# Creating a BDS Finding ADaM

# Introduction

This article describes creating a BDS finding ADaM. Examples are currently presented and tested in the context of ADVS. However, the examples could be applied to other BDS Finding ADaMs such as ADEG, ADLB, etc. where a single result is captured in an SDTM Finding domain on a single date and/or time.

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

# Programming Workflow

- Read in Data
- Derive/Impute Numeric Date/Time and Analysis Day (`ADT`, `ADTM`, `ADY`, `ADTF`, `ATMF`)
- Assign `PARAMCD`, `PARAM`, `PARAMN`, `PARCAT1`
- Derive Results (`AVAL`, `AVALC`)
- Derive Additional Parameters (e.g. `BSA`, `BMI`, or `MAP` for `ADVS`)
- Derive Timing Variables (e.g. `APHASE`, `AVISIT`, `APERIOD`)
- Timing Flag Variables (e.g. `ONTRTFL`)
- Assign Reference Range Indicator (`ANRIND`)
- Derive Baseline (`BASETYPE`, `ABLFL`, `BASE`, `BASEC`, `BNRIND`)
- Derive Change from Baseline (`CHG`, `PCHG`)
- Derive Shift (e.g.`SHIFT1`)
- Derive Analysis Ratio (e.g. `R2BASE`)
- Derive Analysis Flags (e.g. `ANL01FL`)
- Assign Treatment (`TRTA`, `TRTP`)
- Derive Categorization Variables (`AVALCATy`)
- Derive Criterion Variables (`CRITy`, `CRITyFL`, `CRITyFN`)
- Derive New Rows
- Assign `ASEQ`
- Add ADSL variables
- Add Labels and Attributes

## Read in Data

To start, all data frames needed for the creation of `ADVS` should be read into the environment. This will be a company specific process. Some of the data frames needed may be `VS` and `ADSL`.

For example purpose, the CDISC Pilot SDTM and ADaM datasets—which are included in `{pharmaversesdtm}`—are used.

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

    vs <- pharmaversesdtm::vs
    adsl <- admiral::admiral_adsl

    vs <- convert_blanks_to_na(vs)

At this step, it may be useful to join `ADSL` to your `VS` domain. Only the `ADSL` variables used for derivations are selected at this step. The rest of the relevant `ADSL` variables would be added later.

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

    advs <- derive_vars_merged(
      vs,
      dataset_add = adsl,
      new_vars = adsl_vars,
      by_vars = exprs(STUDYID, USUBJID)
    )

USUBJID | VSTESTCD | VSDTC | VISIT | TRTSDT | TRTEDT | TRT01A | TRT01P
--- | --- | --- | --- | --- | --- | --- | ---
01-701-1015 | DIABP | 2014-01-16 | WEEK 2 | 2014-01-02 | 2014-07-02 | Placebo | Placebo
01-701-1015 | DIABP | 2014-01-16 | WEEK 2 | 2014-01-02 | 2014-07-02 | Placebo | Placebo
01-701-1015 | DIABP | 2014-01-16 | WEEK 2 | 2014-01-02 | 2014-07-02 | Placebo | Placebo
01-701-1023 | DIABP | 2012-08-27 | WEEK 2 | 2012-08-05 | 2012-09-01 | Placebo | Placebo
01-701-1023 | DIABP | 2012-08-27 | WEEK 2 | 2012-08-05 | 2012-09-01 | Placebo | Placebo
01-701-1023 | DIABP | 2012-08-27 | WEEK 2 | 2012-08-05 | 2012-09-01 | Placebo | Placebo
01-703-1086 | DIABP | 2012-09-16 | WEEK 2 | 2012-09-02 | 2012-12-04 | Xanomeline Low Dose | Xanomeline Low Dose
01-703-1086 | DIABP | 2012-09-16 | WEEK 2 | 2012-09-02 | 2012-12-04 | Xanomeline Low Dose | Xanomeline Low Dose
01-703-1086 | DIABP | 2012-09-16 | WEEK 2 | 2012-09-02 | 2012-12-04 | Xanomeline Low Dose | Xanomeline Low Dose
01-703-1096 | DIABP | 2013-02-09 | WEEK 2 | 2013-01-25 | 2013-03-16 | Placebo | Placebo

## Derive/Impute Numeric Date/Time and Analysis Day (`ADT`, `ADTM`, `ADY`, `ADTF`, `ATMF`)

The function `derive_vars_dt()` can be used to derive `ADT`. This function allows the user to impute the date as well.

Example calls:

    advs <- derive_vars_dt(advs, new_vars_prefix = "A", dtc = VSDTC)

USUBJID | VISIT | VSDTC | ADT
--- | --- | --- | ---
01-701-1015 | SCREENING 1 | 2013-12-26 | 2013-12-26
01-701-1015 | SCREENING 1 | 2013-12-26 | 2013-12-26
01-701-1015 | SCREENING 1 | 2013-12-26 | 2013-12-26
01-701-1015 | SCREENING 2 | 2013-12-31 | 2013-12-31
01-701-1015 | SCREENING 2 | 2013-12-31 | 2013-12-31
01-701-1015 | SCREENING 2 | 2013-12-31 | 2013-12-31
01-701-1015 | BASELINE | 2014-01-02 | 2014-01-02
01-701-1015 | BASELINE | 2014-01-02 | 2014-01-02
01-701-1015 | BASELINE | 2014-01-02 | 2014-01-02
01-701-1015 | AMBUL ECG PLACEMENT | 2014-01-14 | 2014-01-14

If imputation is needed and the date is to be imputed to the first of the month, the call would be:

    advs <- derive_vars_dt(
      advs,
      new_vars_prefix = "A",
      dtc = VSDTC,
      highest_imputation = "M"
    )

USUBJID | VISIT | VSDTC | ADT | ADTF
--- | --- | --- | --- | ---
01-716-1024 | SCREENING 1 | 2012-07 | 2012-07-01 | D
01-716-1024 | SCREENING 1 | 2012-07 | 2012-07-01 | D
01-716-1024 | SCREENING 1 | 2012-07 | 2012-07-01 | D
01-716-1024 | SCREENING 2 | 2012-07-07 | 2012-07-07 | NA
01-716-1024 | SCREENING 2 | 2012-07-07 | 2012-07-07 | NA
01-716-1024 | SCREENING 2 | 2012-07-07 | 2012-07-07 | NA
01-716-1024 | BASELINE | 2012-07-09 | 2012-07-09 | NA
01-716-1024 | BASELINE | 2012-07-09 | 2012-07-09 | NA
01-716-1024 | BASELINE | 2012-07-09 | 2012-07-09 | NA
01-716-1024 | AMBUL ECG PLACEMENT | 2012-07-22 | 2012-07-22 | NA

Similarly, `ADTM` may be created using the function `derive_vars_dtm()`. Imputation may be done on both the date and time components of `ADTM`.

    # CDISC Pilot data does not contain times and the output of the derivation
    # ADTM is not presented.
    advs <- derive_vars_dtm(
      advs,
      new_vars_prefix = "A",
      dtc = VSDTC,
      highest_imputation = "M"
    )

By default, the variable `ADTF` for `derive_vars_dt()` or `ADTF` and `ATMF` for `derive_vars_dtm()` will be created and populated with the controlled terminology outlined in the ADaM IG for date imputations.

See also Date and Time Imputation.

