This article describes creating an ADBCVA ADaM with Best-Corrected Visual Acuity (BCVA) 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 ADBCVA 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.*

As the name ADBCVA implies, `{admiralophtha}`

suggests to
populate ADBCVA solely with BCVA records from the OE SDTM.

The examples of this vignette require the following packages.

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

- Initial Set Up of ADBCVA
- Deriving LogMAR Score Parameters
- Further Derivations of Standard BDS Variables
- Deriving Analysis Value Categories for Snellen Scores
- Deriving Criterion Flags for BCVA Change
- Additional Notes
- Example Script

As with all BDS ADaM datasets, one should start from the OE SDTM,
where only the BCVA 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
<- admiral_adsl %>%
adsl as.data.frame() %>%
mutate(STUDYEYE = sample(c("LEFT", "RIGHT"), n(), replace = TRUE)) %>%
convert_blanks_to_na()
<- convert_blanks_to_na(oe_ophtha) %>%
oe ungroup()
# ---- Lookup table ----
<- tibble::tribble(
param_lookup ~OETESTCD, ~OECAT, ~OESCAT, ~AFEYE, ~PARAMCD, ~PARAM, ~PARAMN,
"VACSCORE", "BEST CORRECTED VISUAL ACUITY", "OVERALL EVALUATION", "Study Eye", "SBCVA", "Study Eye Visual Acuity Score (letters)", 1, # nolint
"VACSCORE", "BEST CORRECTED VISUAL ACUITY", "OVERALL EVALUATION", "Fellow Eye", "FBCVA", "Fellow Eye Visual Acuity Score (letters)", 2, # nolint
)
```

Following this setup, the programmer can start constructing ADBCVA.
The first step is to subset OE to only BCVA parameters and merge 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`

).

```
<- exprs(TRTSDT, TRTEDT, TRT01A, TRT01P, STUDYEYE)
adsl_vars
<- oe %>%
adbcva filter(
%in% c("VACSCORE")
OETESTCD %>%
) derive_vars_merged(
dataset_add = adsl,
new_vars = adsl_vars,
by_vars = exprs(STUDYID, USUBJID)
)
```

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()`

.

```
<- adbcva %>%
adbcva mutate(
AVAL = OESTRESN,
AVALU = "letters",
DTYPE = NA_character_
%>%
) derive_var_afeye(OELOC, OELAT)
```

Moving forwards, `PARAM`

and `PARAMCD`

can be
assigned using `derive_vars_merged()`

from
`{admiral}`

and the lookup table `param_lookup`

generated above.

```
<- adbcva %>%
adbcva derive_vars_merged(
dataset_add = param_lookup,
new_vars = exprs(PARAM, PARAMCD),
by_vars = exprs(OETESTCD, AFEYE),
filter_add = PARAMCD %in% c("SBCVA", "FBCVA")
)
```

Often ADBCVA datasets contain derived records for BCVA in LogMAR
units. This can easily be achieved as follows using
`derive_param_computed()`

. The conversion of units is done
using `convert_etdrs_to_logmar()`

. Two separate calls are
required due to the parameters being split by study and fellow eye. Once
these extra parameters are added, all the records that will be in the
end dataset are now present, so `AVALC`

and day/date
variables such as `ADY`

and `ADT`

can be
derived.

```
<- adbcva %>%
adbcva derive_param_computed(
by_vars = c(exprs(STUDYID, USUBJID, VISIT, VISITNUM, OEDY, OEDTC), adsl_vars),
parameters = c("SBCVA"),
analysis_value = convert_etdrs_to_logmar(AVAL.SBCVA),
set_values_to = exprs(
PARAMCD = "SBCVALOG",
PARAM = "Study Eye Visual Acuity LogMAR Score",
DTYPE = "DERIVED",
AVALU = "LogMAR"
)%>%
) derive_param_computed(
by_vars = c(exprs(STUDYID, USUBJID, VISIT, OEDY, OEDTC), adsl_vars),
parameters = c("FBCVA"),
analysis_value = convert_etdrs_to_logmar(AVAL.FBCVA),
set_values_to = exprs(
PARAMCD = "FBCVALOG",
PARAM = "Fellow Eye Visual Acuity LogMAR Score",
DTYPE = "DERIVED",
AVALU = "LogMAR"
)%>%
) mutate(AVALC = as.character(AVAL)) %>%
derive_vars_dt(
new_vars_prefix = "A",
dtc = OEDTC,
flag_imputation = "none"
%>%
) derive_vars_dy(reference_date = TRTSDT, source_vars = exprs(ADT))
```

Importantly, the above calls to `derive_param_computed()`

list the SDTM variables `VISIT`

, `VISITNUM`

,
`OEDY`

and `OEDTC`

as `by_vars`

for the
function. This is because they will be necessary to derive ADaM
variables such as `AVISIT`

and `ADY`

in successive
steps. Once all the ADaM variables which require them are derived, the
SDTM variables should be set to missing for the derived records, as per
ADaM standards:

