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Creating a BDS Exposure ADaM

Introduction

This article describes creating an Exposure ADaM using the BDS structure. Examples are currently presented using an underlying EX domain where the EX domain represents data as collected on the CRF and the ADEX ADaM is output. However, the examples can be applied to situations where an EC domain is used as input and/or ADEC or another exposure ADaM is created.

There are many different approaches to modeling exposure data. This vignette gives examples of creating PARAMCD and AVAL combinations using exposure data. This vignette is not meant to be a guide or standard for the structure of exposure analysis datasets.

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)
Compute Duration for a Record
Create 1:1 Mapping Records
Create Summary Records
Assign PARAMCD, PARAMN, etc. from Reference Tables
Derive Categorization Variables (AVALCATx)
Assign ASEQ
Add ADSL variables ASEQ
Add Labels and Attributes

Read in Data

To start, all data frames needed for the creation of ADEX should be read into the environment. This will be a company specific process. Some of the data frames needed may be EX 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)

data("admiral_adsl")
data("ex")

adsl <- admiral_adsl
ex <- convert_blanks_to_na(ex)

At this step, it may be useful to join ADSL to your EX domain as well. 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, TRTSDTM, TRTEDT, TRTEDTM)

adex <- derive_vars_merged(
  ex,
  dataset_add = adsl,
  new_vars = adsl_vars,
  by_vars = exprs(STUDYID, USUBJID)
)

USUBJID	EXTRT	EXDOSE	EXDOSFRQ	VISIT	EXSTDTC	EXENDTC	TRTSDTM	TRTEDTM
01-701-1015	PLACEBO	0	QD	BASELINE	2014-01-02	2014-01-16	2014-01-02	2014-07-02 23:59:59
01-701-1015	PLACEBO	0	QD	WEEK 2	2014-01-17	2014-06-18	2014-01-02	2014-07-02 23:59:59
01-701-1015	PLACEBO	0	QD	WEEK 24	2014-06-19	2014-07-02	2014-01-02	2014-07-02 23:59:59
01-701-1023	PLACEBO	0	QD	BASELINE	2012-08-05	2012-08-27	2012-08-05	2012-09-01 23:59:59
01-701-1023	PLACEBO	0	QD	WEEK 2	2012-08-28	2012-09-01	2012-08-05	2012-09-01 23:59:59
01-703-1086	XANOMELINE	54	QD	BASELINE	2012-09-02	2012-09-16	2012-09-02	2012-12-04 23:59:59
01-703-1086	XANOMELINE	54	QD	WEEK 2	2012-09-17	2012-12-04	2012-09-02	2012-12-04 23:59:59
01-703-1096	PLACEBO	0	QD	BASELINE	2013-01-25	2013-02-09	2013-01-25	2013-03-16 23:59:59
01-703-1096	PLACEBO	0	QD	WEEK 2	2013-02-10	2013-03-16	2013-01-25	2013-03-16 23:59:59
01-707-1037	XANOMELINE	54	QD	BASELINE	2013-12-20	2013-12-24	2013-12-20	2013-12-24 23:59:59

The CDISC pilot EX domain data does not contain a dose adjustment flag or the planned dose information. For demonstration purposes, this will be added to the data.

adex <- adex %>%
  mutate(
    EXADJ = case_when(
      USUBJID == "01-701-1028" & VISIT %in% c("WEEK 2") ~ "ADVERSE EVENT",
      USUBJID == "01-701-1148" & VISIT %in% c("WEEK 2", "WEEK 24") ~ "MEDICATION ERROR",
      TRUE ~ NA_character_
    ),
    EXDOSE = case_when(
      USUBJID == "01-701-1028" & VISIT %in% c("WEEK 2") ~ 0,
      USUBJID == "01-701-1148" & VISIT %in% c("WEEK 2", "WEEK 24") ~ 0,
      TRUE ~ EXDOSE
    )
  ) %>%
  mutate(EXPLDOS = if_else(EXTRT == "PLACEBO", 0, 54))

distinct(adex, EXTRT, EXPLDOS)
#> # A tibble: 2 × 2
#>   EXTRT      EXPLDOS
#>   <chr>        <dbl>
#> 1 PLACEBO          0
#> 2 XANOMELINE      54
count(adex, EXADJ)
#> # A tibble: 1 × 2
#>   EXADJ     n
#>   <chr> <int>
#> 1 <NA>     13