Once `ADT` is derived, the function `derive_vars_dy()` can be used to derive `ADY`. This example assumes both `ADT` and `TRTSDT` exist on the data frame.

    advs <-
      derive_vars_dy(advs, reference_date = TRTSDT, source_vars = exprs(ADT))

USUBJID | VISIT | ADT | ADY | TRTSDT
--- | --- | --- | --- | ---
01-716-1024 | SCREENING 1 | 2012-07-06 | -3 | 2012-07-09
01-716-1024 | SCREENING 1 | 2012-07-06 | -3 | 2012-07-09
01-716-1024 | SCREENING 1 | 2012-07-06 | -3 | 2012-07-09
01-716-1024 | SCREENING 2 | 2012-07-07 | -2 | 2012-07-09
01-716-1024 | SCREENING 2 | 2012-07-07 | -2 | 2012-07-09
01-716-1024 | SCREENING 2 | 2012-07-07 | -2 | 2012-07-09
01-716-1024 | BASELINE | 2012-07-09 | 1 | 2012-07-09
01-716-1024 | BASELINE | 2012-07-09 | 1 | 2012-07-09
01-716-1024 | BASELINE | 2012-07-09 | 1 | 2012-07-09
01-716-1024 | AMBUL ECG PLACEMENT | 2012-07-22 | 14 | 2012-07-09

## Assign `PARAMCD`, `PARAM`, `PARAMN`, `PARCAT1`

To assign parameter level values such as `PARAMCD`, `PARAM`, `PARAMN`, `PARCAT1`, etc., a lookup can be created to join to the source data.

For example, when creating `ADVS`, a lookup based on the SDTM `--TESTCD` value may be created:

`VSTESTCD` | `PARAMCD` | `PARAM` | `PARAMN` | `PARCAT1` | `PARCAT1N`
--- | --- | --- | --- | --- | ---
HEIGHT | HEIGHT | Height (cm) | 1 | Subject Characteristic | 1
WEIGHT | WEIGHT | Weight (kg) | 2 | Subject Characteristic | 1
DIABP | DIABP | Diastolic Blood Pressure (mmHg) | 3 | Vital Sign | 2
MAP | MAP | Mean Arterial Pressure | 4 | Vital Sign | 2
PULSE | PULSE | Pulse Rate (beats/min) | 5 | Vital Sign | 2
SYSBP | SYSBP | Systolic Blood Pressure (mmHg) | 6 | Vital Sign | 2
TEMP | TEMP | Temperature (C) | 7 | Vital Sign | 2

This lookup may now be joined to the source data:

At this stage, only `PARAMCD` is required to perform the derivations. Additional derived parameters may be added, so only `PARAMCD` is joined to the datasets at this point. All other variables related to `PARAMCD` (e.g. `PARAM`, `PARCAT1`, …) will be added when all `PARAMCD` are derived.

    advs <- derive_vars_merged_lookup(
      advs,
      dataset_add = param_lookup,
      new_vars = exprs(PARAMCD),
      by_vars = exprs(VSTESTCD)
    )
    #> All `VSTESTCD` are mapped.

USUBJID | VSTESTCD | PARAMCD
--- | --- | ---
01-701-1015 | DIABP | DIABP
01-701-1015 | HEIGHT | HEIGHT
01-701-1015 | PULSE | PULSE
01-701-1015 | SYSBP | SYSBP
01-701-1015 | TEMP | TEMP
01-701-1015 | WEIGHT | WEIGHT
01-701-1023 | DIABP | DIABP
01-701-1023 | HEIGHT | HEIGHT
01-701-1023 | PULSE | PULSE
01-701-1023 | SYSBP | SYSBP

Please note, it may be necessary to include other variables in the join. For example, perhaps the `PARAMCD` is based on `VSTESTCD` and `VSPOS`, it may be necessary to expand this lookup or create a separate look up for `PARAMCD`.

If more than one lookup table, e.g., company parameter mappings and project parameter mappings, are available, `consolidate_metadata()` can be used to consolidate these into a single lookup table.

Additionally note that each parameter is mapped to only one `PARCAT1` variable. This is described in section 3.3.4.1 of the ADaM Implementation Guide, version 1.3: “Any given `PARAM` may be associated with at-most one level of `PARCATy` (e.g., one level of `PARCAT1` and one level of `PARCAT2`)”.

## Derive Results (`AVAL`, `AVALC`)

The mapping of `AVAL` and `AVALC` is left to the ADaM programmer. An example mapping may be:

    advs <- mutate(
      advs,
      AVAL = VSSTRESN
    )

In this example, as is often the case for ADVS, all `AVAL` values are numeric without any corresponding non-redundant text value for `AVALC`. Per recommendation in ADaMIG v1.3 we do not map `AVALC`.

VSTESTCD | PARAMCD | VSSTRESN | VSSTRESC | AVAL
--- | --- | --- | --- | ---
DIABP | DIABP | 74 | 74 | 74
DIABP | DIABP | 74 | 74 | 74
DIABP | DIABP | 72 | 72 | 72
DIABP | DIABP | 78 | 78 | 78
DIABP | DIABP | 84 | 84 | 84
DIABP | DIABP | 78 | 78 | 78
DIABP | DIABP | 80 | 80 | 80
DIABP | DIABP | 80 | 80 | 80
DIABP | DIABP | 84 | 84 | 84
DIABP | DIABP | 90 | 90 | 90

## Derive Additional Parameters (e.g. `BSA`, `BMI` or `MAP` for `ADVS`)

Optionally derive new parameters creating `PARAMCD` and `AVAL`. Note that only variables specified in the `by_vars` argument will be populated in the newly created records. This is relevant to the functions `derive_param_map`, `derive_param_bsa`, `derive_param_bmi`, and `derive_param_qtc`.

Below is an example of creating `Mean Arterial Pressure` for `ADVS`, see also Example 3 in section below Derive New Rows for alternative way of creating new parameters.

    advs <- derive_param_map(
      advs,
      by_vars = exprs(STUDYID, USUBJID, !!!adsl_vars, VISIT, VISITNUM, ADT, ADY, VSTPT, VSTPTNUM),
      set_values_to = exprs(PARAMCD = "MAP"),
      get_unit_expr = VSSTRESU,
      filter = VSSTAT != "NOT DONE" | is.na(VSSTAT)
    )

VSTESTCD | PARAMCD | VISIT | VSTPT | AVAL
--- | --- | --- | --- | ---
DIABP | DIABP | SCREENING 1 | AFTER LYING DOWN FOR 5 MINUTES | 64.00000
NA | MAP | SCREENING 1 | AFTER LYING DOWN FOR 5 MINUTES | 86.33333
SYSBP | SYSBP | SCREENING 1 | AFTER LYING DOWN FOR 5 MINUTES | 131.00000
DIABP | DIABP | SCREENING 1 | AFTER STANDING FOR 1 MINUTE | 83.00000
NA | MAP | SCREENING 1 | AFTER STANDING FOR 1 MINUTE | 98.33333
SYSBP | SYSBP | SCREENING 1 | AFTER STANDING FOR 1 MINUTE | 129.00000
DIABP | DIABP | SCREENING 1 | AFTER STANDING FOR 3 MINUTES | 57.00000
NA | MAP | SCREENING 1 | AFTER STANDING FOR 3 MINUTES | 87.00000
SYSBP | SYSBP | SCREENING 1 | AFTER STANDING FOR 3 MINUTES | 147.00000
DIABP | DIABP | SCREENING 2 | AFTER LYING DOWN FOR 5 MINUTES | 68.00000

Likewise, function call below, to create parameter `Body Surface Area` (BSA) and `Body Mass Index` (BMI) for `ADVS` domain. Note that if height is collected only once use `constant_by_vars` to specify the subject-level variable to merge on. Otherwise BSA and BMI are only calculated for visits where both are collected.

    advs <- derive_param_bsa(
      advs,
      by_vars = exprs(STUDYID, USUBJID, !!!adsl_vars, VISIT, VISITNUM, ADT, ADY, VSTPT, VSTPTNUM),
      method = "Mosteller",
      set_values_to = exprs(PARAMCD = "BSA"),
      get_unit_expr = VSSTRESU,
      filter = VSSTAT != "NOT DONE" | is.na(VSSTAT),
      constant_by_vars = exprs(USUBJID)
    )

    advs <- derive_param_bmi(
      advs,
      by_vars = exprs(STUDYID, USUBJID, !!!adsl_vars, VISIT, VISITNUM, ADT, ADY, VSTPT, VSTPTNUM),
      set_values_to = exprs(PARAMCD = "BMI"),
      get_unit_expr = VSSTRESU,
      filter = VSSTAT != "NOT DONE" | is.na(VSSTAT),
      constant_by_vars = exprs(USUBJID)
    )