```
<- adbcva %>%
adbcva mutate(
VISIT = ifelse(PARAMCD %in% c("SBCVALOG", "FBCVALOG"), NA_character_, VISIT),
VISITNUM = ifelse(PARAMCD %in% c("SBCVALOG", "FBCVALOG"), NA, VISITNUM),
OEDY = ifelse(PARAMCD %in% c("SBCVALOG", "FBCVALOG"), NA, OEDY),
OEDTC = ifelse(PARAMCD %in% c("SBCVALOG", "FBCVALOG"), NA_character_, OEDTC)
)
```

The user is invited to consult the article on creating
a BDS dataset from SDTM to learn how to add standard BDS variables
to ADBCVA. Henceforth, for the purposes of this article, the following
sections use the ADBCVA dataset generated by the corresponding
`{admiralophtha}`

template program as a starting point.

**Note**: This dataset already comes with some criterion
flags and analysis value categorisation variables, so for illustration
purposes these are removed.

```
data("admiralophtha_adbcva")
<- admiralophtha_adbcva %>%
adbcva select(-starts_with("CRIT"), -starts_with("AVALCA"))
```

Some ophthalmology studies may desire to subdivide BCVA records
according to which Snellen category they fall into (eg, 20/320, 20/100,
20/20 etc). This is best done through the use of
`AVALCATx`

/`AVALCAxN`

variable pairs. Currently,
`{admiralophtha}`

does not provide specific functionality to
create `AVALCATx`

/`AVALCAxN`

pairs, although this
may be included in future releases of the package. With the current
toolset, the suggested approach to derive such variables is to:

- Create a lookup table which assigns numeric equivalents
(i.e.
`AVALCAxN`

) to Snellen categories. - Create a format function to map each
`AVAL`

to a numeric category. - Add
`AVALCAxN`

through a mutate statement using the format function. - Add
`AVALCATx`

using`derive_vars_merged`

in combination with the lookup table.

