Cross Check between Define.xml and blankcrf.pdf

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 • http://support.sas.com/demosdownloads/setupcat.jsp?cat=Base+SAS+Software

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

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 • PrafullaGirase, 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.