cross check between define.xml and blankcrf.pdf galderma, llt jeff xia, sangeetha mahalingam
TRANSCRIPT
Cross Check between Define.xml and blankcrf.pdf
Galderma, LLTJeff 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 Message
6 6STUDYIDVariable : STUDYID annotated in CRF, but in Define.xml, origin is not mentioned as CRF Page
6 6EDUOTHVariable : EDUOTH annotated in CRF, but in Define.xml, origin is not mentioned as CRF Page
7 7MHPRESPVariable : MHPRESP annotated in CRF, but in Define.xml, origin is not mentioned as CRF Page
7 7MHOCCURVariable : MHOCCUR annotated in CRF, but in Define.xml, origin is not mentioned as CRF Page
10 10 PESTATVariable : PESTAT annotated in CRF, but in Define.xml, origin is not mentioned as CRF Page
12 12 EGCLSPVariable : 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.