This article describes creating an ADCE ADaM for the
analysis of Vaccine Reactogenicity Data collected in SDTM
CE domain. The current presented example is tested using
CE SDTM domains and ADSL ADaM domain. However,
other domains could be used if needed (eg temperature data collected in
VS).
Note: All examples assume CDISC SDTM and/or ADaM format as input unless otherwise specified.
TOXGR or SEV)ADSLAssumption: The CE domain has already been merged with
the SUPPCE dataset. If this is not yet the case, join
SUPPCE onto parent CE domain using
metatools::combine_supp(CE, SUPPCE).
library(admiraldev)
library(admiral)
library(dplyr)
library(lubridate)
library(admiralvaccine)
library(pharmaversesdtm)
data("ce_vaccine")
data("admiralvaccine_adsl")
adsl <- admiralvaccine_adsl
ce <- ce_vaccine
ce <- convert_blanks_to_na(ce)
adsl <- convert_blanks_to_na(adsl)| USUBJID | TRTSDT | TRTEDT | TRT01A | AP01SDT | AP01EDT | AP02SDT | AP02EDT |
|---|---|---|---|---|---|---|---|
| ABC-1001 | 2021-11-03 | 2021-12-30 | VACCINE A | 2021-11-03 | 2021-12-29 | 2021-12-30 | 2022-04-27 |
| ABC-1002 | 2021-10-07 | 2021-12-16 | VACCINE A | 2021-10-07 | 2021-12-15 | 2021-12-16 | 2022-06-14 |
This step involves company-specific pre-processing of required input dataset for further analysis. In this step, we will filter records that has only reactogenicity events.
Create period dataset - for joining period information onto
CE records. Need to remove datetime variables as otherwise
causes duplicate issues.
adsl2 <- adsl %>%
select(-c(starts_with("AP") & ends_with("DTM")))
adperiods <- create_period_dataset(
adsl2,
new_vars = exprs(APERSDT = APxxSDT, APEREDT = APxxEDT)
)| USUBJID | APERIOD | APERSDT | APEREDT |
|---|---|---|---|
| ABC-1001 | 1 | 2021-11-03 | 2021-12-29 |
| ABC-1001 | 2 | 2021-12-30 | 2022-04-27 |
| ABC-1002 | 1 | 2021-10-07 | 2021-12-15 |
| ABC-1002 | 2 | 2021-12-16 | 2022-06-14 |
At this step, it may be useful to join ADSL to your
CE 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)
adce <- adce %>%
# join ADSL to CE
derive_vars_merged(
dataset_add = adsl,
new_vars = adsl_vars,
by = exprs(STUDYID, USUBJID)
) %>%
derive_vars_dt(
dtc = CESTDTC,
new_vars_prefix = "AST",
highest_imputation = "n"
) %>%
derive_vars_dt(
dtc = CEENDTC,
new_vars_prefix = "AEN",
highest_imputation = "n"
) %>%
derive_vars_dy(
reference_date = TRTSDT,
source_vars = exprs(ASTDT, AENDT)
)| USUBJID | TRTSDT | CESTDTC | CEENDTC | ASTDT | AENDT | ASTDY | AENDY |
|---|---|---|---|---|---|---|---|
| ABC-1001 | 2021-11-03 | NA | NA | NA | NA | NA | NA |
| ABC-1001 | 2021-11-03 | 2021-11-04 | 2021-11-07 | 2021-11-04 | 2021-11-07 | 2 | 5 |
| ABC-1001 | 2021-11-03 | 2021-11-04 | 2021-11-04 | 2021-11-04 | 2021-11-04 | 2 | 2 |
| ABC-1001 | 2021-11-03 | 2021-11-03 | 2021-11-09 | 2021-11-03 | 2021-11-09 | 1 | 7 |
| ABC-1001 | 2021-11-03 | NA | NA | NA | NA | NA | NA |
| ABC-1001 | 2021-11-03 | 2021-11-03 | 2021-11-04 | 2021-11-03 | 2021-11-04 | 1 | 2 |
| ABC-1001 | 2021-11-03 | NA | NA | NA | NA | NA | NA |
| ABC-1001 | 2021-11-03 | NA | NA | NA | NA | NA | NA |
| ABC-1001 | 2021-11-03 | 2021-11-04 | 2021-11-04 | 2021-11-04 | 2021-11-04 | 2 | 2 |
| ABC-1001 | 2021-11-03 | 2021-11-04 | 2021-11-04 | 2021-11-04 | 2021-11-04 | 2 | 2 |
Also add analysis version of
CEREL(AREL).
