm)
library(dplyr, warn.conflicts = FALSE)
library(stringr)
library(tibble)

data("dm")
data("ds")
data("ex")
data("ae")
dm <- convert_blanks_to_na(dm)
ds <- convert_blanks_to_na(ds)
ex <- convert_blanks_to_na(ex)
ae <- convert_blanks_to_na(ae)

# Filter test patients and make more realistic and interesting for the examples
dm <- filter(dm, USUBJID %in% c("01-701-1111", "01-701-1047", "01-701-1057"))
ds <- filter(ds, USUBJID %in% c("01-701-1111", "01-701-1047", "01-701-1057")) %>%
  mutate(DSSTDTC = case_when(
    USUBJID == "01-701-1111" & DSDECOD == "RANDOMIZED" ~ "2012-08-01",
    TRUE ~ DSSTDTC
  ))
ex <- filter(ex, USUBJID %in% c("01-701-1111", "01-701-1047", "01-701-1057"))
ae <- filter(ae, USUBJID %in% c("01-701-1111", "01-701-1047")) %>%
  mutate(AESTDTC = case_when(
    USUBJID == "01-701-1111" & AESTDY == "-61" ~ "2012-09-14",
    TRUE ~ AESTDTC
  )) %>%
  mutate(AESTDY = case_when(
    USUBJID == "01-701-1111" & AESTDY == "-61" ~ 8,
    TRUE ~ AESTDY
  ))

Difference between merged and joined functions

Firstly, we need to address the question all new users will have... why do we have "merged" and "joined" functions and are they not the same thing??

Essentially in both sets of functions we are trying to take information from an additional dataframe (passed into the dataset_add argument) and join it to our original dataframe (passed into the dataset argument). The subtle difference is that "merged" functions select the relevant information from the additional dataframe and then adds it to the original dataframe; whilst "joined" functions allow an extra filter condition after the join to further select the relevant information.

So in derive_vars_joined() for example, the filter conditions can depend on variables from both dataframes; whilst in derive_vars_merged() only variables from the additional dataframe can be used. Examples will be shown in the below sections to further explain the difference.

In principle though, we actually could achieve every "merged" function result using the equivalent "joined" function. However, the "joined" functions require much more resources (time and memory), hence why we include both options for users.

merged functions {#merged}

Description

As explained above, this simpler set of functions for joins selects relevant information from the additional dataframe and joins it to the original dataframe.

The additional dataframe can be filtered based on a user-defined condition passed into the filter_add argument and/or (where relevant) by selecting the first or last observation for each by group (order and mode arguments) and then joined with the input dataframe by user-specified variables passed into by_vars argument. Variables from the additional dataframe can be joined to the input dataframe as they are or can be renamed (new_vars argument).

The dataframe returned from the function call contains all observations and variables from the original dataframe (with or without filtering applied) and additionally the variable(s) specified for new_var/new_vars from the additional dataframe. This is achieved via an underlying dplyr::left_join. For observations without a match in the additional dataframe the new variable(s) are set to NA. Observations in the additional dataframe which have no match in the original dataframe are ignored.

Examples

A simple call to derive ADSL randomization date (ADSL.RANDDT) from an intermediate additional dataframe would use derive_vars_merged() as follows.

# Use DM domain as basis to build ADSL
adsl_01 <- dm %>%
  select(-DOMAIN)

# Convert disposition character date to numeric date and
# join as randomization date to ADSL
adsl_02 <- adsl_01 %>%
  derive_vars_merged(
    dataset_add = ds,
    filter_add = DSDECOD == "RANDOMIZED",
    by_vars = exprs(STUDYID, USUBJID),
    new_vars = exprs(RANDDT = convert_dtc_to_dt(DSSTDTC))
  )

This call would return the input dataframe with the variable RANDDT added.

Now, an example to add first treatment datetime (ADSL.TRTSDT), where we need to make use of derive_vars_merged() with the mode and order arguments to select the required observations from the additional dataframe. Note: the filter_add argument here shows a possible method for checking only for valid doses.

