Understanding EC vs. EX Domains in SDTM: When to Use Each
Understanding EC vs. EX Domains in SDTM: When to Use Each
In SDTM, the EC (Exposure as Collected) and EX (Exposure) domains are both used to capture data related to drug or therapy exposure, but they serve different purposes depending on how the exposure data is collected.
EC (Exposure as Collected) Domain
The EC domain is intended to capture exposure data exactly as it is collected in the study. This is useful when the collected exposure data is complex or variable, such as when doses or regimens vary between subjects or over time.
Use EC when:
- The collected data cannot be easily derived into planned doses or regimens.
- Exposure is captured in a format that includes variations such as adjustments, interruptions, or titrations.
- When the study involves complex exposure schemes (e.g., titration or dose adjustments based on lab values).
SDTM IG 3.3 and 3.4 Guidance for EC:
- EC is meant for direct representation of collected exposure data.
- EC should be used when the exposure data cannot be directly mapped into the planned dosing regimen captured in EX.
- EC also allows capturing the exact timestamps or administration details, even if those details change frequently.
EX (Exposure) Domain
The EX domain is designed to represent planned exposure data—what was intended or scheduled in the study protocol. EX typically includes drug administration data that reflects the planned dosage, route, and frequency, regardless of minor deviations in administration.
Use EX when:
- The exposure data can be described using the planned protocol-specified doses.
- The collected data aligns well with planned dosing schedules (e.g., consistent dose across subjects and visits).
SDTM IG 3.3 and 3.4 Guidance for EX:
- EX captures planned exposure (e.g., what the protocol intended to administer).
- It’s used for studies where exposure data is straightforward and corresponds directly to what was scheduled.
- Even when exposure data is collected in variable amounts, EX can still be used if the planned dose was administered as intended.
Key Differences Between EC and EX in SDTM IG 3.3 and 3.4:
- EC: Focuses on capturing the exact details of exposure as they were collected, reflecting actual administration, including variability.
- EX: Reflects the planned or intended exposure based on the study design, following the study’s dosing protocol.
SDTM IG 3.3 vs. SDTM IG 3.4:
The SDTM IG 3.4 version introduces more clarifications on when to use EC vs. EX, emphasizing the importance of using EC when there is variability in exposure that cannot be easily captured in EX. SDTM IG 3.4 also provides additional examples and details on mapping complex exposure data, particularly for biologics or therapies with varying administration schedules.
In summary, EC is used for more complex, collected exposure data, while EX is used for planned, consistent exposures based on the protocol. The SDTM IG 3.3 and 3.4 versions emphasize using EC when there is significant variation in the collected data.
When to Use the EC Domain
The EC domain captures the exact exposure data as it is collected in the study. This is especially useful when exposure data varies between subjects, such as in cases of dose titrations, interruptions, or other adjustments. The key feature of the EC domain is its ability to reflect actual data, making it indispensable in complex trials where the administration schedule doesn’t always follow the protocol exactly.
For instance, if subjects are receiving doses that are adjusted based on their responses or lab results, or if subjects experience dose interruptions, the EC domain should be used to capture this variability. It provides an accurate picture of what really happened, even if the data does not align with the protocol-specified dose.
Example: Titration or Adjusted Dosing Scenario
In a trial where Drug B’s dose is titrated based on a subject’s response, one subject might start at 25 mg and increase to 50 mg after 10 days. Another subject could remain at 25 mg due to adverse events, and a third subject might increase to 75 mg. These variations should be captured in the EC domain.
STUDYID |
USUBJID |
ECDOSE |
ECDOSU |
ECDOSFRM |
ECSTDTC |
ECENDTC |
ECREASND |
ABC123 |
001 |
25 |
mg |
Tablet |
2024-01-01 |
2024-01-10 |
Titration |
ABC123 |
001 |
50 |
mg |
Tablet |
2024-01-11 |
2024-01-14 |
|
ABC123 |
002 |
25 |
mg |
Tablet |
2024-01-01 |
2024-01-15 |
Adverse Event |
When to Use the EX Domain
The EX domain captures the planned exposure based on the study protocol. It is used when the actual exposure follows the protocol as intended. The EX domain should be used for trials where the dosing regimen is straightforward and subjects receive the planned doses at scheduled times.
For example, if a trial protocol specifies that subjects receive 50 mg of Drug A daily for 30 days, and all subjects follow this schedule without any variations, the EX domain can capture this data.
Example: Simple Dosing Scenario
In a study where Drug A is administered in a fixed dose of 50 mg daily, the EX domain captures the planned exposure:
STUDYID |
USUBJID |
EXTRT |
EXDOSE |
EXDOSU |
EXROUTE |
EXSTDTC |
XYZ456 |
001 |
Drug A |
50 |
mg |
Oral |
2024-02-01 |
XYZ456 |
002 |
Drug A |
50 |
mg |
Oral |
2024-02-01 |
Using Both EC and EX Domains Together
In some cases, both domains can be used together to represent the planned vs. actual exposure. For instance, the EX domain captures the protocol-specified dose (e.g., 50 mg daily), while the EC domain captures deviations, such as dose interruptions or adjustments. This approach provides a complete picture of the exposure.
Example: Combined Use of EC and EX Domains
In a study where Drug D is administered as 50 mg daily but a subject misses doses due to personal reasons, the EX domain would capture the planned regimen, while the EC domain would record the missed doses.
EX Domain (Planned Dose):
STUDYID |
USUBJID |
EXTRT |
EXDOSE |
EXDOSU |
EXROUTE |
EXSTDTC |
DEF789 |
001 |
Drug D |
50 |
mg |
Oral |
2024-03-01 |
EC Domain (Actual Doses with Missed Doses):
STUDYID |
USUBJID |
ECDOSE |
ECDOSU |
ECDOSFRM |
ECSTDTC |
ECENDTC |
ECREASND |
DEF789 |
001 |
50 |
mg |
Tablet |
2024-03-01 |
2024-03-05 |
|
DEF789 |
001 |
50 |
mg |
Tablet |
2024-03-07 |
2024-03-30 |
Missed Dose |
Key Takeaways from SDTM IG 3.3 and 3.4
The SDTM IG (Implementation Guide) versions 3.3 and 3.4 provide specific guidance on when to use the EC and EX domains:
- EC Domain should be used when the collected exposure data includes dose adjustments, interruptions, or variations from the planned exposure.
- EX Domain is suitable for straightforward, consistent administration as per the protocol.
- SDTM IG 3.4 provides further clarity on the importance of capturing deviations in the EC domain when complex administration schedules are involved.
Conclusion
The EC and EX domains both play important roles in capturing exposure data in clinical trials. By understanding when to use each domain, you can ensure that your study data accurately reflects both the planned and actual administration of investigational treatments. As the SDTM guidelines evolve, leveraging both domains appropriately helps ensure that data is captured comprehensively and consistently.
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