adce <-
derive_vars_joined(
adce,
dataset_add = adperiods,
by_vars = exprs(STUDYID, USUBJID),
filter_join = ASTDT >= APERSDT & ASTDT <= APEREDT,
join_type = "all"
) %>%
mutate(
APERSTDY = as.integer(ASTDT - APERSDT) + 1,
AREL = CEREL
)| USUBJID | TRTSDT | ASTDT | AENDT | ASTDY | AENDY | APERIOD | APERSDT | APERSTDY |
|---|---|---|---|---|---|---|---|---|
| ABC-1001 | 2021-11-03 | NA | NA | NA | NA | NA | NA | NA |
| ABC-1001 | 2021-11-03 | 2021-11-04 | 2021-11-07 | 2 | 5 | 1 | 2021-11-03 | 2 |
| ABC-1001 | 2021-11-03 | 2021-11-04 | 2021-11-04 | 2 | 2 | 1 | 2021-11-03 | 2 |
| ABC-1001 | 2021-11-03 | 2021-11-03 | 2021-11-09 | 1 | 7 | 1 | 2021-11-03 | 1 |
| ABC-1001 | 2021-11-03 | NA | NA | NA | NA | NA | NA | NA |
| ABC-1001 | 2021-11-03 | 2021-11-03 | 2021-11-04 | 1 | 2 | 1 | 2021-11-03 | 1 |
| ABC-1001 | 2021-11-03 | NA | NA | NA | NA | NA | NA | NA |
| ABC-1001 | 2021-11-03 | NA | NA | NA | NA | NA | NA | NA |
| ABC-1001 | 2021-11-03 | 2021-11-04 | 2021-11-04 | 2 | 2 | 1 | 2021-11-03 | 2 |
| ABC-1001 | 2021-11-03 | 2021-11-04 | 2021-11-04 | 2 | 2 | 1 | 2021-11-03 | 2 |
TOXGR or SEV)Depending on which variable is collected for the Grading
(TOXGR or SEV) in CE domain,
derive the associated analysis version. In current example,
SEV is collected, so the code is using this as an example.
In addition, derivation of Extreme Flags: in current example: flag the
first occurrence of the most severe grade within a Period
(AOCC01FL).
adce <- adce %>%
mutate(
ASEV = CESEV,
ASEVN = as.integer(factor(ASEV,
levels = c("MILD", "MODERATE", "SEVERE", "DEATH THREATENING")
))
) %>%
restrict_derivation(
derivation = derive_var_extreme_flag,
args = params(
by_vars = exprs(USUBJID, APERIOD),
order = exprs(desc(ASEVN), ASTDY, CEDECOD),
new_var = AOCC01FL,
mode = "first"
),
filter = !is.na(APERIOD) & !is.na(ASEV)
)| USUBJID | TRTSDT | ASTDT | APERIOD | APERSDT | APERSTDY | CEDECOD | ASEVN | AOCC01FL | CESEQ |
|---|---|---|---|---|---|---|---|---|---|
| ABC-1001 | 2021-11-03 | 2021-11-03 | 1 | 2021-11-03 | 1 | Swelling | 2 | Y | 4 |
| ABC-1001 | 2021-11-03 | 2021-11-04 | 1 | 2021-11-03 | 2 | Erythema | 2 | NA | 3 |
| ABC-1001 | 2021-11-03 | 2021-11-04 | 1 | 2021-11-03 | 2 | Injection site pain | 2 | NA | 2 |
| ABC-1001 | 2021-11-03 | 2021-11-03 | 1 | 2021-11-03 | 1 | Fatigue | 1 | NA | 6 |
| ABC-1001 | 2021-11-03 | 2021-11-04 | 1 | 2021-11-03 | 2 | Arthralgia | 1 | NA | 9 |
| ABC-1001 | 2021-11-03 | 2021-11-04 | 1 | 2021-11-03 | 2 | Myalgia | 1 | NA | 10 |
| ABC-1002 | 2021-10-07 | 2021-10-11 | 1 | 2021-10-07 | 5 | Headache | 2 | Y | 8 |
| ABC-1002 | 2021-10-07 | 2021-10-09 | 1 | 2021-10-07 | 3 | Erythema | 1 | NA | 3 |
| ABC-1002 | 2021-10-07 | 2021-12-16 | 2 | 2021-12-16 | 1 | Injection site pain | 1 | Y | 13 |