```
<- tibble::tribble(
avalcat_lookup ~PARAMCD, ~AVALCA1N, ~AVALCAT1,
"SBCVA", 1000, "< 20/800",
"SBCVA", 800, "20/800",
"SBCVA", 640, "20/640",
"SBCVA", 500, "20/500",
"SBCVA", 400, "20/400",
"SBCVA", 320, "20/320",
"SBCVA", 250, "20/250",
"SBCVA", 200, "20/200",
"SBCVA", 160, "20/160",
"SBCVA", 125, "20/125",
"SBCVA", 100, "20/100",
"SBCVA", 80, "20/80",
"SBCVA", 63, "20/63",
"SBCVA", 50, "20/50",
"SBCVA", 40, "20/40",
"SBCVA", 32, "20/32",
"SBCVA", 25, "20/25",
"SBCVA", 20, "20/20",
"SBCVA", 16, "20/16",
"SBCVA", 12, "20/12",
"SBCVA", 1, "> 20/12",
)
<- avalcat_lookup %>%
avalcat_lookup mutate(PARAMCD = "FBCVA") %>%
rbind(avalcat_lookup)
<- function(param, aval) {
format_avalcat1n case_when(
%in% c("SBCVA", "FBCVA") & aval >= 0 & aval <= 3 ~ 1000,
param %in% c("SBCVA", "FBCVA") & aval >= 4 & aval <= 8 ~ 800,
param %in% c("SBCVA", "FBCVA") & aval >= 9 & aval <= 13 ~ 640,
param %in% c("SBCVA", "FBCVA") & aval >= 14 & aval <= 18 ~ 500,
param %in% c("SBCVA", "FBCVA") & aval >= 19 & aval <= 23 ~ 400,
param %in% c("SBCVA", "FBCVA") & aval >= 24 & aval <= 28 ~ 320,
param %in% c("SBCVA", "FBCVA") & aval >= 29 & aval <= 33 ~ 250,
param %in% c("SBCVA", "FBCVA") & aval >= 34 & aval <= 38 ~ 200,
param %in% c("SBCVA", "FBCVA") & aval >= 39 & aval <= 43 ~ 160,
param %in% c("SBCVA", "FBCVA") & aval >= 44 & aval <= 48 ~ 125,
param %in% c("SBCVA", "FBCVA") & aval >= 49 & aval <= 53 ~ 100,
param %in% c("SBCVA", "FBCVA") & aval >= 54 & aval <= 58 ~ 80,
param %in% c("SBCVA", "FBCVA") & aval >= 59 & aval <= 63 ~ 63,
param %in% c("SBCVA", "FBCVA") & aval >= 64 & aval <= 68 ~ 50,
param %in% c("SBCVA", "FBCVA") & aval >= 69 & aval <= 73 ~ 40,
param %in% c("SBCVA", "FBCVA") & aval >= 74 & aval <= 78 ~ 32,
param %in% c("SBCVA", "FBCVA") & aval >= 79 & aval <= 83 ~ 25,
param %in% c("SBCVA", "FBCVA") & aval >= 84 & aval <= 88 ~ 20,
param %in% c("SBCVA", "FBCVA") & aval >= 89 & aval <= 93 ~ 16,
param %in% c("SBCVA", "FBCVA") & aval >= 94 & aval <= 97 ~ 12,
param %in% c("SBCVA", "FBCVA") & aval >= 98 ~ 1
param
)
}
<- adbcva %>%
adbcva mutate(AVALCA1N = format_avalcat1n(param = PARAMCD, aval = AVAL)) %>%
derive_vars_merged(
avalcat_lookup,by = exprs(PARAMCD, AVALCA1N)
)
```

The resulting output is shown below (limited to the first patient only):

USUBJID | PARAMCD | AVAL | AVALCAT1 | AVALCA1N |
---|---|---|---|---|

01-701-1015 | FBCVA | 82 | 20/25 | 25 |

01-701-1015 | FBCVA | 77 | 20/32 | 32 |

01-701-1015 | FBCVA | 77 | 20/32 | 32 |

01-701-1015 | FBCVA | 64 | 20/50 | 50 |

01-701-1015 | FBCVA | 92 | 20/16 | 16 |

01-701-1015 | FBCVA | 41 | 20/160 | 160 |

01-701-1015 | FBCVA | 52 | 20/100 | 100 |

01-701-1015 | FBCVA | 2 | < 20/800 | 1000 |

01-701-1015 | FBCVA | 44 | 20/125 | 125 |

01-701-1015 | SBCVA | 97 | 20/12 | 12 |

`{admiralophtha}`

suggests the use of criterion flag
variable pairs (`CRITx`

/`CRITxFL`

) to program BCVA
endpoints such as *Avoiding a loss of x letters* or *Gain of y
letters* or *Gain of between x and y letters* (relative to
baseline or other basetypes). The package provides the function
`derive_var_bcvacritxfl()`

to program these endpoints
efficiently and consistently. In terms of the logic to apply to the
variable `CHG`

, the endpoints fall into three classes, which
can be represented by inequalities:

- Class 1:
`CHG`

value lying inside a range,`a <= CHG <= b`

. - Class 2:
`CHG`

value below an upper limit,`CHG <= a`

. - Class 3:
`CHG`

value above a lower limit,`CHG => b`

.

By using `derive_var_bcvacritxfl()`

, the ADaM programmer
can implement all three types of endpoint at once. This is achieved by
feeding the appropriate ranges, upper limits and lower limits to the
`bcva_ranges`

, `bcva_uplims`

and
`bcva_lowlims`

arguments of the function. For instance, let’s
suppose that the endpoints of interest are:

*Gain of between 5 and 10 letters relative to baseline*(Class 1:`5 <= CHG <= 10`

)*Gain of 25 letters or fewer relative to baseline*(Class 2:`CHG <= 25`

)*Loss of 5 letters or more relative to baseline*(Class 2:`CHG <= -5`

)*Gain of 15 letters or more relative to baseline*(Class 3:`CHG >= 15`

)*Loss of 10 letters or fewer relative to baseline*(Class 3:`CHG >= -10`

).

Then, the following call will implement criterion variable/flag pairs
for the endpoints above. The `CRITx`

variables will
automatically encode the correct inequality. Note that that
`restrict_derivation()`

is wrapped around the call so as to
only derive the variables for the relevant parameters. In this way, the
`filter`

argument can be altered to restrict derivation to
only relevant records. Note also that the argument
`crit_var = exprs(CHG)`

has to be specified so that the
criterion flags are derived with respect to the correct variable.

