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

Overview Requirements Regulatory Technical define.xml Sections/Elements Process Flow at Accovion CDISC German Speaking User Group Meeting, 11-Mar-2010

Regulatory Requirements 20/05/2018 Regulatory Requirements eCTD‘s Study Data Specifications V1.5.1 ADaM SDTM “Dataset documentation includes data definitions and annotated case report forms.” SDTM: define.xml ADaM: define.pdf / define.xml ? CDISC German Speaking User Group Meeting, 11-Mar-2010

Why define.xml Benefit of define.xml not restricted to submissions 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 CDISC German Speaking User Group Meeting, 11-Mar-2010

CDISC German Speaking User Group Meeting, 11-Mar-2010

CDISC German Speaking User Group Meeting, 11-Mar-2010

XML Basics Schema (extension: .XSD) XML File (extension: .XML) 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 CDISC German Speaking User Group Meeting, 11-Mar-2010

Advantages of XML – Basic Technology <?xml version="1.0" encoding="ISO-8859-1"?> <?xml-stylesheet type="text/xsl" href="define1-0-0.xsl"?> <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 CDISC German Speaking User Group Meeting, 11-Mar-2010

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 CDISC German Speaking User Group Meeting, 11-Mar-2010

Data Metadata CDISC German Speaking User Group Meeting, 11-Mar-2010

Variable Metadata Change for Origin in SDTM IG 3.1.2: Sponsor Defined, Assigned, eDT, Protocol CDISC German Speaking User Group Meeting, 11-Mar-2010

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"/> </ItemGroupDef> <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"> <def:ValueListRef ValueListOID="ValueList.LB.LBTESTCD"/> </ItemDef> <ItemDef OID="LB.LBBLFL" Name="LBBLFL" DataType="text" Length="1" Origin="Derived" def:Label="Baseline Flag" def:ComputationMethodOID="COMPMETHOD.LBBLFL"> <CodeListRef CodeListOID="YF"/> </ItemDef> CDISC German Speaking User Group Meeting, 11-Mar-2010

Variable Value Level Metadata CDISC German Speaking User Group Meeting, 11-Mar-2010

Computational Algorithms Complex Derivations Derivations Used More than Once CDISC German Speaking User Group Meeting, 11-Mar-2010

Controlled Terminology/Code Lists External dictionary references incl. versions e.g., MEDDRA, WHODRUG CDISC German Speaking User Group Meeting, 11-Mar-2010

Annotated CRF (blankcrf.pdf) 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 CDISC German Speaking User Group Meeting, 11-Mar-2010

SDTM Process Flow at Accovion Annotated CRF Specifications define.xml (SDTM) Mapping programs SDTM = dataset templates = source for define.xml red: e-submission deliverables Communication CDISC German Speaking User Group Meeting, 11-Mar-2010

ADaM Process Flow at Accovion define.xml (ADaM) ADaM Specifications Datasets creation programs - Analysis datasets ADaM SDTM SAP = dataset templates Results creation programs - Analysis results Analysis results (TLGs) red: (potential) e-submission deliverables source for define.xml Communication CDISC German Speaking User Group Meeting, 11-Mar-2010

References CDISC Website (http://www.cdisc.org/) CRT-DDS (define.xml) standard V1.0 (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) CDISC SDTM/ADaM Pilot (sample submission package) (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) CDISC German Speaking User Group Meeting, 11-Mar-2010

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 CDISC German Speaking User Group Meeting, 11-Mar-2010