USUBJID | VSTESTCD | PARAMCD | VISIT | VSTPT | AVAL
--- | --- | --- | --- | --- | ---
01-701-1015 | NA | BMI | SCREENING 1 | NA | 24.871928
01-701-1015 | NA | BSA | SCREENING 1 | NA | 1.486264
01-701-1015 | NA | BMI | BASELINE | NA | 25.079271
01-701-1015 | NA | BSA | BASELINE | NA | 1.492447
01-701-1015 | NA | BMI | WEEK 2 | NA | 24.452635
01-701-1015 | NA | BSA | WEEK 2 | NA | 1.473683
01-701-1015 | NA | BMI | WEEK 4 | NA | 24.871928
01-701-1015 | NA | BSA | WEEK 4 | NA | 1.486264
01-701-1015 | NA | BMI | WEEK 6 | NA | 24.452635
01-701-1015 | NA | BSA | WEEK 6 | NA | 1.473683

Similarly, for `ADEG`, the parameters `QTCBF` `QTCBS` and `QTCL` can be created with a function call. See example below for `PARAMCD` = `QTCF`.

    adeg <- tibble::tribble(
      ~USUBJID, ~EGSTRESU, ~PARAMCD, ~AVAL,          ~VISIT,
      "P01",       "msec",     "QT",   350, "CYCLE 1 DAY 1",
      "P01",       "msec",     "QT",   370, "CYCLE 2 DAY 1",
      "P01",       "msec",     "RR",   842, "CYCLE 1 DAY 1",
      "P01",       "msec",     "RR",   710, "CYCLE 2 DAY 1"
    )

    adeg <- derive_param_qtc(
      adeg,
      by_vars = exprs(USUBJID, VISIT),
      method = "Fridericia",
      set_values_to = exprs(PARAMCD = "QTCFR"),
      get_unit_expr = EGSTRESU
    )

Similarly, for `ADLB`, the function `derive_param_wbc_abs()` can be used to create new parameter for lab differentials converted to absolute values. See example below:

    adlb <- tibble::tribble(
      ~USUBJID, ~PARAMCD, ~AVAL,                        ~PARAM,          ~VISIT,
      "P01",       "WBC",    33,    "Leukocyte Count (10^9/L)", "CYCLE 1 DAY 1",
      "P01",       "WBC",    38,    "Leukocyte Count (10^9/L)", "CYCLE 2 DAY 1",
      "P01",     "LYMLE",  0.90, "Lymphocytes (fraction of 1)", "CYCLE 1 DAY 1",
      "P01",     "LYMLE",  0.70, "Lymphocytes (fraction of 1)", "CYCLE 2 DAY 1"
    )

    derive_param_wbc_abs(
      dataset = adlb,
      by_vars = exprs(USUBJID, VISIT),
      set_values_to = exprs(
        PARAMCD = "LYMPH",
        PARAM = "Lymphocytes Abs (10^9/L)",
        DTYPE = "CALCULATION"
      ),
      get_unit_expr = extract_unit(PARAM),
      wbc_code = "WBC",
      diff_code = "LYMLE",
      diff_type = "fraction"
    )

When all `PARAMCD` have been derived and added to the dataset, the other information from the look-up table (`PARAM`, `PARCAT1`,…) should be added.

    # Derive PARAM and PARAMN
    advs <- derive_vars_merged(
      advs,
      dataset_add = select(param_lookup, -VSTESTCD),
      by_vars = exprs(PARAMCD)
    )

VSTESTCD | PARAMCD | PARAM | PARAMN | PARCAT1 | PARCAT1N
--- | --- | --- | --- | --- | ---
DIABP | DIABP | Diastolic Blood Pressure (mmHg) | 3 | Vital Sign | 2
DIABP | DIABP | Diastolic Blood Pressure (mmHg) | 3 | Vital Sign | 2
DIABP | DIABP | Diastolic Blood Pressure (mmHg) | 3 | Vital Sign | 2
DIABP | DIABP | Diastolic Blood Pressure (mmHg) | 3 | Vital Sign | 2
DIABP | DIABP | Diastolic Blood Pressure (mmHg) | 3 | Vital Sign | 2
DIABP | DIABP | Diastolic Blood Pressure (mmHg) | 3 | Vital Sign | 2
DIABP | DIABP | Diastolic Blood Pressure (mmHg) | 3 | Vital Sign | 2
DIABP | DIABP | Diastolic Blood Pressure (mmHg) | 3 | Vital Sign | 2
DIABP | DIABP | Diastolic Blood Pressure (mmHg) | 3 | Vital Sign | 2
DIABP | DIABP | Diastolic Blood Pressure (mmHg) | 3 | Vital Sign | 2

## Derive Timing Variables (e.g. `APHASE`, `AVISIT`, `APERIOD`)

Categorical timing variables are protocol and analysis dependent. Below is a simple example.

    advs <- advs %>%
      mutate(
        AVISIT = case_when(
          str_detect(VISIT, "SCREEN") ~ NA_character_,
          str_detect(VISIT, "UNSCHED") ~ NA_character_,
          str_detect(VISIT, "RETRIEVAL") ~ NA_character_,
          str_detect(VISIT, "AMBUL") ~ NA_character_,
          !is.na(VISIT) ~ str_to_title(VISIT)
        ),
        AVISITN = as.numeric(case_when(
          VISIT == "BASELINE" ~ "0",
          str_detect(VISIT, "WEEK") ~ str_trim(str_replace(VISIT, "WEEK", ""))
        )),
        ATPT = VSTPT,
        ATPTN = VSTPTNUM
      )

    count(advs, VISITNUM, VISIT, AVISITN, AVISIT)
    #> # A tibble: 15 × 5
    #>    VISITNUM VISIT               AVISITN AVISIT       n
    #>       <dbl> <chr>                 <dbl> <chr>    <int>
    #>  1      1   SCREENING 1              NA <NA>       102
    #>  2      2   SCREENING 2              NA <NA>        78
    #>  3      3   BASELINE                  0 Baseline    96
    #>  4      3.5 AMBUL ECG PLACEMENT      NA <NA>        65
    #>  5      4   WEEK 2                    2 Week 2      96
    #>  6      5   WEEK 4                    4 Week 4      80
    #>  7      6   AMBUL ECG REMOVAL        NA <NA>        52
    #>  8      7   WEEK 6                    6 Week 6      48
    #>  9      8   WEEK 8                    8 Week 8      48
    #> 10      9   WEEK 12                  12 Week 12     48
    #> 11     10   WEEK 16                  16 Week 16     48
    #> 12     11   WEEK 20                  20 Week 20     32
    #> 13     12   WEEK 24                  24 Week 24     32
    #> 14     13   WEEK 26                  26 Week 26     32
    #> 15    201   RETRIEVAL                NA <NA>        26

    count(advs, VSTPTNUM, VSTPT, ATPTN, ATPT)
    #> # A tibble: 4 × 5
    #>   VSTPTNUM VSTPT                          ATPTN ATPT                           n
    #>      <dbl> <chr>                          <dbl> <chr>                      <int>
    #> 1      815 AFTER LYING DOWN FOR 5 MINUTES   815 AFTER LYING DOWN FOR 5 MI…   232
    #> 2      816 AFTER STANDING FOR 1 MINUTE      816 AFTER STANDING FOR 1 MINU…   232
    #> 3      817 AFTER STANDING FOR 3 MINUTES     817 AFTER STANDING FOR 3 MINU…   232
    #> 4       NA <NA>                              NA <NA>                         187

For assigning visits based on time windows and deriving periods, subperiods, and phase variables see the “Visit and Period Variables” vignette.

## Timing Flag Variables (e.g. `ONTRTFL`)

In some analyses, it may be necessary to flag an observation as on-treatment. The admiral function `derive_var_ontrtfl()` can be used.