```
<- adbcva %>% restrict_derivation(
adbcva derivation = derive_var_bcvacritxfl,
args = params(
crit_var = exprs(CHG),
bcva_ranges = list(c(5, 10)),
bcva_uplims = list(25, -5),
bcva_lowlims = list(15, -10)
),filter = PARAMCD %in% c("SBCVA", "FBCVA")
)
```

The resulting output is shown below (limited to the first patient only):

USUBJID | PARAMCD | AVAL | CHG | CRIT1 | CRIT1FL | CRIT2 | CRIT2FL | CRIT3 | CRIT3FL | CRIT4 | CRIT4FL | CRIT5 | CRIT5FL |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|

01-701-1015 | FBCVA | 82 | 5 | 5 <= CHG <= 10 | Y | CHG <= 25 | Y | CHG <= -5 | N | CHG >= 15 | N | CHG >= -10 | Y |

01-701-1015 | FBCVA | 77 | 0 | 5 <= CHG <= 10 | N | CHG <= 25 | Y | CHG <= -5 | N | CHG >= 15 | N | CHG >= -10 | Y |

01-701-1015 | FBCVA | 77 | 0 | 5 <= CHG <= 10 | N | CHG <= 25 | Y | CHG <= -5 | N | CHG >= 15 | N | CHG >= -10 | Y |

01-701-1015 | FBCVA | 64 | -13 | 5 <= CHG <= 10 | N | CHG <= 25 | Y | CHG <= -5 | Y | CHG >= 15 | N | CHG >= -10 | N |

01-701-1015 | FBCVA | 92 | 15 | 5 <= CHG <= 10 | N | CHG <= 25 | Y | CHG <= -5 | N | CHG >= 15 | Y | CHG >= -10 | Y |

01-701-1015 | FBCVA | 41 | -36 | 5 <= CHG <= 10 | N | CHG <= 25 | Y | CHG <= -5 | Y | CHG >= 15 | N | CHG >= -10 | N |

01-701-1015 | FBCVA | 52 | -25 | 5 <= CHG <= 10 | N | CHG <= 25 | Y | CHG <= -5 | Y | CHG >= 15 | N | CHG >= -10 | N |

01-701-1015 | FBCVA | 2 | -75 | 5 <= CHG <= 10 | N | CHG <= 25 | Y | CHG <= -5 | Y | CHG >= 15 | N | CHG >= -10 | N |

01-701-1015 | FBCVA | 44 | -33 | 5 <= CHG <= 10 | N | CHG <= 25 | Y | CHG <= -5 | Y | CHG >= 15 | N | CHG >= -10 | N |

01-701-1015 | SBCVA | 97 | 62 | 5 <= CHG <= 10 | N | CHG <= 25 | N | CHG <= -5 | N | CHG >= 15 | Y | CHG >= -10 | Y |

It is also possible to assign significance to the “x” in
`CRITxFL`

. For instance, one could designate all criterion
flags of Class 1 as `CRIT1yFL`

, Class 2 as
`CRIT2yFL`

, and Class 3 as `CRIT3yFL`

. The
argument `critxfl_index`

allows a simple implementation of
this in conjunction with three separate calls to
`derive_var_bcvacritxfl()`

:

```
<- adbcva %>%
adbcva restrict_derivation(
derivation = derive_var_bcvacritxfl,
args = params(
crit_var = exprs(CHG),
bcva_ranges = list(c(5, 10)),
critxfl_index = 10
),filter = PARAMCD %in% c("SBCVA", "FBCVA")
%>%
) restrict_derivation(
derivation = derive_var_bcvacritxfl,
args = params(
crit_var = exprs(CHG),
bcva_uplims = list(25, -5),
critxfl_index = 20
),filter = PARAMCD %in% c("SBCVA", "FBCVA")
%>%
) restrict_derivation(
derivation = derive_var_bcvacritxfl,
args = params(
crit_var = exprs(CHG),
bcva_lowlims = list(15, -10),
critxfl_index = 30
),filter = PARAMCD %in% c("SBCVA", "FBCVA")
)
```

When interpreting endpoints such as

*Loss of 5 letters or fewer relative to baseline*, it is implicitly assumed in this article that this also includes the case where letters are*gained*, so that the inequality reads`CHG >= -5`

. One would then use the`bcva_lowlims = list(-5)`

argument of`derive_var_bcvacritxfl()`

to program such an endpoint. If this is not the case, i.e. one wishes to exclude cases of letter gains, then the inequality of interest would instead be`-5 <= CHG <= -1`

. Importantly,`derive_var_bcvacritxfl()`

could still be used, but with the argument`bcva_ranges = list(c(-5, -1))`

.This vignette extensively showcases the use of

`derive_var_bcvacritxfl()`

applied to the variable`CHG`

, but through the argument`crit_var`

the function can also be used to create criterion flag relative to other variables (e.g.`crit_var = exprs(AVAL)`

for`AVAL`

).

ADaM | Sample Code |
---|---|

ADBCVA | ad_adbcva.R |