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:

adex <- derive_vars_dt(adex, new_vars_prefix = "AST", dtc = EXSTDTC)
adex <- derive_vars_dt(adex, new_vars_prefix = "AEN", dtc = EXENDTC)

USUBJID	VISIT	EXSTDTC	EXENDTC	ASTDT	AENDT
01-701-1015	BASELINE	2014-01-02	2014-01-16	2014-01-02	2014-01-16
01-701-1015	WEEK 2	2014-01-17	2014-06-18	2014-01-17	2014-06-18
01-701-1015	WEEK 24	2014-06-19	2014-07-02	2014-06-19	2014-07-02
01-701-1023	BASELINE	2012-08-05	2012-08-27	2012-08-05	2012-08-27
01-701-1023	WEEK 2	2012-08-28	2012-09-01	2012-08-28	2012-09-01
01-703-1086	BASELINE	2012-09-02	2012-09-16	2012-09-02	2012-09-16
01-703-1086	WEEK 2	2012-09-17	2012-12-04	2012-09-17	2012-12-04
01-703-1096	BASELINE	2013-01-25	2013-02-09	2013-01-25	2013-02-09
01-703-1096	WEEK 2	2013-02-10	2013-03-16	2013-02-10	2013-03-16
01-707-1037	BASELINE	2013-12-20	2013-12-24	2013-12-20	2013-12-24

The next examples demonstrates the datetime imputation features available in the derive_vars_dtm() function, where the time is imputed as “00:00:00”:

adex <- derive_vars_dtm(
  adex,
  dtc = EXSTDTC,
  highest_imputation = "M",
  new_vars_prefix = "AST"
)

adex <- derive_vars_dtm(
  adex,
  dtc = EXENDTC,
  highest_imputation = "M",
  date_imputation = "last",
  new_vars_prefix = "AEN"
)

USUBJID	VISIT	EXSTDTC	EXENDTC	ASTDTM	AENDTM
01-701-1015	BASELINE	2014-01-02	2014-01-16	2014-01-02	2014-01-16
01-701-1015	WEEK 2	2014-01-17	2014-06-18	2014-01-17	2014-06-18
01-701-1015	WEEK 24	2014-06-19	2014-07-02	2014-06-19	2014-07-02
01-701-1023	BASELINE	2012-08-05	2012-08-27	2012-08-05	2012-08-27
01-701-1023	WEEK 2	2012-08-28	2012-09-01	2012-08-28	2012-09-01
01-703-1086	BASELINE	2012-09-02	2012-09-16	2012-09-02	2012-09-16
01-703-1086	WEEK 2	2012-09-17	2012-12-04	2012-09-17	2012-12-04
01-703-1096	BASELINE	2013-01-25	2013-02-09	2013-01-25	2013-02-09
01-703-1096	WEEK 2	2013-02-10	2013-03-16	2013-02-10	2013-03-16
01-707-1037	BASELINE	2013-12-20	2013-12-24	2013-12-20	2013-12-24

The example above imputes the start date to the first first day of the month and imputes the end date to the last day of the month.

Please see the Date and Time Imputation for additional examples on calculating and imputing analysis dates.

Next, the analysis study days can be derived:

adex <-
  derive_vars_dy(adex,
    reference_date = TRTSDT,
    source_vars = exprs(ASTDT, AENDT)
  )

USUBJID	VISIT	ASTDT	ASTDY	AENDT	AENDY	TRTSDT
01-701-1015	BASELINE	2014-01-02	1	2014-01-16	15	2014-01-02
01-701-1015	WEEK 2	2014-01-17	16	2014-06-18	168	2014-01-02
01-701-1015	WEEK 24	2014-06-19	169	2014-07-02	182	2014-01-02
01-701-1023	BASELINE	2012-08-05	1	2012-08-27	23	2012-08-05
01-701-1023	WEEK 2	2012-08-28	24	2012-09-01	28	2012-08-05
01-703-1086	BASELINE	2012-09-02	1	2012-09-16	15	2012-09-02
01-703-1086	WEEK 2	2012-09-17	16	2012-12-04	94	2012-09-02
01-703-1096	BASELINE	2013-01-25	1	2013-02-09	16	2013-01-25
01-703-1096	WEEK 2	2013-02-10	17	2013-03-16	51	2013-01-25
01-707-1037	BASELINE	2013-12-20	1	2013-12-24	5	2013-12-20