For example, if on-treatment is defined as any observation between treatment start and treatment end, the flag may be derived as:

    advs <- derive_var_ontrtfl(
      advs,
      start_date = ADT,
      ref_start_date = TRTSDT,
      ref_end_date = TRTEDT
    )

USUBJID | PARAMCD | ADT | TRTSDT | TRTEDT | ONTRTFL
--- | --- | --- | --- | --- | ---
01-701-1015 | DIABP | 2014-01-16 | 2014-01-02 | 2014-07-02 | Y
01-701-1015 | DIABP | 2014-01-16 | 2014-01-02 | 2014-07-02 | Y
01-701-1015 | DIABP | 2014-01-16 | 2014-01-02 | 2014-07-02 | Y
01-701-1023 | DIABP | 2012-08-27 | 2012-08-05 | 2012-09-01 | Y
01-701-1023 | DIABP | 2012-08-27 | 2012-08-05 | 2012-09-01 | Y
01-701-1023 | DIABP | 2012-08-27 | 2012-08-05 | 2012-09-01 | Y
01-703-1086 | DIABP | 2012-09-16 | 2012-09-02 | 2012-12-04 | Y
01-703-1086 | DIABP | 2012-09-16 | 2012-09-02 | 2012-12-04 | Y
01-703-1086 | DIABP | 2012-09-16 | 2012-09-02 | 2012-12-04 | Y
01-703-1096 | DIABP | 2013-02-09 | 2013-01-25 | 2013-03-16 | Y

This function returns the original data frame with the column `ONTRTFL` added. Additionally, this function does have functionality to handle a window on the `ref_end_date`. For example, if on-treatment is defined as between treatment start and treatment end plus 60 days, the call would be:

    advs <- derive_var_ontrtfl(
      advs,
      start_date = ADT,
      ref_start_date = TRTSDT,
      ref_end_date = TRTEDT,
      ref_end_window = 60
    )

In addition, the function does allow you to filter out pre-treatment observations that occurred on the start date. For example, if observations with `VSTPT == PRE` should not be considered on-treatment when the observation date falls between the treatment start and end date, the user may specify this using the `filter_pre_timepoint` parameter:

    advs <- derive_var_ontrtfl(
      advs,
      start_date = ADT,
      ref_start_date = TRTSDT,
      ref_end_date = TRTEDT,
      filter_pre_timepoint = ATPT == "AFTER LYING DOWN FOR 5 MINUTES"
    )

Lastly, the function does allow you to create any on-treatment flag based on the analysis needs. For example, if variable `ONTR01FL` is needed, showing the on-treatment flag during Period 01, you need to set `new var = ONTR01FL`. In addition, for Period 01 Start Date and Period 01 End Date, you need `ref_start_date = AP01SDT` and `ref_end_date = AP01EDT`.

    advs <- derive_var_ontrtfl(
      advs,
      new_var = ONTR01FL,
      start_date = ASTDT,
      end_date = AENDT,
      ref_start_date = AP01SDT,
      ref_end_date = AP01EDT,
      span_period = TRUE
    )

USUBJID | ASTDT | AENDT | AP01SDT | AP01EDT | ONTR01FL
--- | --- | --- | --- | --- | ---
P01 | 2020-03-15 | 2020-12-01 | 2020-01-01 | 2020-03-01 | NA
P02 | 2019-04-30 | 2020-03-15 | 2020-01-01 | 2020-03-01 | Y
P03 | 2019-04-30 | NA | 2020-01-01 | 2020-03-01 | Y

## Assign Reference Range Indicator (`ANRIND`)

The admiral function `derive_var_anrind()` may be used to derive the reference range indicator `ANRIND`.

This function requires the reference range boundaries to exist on the data frame (`ANRLO`, `ANRHI`) and also accommodates the additional boundaries `A1LO` and `A1HI`.

The function is called as:

    advs <- derive_var_anrind(advs)

USUBJID | PARAMCD | AVAL | ANRLO | ANRHI | A1LO | A1HI | ANRIND
--- | --- | --- | --- | --- | --- | --- | ---
01-701-1015 | DIABP | 56 | 60 | 80 | 40 | 90 | LOW
01-701-1015 | DIABP | 50 | 60 | 80 | 40 | 90 | LOW
01-701-1015 | DIABP | 54 | 60 | 80 | 40 | 90 | LOW
01-701-1023 | DIABP | 88 | 60 | 80 | 40 | 90 | HIGH
01-701-1023 | DIABP | 86 | 60 | 80 | 40 | 90 | HIGH
01-701-1023 | DIABP | 90 | 60 | 80 | 40 | 90 | HIGH
01-703-1086 | DIABP | 68 | 60 | 80 | 40 | 90 | NORMAL
01-703-1086 | DIABP | 74 | 60 | 80 | 40 | 90 | NORMAL
01-703-1086 | DIABP | 70 | 60 | 80 | 40 | 90 | NORMAL
01-703-1096 | DIABP | 74 | 60 | 80 | 40 | 90 | NORMAL

## Derive Baseline (`BASETYPE`, `ABLFL`, `BASE`, `BNRIND`)

The `BASETYPE` should be derived using the function `derive_basetype_records()`. The parameter `basetypes` of this function requires a named list of expression detailing how the `BASETYPE` should be assigned. Note, if a record falls into multiple expressions within the basetypes expression, a row will be produced for each `BASETYPE`.

    advs <- derive_basetype_records(
      dataset = advs,
      basetypes = exprs(
        "LAST: AFTER LYING DOWN FOR 5 MINUTES" = ATPTN == 815,
        "LAST: AFTER STANDING FOR 1 MINUTE" = ATPTN == 816,
        "LAST: AFTER STANDING FOR 3 MINUTES" = ATPTN == 817,
        "LAST" = is.na(ATPTN)
      )
    )

    count(advs, ATPT, ATPTN, BASETYPE)
    #> # A tibble: 4 × 4
    #>   ATPT                           ATPTN BASETYPE                                n
    #>   <chr>                          <dbl> <chr>                               <int>
    #> 1 AFTER LYING DOWN FOR 5 MINUTES   815 LAST: AFTER LYING DOWN FOR 5 MINUT…   232
    #> 2 AFTER STANDING FOR 1 MINUTE      816 LAST: AFTER STANDING FOR 1 MINUTE     232
    #> 3 AFTER STANDING FOR 3 MINUTES     817 LAST: AFTER STANDING FOR 3 MINUTES    232
    #> 4 <NA>                              NA LAST                                  187

It is important to derive `BASETYPE` first so that it can be utilized in subsequent derivations. This will be important if the data frame contains multiple values for `BASETYPE`.

Next, the analysis baseline flag `ABLFL` can be derived using the `{admiral}` function `derive_var_extreme_flag()`. For example, if baseline is defined as the last non-missing `AVAL` prior or on `TRTSDT`, the function call for `ABLFL` would be:

    advs <- restrict_derivation(
      advs,
      derivation = derive_var_extreme_flag,
      args = params(
        by_vars = exprs(STUDYID, USUBJID, BASETYPE, PARAMCD),
        order = exprs(ADT, ATPTN, VISITNUM),
        new_var = ABLFL,
        mode = "last"
      ),
      filter = (!is.na(AVAL) & ADT <= TRTSDT & !is.na(BASETYPE))
    )

USUBJID | BASETYPE | PARAMCD | ADT | TRTSDT | ATPTN | ABLFL
--- | --- | --- | --- | --- | --- | ---
01-701-1015 | LAST: AFTER LYING DOWN FOR 5 MINUTES | DIABP | 2014-01-02 | 2014-01-02 | 815 | Y
01-701-1015 | LAST: AFTER STANDING FOR 1 MINUTE | DIABP | 2014-01-02 | 2014-01-02 | 816 | Y
01-701-1015 | LAST: AFTER STANDING FOR 3 MINUTES | DIABP | 2014-01-02 | 2014-01-02 | 817 | Y
01-701-1023 | LAST: AFTER LYING DOWN FOR 5 MINUTES | DIABP | 2012-08-05 | 2012-08-05 | 815 | Y
01-701-1023 | LAST: AFTER STANDING FOR 1 MINUTE | DIABP | 2012-08-05 | 2012-08-05 | 816 | Y
01-701-1023 | LAST: AFTER STANDING FOR 3 MINUTES | DIABP | 2012-08-05 | 2012-08-05 | 817 | Y
01-703-1086 | LAST: AFTER LYING DOWN FOR 5 MINUTES | DIABP | 2012-09-02 | 2012-09-02 | 815 | Y
01-703-1086 | LAST: AFTER STANDING FOR 1 MINUTE | DIABP | 2012-09-02 | 2012-09-02 | 816 | Y
01-703-1086 | LAST: AFTER STANDING FOR 3 MINUTES | DIABP | 2012-09-02 | 2012-09-02 | 817 | Y
01-703-1096 | LAST: AFTER LYING DOWN FOR 5 MINUTES | DIABP | 2013-01-25 | 2013-01-25 | 815 | Y

Note: Additional examples of the `derive_var_extreme_flag()` function can be found above.

