1. Cross Check between Define.xml and blankcrf.pdf
Galderma, LLT
Jeff Xia, Sangeetha Mahalingam

2. SDTM Submission Package
FDA has specific rules in organizing study files in a NDA submission

3. SDTM Define package
SDTM define package is stored in the subfolder of Tabulations
define.xml
blankcrf.pdf
SAS xpt files
Supporting documents, e.g., style sheet

4. Importance of Define.xml
A critical component of data submission is the define file. A properly functioning define.xml file is an important part of the submission of standardized electronic datasets and should not be considered optional.
An insufficiently documented define file is a common deficiency that reviewers have noted, including the Origin of the variable

5. Origin field in Define.xml
Indicator of the origin of the variable.
CRF Page #
Derived
eDT
Assigned
Protocol
Hyperlink is provided to display the specific CRF Pages by using the stylesheet

6. Validity of Origin field
The CRF Page number is valid
If the reviewer clicks the hyperlink of a CRF Page, then there should be a annotation in corresponding CRF Page

7. Validity of Origin field (Cont.)
All the CRF Page with the same annotation should be listed in the Origin field for that variable in the define.xml

8. Too much to check manually

9. A programming way to check
Step 1: Read define.xml into SAS dataset
Setp 2: Read annotation of blankcrf.pdf into SAS dataset
Origin compare checks between the datasets created in Step 1 and Step 2 and the discrepancies are outputted in a listing

10. XML Mapper Download SAS XML mapper

11. How to customize a xml mapper
Wendi L Wright, 2010, How to Create an XML Map with the XML Mapper

12. Syntax for reading xml into SAS dataset
filename define “---\define.xml";
**** Define file location;
filename sxlemap “---\DefineXML.map"; **** define XML mapper file location;
libname define XML XMLMAP=sxlemap access=readonly;

13. Read Comments in PDF to SAS Dataset
Export Annotation in blankcrf to Data file (XFDF, a xml version of form data in PDF)
Version: Adobe Acrobat Pro

14. Read Comments in PDF to SAS Dataset (cont.)

15. Read Comments in PDF to SAS Dataset (cont.)
Develop a customized xml mapper for XFDF
Read XFDF into SAS Dataset

16. SAS Dataset of CRF Annotation

17. Sample Findings of Cross Check
CDISC - Compare define origin with CRF annotation
XML Page
CRF Page
CRF Annotation
Message 6
STUDYID
Variable : STUDYID annotated in CRF, but in Define.xml, origin is not mentioned as CRF Page
EDUOTH
Variable : EDUOTH annotated in CRF, but in Define.xml, origin is not mentioned as CRF Page 7
MHPRESP
Variable : MHPRESP annotated in CRF, but in Define.xml, origin is not mentioned as CRF Page
MHOCCUR
Variable : MHOCCUR annotated in CRF, but in Define.xml, origin is not mentioned as CRF Page 10
PESTAT
Variable : PESTAT annotated in CRF, but in Define.xml, origin is not mentioned as CRF Page 12
EGCLSP
Variable : EGCLSP annotated in CRF, but in Define.xml, origin is not mentioned as CRF Page

18. Standard Expression of Annotation
Consistent across studies in the same NDA submission,
Easier for programming in the cross check
RACEOTH in SUPPDM
SUPPDM.QVAL where QNAM = RACEOTH
VSORRES where VSTESTCD = HEIGHT
Domain: VS
VS: Vital Signs

19. More checks
Check the QNAM, --TESTCD, --TEST among define.xml, SAS xpt files and annotation of blankcrf
Check the contents in the TOC section of define.xml
Class
Structure
Key
Location
Significant digits in VLM
Comments for common variables, e.g. STUDYID

20. Reference
Joel Campbell, Ryan Wilkins, Importing and Parsing Comments From a PDF Document With Help From Perl Regular Expressions, PgarmaSUG 2011
Prafulla Girase, Robert Agostinelli, Automating Validation of Define.xml using SAS, PharmaSUG 2013
FDA, CDER Common Data Standards Issues Document, Version 1.1, Dec 2011

21. Thanks
The SAS Implementation of the cross check in this presentation was done by Sangeetha Mahalingam.