Determining If an Event Is a Treatment Emergent Adverse Event

JMP Clinical uses the TreatmentEmergent SAS macro to determine whether records might be:

•	Treatment emergent. These are data that begin on or after the first dose of any study drug.

•	Pre-treatment. These are data that begin prior to the first dose of any study drug.

•	On Treatment. Those are events that begin on or after the first dose of any study drug until the last date of dosing plus the offset 1 for end of dosing

•	Off-treatment follow-up. These are events that begin after the last date of dosing plus the offset for the end of dosing

This macro can be applied to event domains (including AE and CE ), intervention domains (including CM ) and findings domains (including VS ).

Algorithm

The macro used to calculate TEAEs incorporates the following:

•	Dates with partial times are imputed to the earliest time, 00 seconds, 00 minutes, or 00 hours.

•	Partial dates impute to earliest day (1st), and earliest month (Jan). Dates that are completely missing are not imputed. Observations recorded in MH are assumed to have occurred prior to initial dosing.

•	If either xx.xxTRTEM or xx.TRTEMFL are present with a value of either Yes or Y , the event is considered as treatment emergent.

•	The start dates for dosing are determined from ADSL .TRTSDTM . If ADSL.TRTSDTM is not present, ADSL.TRTSDT is used. If ADSL.TRTSDT is not present, DM.RFXSTDTC is used. If DM.RFXSTDTC is not present, the earliest date in EX.EXSTDTC is used. If EX.EXSTDTC is not present, DM.RFSTDTC is used.

•	The end dates for dosing are determined from ADSL.TRTEDTM . If ADSL.TRTEDTM is not present, ADSL.TRTEDT is used. If ADSL.TRTEDT is not present, DM.RFXENDTC is used. If DM.RFXENDTC is not present, the latest date in EX.EXENDTC is used. If EX.EXENDTC is not present, DM.RFENDTC is used.

•	If neither the date of the event, intervention or finding nor the dosing start date has a time component treatment emergence status is based solely on the date.

•	For AE , CM , and CE , if the date listed is on or after the dosing start date, the event is considered treatment emergent.

•	All non-treatment emergent events are considered pre-treatment events.

•	Note : All events are considered pre-treatment for those subjects not on treatment.

•	For on-treatment events:

•	When neither the date of event, nor the intervention of finding nor the dosing end date has a time component, comparisons are based solely on date.

•	For those cases in which the start date is known but the end date is missing, comparisons are based solely on the date and the event is considered on-treatment when the date of the event occurs after the start date.

•	For those cases in which both the start date and the end date are known, comparisons are based solely on the date and the event is considered on-treatment when the date of the event occurs between the start date and end date (plus the offset).

•	For off-treatment follow-up events:

•	When neither the date of event, nor the intervention of finding nor the dosing end date has a time component, comparisons are based solely on date.

•	For those cases in which both the start date and the end date are known, the event is considered off-treatment follow-up when the date of the event occurs after the end date (plus the offset).

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1

The offset for the end of dosing is considered to be a defined number of days