Compute duration for a record

To compute the duration of treatment or exposure for a record, the derive_vars_duration() function can be used.

adex <- adex %>%
  derive_vars_duration(
    new_var = EXDURD,
    start_date = ASTDT,
    end_date = AENDT
  )

USUBJID	VISIT	ASTDT	ASTDY	AENDT	AENDY	EXDURD
01-701-1015	BASELINE	2014-01-02	1	2014-01-16	15	15
01-701-1015	WEEK 2	2014-01-17	16	2014-06-18	168	153
01-701-1015	WEEK 24	2014-06-19	169	2014-07-02	182	14
01-701-1023	BASELINE	2012-08-05	1	2012-08-27	23	23
01-701-1023	WEEK 2	2012-08-28	24	2012-09-01	28	5
01-703-1086	BASELINE	2012-09-02	1	2012-09-16	15	15
01-703-1086	WEEK 2	2012-09-17	16	2012-12-04	94	79
01-703-1096	BASELINE	2013-01-25	1	2013-02-09	16	16
01-703-1096	WEEK 2	2013-02-10	17	2013-03-16	51	35
01-707-1037	BASELINE	2013-12-20	1	2013-12-24	5	5

The units of the calculated duration can also be changed. In this example, the duration is output as years:

adex <- adex %>%
  derive_vars_duration(
    new_var = EXDURDY,
    out_unit = "years",
    start_date = ASTDT,
    end_date = AENDT
  )

USUBJID	VISIT	ASTDT	AENDT	EXDURD	EXDURDY
01-701-1015	BASELINE	2014-01-02	2014-01-16	15	0.0410678
01-701-1015	WEEK 2	2014-01-17	2014-06-18	153	0.4188912
01-701-1015	WEEK 24	2014-06-19	2014-07-02	14	0.0383299
01-701-1023	BASELINE	2012-08-05	2012-08-27	23	0.0629706
01-701-1023	WEEK 2	2012-08-28	2012-09-01	5	0.0136893
01-703-1086	BASELINE	2012-09-02	2012-09-16	15	0.0410678
01-703-1086	WEEK 2	2012-09-17	2012-12-04	79	0.2162902
01-703-1096	BASELINE	2013-01-25	2013-02-09	16	0.0438056
01-703-1096	WEEK 2	2013-02-10	2013-03-16	35	0.0958248
01-707-1037	BASELINE	2013-12-20	2013-12-24	5	0.0136893

Please refer to the derive_vars_duration() documentation for detailed information on the input parameters.

It may be necessary to calculate additional intermediate values. For example, the cumulative doses received and cumulative planned doses may be calculated as:

adex <- adex %>%
  mutate(
    DOSEO = EXDOSE * EXDURD,
    PDOSEO = EXPLDOS * EXDURD
  )

USUBJID	EXDOSE	EXPLDOS	EXDURD	DOSEO	PDOSEO
01-701-1015	0	0	15	0	0
01-701-1015	0	0	153	0	0
01-701-1015	0	0	14	0	0
01-701-1023	0	0	23	0	0
01-701-1023	0	0	5	0	0
01-703-1086	54	54	15	810	810
01-703-1086	54	54	79	4266	4266
01-703-1096	0	0	16	0	0
01-703-1096	0	0	35	0	0
01-707-1037	54	54	5	270	270

It may be of additional interest to turn a single record containing dosing summary information into a set of multiple single records, each representing a single dose over the interval specified by the summary record. This is another approach to deriving a total dose parameter when EXDOSFRQ != ONCE.

The function create_single_dose_dataset() can be used to expand a record containing a start date, an end date, and a dosing frequency to a corresponding set of records each representing one dose (i.e. EXDOSFRQ == "ONCE").

single_dose <- adex %>%
  filter(USUBJID == "01-701-1015" & EXSTDY == 1) %>%
  create_single_dose_dataset(keep_source_vars = exprs(USUBJID, EXDOSE, EXPLDOS, EXDOSFRQ, ASTDT, AENDT))

USUBJID	EXDOSFRQ	ASTDT	AENDT
01-701-1015	ONCE	2014-01-02	2014-01-02
01-701-1015	ONCE	2014-01-03	2014-01-03
01-701-1015	ONCE	2014-01-04	2014-01-04
01-701-1015	ONCE	2014-01-05	2014-01-05
01-701-1015	ONCE	2014-01-06	2014-01-06
01-701-1015	ONCE	2014-01-07	2014-01-07
01-701-1015	ONCE	2014-01-08	2014-01-08
01-701-1015	ONCE	2014-01-09	2014-01-09
01-701-1015	ONCE	2014-01-10	2014-01-10
01-701-1015	ONCE	2014-01-11	2014-01-11

Create 1:1 mapping records

The first set of exposure records to create will be records mapped 1:1 to an existing collected exposure record in SDTM. For these records, the AVAL or AVALC would be calculated using columns that exist on the data and no summarizing of records would be necessary.

