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

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

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

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

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

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

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

Too much to check manually

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

XML Mapper Download SAS XML mapper http://support.sas.com/demosdownloads/setupcat.jsp?cat=Base+SAS+Software

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

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;

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

Read Comments in PDF to SAS Dataset (cont.)

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

SAS Dataset of CRF Annotation

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

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

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

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

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