# Convert exposure start date to numeric date without imputation,
# determine first exposure datetime and add to ADSL
adsl_03 <- adsl_02 %>%
  derive_vars_merged(
    dataset_add = ex,
    filter_add = (EXDOSE > 0 | (EXDOSE == 0 & str_detect(EXTRT, "PLACEBO"))) &
      !is.na(TRTSDT),
    new_vars = exprs(TRTSDT = convert_dtc_to_dt(EXSTDTC)),
    order = exprs(TRTSDT, EXSEQ),
    mode = "first",
    by_vars = exprs(STUDYID, USUBJID)
  )

This call would return the input dataframe with TRTSDT added.

Beyond derive_vars_merged(), other "merged" functions offer specific common analysis needs. For example, below shows an example of using derive_var_merged_exist_flag() for adding safety population flag (ADSL.SAFFL).

In this case we create a new flag variable (new_var argument) based on information we take from the additional dataframe to tell us if a certain condition is met. For all by groups (by_vars argument) where the check evaluates as TRUE at least once the flag is set to "Y" (or whatever user passes in true_value argument).

Note: we have extra arguments available here for patients that do not meet the condition. In the below example, we set patients in EX with no valid dose to "N" (false_value) and the same for patients with no observations at all in EX (missing_value).

# Add safety population flag to ADSL
adsl_04 <- adsl_03 %>%
  derive_var_merged_exist_flag(
    dataset_add = ex,
    by_vars = exprs(STUDYID, USUBJID),
    new_var = SAFFL,
    condition = (EXDOSE > 0 | (EXDOSE == 0 & str_detect(EXTRT, "PLACEBO"))),
    false_value = "N",
    missing_value = "N"
  )

Here's how all these above derived variables then look in the dataset.

dataset_vignette(
  dataset = adsl_04,
  display_vars = exprs(USUBJID, RANDDT, TRTSDT, SAFFL)
)

Some further examples of "merged" functions are derive_vars_merged_lookup() to join a user-defined lookup table as commonly used in BDS ADaMs or derive_var_merged_summary() to merge summarized values from the additional dataframe.

joined functions {#joined}

Description

For any "joined" function remember from above that the main difference is that given the additional option to filter after the join, it means that selection of the observations to add from the additional dataframe can depend on variables from both this and the original dataframe.

So, as with the "merged" functions the additional dataframe can first be filtered based on a user-defined condition passed into the filter_add argument. Then it is joined with the input dataframe by user-specified variables passed into by_vars argument. The joined dataframe can then be further restricted by the filter_join condition, before optionally selecting the first or last observation for each by group (order and mode arguments). Finally the joined variables from the additional dataframe can be renamed (new_vars argument).

To illustrate this, imagine that in the above randomization date example you only wanted the date populated for patients randomized within 30 days of first treatment. You would now need to check both the additional DS and the original ADSL dataframes, so this would not be possible in one step using the "merged" functions.

Examples

The above mentioned randomization date variable (let's call it RAND30DT here) would use derive_vars_joined() as follows.

# Convert disposition character date to numeric date without imputation
ds_ext <- derive_vars_dt(
  dataset = ds,
  dtc = DSSTDTC,
  new_vars_prefix = "DSST"
)

# Join randomization date to ADSL only for safety population patients
adsl_05 <- adsl_04 %>%
  derive_vars_joined(
    dataset_add = ds_ext,
    filter_add = DSDECOD == "RANDOMIZED",
    by_vars = exprs(STUDYID, USUBJID),
    new_vars = exprs(RAND30DT = DSSTDT),
    filter_join = DSSTDT >= TRTSDT - 30
  )

dataset_vignette(
  dataset = adsl_05,
  display_vars = exprs(USUBJID, RANDDT, TRTSDT, RAND30DT)
)

Now, let's consider another example of derive_vars_joined(). For this we'll need to additionally use the join_vars argument, which is where the user needs to call out any variables from the additional dataframe being used in filter_join. Note: If a specified variable exists in both dataframes, then the suffix ".join" is added to the variable from the additional dataframe.