These records may be used for input into summary records or be used individually for summarization in outputs. Some examples may be exposure duration, dose administered, dose adjusted, etc. based on one exposure record in SDTM.

These records can be derived using simple dplyr::mutate assignments and then combined:

adex_durd <- adex %>%
  mutate(
    PARAMCD = "DURD",
    AVAL = EXDURD
  )

adex_dose <- adex %>%
  mutate(
    PARAMCD = "DOSE",
    AVAL = DOSEO
  )

adex_pldos <- adex %>%
  mutate(
    PARAMCD = "PLDOSE",
    AVAL = PDOSEO
  )

adex_adj <- adex %>%
  mutate(
    PARAMCD = "ADJ",
    AVALC = if_else(!is.na(EXADJ), "Y", NA_character_)
  )

adex_adjae <- adex %>%
  mutate(
    PARAMCD = "ADJAE",
    AVALC = if_else(EXADJ == "ADVERSE EVENT", "Y", NA_character_)
  )

adex <- bind_rows(
  adex_durd,
  adex_dose,
  adex_pldos,
  adex_adj,
  adex_adjae
) %>%
  mutate(PARCAT1 = "INDIVIDUAL")

count(adex, PARAMCD)
#> # A tibble: 5 × 2
#>   PARAMCD     n
#>   <chr>   <int>
#> 1 ADJ        13
#> 2 ADJAE      13
#> 3 DOSE       13
#> 4 DURD       13
#> 5 PLDOSE     13

USUBJID	VISIT	ASTDT	AENDT	PARAMCD	AVAL	AVALC
01-701-1015	BASELINE	2014-01-02	2014-01-16	PLDOSE	0	NA
01-701-1015	BASELINE	2014-01-02	2014-01-16	DURD	15	NA
01-701-1015	BASELINE	2014-01-02	2014-01-16	DOSE	0	NA
01-701-1015	BASELINE	2014-01-02	2014-01-16	ADJAE	NA	NA
01-701-1015	BASELINE	2014-01-02	2014-01-16	ADJ	NA	NA
01-701-1015	WEEK 2	2014-01-17	2014-06-18	PLDOSE	0	NA
01-701-1015	WEEK 2	2014-01-17	2014-06-18	DURD	153	NA
01-701-1015	WEEK 2	2014-01-17	2014-06-18	DOSE	0	NA
01-701-1015	WEEK 2	2014-01-17	2014-06-18	ADJAE	NA	NA
01-701-1015	WEEK 2	2014-01-17	2014-06-18	ADJ	NA	NA

Create Summary Records

Exposure is commonly analyzed by a timing interval (e.g. APHASE, APERIOD, AVISIT, etc.). For these types of calculations, the derive_param_exposure() function may be used. In addition to creating a summarized AVAL, the function will also compute minimum and maximum dates for the record.

For example, to calculate the total dose by subject and treatment,

adex <- derive_param_exposure(
  adex,
  dataset_add = adex,
  by_vars = exprs(STUDYID, USUBJID, !!!adsl_vars),
  input_code = "DOSE",
  set_values_to = exprs(
    PARAMCD = "TDOSE",
    PARCAT1 = "OVERALL",
    AVAL = sum(AVAL, na.rm = TRUE)
  )
)

