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/setupca t.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 6 6 STUDYID 6 6 EDUOTH 7 7 MHPRESP 7 7 MHOCCUR 10 10 PESTAT 12 12 EGCLSP Message Variable : STUDYID annotated in CRF, but in Define.xml, origin is not mentioned as CRF Page Variable : EDUOTH annotated in CRF, but in Define.xml, origin is not mentioned as CRF Page Variable : MHPRESP annotated in CRF, but in Define.xml, origin is not mentioned as CRF Page Variable : MHOCCUR annotated in CRF, but in Define.xml, origin is not mentioned as CRF Page Variable : PESTAT annotated in CRF, but in Define.xml, origin is not mentioned as CRF Page 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.