Lastly, the `BASE`, and `BNRIND` columns can be derived using the `{admiral}` function `derive_var_base()`. Example calls are:

    advs <- derive_var_base(
      advs,
      by_vars = exprs(STUDYID, USUBJID, PARAMCD, BASETYPE),
      source_var = AVAL,
      new_var = BASE
    )

    advs <- derive_var_base(
      advs,
      by_vars = exprs(STUDYID, USUBJID, PARAMCD, BASETYPE),
      source_var = ANRIND,
      new_var = BNRIND
    )

USUBJID | BASETYPE | PARAMCD | ABLFL | BASE | ANRIND | BNRIND
--- | --- | --- | --- | --- | --- | ---
01-701-1015 | LAST: AFTER LYING DOWN FOR 5 MINUTES | DIABP | Y | 56 | LOW | LOW
01-701-1015 | LAST: AFTER STANDING FOR 1 MINUTE | DIABP | Y | 51 | LOW | LOW
01-701-1015 | LAST: AFTER STANDING FOR 3 MINUTES | DIABP | Y | 61 | NORMAL | NORMAL
01-701-1023 | LAST: AFTER LYING DOWN FOR 5 MINUTES | DIABP | Y | 84 | HIGH | HIGH
01-701-1023 | LAST: AFTER STANDING FOR 1 MINUTE | DIABP | Y | 86 | HIGH | HIGH
01-701-1023 | LAST: AFTER STANDING FOR 3 MINUTES | DIABP | Y | 88 | HIGH | HIGH
01-703-1086 | LAST: AFTER LYING DOWN FOR 5 MINUTES | DIABP | Y | 80 | NORMAL | NORMAL
01-703-1086 | LAST: AFTER STANDING FOR 1 MINUTE | DIABP | Y | 82 | HIGH | HIGH
01-703-1086 | LAST: AFTER STANDING FOR 3 MINUTES | DIABP | Y | 72 | NORMAL | NORMAL
01-703-1096 | LAST: AFTER LYING DOWN FOR 5 MINUTES | DIABP | Y | 70 | NORMAL | NORMAL

## Derive Change from Baseline (`CHG`, `PCHG`)

Change and percent change from baseline can be derived using the `{admiral}` functions `derive_var_chg()` and `derive_var_pchg()`. These functions expect `AVAL` and `BASE` to exist in the data frame. The `CHG` is simply `AVAL - BASE` and the `PCHG` is `(AVAL - BASE) / absolute value (BASE) * 100`. Examples calls are:

    advs <- derive_var_chg(advs)

    advs <- derive_var_pchg(advs)

USUBJID | VISIT | BASE | AVAL | CHG | PCHG
--- | --- | --- | --- | --- | ---
01-701-1015 | WEEK 2 | 56 | 56 | 0 | 0.000000
01-701-1015 | WEEK 8 | 56 | 67 | 11 | 19.642857
01-701-1023 | WEEK 2 | 84 | 88 | 4 | 4.761905
01-703-1086 | WEEK 2 | 80 | 68 | -12 | -15.000000
01-703-1086 | WEEK 8 | 80 | 80 | 0 | 0.000000
01-703-1096 | WEEK 2 | 70 | 74 | 4 | 5.714286
01-707-1037 | WEEK 2 | 88 | 72 | -16 | -18.181818
01-716-1024 | WEEK 2 | 80 | 86 | 6 | 7.500000
01-716-1024 | WEEK 8 | 80 | 78 | -2 | -2.500000
01-701-1015 | WEEK 2 | 51 | 50 | -1 | -1.960784

If the variables should not be derived for all records, e.g., for post-baseline records only, `restrict_derivation()` can be used.

## Derive Shift (e.g. `SHIFT1`)

Shift variables can be derived using the `{admiral}` function `derive_var_shift()`. This function derives a character shift variable concatenating shift in values based on a user-defined pairing, e.g., shift from baseline reference range `BNRIND` to analysis reference range `ANRIND`. Examples calls are:

    advs <- derive_var_shift(advs,
      new_var = SHIFT1,
      from_var = BNRIND,
      to_var = ANRIND
    )

USUBJID | SHIFT1 | BNRIND | ANRIND | VISIT
--- | --- | --- | --- | ---
01-701-1015 | LOW to LOW | LOW | LOW | WEEK 2
01-701-1015 | LOW to NORMAL | LOW | NORMAL | WEEK 8
01-701-1023 | HIGH to HIGH | HIGH | HIGH | WEEK 2
01-703-1086 | NORMAL to NORMAL | NORMAL | NORMAL | WEEK 2
01-703-1086 | NORMAL to NORMAL | NORMAL | NORMAL | WEEK 8
01-703-1096 | NORMAL to NORMAL | NORMAL | NORMAL | WEEK 2
01-707-1037 | HIGH to NORMAL | HIGH | NORMAL | WEEK 2
01-716-1024 | NORMAL to HIGH | NORMAL | HIGH | WEEK 2
01-716-1024 | NORMAL to NORMAL | NORMAL | NORMAL | WEEK 8
01-701-1015 | LOW to LOW | LOW | LOW | WEEK 2

If the variables should not be derived for all records, e.g., for post-baseline records only, `restrict_derivation()` can be used.

## Derive Analysis Ratio (`R2BASE`)

Analysis ratio variables can be derived using the `{admiral}` function `derive_var_analysis_ratio()`. This function derives a ratio variable based on user-specified pair. For example, Ratio to Baseline is calculated by `AVAL / BASE` and the function appends a new variable `R2BASE` to the dataset. This function can also derive `R2AyHI` and `R2AyLO` values. Examples calls are:

    advs <- derive_var_analysis_ratio(advs,
      numer_var = AVAL,
      denom_var = BASE
    )

    advs <- derive_var_analysis_ratio(advs,
      numer_var = AVAL,
      denom_var = ANRLO,
      new_var = R01ANRLO
    )

USUBJID | VISIT | BASE | AVAL | ANRLO | R2BASE | R01ANRLO
--- | --- | --- | --- | --- | --- | ---
01-701-1015 | WEEK 2 | 56 | 56 | 60 | 1.0000000 | 0.9333333
01-701-1015 | WEEK 8 | 56 | 67 | 60 | 1.1964286 | 1.1166667
01-701-1023 | WEEK 2 | 84 | 88 | 60 | 1.0476190 | 1.4666667
01-703-1086 | WEEK 2 | 80 | 68 | 60 | 0.8500000 | 1.1333333
01-703-1086 | WEEK 8 | 80 | 80 | 60 | 1.0000000 | 1.3333333
01-703-1096 | WEEK 2 | 70 | 74 | 60 | 1.0571429 | 1.2333333
01-707-1037 | WEEK 2 | 88 | 72 | 60 | 0.8181818 | 1.2000000
01-716-1024 | WEEK 2 | 80 | 86 | 60 | 1.0750000 | 1.4333333
01-716-1024 | WEEK 8 | 80 | 78 | 60 | 0.9750000 | 1.3000000
01-701-1015 | WEEK 2 | 51 | 50 | 60 | 0.9803922 | 0.8333333

If the variables should not be derived for all records, e.g., for post-baseline records only, `restrict_derivation()` can be used.

