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.