USUBJID	VISIT	PARCAT1	PARAMCD	AVAL	ASTDT	AENDT
01-701-1015	BASELINE	INDIVIDUAL	ADJ	NA	2014-01-02	2014-01-16
01-701-1015	WEEK 2	INDIVIDUAL	ADJ	NA	2014-01-17	2014-06-18
01-701-1015	WEEK 24	INDIVIDUAL	ADJ	NA	2014-06-19	2014-07-02
01-701-1015	BASELINE	INDIVIDUAL	ADJAE	NA	2014-01-02	2014-01-16
01-701-1015	WEEK 2	INDIVIDUAL	ADJAE	NA	2014-01-17	2014-06-18
01-701-1015	WEEK 24	INDIVIDUAL	ADJAE	NA	2014-06-19	2014-07-02
01-701-1015	BASELINE	INDIVIDUAL	DOSE	0	2014-01-02	2014-01-16
01-701-1015	WEEK 2	INDIVIDUAL	DOSE	0	2014-01-17	2014-06-18
01-701-1015	WEEK 24	INDIVIDUAL	DOSE	0	2014-06-19	2014-07-02
01-701-1015	BASELINE	INDIVIDUAL	DURD	15	2014-01-02	2014-01-16

A record with PARAMCD == "TDOSE" is created with PARCAT1 set to "OVERALL" using the records in ADEX where PARAMCD == "DOSE" by summing AVAL. In addition, the ASTDT, and AENDT are created as the minimum and maximum date/times associated with each by_vars grouping. Note that, in addition to PARAMCD, PARCAT1, AVAL, ASTDT and AENDT, only those variables specified in the by_vars argument will be populated in the new records.

Multiple parameters (records) may be created at one time using the call_derivation() function:

adex <- adex %>%
  call_derivation(
    derivation = derive_param_exposure,
    variable_params = list(
      params(
        set_values_to = exprs(
          PARAMCD = "TDOSE",
          PARCAT1 = "OVERALL",
          AVAL = sum(AVAL, na.rm = TRUE)
        ),
        input_code = "DOSE"
      ),
      params(
        set_values_to = exprs(
          PARAMCD = "TPDOSE",
          PARCAT1 = "OVERALL",
          AVAL = sum(AVAL, na.rm = TRUE)
        ),
        input_code = "PLDOSE"
      ),
      params(
        set_values_to = exprs(
          PARAMCD = "TDURD",
          PARCAT1 = "OVERALL",
          AVAL = sum(AVAL, na.rm = TRUE)
        ),
        input_code = "DURD"
      ),
      params(
        set_values_to = exprs(
          PARAMCD = "TADJ",
          PARCAT1 = "OVERALL",
          AVALC = if_else(sum(!is.na(AVALC)) > 0, "Y", NA_character_)
        ),
        input_code = "ADJ"
      ),
      params(
        set_values_to = exprs(
          PARAMCD = "TADJAE",
          PARCAT1 = "OVERALL",
          AVALC = if_else(sum(!is.na(AVALC)) > 0, "Y", NA_character_)
        ),
        input_code = "ADJAE"
      )
    ),
    dataset_add = adex,
    by_vars = exprs(STUDYID, USUBJID, !!!adsl_vars)
  )

count(adex, PARAMCD, PARCAT1)
#> # A tibble: 10 × 3
#>    PARAMCD PARCAT1        n
#>    <chr>   <chr>      <int>
#>  1 ADJ     INDIVIDUAL    13
#>  2 ADJAE   INDIVIDUAL    13
#>  3 DOSE    INDIVIDUAL    13
#>  4 DURD    INDIVIDUAL    13
#>  5 PLDOSE  INDIVIDUAL    13
#>  6 TADJ    OVERALL        6
#>  7 TADJAE  OVERALL        6
#>  8 TDOSE   OVERALL        6
#>  9 TDURD   OVERALL        6
#> 10 TPDOSE  OVERALL        6

USUBJID	VISIT	PARCAT1	PARAMCD	AVAL	AVALC	ASTDT	AENDT
01-701-1015	BASELINE	INDIVIDUAL	ADJ	NA	NA	2014-01-02	2014-01-16
01-701-1015	WEEK 2	INDIVIDUAL	ADJ	NA	NA	2014-01-17	2014-06-18
01-701-1015	WEEK 24	INDIVIDUAL	ADJ	NA	NA	2014-06-19	2014-07-02
01-701-1015	BASELINE	INDIVIDUAL	ADJAE	NA	NA	2014-01-02	2014-01-16
01-701-1015	WEEK 2	INDIVIDUAL	ADJAE	NA	NA	2014-01-17	2014-06-18
01-701-1015	WEEK 24	INDIVIDUAL	ADJAE	NA	NA	2014-06-19	2014-07-02
01-701-1015	BASELINE	INDIVIDUAL	DOSE	0	NA	2014-01-02	2014-01-16
01-701-1015	WEEK 2	INDIVIDUAL	DOSE	0	NA	2014-01-17	2014-06-18
01-701-1015	WEEK 24	INDIVIDUAL	DOSE	0	NA	2014-06-19	2014-07-02
01-701-1015	BASELINE	INDIVIDUAL	DURD	15	NA	2014-01-02	2014-01-16