## Derive Analysis Flags (e.g. `ANL01FL`)

In most finding ADaMs, an analysis flag is derived to identify the appropriate observation(s) to use for a particular analysis when a subject has multiple observations within a particular timing period.

In this situation, an analysis flag (e.g. `ANLxxFL`) may be used to choose the appropriate record for analysis.

This flag may be derived using the `{admiral}` function `derive_var_extreme_flag()`. For this example, we will assume we would like to choose the latest and highest value by `USUBJID`, `PARAMCD`, `AVISIT`, and `ATPT`.

    advs <- restrict_derivation(
      advs,
      derivation = derive_var_extreme_flag,
      args = params(
        by_vars = exprs(STUDYID, USUBJID, BASETYPE, PARAMCD, AVISIT),
        order = exprs(ADT, ATPTN, AVAL),
        new_var = ANL01FL,
        mode = "last"
      ),
      filter = !is.na(AVISITN)
    )

USUBJID | PARAMCD | AVISIT | ATPTN | ADT | AVAL | ANL01FL
--- | --- | --- | --- | --- | --- | ---
01-701-1015 | DIABP | Week 2 | 815 | 2014-01-16 | 56 | Y
01-701-1015 | DIABP | Week 8 | 815 | 2014-03-05 | 67 | Y
01-701-1015 | DIABP | Week 2 | 816 | 2014-01-16 | 50 | Y
01-701-1015 | DIABP | Week 8 | 816 | 2014-03-05 | 62 | Y
01-701-1015 | DIABP | Week 2 | 817 | 2014-01-16 | 54 | Y
01-701-1015 | DIABP | Week 8 | 817 | 2014-03-05 | 71 | Y
01-701-1023 | DIABP | Week 2 | 815 | 2012-08-27 | 88 | Y
01-701-1023 | DIABP | Week 2 | 816 | 2012-08-27 | 86 | Y
01-701-1023 | DIABP | Week 2 | 817 | 2012-08-27 | 90 | Y
01-703-1086 | DIABP | Week 2 | 815 | 2012-09-16 | 68 | Y

Another common example would be flagging the worst value for a subject, parameter, and visit. For this example, we will assume we have 3 `PARAMCD` values (`SYSBP`, `DIABP`, and `RESP`). We will also assume high is worst for `SYSBP` and `DIABP` and low is worst for `RESP`.

    advs <- slice_derivation(
      advs,
      derivation = derive_var_extreme_flag,
      args = params(
        by_vars = exprs(STUDYID, USUBJID, BASETYPE, PARAMCD, AVISIT),
        order = exprs(ADT, ATPTN),
        new_var = WORSTFL,
        mode = "first"
      ),
      derivation_slice(
        filter = PARAMCD %in% c("SYSBP", "DIABP") & (!is.na(AVISIT) & !is.na(AVAL))
      ),
      derivation_slice(
        filter = PARAMCD %in% "PULSE" & (!is.na(AVISIT) & !is.na(AVAL)),
        args = params(mode = "last")
      )
    ) %>%
      arrange(STUDYID, USUBJID, BASETYPE, PARAMCD, AVISIT)

USUBJID | PARAMCD | AVISIT | AVAL | ADT | ATPTN | WORSTFL
--- | --- | --- | --- | --- | --- | ---
01-701-1015 | DIABP | Baseline | 56 | 2014-01-02 | 815 | Y
01-701-1015 | DIABP | Week 12 | 68 | 2014-03-26 | 815 | Y
01-701-1015 | DIABP | Week 16 | 66 | 2014-05-07 | 815 | Y
01-701-1015 | DIABP | Week 2 | 56 | 2014-01-16 | 815 | Y
01-701-1015 | DIABP | Week 20 | 67 | 2014-05-21 | 815 | Y
01-701-1015 | DIABP | Week 24 | 63 | 2014-06-18 | 815 | Y
01-701-1015 | DIABP | Week 26 | 61 | 2014-07-02 | 815 | Y
01-701-1015 | DIABP | Week 4 | 64 | 2014-01-30 | 815 | Y
01-701-1015 | DIABP | Week 6 | 55 | 2014-02-12 | 815 | Y
01-701-1015 | DIABP | Week 8 | 67 | 2014-03-05 | 815 | Y

## Assign Treatment (`TRTA`, `TRTP`)

`TRTA` and `TRTP` must match at least one value of the character treatment variables in ADSL (e.g., `TRTxxA`/`TRTxxP`, `TRTSEQA`/`TRTSEQP`, `TRxxAGy`/`TRxxPGy`).

An example of a simple implementation for a study without periods could be:

    advs <- mutate(advs, TRTP = TRT01P, TRTA = TRT01A)

    count(advs, TRTP, TRTA, TRT01P, TRT01A)
    #> # A tibble: 2 × 5
    #>   TRTP                TRTA                TRT01P              TRT01A           n
    #>   <chr>               <chr>               <chr>               <chr>        <int>
    #> 1 Placebo             Placebo             Placebo             Placebo        640
    #> 2 Xanomeline Low Dose Xanomeline Low Dose Xanomeline Low Dose Xanomeline …   243

For studies with periods see the “Visit and Period Variables” vignette.

## Derive Categorization Variables (`AVALCATy`)

We can use the `derive_vars_cat()` function to derive the categorization variables.

    avalcat_lookup <- exprs(
      ~PARAMCD,  ~condition,   ~AVALCAT1, ~AVALCA1N,
      "HEIGHT",  AVAL > 140,   ">140 cm",         1,
      "HEIGHT", AVAL <= 140, "<= 140 cm",         2
    )
    advs <- advs %>%
      derive_vars_cat(
        definition = avalcat_lookup,
        by_vars = exprs(PARAMCD)
      )

USUBJID | PARAMCD | AVAL | AVALCA1N | AVALCAT1
--- | --- | --- | --- | ---
01-701-1015 | HEIGHT | 147.32 | 1 | >140 cm
01-701-1023 | HEIGHT | 162.56 | 1 | >140 cm
01-703-1086 | HEIGHT | 195.58 | 1 | >140 cm
01-703-1096 | HEIGHT | 160.02 | 1 | >140 cm
01-707-1037 | HEIGHT | 152.40 | 1 | >140 cm
01-716-1024 | HEIGHT | 154.94 | 1 | >140 cm

## Derive Criterion Variables (`CRITy`, `CRITyFL`, `CRITyFN`)

For deriving criterion variables (`CRITy`, `CRITyFL`, `CRITyFN`) `{admiral}` provides `derive_vars_crit_flag()`. It ensures that they are derived in an ADaM-compliant way (see documentation of the function for details).

In most cases the criterion depends on the parameter. The higher order functions `restrict_derivation()` and `slice_derivation()` are useful in this case. In the following example the criterion flags for systolic and diastolic blood pressure from the ADaM IG are derived.

