phuse sde, 28-may-20081 1 a sas based solution for define.xml monika kawohl statistical programming...

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PhUSE SDE, 28-May-2008 1

A SAS based Solutionfor

define.xml

Monika KawohlStatistical Programming

Accovion

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Presentation Topic – define.xml

Excerpt from the CDISC Draft Metadata Submission Guidelines define.xml Sample

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Presentation Outline

Electronic Submission Context & Purpose

XML Basics

define.xml Sections/Elements

define.xml Generation Process

Expected define.xml Enhancements

Summary & Conclusions

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Electronic Submission Context & Purpose

Define Document Mandatory when Submitting Data to FDA

Purpose

• Describe Structure and Contents of Data

• Facilitate Review via Standardized Metadata Format

Aim: More Efficient Overall Review Process

define.xml Preferred Data Definition Format for SDTM

• define.xml Human- and Machine-Readable

Benefit of define.xml not Restricted to Submissions

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define.xml Documentation/Samples

CDISC Case Report Tabulation Data Definition Specification (define.xml),Version 1.0, February 9, 2005

Sample define.xml Included

CDISC Metadata Submission Guidelines, Appendix to the SDTM IG V3.1.1, Draft Version 0.9, July 25, 2007

Sample define.xml Included as Part of Sample Submission

CDISC SDTM/ADaM Pilot (Pilot 1), January 31, 2008

Mock Submission Package Available for CDISC Members

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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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<?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

Interaction of XML, XSL, XSD

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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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Data Metadata

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Data Metadata – XML Code

<ItemGroupDef OID="LB" Name="LB" Repeating="Yes" IsReferenceData="No" Purpose="Tabulation" def:Label="Laboratory Tests" def:Structure="One record per lab test per time point per visit per subject" def:DomainKeys="STUDYID,USUBJID,LBTESTCD,VISITNUM,LBTPTNUM" def:Class="Findings" def:ArchiveLocationID="Location.LB"> ... <def:leaf ID="Location.LB" xlink:href="LB.xpt"> <def:title>lb.xpt</def:title> </def:leaf>

</ItemGroupDef>

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Variable Metadata

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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" Comment="CRF Pages 5, 10, 15, 20" 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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Variable Value Level Metadata – XML Code<def:ValueListDef OID="ValueList.LB.LBTESTCD"> <ItemRef ItemOID="LB.LBTESTCD.ALB" OrderNumber="1" Mandatory="No"/> ... </def:ValueListDef>... <ItemDef OID="LB.LBTESTCD.ALB" Name="ALB" DataType="float" Length="8" SignificantDigits="1" Origin="CRF" Comment="CRF Pages 5, 15" def:Label="Albumin" def:DisplayFormat="5.1"/>

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Computational Algorithms

Complex Derivations

Derivations Used More than Once

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Computational Algorithms – XML Code

<def:ComputationMethod OID="COMPMETHOD.LBBLFL"> Derive mean of pre-treatment measurements. Create new record with result and flag LBBLFL='Y'</def:ComputationMethod> ... <ItemDef OID="LB.LBBLFL" Name="LBBLFL" DataType="text" Length="1" Origin="Derived" def:Label="Baseline Flag" def:ComputationMethodOID="COMPMETHOD.LBBLFL"> <CodeListRef CodeListOID="YF"/> </ItemDef>

Masking of Special Characters

• Ampersand, Apostrophe, Quote, Less Than, Greater Than

• ' ‘

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Controlled Terminology/Code Lists

External Dictionary References incl. Versions

• e.g., MEDDRA, WHODRUG

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Controlled Terminology/Code Lists– XML Code<ItemDef OID="LB.LBBLFL" Name="LBBLFL" DataType="text" Length="1“ Origin="Derived" def:Label="Baseline Flag" def:ComputationMethodOID="COMPMETHOD.LBBLFL"> <CodeListRef CodeListOID="YF"/> </ItemDef> ...<CodeList OID="YF" Name="YF" DataType="text"> <CodeListItem CodedValue="Y"> <Decode> <TranslatedText xml:lang="en">YES</TranslatedText> </Decode> </CodeListItem></CodeList>

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Annotated CRF (blankcrf.pdf)

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Supplemental Data Definitions

Optional

PDF Document

Additional Information Useful for Data Review

• General Assumptions

• Flowcharts

• Derivation Dependancies

• Reviewers' Guide

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define.xml - SAS Based Generation ProcessUse All Metadata Already Available in SAS

Provide Additional Information Required

• Set-up at Design and Specification Level

• Format: Excel Spreadsheets

• Contents: CDISC Terminology, Study Specific Metadata (CRF Pages)

Combine Metadata and Additional Information in SAS

Create XML File in SAS

Use Stylesheet Provided with CDISC Sample

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Available Metadata vs. Additional Information RequiredMetadata Section

Available Required

Dataset SAS Dictionary Tables:

Name, Label

CDISC Metadata Terminology

Class, Structure, Keys

Attributes for Machine-readability

Variable SAS Dictionary Tables:

Name, Label, Type, Format

Length, Significant Digits

CDISC Metadata Terminology

Role, (Origin)

Study Specific Metadata

(Origin), Comment

• CRF Page References

• Derivation Descriptions

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Available Metadata vs. Additional Information Req. - ContinuedMetadata Section

Available Required

Variable Value Level

Parent Dataset Contents:

Values of --TESTCD, --TEST

Values of QNAM, QLABEL

(Attributes of Parent Variables:)

e.g., Type, Length

e.g., CRF Page References

Adaptation on Value Level:

Type, Length, Format

Significant Digits, Display Format

Origin, Comment

Computational Algorithms - Reference Name

Derivation Description

Code Lists SAS Format Library:

Name, Code, Decode, Type-

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Excel File Format for Variable Metadata

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Process Flow

SASFormats

DatasetMetadata

VariableMetadata

Computa-tional

Algorithms

EXCEL

SASDatasets

EXCELDraft


Metadata

EXCELEdited


Metadata

DEFINE.XML

AnnotatedCRF

Supple-mentalData

Definitions

XPTFiles

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Automated Consistency Checks

SDTM Adherence Checks

• Availability of Datasets and Variables

• Order of Variables in Dataset

• Labels and Data Type

• Variables with Controlled Terminology(SAS Format Attached)

Consistency Checks for Well-formed XML Code

• Intra Document Links, e.g. Computational Methods

Additional Manual Checks Required

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Expected Enhancements – ADaM IntegrationAspects of CDISC Pilot 1 => CDISC define.xml Standard

Link to Analysis Metadata (s.b.)

Link to CSR Table

Link to Variable Metadata of ADSL

Link to SAP

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Expected Enhancements - Continued

Correction of Software Issues with 2007 define.xml Sample

Adaptation to Latest CDISC ODM Standard

• V2.0 => V3.0

Improved Printability

• Stylesheet Enhancements

• Alternative Options (define_xml_printable.pdf)

Extension for CDISC ADaM Specific Metadata

Executable Computational Algorithm?

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Summary & Conclusions

Presented Solution Just One of Many Options

• Driven by Available Skills

• XML Code Easy to Implement according to CDISC Standards

• Biggest Challenge: Process Set-up

Advantages

• Early Integration (Design and Specification Level)

Increased Consistency, Lower Risk of Redundancy

• SDTM Adherence Check

• Built-in Consistency with SAS Datasets

CDISC define.xml Standard is Work in Progress


Thank you!

Questions?

phuse sde, 28-may-20081 1 a sas based solution for define.xml monika kawohl statistical programming...

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