In Oncology trials, for censoring the patients for any time-to-event analysis (e.g., progression free survival analysis, duration of response, etc.), it is necessary to check if the patients have started any new anti-cancer therapy. Anti-cancer therapy generally includes radiation therapy, cancer related surgery and any systemic anti-cancer therapy such as chemotherapy, t-cell therapy, etc. These therapies can be collected on a prior or on-treatment CRF pages, with radiation and surgery being mapped to the SDTM PR domain and systemic anti-cancer therapy being mapped to the SDTM CM domain. Collection and mapping may vary with each company and it is important that only on-treatment therapies are considered for the censoring of time-to-event. Generally, if the patients start a new anti-cancer therapy that were on-treatment, they should be discontinued from the study treatment and no further efficacy assessments should be performed.
This article describes a process for creating a new anti-cancer start date from a single and multiple source SDTMs.
ADSL
To start, all data frames needed for the creation of the new
anti-cancer therapy start date (NACTDT
) should be read into
the environment. This will be a company specific process. Some of the
data frames needed may be CM
and PR
.
For example purpose, CM
and PR
has been
generated (based on CDISC Pilot test data), with oncology specific test
data.
library(admiral)
library(pharmaverseadam)
library(dplyr)
data("adsl")
adsl_onco <- adsl
data("adrs_onco")
cm <- tribble(
~STUDYID, ~USUBJID, ~CMCAT, ~CMSCAT, ~CMTRT, ~CMSTDTC,
"CDISCPILOT01", "01-701-1015", "PRIOR TREATMENT", "CHEMOTHERAPY", "DEXRAZOXANE", NA,
"CDISCPILOT01", "01-701-1015", "ON TREATMENT", "CHEMOTHERAPY", "DEXROZOXANE", "2014-07-02",
"CDISCPILOT01", "01-701-1015", "ON TREATMENT", "CHEMOTHERAPY", "DEXROZOXANE", "2014-06-19",
"CDISCPILOT01", "01-701-1028", "PRIOR TREATMENT", "CHEMOTHERAPY", "METHOTREXATE", NA,
"CDISCPILOT01", "01-701-1028", "ON TREATMENT", "CHEMOTHERAPY", "METHOTREXATE", "2014-01-14",
"CDISCPILOT01", "01-701-1034", "PRIOR TREATMENT", "CHEMOTHERAPY", "OLAPARIB", NA,
"CDISCPILOT01", "01-701-1034", "ON TREATMENT", "CHEMOTHERAPY", "OLAPARIB", "2014-12-30",
"CDISCPILOT01", "01-701-1097", "PRIOR TREATMENT", "CHEMOTHERAPY", "TEMODAL", NA,
"CDISCPILOT01", "01-701-1097", "ON TREATMENT", "CHEMOTHERAPY", "TEMODAL", "2013-12-31",
)
pr <- tribble(
~STUDYID, ~USUBJID, ~PRCAT, ~PRSCAT, ~PRTRT, ~PRSTDTC,
"CDISCPILOT01", "01-701-1015", "CANCER RELATED", "ON TREATMENT", "SURGERY", "2014-06-18",
"CDISCPILOT01", "01-701-1034", "CANCER RELATED", "ON TREATMENT", "SURGERY", "2014-12-16",
"CDISCPILOT01", "01-701-1028", "CANCER RELATED", "PRIOR TREATMENT", "SURGERY", NA,
)
To derive the New Anti-Cancer Therapy start date with data from a
single source, the function admiral::derive_vars_merged()
can be used. If numeric date is required,
admiral::convert_dtc_to_dt
, or if time part is needed,
admiral::convert_dtc_to_dtm()
can be used as part of an
expression for the new_vars
argument.
adsl <- derive_vars_merged(
adsl_onco,
dataset_add = cm,
by_vars = get_admiral_option("subject_keys"),
order = exprs(NACTDT),
mode = "first",
new_vars = exprs(NACTDT = convert_dtc_to_dt(CMSTDTC)),
filter_add = CMSCAT == "CHEMOTHERAPY" & CMCAT == "ON TREATMENT"
)
USUBJID | NACTDT |
---|---|
01-701-1015 | 2014-06-19 |
01-701-1028 | 2014-01-14 |
01-701-1034 | 2014-12-30 |
01-701-1097 | 2013-12-31 |
To derive the New Anti-Cancer Therapy start date with data from
multiple sources, the function
admiral::derive_vars_extreme_event()
can be used.