The first criterion is based on `AVAL` and is derived for systolic and diastolic blood pressure. `slice_derivation()` us used to specify the condition and description of the criterion depending on the parameter.

    advs <- advs %>%
      slice_derivation(
        derivation = derive_vars_crit_flag,
        args = params(
          values_yn = TRUE,
          create_numeric_flag = TRUE
        ),
        derivation_slice(
          filter = PARAMCD == "SYSBP",
          args = params(
            condition = AVAL > 160,
            description = "Systolic Pressure > 160"
          )
        ),
        derivation_slice(
          filter = PARAMCD == "DIABP",
          args = params(
            condition = AVAL > 95,
            description = "Diastolic Pressure > 95"
          )
        )
      )

USUBJID | PARAMCD | AVAL | CHG | CRIT1 | CRIT1FL | CRIT1FN
--- | --- | --- | --- | --- | --- | ---
01-701-1015 | DIABP | 56 | 0 | Diastolic Pressure > 95 | N | 0
01-701-1015 | SYSBP | 130 | 0 | Systolic Pressure > 160 | N | 0
01-701-1015 | DIABP | 51 | 0 | Diastolic Pressure > 95 | N | 0
01-701-1015 | SYSBP | 121 | 0 | Systolic Pressure > 160 | N | 0
01-701-1015 | DIABP | 61 | 0 | Diastolic Pressure > 95 | N | 0
01-701-1015 | SYSBP | 131 | 0 | Systolic Pressure > 160 | N | 0
01-701-1015 | DIABP | 56 | 0 | Diastolic Pressure > 95 | N | 0
01-701-1015 | SYSBP | 114 | -16 | Systolic Pressure > 160 | N | 0
01-701-1015 | DIABP | 50 | -1 | Diastolic Pressure > 95 | N | 0
01-701-1015 | SYSBP | 121 | 0 | Systolic Pressure > 160 | N | 0

The second criterion is based on `AVAL` and `CHG` and is derived for systolic blood pressure only. Thus `restrict_derivation()` is used.

    advs <- advs %>%
      restrict_derivation(
        derivation = derive_vars_crit_flag,
        args = params(
          condition = AVAL > 160 & CHG > 10,
          description = "Systolic Pressure > 160 and Change from Baseline in Systolic Pressure > 10",
          crit_nr = 2,
          values_yn = TRUE,
          create_numeric_flag = TRUE
        ),
        filter = PARAMCD == "SYSBP"
      )

USUBJID | PARAMCD | AVAL | CHG | CRIT2 | CRIT2FL | CRIT2FN
--- | --- | --- | --- | --- | --- | ---
01-701-1015 | SYSBP | 130 | 0 | Systolic Pressure > 160 and Change from Baseline in Systolic Pressure > 10 | N | 0
01-701-1015 | SYSBP | 121 | 0 | Systolic Pressure > 160 and Change from Baseline in Systolic Pressure > 10 | N | 0
01-701-1015 | SYSBP | 131 | 0 | Systolic Pressure > 160 and Change from Baseline in Systolic Pressure > 10 | N | 0
01-701-1015 | SYSBP | 114 | -16 | Systolic Pressure > 160 and Change from Baseline in Systolic Pressure > 10 | N | 0
01-701-1015 | SYSBP | 121 | 0 | Systolic Pressure > 160 and Change from Baseline in Systolic Pressure > 10 | N | 0
01-701-1015 | SYSBP | 132 | 1 | Systolic Pressure > 160 and Change from Baseline in Systolic Pressure > 10 | N | 0
01-701-1015 | SYSBP | 138 | 8 | Systolic Pressure > 160 and Change from Baseline in Systolic Pressure > 10 | N | 0
01-701-1015 | SYSBP | 137 | 16 | Systolic Pressure > 160 and Change from Baseline in Systolic Pressure > 10 | N | 0
01-701-1015 | SYSBP | 132 | 1 | Systolic Pressure > 160 and Change from Baseline in Systolic Pressure > 10 | N | 0
01-701-1015 | SYSBP | 148 | 18 | Systolic Pressure > 160 and Change from Baseline in Systolic Pressure > 10 | N | 0

## Derive New Rows

When deriving new rows for a data frame, it is essential the programmer takes time to insert this derivation in the correct location of the code. The location will vary depending on what previous computations should be retained on the new record and what computations must be done with the new records.

### Example 1 (Creating a New Record):

To add a new record based on the selection of a certain criterion (e.g. minimum, maximum) `derive_extreme_records()` can be used. The new records include all variables of the selected records.

#### Adding a New Record for the Last Value

For each subject and Vital Signs parameter, add a record holding last valid observation before end of treatment. Set `AVISIT` to `"End of Treatment"` and assign a unique `AVISITN` value.

    advs_ex1 <- advs %>%
      derive_extreme_records(
        dataset_add = advs,
        by_vars = exprs(STUDYID, USUBJID, PARAMCD),
        order = exprs(ADT, AVISITN, ATPTN, AVAL),
        mode = "last",
        filter_add = (4 < AVISITN & AVISITN <= 12 & ANL01FL == "Y"),
        set_values_to = exprs(
          AVISIT = "End of Treatment",
          AVISITN = 99,
          DTYPE = "LOV"
        )
      )

USUBJID | PARAMCD | ADT | AVISITN | AVISIT | ATPTN | AVAL | DTYPE | ANL01FL
--- | --- | --- | --- | --- | --- | --- | --- | ---
01-701-1015 | BMI | 2014-03-26 | 99 | End of Treatment | NA | 24.45264 | LOV | Y
01-701-1015 | BMI | 2014-07-02 | 26 | Week 26 | NA | 24.65998 | NA | Y
01-701-1015 | BMI | 2014-06-18 | 24 | Week 24 | NA | 24.45264 | NA | Y
01-701-1015 | BMI | 2014-05-21 | 20 | Week 20 | NA | 24.45264 | NA | Y
01-701-1015 | BMI | 2014-05-07 | 16 | Week 16 | NA | 24.45264 | NA | Y
01-701-1015 | BMI | 2014-03-26 | 12 | Week 12 | NA | 24.45264 | NA | Y
01-701-1015 | BMI | 2014-03-05 | 8 | Week 8 | NA | 24.45264 | NA | Y
01-701-1015 | BMI | 2014-02-12 | 6 | Week 6 | NA | 24.45264 | NA | Y
01-701-1015 | BMI | 2014-01-30 | 4 | Week 4 | NA | 24.87193 | NA | Y
01-701-1015 | BMI | 2014-01-16 | 2 | Week 2 | NA | 24.45264 | NA | Y

#### Adding a New Record for the Minimum Value

For each subject and Vital Signs parameter, add a record holding the minimum value before end of treatment. If the minimum is attained by multiple observations the first one is selected. Set `AVISIT` to `"Minimum on Treatment"` and assign a unique `AVISITN` value.

    advs_ex1 <- advs %>%
      derive_extreme_records(
        dataset_add = advs,
        by_vars = exprs(STUDYID, USUBJID, PARAMCD),
        order = exprs(AVAL, ADT, AVISITN, ATPTN),
        mode = "first",
        filter_add = (4 < AVISITN & AVISITN <= 12 & ANL01FL == "Y" & !is.na(AVAL)),
        set_values_to = exprs(
          AVISIT = "Minimum on Treatment",
          AVISITN = 98,
          DTYPE = "MINIMUM"
        )
      )

USUBJID | PARAMCD | ADT | AVISITN | AVISIT | ATPTN | AVAL | DTYPE | ANL01FL
--- | --- | --- | --- | --- | --- | --- | --- | ---
01-701-1015 | BMI | 2014-02-12 | 98 | Minimum on Treatment | NA | 24.45264 | MINIMUM | Y
01-701-1015 | BMI | 2014-07-02 | 26 | Week 26 | NA | 24.65998 | NA | Y
01-701-1015 | BMI | 2014-06-18 | 24 | Week 24 | NA | 24.45264 | NA | Y
01-701-1015 | BMI | 2014-05-21 | 20 | Week 20 | NA | 24.45264 | NA | Y
01-701-1015 | BMI | 2014-05-07 | 16 | Week 16 | NA | 24.45264 | NA | Y
01-701-1015 | BMI | 2014-03-26 | 12 | Week 12 | NA | 24.45264 | NA | Y
01-701-1015 | BMI | 2014-03-05 | 8 | Week 8 | NA | 24.45264 | NA | Y
01-701-1015 | BMI | 2014-02-12 | 6 | Week 6 | NA | 24.45264 | NA | Y
01-701-1015 | BMI | 2014-01-30 | 4 | Week 4 | NA | 24.87193 | NA | Y
01-701-1015 | BMI | 2014-01-16 | 2 | Week 2 | NA | 24.45264 | NA | Y

### Example 2 (Deriving a Summary Record)

For adding new records based on aggregating records `derive_summary_records()` can be used. For the new records only the variables specified by `by_vars` and `set_values_to` are populated.

