Common Questions about Define-XML and the Stylesheet

Q: Which versions of Define-XML does the FDA/PMDA currently accept for submissions?

According to both the FDA and PMDA Data Standards Catalogs, Define-XML v2.0 and v2.1 are currently being accepted. For FDA, support for Define-XML v1.0 ended on March 15, 2018, and the study start date should be used to determine which version of Define-XML is required. However, it is noted in the Study Data Technical Conformance Guide that “Define-XML version 2.0 or later is strongly preferred.” For PMDA, support for Define-XML v1.0 ends on March 31, 2025. 

Q: What is the difference between Origin, Source, and Type?

The def:Origin element was introduced in Define-XML 2.0.0. When using that standard, it was intended to define the Origin metadata for variables in SDTM or SEND datasets or Source metadata for ADaM datasets. Source, on the other hand, only referred to def:Origin/Description which must be provided to indicate the source when def:Origin@Type=”Predecessor” in that standard. Conventions described in IG documents for the specific standard should be followed. 

In Define-XML v2.1, the def:Origin element was updated to include both Type and Source attributes. Values for Origin, Type and Source are included in non-extensible codelists within CDISC Controlled Terminology. For SDTM datasets, the Type and Source attributes are required. For ADaM datasets, Type and Source attributes are also required except when using “Predecessor” where the Source attribute is not used. For SEND datasets, only the Type attribute is used. 

Q: How are hyperlinks created in the define?

Hyperlinks are generated when there are def:leaf elements. See section 5.3.15 of the Define-XML Specification v2.0 or section 4.6 of the Define-XML Specification v2.1 for more information. 

Q: What is a “formal expression”?

A formal expression provides machine readable code to compute or impute the value of an ItemDef. See section 5.3.13.1 of the Define-XML Specification v2.0 or section 5.3.14.1 Define-XML Specification v2.1 for more information. In P21E, the formal expression is created when Expression Context and Expression Code are populated on the methods tab. 

Q: How should you handle multiple origins for the same variable (i.e. CRF, Assigned)?

When there is more than one origin for a variable, value-level metadata should be created for that variable.

Q: Should we have labels for all VLM?

Yes, labels should be provided for VLM.

Q: How can we define the order value in codelists?

Individual terms within codelists can be ordered using the OrderNumber attribute on the EnumeratedItem and CodeListItem elements. 

Q: Does the define 2.0 stylesheet work with define 2.1?

A different stylesheet for define 2.0 and define 2.1 should be used, and both are available on the CDISC website. 

Q: Can I start using the updated Style sheet for submissions?

There is no formal requirement (at this time) regarding which version of the stylesheet to submit. We recommend using the latest version applicable for your version of define.xml.

Q: Should we mention what stylesheet is used in reviewer’s guide?

The PHUSE template does not provide a row in the study data standards and inventory section for this information; however, you can always add it but there is no formal requirement at this time.

Q: Are there different versions of for SEND, SDTM, and ADaM?

No, stylesheets are compatible based only on the version of Define-XML being used. The stylesheet used for define v2.0 can be used for SEND, SDTM, or ADaM. 

Many organizations don’t worry about creating the define.xml file until right before submission. Others create the file while the study is still ongoing, to benefit from time, cost and process efficiencies.  

Regardless of your approach, you should be familiar with the 6 dos and don’ts contained in our FREE Define-XML guide.