1. Monika Kawohl Statistical Programming Accovion GmbH Tutorial: define.xml

2. CDISC German Speaking User Group Meeting, 11-Mar-20102 Overview Requirements Regulatory Technical define.xml Sections/Elements Process Flow at Accovion

3. CDISC German Speaking User Group Meeting, 11-Mar-20103 Regulatory Requirements eCTD‘s Study Data Specifications V1.5.1 SDTM “ Dataset documentation includes data definitions and annotated case report forms.” SDTM: define.xml ADaM: define.pdf / define.xml ? ADaM

4. CDISC German Speaking User Group Meeting, 11-Mar-20104 Why define.xml Metadata = data about data Human-readable description to familiarize with data What is included? Where does the data come from? Derivation rules, if applicable Machine-readable metadata to facilitate... SDTM data consistency check Upload into JANUS data warehouse Preferred => mandatory format: define.xml Benefit of define.xml not restricted to submissions

5. CDISC German Speaking User Group Meeting, 11-Mar-20105

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7. 7 XML Basics Schema (extension:.XSD) Declaration of elements and their attributes Prerequisite for machine-readability XML File (extension:.XML) Data and metadata in machine-readable format Usage of elements and attributes as defined in schema Style Sheet (extension:.XSL) Definition of layout in browser tool for Human-Readability Usage of elements and attributes as defined in schema

8. CDISC German Speaking User Group Meeting, 11-Mar-20108 Advantages of XML – Basic Technology <ODM... <ItemGroupDef OID="DM" Name="DM" Repeating="No" IsReferenceData="No" Purpose="Tabulation" def:Label="Demographics" def:Structure="One record per subject" def:DomainKeys="STUDYID, USUBJID" def:Class="Special Purpose" def:ArchiveLocationID="Location.DM">... style sheet reference

9. CDISC German Speaking User Group Meeting, 11-Mar-20109 define.xml Sections/Elements Data Metadata (TOC) Variable Metadata Variable Value Level Metadata (Computational Algorithms) Controlled Terminology/Code Lists Annotated CRF Optional: Supplemental Data Definition Document Navigation via Bookmarks and Hyperlinks

10. CDISC German Speaking User Group Meeting, 11-Mar-201010 Data Metadata

11. CDISC German Speaking User Group Meeting, 11-Mar-201011 Variable Metadata Change for Origin in SDTM IG 3.1.2: Sponsor Defined, Assigned, eDT, Protocol

12. CDISC German Speaking User Group Meeting, 11-Mar-201012 Variable Metadata – XML Code <ItemGroupDef OID="LB"... <ItemRef ItemOID="LB.LBTESTCD" OrderNumber="5" Mandatory="Yes" Role="Topic"/>... <ItemRef ItemOID="LB.LBBLFL" OrderNumber="22" Mandatory="No" Role="Record Qualifier"/>... <ItemDef OID="LB.LBTESTCD" Name="LBTESTCD" DataType="text" Length="8" Origin="CRF Pages 5, 10, 15, 20" Comment="" def:Label="LAB Test or Examination Short Name">... <ItemDef OID="LB.LBBLFL" Name="LBBLFL" DataType="text" Length="1" Origin="Derived" def:Label="Baseline Flag" def:ComputationMethodOID="COMPMETHOD.LBBLFL">

13. CDISC German Speaking User Group Meeting, 11-Mar-201013 Variable Value Level Metadata

14. CDISC German Speaking User Group Meeting, 11-Mar-201014 Computational Algorithms Complex Derivations Derivations Used More than Once

15. CDISC German Speaking User Group Meeting, 11-Mar-201015 Controlled Terminology/Code Lists External dictionary references incl. versions e.g., MEDDRA, WHODRUG

16. CDISC German Speaking User Group Meeting, 11-Mar-201016 See Draft CDISC Metadata Submission Guidelines Annotate unique pages, reference from repeat pages Annotate variables, variables values (cf. value level metadata) Mark items that are not submitted Annotated CRF (blankcrf.pdf)

17. CDISC German Speaking User Group Meeting, 11-Mar-201017 SDTM Process Flow at Accovion Annotated CRF Communication = dataset templates = source for define.xml SDTM red: e-submission deliverables Specifications Mapping programs define.xml (SDTM)

18. CDISC German Speaking User Group Meeting, 11-Mar-201018 ADaM Process Flow at Accovion Communication SDTM SAP ADaM Results creation programs Analysis results (TLGs) - Analysis datasets - Analysis results = dataset templates source for define.xml define.xml (ADaM) Datasets creation programs ADaM Specifications red: (potential) e-submission deliverables

19. CDISC German Speaking User Group Meeting, 11-Mar-201019 References CDISC Website (http://www.cdisc.org/) CRT-DDS (define.xml) standard V1.0 (http://www.cdisc.org/models/def/v1.0/index.html)http://www.cdisc.org/models/def/v1.0/index.html Metadata Submission Guidelines, Appendix to SDTM IG V3.1.1 (http://www.cdisc.org/content1210)http://www.cdisc.org/content1210 CDISC SDTM/ADaM Pilot (sample submission package) (http://www.cdisc.org/content1037)http://www.cdisc.org/content1037 eCTD‘s Study Data Specifications V1.5.1 (http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/For msSubmissionRequirements/ElectronicSubmissions/UCM199759.pdf)http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/For msSubmissionRequirements/ElectronicSubmissions/UCM199759.pdf

20. CDISC German Speaking User Group Meeting, 11-Mar-201020 Thank you! Questions? Contact Information: Monika Kawohl Senior Statistical Programmer Accovion GmbH Softwarecenter 3 35037 Marburg Germany Phone: +49-6421-94849-20 Fax: +49-6421-94849-61 Email: monika.kawohl@accovion.com