Creating ADOE

Introduction

This article describes creating an ADOE ADaM with Ophthalmology Exam Analysis data for ophthalmology endpoints. It is to be used in conjunction with the article on creating a BDS dataset from SDTM. As such, derivations and processes that are not specific to ADOE are absent, and the user is invited to consult the aforementioned article for guidance.

Note: All examples assume CDISC SDTM and/or ADaM format as input unless otherwise specified.

Dataset Contents

admiralophtha suggests to populate ADOE with general miscellaneous ophthalmology parameters. Any efficacy endpoint-related parameters (eg. BCVA tests) should be placed in separate datasets (eg. ADBCVA).

Required Packages

The examples of this vignette require the following packages.

library(dplyr)
library(admiral)
library(pharmaversesdtm)
library(admiraldev)
library(admiralophtha)
library(stringr)

Programming Workflow

• Initial Set Up of ADOE
• Further Derivations of Standard BDS Variables
• Example Script

Initial set up of ADOE

As with all BDS ADaM datasets, one should start from the OE SDTM, where only the general ophthalmology records are of interest. For the purposes of the next two sections, we shall be using the admiral OE and ADSL test data. We will also require a lookup table for the mapping of parameter codes.

Note: to simulate an ophthalmology study, we add a randomly generated STUDYEYE variable to ADSL, but in practice STUDYEYE will already have been derived using derive_var_studyeye().

data("oe_ophtha")
data("admiral_adsl")

# Add STUDYEYE to ADSL to simulate an ophtha dataset
adsl <- admiral_adsl %>%
  as.data.frame() %>%
  mutate(STUDYEYE = sample(c("LEFT", "RIGHT"), n(), replace = TRUE)) %>%
  convert_blanks_to_na()

oe <- convert_blanks_to_na(oe_ophtha)

# Lookup table

# nolint start
param_lookup <- tibble::tribble(
  ~OETESTCD, ~OECAT, ~OESCAT, ~AFEYE, ~PARAMCD, ~PARAM, ~PARAMN,
  "CSUBTH", "OPHTHALMIC ASSESSMENTS", "SD-OCT CST SINGLE FORM", "Study Eye", "SCSUBTH", "Study Eye Center Subfield Thickness (um)", 1,
  "CSUBTH", "OPHTHALMIC ASSESSMENTS", "SD-OCT CST SINGLE FORM", "Fellow Eye", "FCSUBTH", "Fellow Eye Center Subfield Thickness (um)", 2,
  "DRSSR", "OPHTHALMIC ASSESSMENTS", "SD-OCT CST SINGLE FORM", "Study Eye", "SDRSSR", "Study Eye Diabetic Retinopathy Severity", 3,
  "DRSSR", "OPHTHALMIC ASSESSMENTS", "SD-OCT CST SINGLE FORM", "Fellow Eye", "FDRSSR", "Fellow Eye Diabetic Retinopathy Severity", 4,
  "IOP", "INTRAOCULAR PRESSURE", NA_character_, "Study Eye", "SIOP", "Study Eye IOP (mmHg)", 5,
  "IOP", "INTRAOCULAR PRESSURE", NA_character_, "Fellow Eye", "FIOP", "Fellow Eye IOP (mmHg)", 6
)
# nolint end

Following this setup, the programmer can start constructing ADOE. The first step is to subset OE to only general ophthalmology parameters. Then, one can merge the resulting dataset with ADSL. This is required for two reasons: firstly, STUDYEYE is crucial in the mapping of AFEYE and PARAMCD’s. Secondly, the treatment start date (TRTSDT) is also a prerequisite for the derivation of variables such as Analysis Day (ADY).

adsl_vars <- exprs(TRTSDT, TRTEDT, TRT01A, TRT01P, STUDYEYE)

adoe <- oe %>%
  filter(
    OETESTCD %in% c("CSUBTH", "DRSSR", "IOP")
  ) %>%
  derive_vars_merged(
    dataset_add = adsl,
    new_vars = adsl_vars,
    by_vars = get_admiral_option("subject_keys")
  )

The next item of business is to derive AVAL, AVALU, and DTYPE. In this example, due to the small number of parameters their derivation is trivial. AFEYE is also created in this step using the function derive_var_afeye(). To determine the affected eye, this function compares OELAT to the STUDYEYE variable created from the previous step.

adoe <- adoe %>%
  # Calculate AVAL, AVALC, AVALU and DTYPE
  mutate(
    AVAL = OESTRESN,
    AVALC = OESTRESC,
    AVALU = OESTRESU,
    DTYPE = NA_character_
  ) %>%
  # Derive AFEYE needed for PARAMCD derivation
  derive_var_afeye(loc_var = OELOC, lat_var = OELAT, loc_vals = c("EYE", "RETINA"))