Dose intensity can be calculated using the function derive_param_doseint(). The planned dose and administered dose are passed into the function and a new record is created with the dose intensity calculation. Again, only those variables specified in the by_vars argument will be populated in this new record.

adex <- adex %>%
  derive_param_doseint(
    by_vars = exprs(STUDYID, USUBJID, !!!adsl_vars),
    set_values_to = exprs(PARAMCD = "TNDOSINT"),
    tadm_code = "TDOSE",
    tpadm_code = "TPDOSE"
  )

USUBJID	VISIT	EXSTDTC	EXENDTC	PARCAT1	PARAMCD	AVAL	ASTDT	AENDT
01-701-1015	BASELINE	2014-01-02	2014-01-16	INDIVIDUAL	DURD	15	2014-01-02	2014-01-16
01-701-1015	WEEK 2	2014-01-17	2014-06-18	INDIVIDUAL	DURD	153	2014-01-17	2014-06-18
01-701-1015	WEEK 24	2014-06-19	2014-07-02	INDIVIDUAL	DURD	14	2014-06-19	2014-07-02
01-701-1023	BASELINE	2012-08-05	2012-08-27	INDIVIDUAL	DURD	23	2012-08-05	2012-08-27
01-701-1023	WEEK 2	2012-08-28	2012-09-01	INDIVIDUAL	DURD	5	2012-08-28	2012-09-01
01-703-1086	BASELINE	2012-09-02	2012-09-16	INDIVIDUAL	DURD	15	2012-09-02	2012-09-16
01-703-1086	WEEK 2	2012-09-17	2012-12-04	INDIVIDUAL	DURD	79	2012-09-17	2012-12-04
01-703-1096	BASELINE	2013-01-25	2013-02-09	INDIVIDUAL	DURD	16	2013-01-25	2013-02-09
01-703-1096	WEEK 2	2013-02-10	2013-03-16	INDIVIDUAL	DURD	35	2013-02-10	2013-03-16
01-707-1037	BASELINE	2013-12-20	2013-12-24	INDIVIDUAL	DURD	5	2013-12-20	2013-12-24

The default calculation for dose intensity is: Administered Doses / Planned Doses * 100.

Please see the derive_param_doseint() documentation to see how planned doses of 0 or NA are handled.

Assign `PARAMCD`, `PARAMN`, etc. from Reference tables

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

For example, when creating ADEX, a lookup based on the ADaM PARAMCD value may be created:

PARAMCD	PARAM	PARAMN
DURD	Study drug duration during constant dosing interval (days)	1
DOSE	Dose administered during constant dosing interval (mg)	2
PLDOSE	Planned dose during constant dosing interval (mg)	3
ADJ	Dose adjusted during constant dosing interval	4
ADJAE	Dose adjusted due to AE during constant dosing interval	5
TDURD	Overall duration (days)	6
TDOSE	Total dose administered (mg)	7
TPDOSE	Total planned dose (mg)	9
TADJ	Dose adjusted during study	10
TADJAE	Dose adjusted during study due to AE	11
TNDOSINT	Overall dose intensity (%)	12

adex <- derive_vars_merged(
  adex,
  dataset_add = param_lookup,
  by_vars = exprs(PARAMCD)
)

count(adex, PARAMCD, PARAM, PARAMN)
#> # A tibble: 11 × 4
#>    PARAMCD  PARAM                                                   PARAMN     n
#>    <chr>    <chr>                                                    <dbl> <int>
#>  1 ADJ      Dose adjusted during constant dosing interval                4    13
#>  2 ADJAE    Dose adjusted  due to AE during constant dosing interv…      5    13
#>  3 DOSE     Dose administered during constant dosing interval (mg)       2    13
#>  4 DURD     Study drug duration during constant dosing interval (d…      1    13
#>  5 PLDOSE   Planned dose during constant dosing interval (mg)            3    13
#>  6 TADJ     Dose adjusted during study                                  10     6
#>  7 TADJAE   Dose adjusted during study due to AE                        11     6
#>  8 TDOSE    Total dose administered (mg)                                 7     6
#>  9 TDURD    Overall duration (days)                                      6     6
#> 10 TNDOSINT Overall dose intensity (%)                                  12     6
#> 11 TPDOSE   Total planned dose (mg)                                      9     6

Please note, this is an example only and additional columns may be needed for the join depending on your lookup/metadata table.

