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Overview
Requirements
• Regulatory
• Technical
define.xml Sections/Elements
Process Flow at Accovion
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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
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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
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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
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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
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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
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Variable Metadata
Change for Origin in SDTM IG 3.1.2: Sponsor Defined, Assigned, eDT, Protocol
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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>
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Variable Value Level Metadata
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Computational Algorithms
Complex Derivations
Derivations Used More than Once
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Controlled Terminology/Code Lists
External dictionary references incl. versions
• e.g., MEDDRA, WHODRUG
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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)
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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)
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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
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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)