| ABC-1002 | 2021-10-07 | 2021-12-17 | 2 | 2021-12-16 | 2 | Erythema | 1 | NA | 14 |
adce <- adce %>%
derive_var_obs_number(
new_var = ASEQ,
by_vars = exprs(STUDYID, USUBJID),
order = exprs(CEDECOD, CELAT, CETPTREF, APERIOD),
check_type = "error"
) %>%
derive_vars_duration(
new_var = ADURN,
new_var_unit = ADURU,
start_date = ASTDT,
end_date = AENDT,
in_unit = "days",
out_unit = "days",
add_one = TRUE,
trunc_out = FALSE
)| USUBJID | TRTSDT | ASTDT | APERIOD | APERSDT | APERSTDY | CEDECOD | ASEVN | AOCC01FL | CESEQ | ASEQ |
|---|---|---|---|---|---|---|---|---|---|---|
| ABC-1001 | 2021-11-03 | 2021-11-04 | 1 | 2021-11-03 | 2 | Arthralgia | 1 | NA | 9 | 1 |
| ABC-1001 | 2021-11-03 | NA | NA | NA | NA | Arthralgia | NA | NA | 20 | 2 |
| ABC-1001 | 2021-11-03 | NA | NA | NA | NA | Chills | NA | NA | 1 | 3 |
| ABC-1001 | 2021-11-03 | NA | NA | NA | NA | Chills | NA | NA | 12 | 4 |
| ABC-1001 | 2021-11-03 | NA | NA | NA | NA | Diarrhoea | NA | NA | 5 | 5 |
| ABC-1001 | 2021-11-03 | NA | NA | NA | NA | Diarrhoea | NA | NA | 16 | 6 |
| ABC-1001 | 2021-11-03 | 2021-11-04 | 1 | 2021-11-03 | 2 | Erythema | 2 | NA | 3 | 7 |
| ABC-1001 | 2021-11-03 | NA | NA | NA | NA | Erythema | NA | NA | 14 | 8 |
| ABC-1001 | 2021-11-03 | 2021-11-03 | 1 | 2021-11-03 | 1 | Fatigue | 1 | NA | 6 | 9 |
| ABC-1001 | 2021-11-03 | NA | NA | NA | NA | Fatigue | NA | NA | 17 | 10 |
ADSLGet list of ADSL vars as per trial specific which needs
to be adjusted when using the template
adsl_list <- adsl %>%
select(STUDYID, USUBJID, TRT01A, TRT01P, AGE, AGEU, SEX, RACE, COUNTRY, ETHNIC, SITEID, SUBJID)
adce <- adce %>%
derive_vars_merged(
dataset_add = adsl_list,
by_vars = exprs(STUDYID, USUBJID)
)| USUBJID | TRTSDT | ASTDT | APERIOD | APERSDT | APERSTDY | CEDECOD | ASEVN | AOCC01FL | CESEQ | ASEQ | AGE | SEX |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ABC-1001 | 2021-11-03 | 2021-11-04 | 1 | 2021-11-03 | 2 | Arthralgia | 1 | NA | 9 | 1 | 74 | F |
| ABC-1001 | 2021-11-03 | NA | NA | NA | NA | Arthralgia | NA | NA | 20 | 2 | 74 | F |
| ABC-1001 | 2021-11-03 | NA | NA | NA | NA | Chills | NA | NA | 1 | 3 | 74 | F |
| ABC-1001 | 2021-11-03 | NA | NA | NA | NA | Chills | NA | NA | 12 | 4 | 74 | F |
| ABC-1001 | 2021-11-03 | NA | NA | NA | NA | Diarrhoea | NA | NA | 5 | 5 | 74 | F |
| ABC-1001 | 2021-11-03 | NA | NA | NA | NA | Diarrhoea | NA | NA | 16 | 6 | 74 | F |
| ABC-1001 | 2021-11-03 | 2021-11-04 | 1 | 2021-11-03 | 2 | Erythema | 2 | NA | 3 | 7 | 74 | F |
| ABC-1001 | 2021-11-03 | NA | NA | NA | NA | Erythema | NA | NA | 14 | 8 | 74 | F |
| ABC-1001 | 2021-11-03 | 2021-11-03 | 1 | 2021-11-03 | 1 | Fatigue | 1 | NA | 6 | 9 | 74 | F |
| ABC-1001 | 2021-11-03 | NA | NA | NA | NA | Fatigue | NA | NA | 17 | 10 | 74 | F |
| ADaM | Sample Code |
|---|---|
| ADCE | ad_adce.R |