Derive Categorization Variables (`AVALCATx`)

{admiral} does not currently have a generic function to aid in assigning AVALCATx/ AVALCAxN values. Below is a simple example of how these values may be assigned using the dplyr::mutate function:

adex <- adex %>%
  mutate(
    AVALCAT1 = case_when(
      PARAMCD %in% c("TDURD") & AVAL < 30 ~ "< 30 days",
      PARAMCD %in% c("TDURD") & AVAL >= 30 & AVAL < 90 ~ ">= 30 and < 90 days",
      PARAMCD %in% c("TDURD") & AVAL >= 90 ~ ">=90 days",
      PARAMCD %in% c("TDOSE", "TPDOSE") & AVAL < 1000 ~ "< 1000 mg",
      PARAMCD %in% c("TDOSE", "TPDOSE") & AVAL >= 1000 ~ ">= 1000 mg",
      TRUE ~ NA_character_
    )
  )

USUBJID	VISIT	PARCAT1	PARAMCD	AVAL	AVALCAT1
01-701-1015	NA	OVERALL	TDOSE	0	< 1000 mg
01-701-1015	NA	OVERALL	TPDOSE	0	< 1000 mg
01-701-1015	NA	OVERALL	TDURD	182	>=90 days
01-701-1015	BASELINE	INDIVIDUAL	DURD	15	NA
01-701-1015	BASELINE	INDIVIDUAL	DOSE	0	NA
01-701-1015	BASELINE	INDIVIDUAL	PLDOSE	0	NA
01-701-1015	BASELINE	INDIVIDUAL	ADJ	NA	NA
01-701-1015	BASELINE	INDIVIDUAL	ADJAE	NA	NA
01-701-1015	WEEK 2	INDIVIDUAL	DURD	153	NA
01-701-1015	WEEK 2	INDIVIDUAL	DOSE	0	NA

Assign `ASEQ`

The {admiral} function derive_var_obs_number() can be used to derive ASEQ. An example call is:

adex <- derive_var_obs_number(
  adex,
  new_var = ASEQ,
  by_vars = exprs(STUDYID, USUBJID),
  order = exprs(PARCAT1, ASTDT, VISIT, VISITNUM, EXSEQ, PARAMN),
  check_type = "error"
)

USUBJID	VISIT	PARCAT1	PARAMCD	AVAL	ASTDT	ASEQ
01-701-1015	BASELINE	INDIVIDUAL	DURD	15	2014-01-02	1
01-701-1015	BASELINE	INDIVIDUAL	DOSE	0	2014-01-02	2
01-701-1015	BASELINE	INDIVIDUAL	PLDOSE	0	2014-01-02	3
01-701-1015	BASELINE	INDIVIDUAL	ADJ	NA	2014-01-02	4
01-701-1015	BASELINE	INDIVIDUAL	ADJAE	NA	2014-01-02	5
01-701-1015	WEEK 2	INDIVIDUAL	DURD	153	2014-01-17	6
01-701-1015	WEEK 2	INDIVIDUAL	DOSE	0	2014-01-17	7
01-701-1015	WEEK 2	INDIVIDUAL	PLDOSE	0	2014-01-17	8
01-701-1015	WEEK 2	INDIVIDUAL	ADJ	NA	2014-01-17	9
01-701-1015	WEEK 2	INDIVIDUAL	ADJAE	NA	2014-01-17	10

Add the `ADSL` variables

If needed, the other ADSL variables can now be added:

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

Add Labels and Attributes

Adding labels and attributes for SAS transport files is supported by the following packages:

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: All these packages are in the experimental phase, but the vision is to have them associated with an End to End pipeline under the umbrella of the pharmaverse. An example of applying metadata and perform associated checks can be found at the pharmaverse E2E example.

Example Script

ADaM	Sourcing Command
ADEX	`use_ad_template("ADEX")`

These binaries (installable software) and packages are in development.
They may not be fully stable and should be used with caution. We make no claims about them.