For each subject, Vital Signs parameter, visit, and date add a record holding the average value for observations on that date. Set `DTYPE` to `AVERAGE`.

    advs_ex2 <- derive_summary_records(
      advs,
      dataset_add = advs,
      by_vars = exprs(STUDYID, USUBJID, PARAMCD, VISITNUM, ADT),
      set_values_to = exprs(
        AVAL = mean(AVAL, na.rm = TRUE),
        DTYPE = "AVERAGE"
      )
    )

USUBJID | PARAMCD | VISITNUM | ADT | AVAL | DTYPE
--- | --- | --- | --- | --- | ---
01-701-1015 | BMI | 1 | 2013-12-26 | 24.87193 | AVERAGE
01-701-1015 | BMI | 1 | 2013-12-26 | 24.87193 | NA
01-701-1015 | BMI | 3 | 2014-01-02 | 25.07927 | AVERAGE
01-701-1015 | BMI | 3 | 2014-01-02 | 25.07927 | NA
01-701-1015 | BMI | 4 | 2014-01-16 | 24.45264 | AVERAGE
01-701-1015 | BMI | 4 | 2014-01-16 | 24.45264 | NA
01-701-1015 | BMI | 5 | 2014-01-30 | 24.87193 | AVERAGE
01-701-1015 | BMI | 5 | 2014-01-30 | 24.87193 | NA
01-701-1015 | BMI | 7 | 2014-02-12 | 24.45264 | AVERAGE
01-701-1015 | BMI | 7 | 2014-02-12 | 24.45264 | NA

### Example 3 (Deriving a New `PARAMCD`)

Use function `derive_param_computed()` to create a new `PARAMCD`. Note that only variables specified in the `by_vars` argument will be populated in the newly created records.

Below is an example of creating `Mean Arterial Pressure` (`PARAMCD = MAP2`) with an alternative formula.

    advs_ex3 <- derive_param_computed(
      advs,
      by_vars = exprs(USUBJID, VISIT, ATPT),
      parameters = c("SYSBP", "DIABP"),
      set_values_to = exprs(
        AVAL = (AVAL.SYSBP - AVAL.DIABP) / 3 + AVAL.DIABP,
        PARAMCD = "MAP2",
        PARAM = "Mean Arterial Pressure 2 (mmHg)"
      )
    )

USUBJID | PARAMCD | VISIT | ATPT | AVAL
--- | --- | --- | --- | ---
01-701-1015 | DIABP | AMBUL ECG PLACEMENT | AFTER LYING DOWN FOR 5 MINUTES | 67.00000
01-701-1015 | MAP2 | AMBUL ECG PLACEMENT | AFTER LYING DOWN FOR 5 MINUTES | 90.33333
01-701-1015 | SYSBP | AMBUL ECG PLACEMENT | AFTER LYING DOWN FOR 5 MINUTES | 137.00000
01-701-1015 | DIABP | AMBUL ECG PLACEMENT | AFTER STANDING FOR 1 MINUTE | 61.00000
01-701-1015 | MAP2 | AMBUL ECG PLACEMENT | AFTER STANDING FOR 1 MINUTE | 83.00000
01-701-1015 | SYSBP | AMBUL ECG PLACEMENT | AFTER STANDING FOR 1 MINUTE | 127.00000
01-701-1015 | DIABP | AMBUL ECG PLACEMENT | AFTER STANDING FOR 3 MINUTES | 65.00000
01-701-1015 | MAP2 | AMBUL ECG PLACEMENT | AFTER STANDING FOR 3 MINUTES | 92.00000
01-701-1015 | SYSBP | AMBUL ECG PLACEMENT | AFTER STANDING FOR 3 MINUTES | 146.00000
01-701-1015 | DIABP | AMBUL ECG REMOVAL | AFTER LYING DOWN FOR 5 MINUTES | 72.00000

## Assign `ASEQ`

The `{admiral}` function `derive_var_obs_number()` can be used to derive `ASEQ`. Note that creating `ASEQ` is not required for all ADaM datasets according to the ADaM IG, and this is just for demonstration purpose. An example call is:

    # Calculate ASEQ (Optional Variable)
    advs <- derive_var_obs_number(
      advs,
      new_var = ASEQ,
      by_vars = exprs(STUDYID, USUBJID),
      order = exprs(PARAMCD, ADT, AVISITN, VISITNUM, ATPTN),
      check_type = "error"
    )

USUBJID | PARAMCD | ADT | AVISITN | ATPTN | VISIT | ASEQ
--- | --- | --- | --- | --- | --- | ---
01-701-1015 | BMI | 2013-12-26 | NA | NA | SCREENING 1 | 1
01-701-1015 | BMI | 2014-01-02 | 0 | NA | BASELINE | 2
01-701-1015 | BMI | 2014-01-16 | 2 | NA | WEEK 2 | 3
01-701-1015 | BMI | 2014-01-30 | 4 | NA | WEEK 4 | 4
01-701-1015 | BMI | 2014-02-12 | 6 | NA | WEEK 6 | 5
01-701-1015 | BMI | 2014-03-05 | 8 | NA | WEEK 8 | 6
01-701-1015 | BMI | 2014-03-26 | 12 | NA | WEEK 12 | 7
01-701-1015 | BMI | 2014-05-07 | 16 | NA | WEEK 16 | 8
01-701-1015 | BMI | 2014-05-21 | 20 | NA | WEEK 20 | 9
01-701-1015 | BMI | 2014-06-18 | 24 | NA | WEEK 24 | 10

## Add ADSL variables

If needed, the other `ADSL` variables can now be added. List of ADSL variables already merged held in vector `adsl_vars`

    advs <- advs %>%
      derive_vars_merged(
        dataset_add = select(adsl, !!!negate_vars(adsl_vars)),
        by_vars = exprs(STUDYID, USUBJID)
      )

USUBJID | RFSTDTC | RFENDTC | DTHDTC | DTHFL | AGE | AGEU
--- | --- | --- | --- | --- | --- | ---
01-701-1015 | 2014-01-02 | 2014-07-02 | NA | NA | 63 | YEARS
01-701-1015 | 2014-01-02 | 2014-07-02 | NA | NA | 63 | YEARS
01-701-1015 | 2014-01-02 | 2014-07-02 | NA | NA | 63 | YEARS
01-701-1015 | 2014-01-02 | 2014-07-02 | NA | NA | 63 | YEARS
01-701-1015 | 2014-01-02 | 2014-07-02 | NA | NA | 63 | YEARS
01-701-1015 | 2014-01-02 | 2014-07-02 | NA | NA | 63 | YEARS
01-701-1015 | 2014-01-02 | 2014-07-02 | NA | NA | 63 | YEARS
01-701-1015 | 2014-01-02 | 2014-07-02 | NA | NA | 63 | YEARS
01-701-1015 | 2014-01-02 | 2014-07-02 | NA | NA | 63 | YEARS
01-701-1015 | 2014-01-02 | 2014-07-02 | NA | NA | 63 | YEARS

## Add Labels and Attributes

Note that attributes may not be preserved in some cases after processing with `{admiral}`. The recommended approach is to apply variable labels and other metadata as a final step in your data derivation process using packages like:

- metacore: establish a common foundation for the use of metadata within an R session.

- metatools: enable the use of metacore objects. Metatools can be used to build datasets or enhance columns in existing datasets as well as checking datasets against the metadata.

- xportr: functionality to associate all metadata information to a local R data frame, perform data set level validation checks and convert into a transport v5 file(xpt).

NOTE: Together with `{admiral}` these packages comprise an End to End pipeline under the umbrella of the pharmaverse. An example of applying metadata and performing associated checks can be found at the pharmaverse E2E example.

# Example Scripts

ADaM | Sourcing Command
--- | ---
`ADEG` | `use_ad_template("ADEG")`
`ADVS` | `use_ad_template("ADVS")`
`ADLB` | `use_ad_template("ADLB")`