Assigning PARAM/PARAMCD and AVISIT/AVISITN

Moving forwards, PARAM and PARAMCD can be assigned using derive_vars_merged() from admiral and the lookup table param_lookup generated above. AVISIT, AVISITN and related timepoint variables can also be derived soon after, though their derivation is generally study-specific. A simple option is included below; please consult the admiral BDS findings vignette for a more detailed discussion.

adoe <- adoe %>%
  # Add PARAM, PARAMCD from lookup table
  derive_vars_merged(
    dataset_add = param_lookup,
    new_vars = exprs(PARAM, PARAMCD),
    by_vars = exprs(OETESTCD, AFEYE)
  ) %>%
  # Derive visit, baseline flag info and BASETYPE
  mutate(
    ATPTN = OETPTNUM,
    ATPT = OETPT,
    AVISIT = case_when(
      str_detect(VISIT, "SCREEN") ~ "Screening",
      !is.na(VISIT) ~ str_to_title(VISIT),
      TRUE ~ NA_character_
    ),
    AVISITN = round(VISITNUM, 0),
    ABLFL = if_else(AVISIT == "Baseline", "Y", NA_character_)
    # In actual studies, ABLFL derivation will likely be more nuanced
    # and leverage derive_var_extreme_flag()
  )

Creating IOP pre to post-dose difference derived parameter

Two derived parameters of interest are the difference between pre and post-dose IOP in each eye at each visit. These records can be added with two calls to derive_param_computed(). Since the calls are very similar, they can be executed in one code block using call_derivation() - please see the Higher Order Functions vignette for more details.

adoe <- adoe %>%
  # Add derived parameter for difference between pre and post dose IOP
  call_derivation(
    derivation = derive_param_computed,
    by_vars = c(get_admiral_option("subject_keys"), !!adsl_vars, exprs(AVISIT, AVISITN)),
    variable_params = list(
      # Study eye
      params(
        parameters = exprs(
          SIOPPRE = PARAMCD == "SIOP" & ATPT == "PRE-DOSE",
          SIOPPOST = PARAMCD == "SIOP" & ATPT == "POST-DOSE"
        ),
        set_values_to = exprs(
          PARAMCD = "SIOPCHG",
          PARAM = "Study Eye IOP Pre to Post Dose Diff (mmHg)",
          PARAMN = 9,
          AVAL = AVAL.SIOPPOST - AVAL.SIOPPRE,
          AVALC = as.character(AVAL)
        )
      ),
      # Fellow eye
      params(
        parameters = exprs(
          FIOPPRE = PARAMCD == "FIOP" & ATPT == "PRE-DOSE",
          FIOPPOST = PARAMCD == "FIOP" & ATPT == "POST-DOSE"
        ),
        set_values_to = exprs(
          PARAMCD = "FIOPCHG",
          PARAM = "Fellow Eye IOP Pre to Post Dose Diff (mmHg)",
          PARAMN = 10,
          AVAL = AVAL.FIOPPOST - AVAL.FIOPPRE,
          AVALC = as.character(AVAL)
        )
      )
    )
  )

Note that within the call to derive_param_computed(), the parameters argument has been used to pass an expression that uniquely identifies which records are the pre-dose IOP and which are the post-dose IOP using the timepoint variable OETPT, because all IOP records are mapped to PARAMCD = "SIOP" or PARAMCD = "FIOP". Users may need to update this expression if their study-specific collection or mapping differs from this standard.

Additionally, it should be noted that for the SIOPCHG and FIOPCHG derived parameters, it is generally recommended not to populate BASE, CHG and PCHG as they are difficult/confusing to interpret. This can be simply achieved in one step, as the derivation of derive_var_base() can be placed inside of restrict_derivation() with a filter added to exclude these parameters. Then, BASE will be set to NA for SIOPCHG and FIOPCHG, so later calls to derive_var_chg() and derive_var_pchg() do not need any changes.

adoe <- adoe %>%
  # Calculate BASE (do not derive for IOP change params)
  restrict_derivation(
    derivation = derive_var_base,
    args = params(
      by_vars = c(get_admiral_option("subject_keys"), exprs(PARAMCD, ATPT)),
      source_var = AVAL,
      new_var = BASE
    ),
    filter = !PARAMCD %in% c("SIOPCHG", "FIOPCHG")
  )

Further Derivations of Standard BDS Variables

The user is invited to consult the article on creating a BDS dataset from SDTM to learn how to add standard BDS variables to ADOE.

Example Script

ADaM	Sample Code
ADOE	ad_adoe.R