Comprehensive QC Checklist for Define.xml and cSDRG
Ensuring Quality and Compliance for FDA and PMDA SDTM Submissions
Introduction
The **Define.xml** and **Clinical Study Data Reviewer’s Guide (cSDRG)** are critical components of SDTM submissions to regulatory agencies like the FDA and PMDA. These documents help reviewers understand the structure, content, and traceability of the datasets submitted. A robust QC process ensures compliance with agency requirements, minimizes errors, and enhances submission success. This blog outlines a detailed manual QC checklist for both Define.xml and cSDRG, emphasizing key differences between FDA and PMDA requirements.
Define.xml QC Checklist
1. Metadata Verification
- Verify all datasets listed in Define.xml are included in the submission package.
- Check that all variable metadata (e.g., variable names, labels, types, and lengths) matches the SDTM datasets.
- Ensure consistency between controlled terminology values and the CDISC Controlled Terminology files.
- Confirm all mandatory fields (e.g., Origin, Value Level Metadata, Comments) are correctly populated.
2. Controlled Terminology
- Ensure variables like
AEDECOD,LBTESTCD, andCMTRTalign with the latest CDISC Controlled Terminology. - Check NCI Codelist codes for correctness and proper linkage to variables.
- Verify that SUPPQUAL domains reference appropriate `QNAM` and `QVAL` values.
3. Links and Traceability
- Ensure all hyperlinks in Define.xml (e.g., links to codelists, Value Level Metadata, and external documents) are functional.
- Verify traceability for derived variables to source data or algorithms.
4. Value Level Metadata
- Check that Value Level Metadata is used for variables with differing attributes (e.g.,
QVALin SUPPQUAL). - Validate metadata application to specific values, ensuring alignment with dataset content.
5. Technical Validation
- Run Define.xml through Pinnacle 21 or a similar validation tool to identify errors or warnings.
- Validate XML structure against the CDISC Define-XML schema (e.g., UTF-8 encoding).
6. Documentation
- Ensure accurate descriptions in the
Commentssection for clarity and traceability. - Check consistency between Define.xml and cSDRG descriptions.
cSDRG QC Checklist
1. Content Consistency
- Ensure alignment with Define.xml in terms of datasets, variables, and controlled terminology.
- Verify consistency with CDISC guidelines for SDRG structure and content.
2. Document Structure
- Ensure all required sections are present:
- Study Design Overview
- Dataset-Specific Considerations
- Traceability and Data Processing
- Controlled Terminology
- Verify the inclusion of Acronyms and Abbreviations.
3. Dataset-Level Review
- Check that all datasets referenced in cSDRG are included in the Define.xml and the submission package.
- Verify clear descriptions of dataset-specific issues (e.g., imputed values, derived variables).
4. Traceability and Data Processing
- Ensure documentation of traceability from raw data to SDTM datasets.
- Validate derivation rules for key variables.
5. Controlled Terminology
- Ensure controlled terminology usage aligns with Define.xml.
- Document any deviations or extensions to standard controlled terminology.
6. Reviewer-Focused Content
- Provide explanations for unusual scenarios (e.g., partial/missing dates, adverse event relationships).
- Tailor descriptions to a reviewer’s perspective for clarity and usability.
7. Formatting and Usability
- Ensure consistent fonts, headings, and numbering throughout the document.
- Verify hyperlinks and table of contents functionality in the PDF format.
FDA vs. PMDA Considerations
While FDA and PMDA share many requirements, there are some critical differences:
| Aspect | FDA | PMDA |
|---|---|---|
| Encoding | UTF-8 | UTF-8 (focus on Japanese character encoding) |
| Validation Tools | Pinnacle 21 Community/Enterprise | Pinnacle 21 with PMDA-specific rules |
| Trial Summary (TS) | Focus on mandatory fields | Greater emphasis on PMDA-specific fields |
| Language | English | English and Japanese |
Conclusion
Ensuring high-quality Define.xml and cSDRG documents is crucial for successful regulatory submissions to FDA and PMDA. Adhering to the detailed QC checklists outlined above will help identify and address issues early, saving time and reducing the risk of rejection. Tailoring your approach to the specific requirements of each agency ensures a smooth review process and enhances submission success rates.