In this case we want to add a datacut flag to AE, only for events occurring up to and including this day. So in this case AE is the original dataframe and the datacut source is the additional dataframe that needs to be joined.

# Create a unique datacut day for each patient
datacut <- tribble(
  ~USUBJID,      ~DCUTDY, ~DCUTFL,
  "01-701-1047",      25, "Y",
  "01-701-1111",       5, "Y"
)

# Join datacut flag to AE only for events up to and including this date
ae_01 <- ae %>%
  derive_vars_joined(
    dataset_add = datacut,
    by_vars = exprs(USUBJID),
    new_vars = exprs(DCUTFL),
    join_vars = exprs(DCUTDY),
    filter_join = AESTDY <= DCUTDY
  )

ae_01 %>%
  select(USUBJID, AEDECOD, AESTDY, DCUTFL) %>%
  arrange(USUBJID, AESTDY) %>%
  dataset_vignette(display_vars = exprs(USUBJID, AEDECOD, AESTDY, DCUTFL))

The derive_vars_joined() function could also be used to join the original dataframe back with itself, which may be necessary if you're comparing across different observations. For example, the below shows how a "nadir" calculation would be achieved which checks for the worst value prior up to that observation.

Here is how you would derive the highest severity AE the patient has occurred post-baseline up to and excluding the current AE day.

# Derive nadir severity (AENADSEV)
# Use a numeric version of severity for sorting with severe=1, moderate=2, mild=3
ae_02 <- ae_01 %>%
  derive_vars_joined(
    dataset_add = ae_01,
    filter_add = AESTDY > 0,
    by_vars = exprs(USUBJID),
    order = exprs(as.integer(factor(AESEV, levels = c("SEVERE", "MODERATE", "MILD")))),
    new_vars = exprs(AENADSEV = AESEV),
    join_vars = exprs(AESTDY),
    filter_join = AESTDY.join < AESTDY,
    mode = "first",
    check_type = "none"
  )

ae_02 %>%
  select(USUBJID, AEDECOD, AESTDY, AESEV, AENADSEV) %>%
  arrange(USUBJID, AESTDY) %>%
  dataset_vignette(display_vars = exprs(USUBJID, AEDECOD, AESTDY, AESEV, AENADSEV))

There exists a further function derive_var_joied_exist_flag(), which follows a similar principle to the "joined" set as explained here. This can be used for whenever one set of observations "confirms" another set in a dataframe, i.e. the flag is only set for your observation if both the observation and some other observation meet both the user-specified criteria.

extreme functions {#extreme}

Description

The "extreme" functions are used for finding the first or last observation (from order and mode arguments) within each by group (by_vars argument).

These can then be output as a flag variable, a date, or as new records dependent on which respective function is used between derive_var_extreme_flag(), derive_var_extreme_dt() or derive_extreme_records() for example.

Example

Building on the above case, let's use derive_var_extreme_flag() to now flag the earliest observation with the highest severity per patient.

# Highest severity flag (AEHSEVFL)
ae_03 <- ae_02 %>%
  derive_var_extreme_flag(
    new_var = AEHSEVFL,
    by_vars = exprs(USUBJID),
    order = exprs(
      as.integer(factor(AESEV, levels = c("SEVERE", "MODERATE", "MILD"))),
      AESTDY, AESEQ
    ),
    mode = "first"
  )

ae_03 %>%
  select(USUBJID, AESTDY, AESEQ, AESEV, AEHSEVFL) %>%
  arrange(USUBJID, AESTDY, AESEQ) %>%
  dataset_vignette(display_vars = exprs(USUBJID, AESTDY, AESEQ, AESEV, AEHSEVFL))

Common further examples of usage of this set of functions could be using derive_var_extreme_dt() for last known alive date calculation or derive_extreme_records() for creating derived minimum or maximum value records.

admiral documentation built on Oct. 19, 2023, 1:08 a.m.