Prior to calling the function, an input event
object
must be created for each source dataset using
admiral::event()
. Within this function, any
company-specific subsetting can be passed to the condition
argument. If numeric version of the dates will be needed,
admiral::convert_dtc_to_dt()
, or if time part is needed,
admiral::convert_dtc_to_dtm()
can be used as part of an
expression for the set_values_to
argument.
cm_date <- event(
dataset_name = "cm",
condition = CMSCAT == "CHEMOTHERAPY" & CMCAT == "ON TREATMENT" & !is.na(CMSTDTC),
set_values_to = exprs(NACTDT = convert_dtc_to_dt(CMSTDTC))
)
pr_date <- event(
dataset_name = "pr",
condition = PRCAT == "CANCER RELATED" & PRSCAT == "ON TREATMENT" & !is.na(PRSTDTC),
set_values_to = exprs(NACTDT = convert_dtc_to_dt(PRSTDTC))
)
ADSL
After completion of the prerequisite step, the new anti-cancer date
can be derived while simultaneously adding it to ADSL
.
adsl <- adsl_onco %>%
derive_vars_extreme_event(
by_vars = get_admiral_option("subject_keys"),
order = exprs(NACTDT),
new_vars = exprs(NACTDT),
events = list(cm_date, pr_date),
source_datasets = list(
cm = cm,
pr = pr
),
mode = "first"
)
USUBJID | NACTDT |
---|---|
01-701-1015 | 2014-06-18 |
01-701-1028 | 2014-01-14 |
01-701-1034 | 2014-12-16 |
01-701-1097 | 2013-12-31 |
Please refer to {admiralonco}
Derive ANL01FL
for an example
on the usage of NACTDT
. Additionally,
{admiralonco}
Creating Your Own
Time-to-Event Source Objects may be referenced for case usage.
The {admiral}
function
admiral::derive_extreme_event()
can be used for deriving
parameter based on the first or last observation from single and
multiple sources.
Based on individual company standards, this parameter may be added to
an event or date dataset such as ADEVENT
or
ADDATES
, which are generally intermediate datasets to
ADTTE
. For demonstration purpose, a new anti-cancer date
parameter will be merged into ADRS
. A list of
event()
objects is expected and this will contain the
sources of the dates and any company specific filtering.
adrs <- derive_extreme_event(
dataset = adrs_onco,
events = list(
event(
dataset_name = "cm",
condition = CMSCAT == "CHEMOTHERAPY" & CMCAT == "ON TREATMENT" & !is.na(CMSTDTC),
set_values_to = exprs(
ADT = convert_dtc_to_dt(CMSTDTC),
AVALC = CMTRT
)
),
event(
dataset_name = "pr",
condition = PRCAT == "CANCER RELATED" & PRSCAT == "ON TREATMENT" & !is.na(PRSTDTC),
set_values_to = exprs(
ADT = convert_dtc_to_dt(PRSTDTC),
AVALC = PRTRT
)
)
),
source_datasets = list(cm = cm, pr = pr),
by_vars = get_admiral_option("subject_keys"),
order = exprs(ADT),
mode = "first",
set_values_to = exprs(
PARAMCD = "NACTDT",
PARAM = "New Anti-Cancer Therapy Start Date"
)
)
USUBJID | PARAMCD | PARAM | ADT | AVALC |
---|---|---|---|---|
01-701-1015 | NACTDT | New Anti-Cancer Therapy Start Date | 2014-06-18 | SURGERY |
01-701-1028 | NACTDT | New Anti-Cancer Therapy Start Date | 2014-01-14 | METHOTREXATE |
01-701-1034 | NACTDT | New Anti-Cancer Therapy Start Date | 2014-12-16 | SURGERY |
01-701-1097 | NACTDT | New Anti-Cancer Therapy Start Date | 2013-12-31 | TEMODAL |