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MANAGING AND ANALYZING CLINICAL DATAMARK LAMBRECHT, PRINCIPAL INDUSTRY CONSULTANT, SAS

BIAS MEETING, MARCH 14TH 2014, MILAN, ITALY.

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TABLE OF CONTENTS

• SAS and CDISC• Clinical trial challenges• The promise for CDISC• SAS response• PROC CDISC, SAS Clinical Standards Toolkit, SAS Clinical Data Integration

• Roadmap and SAS destination• Capabilities and processes supported by SAS• Examples

• Roundtrip in define.xml• Reading a define.xml• ADaM support• Bulk metadata manipulation

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BRIDGv1.0

BRIDGv1.1

BRIDGv3.0

BRIDGv2.2

ADaMv2.1

ADaM IGv1.0

BRIDGv1.1.1

BRIDGv2.0

BRIDGv2.1

SDTMv1.2

SDTM IGv3.1.2

CDASHv1.0

ODMv1.1

SDTMv1.0

SDTM IGv3.1

ODMv1.2

BRIDGv3.0.1

BRIDGv3.0.2

BRIDGv3.0.3

ProtocolModelv1.0

ADaM Val.

Checksv1.0

ODMv1.3.1

SDTMv1.1

SDTM IGv3.1.1

ODMv1.2.1

Define.xmlv1.0

ADaMv2.0

ODMv1.3

Pain

Tuberculosis

Devices

BRIDGv3.1

BRIDGv3.2

PRM Toolsetv1.0

CDASH UGv1.0

SDTMv1.3

SDTM IGv3.1.3

ADaMVal. Checks

v1.2

20122006 2007 2009 2011 20132002 201020082005 2003 2004

/

…

Alzheimerv1.0

SENDv3.0

SDTMv3.1.2Am.1

ADaM Val.

Checksv1.1

CDASHv1.1

SDM.XMLv1.0

Parkinson’sDisease

Virology

Content Standards

Technical Standards

Semantics

2014

…

SDTMv1.4

SDTM IGv3.1.4

Alzheimerv1.1

Asthma

SEND v3.0.1

ProtocolConceptGuide

BRIDG UG v2

ADaM IGv1.1

PKD

Define.xml v2.0

CDASH v1.2

BRIDG v4.0

ADaM MD Guide

CDASH E2BSAE IG

SDTM QSSupplements

SDTM Associated Persons IG

v1.0

SDTM Devices IG v1.1

SEND v3.1

ADaM Integration IG

v1.0

ADaM General Occurrence Model

v1.0

SDTM DeviceSubmission Pilot

SDTMv1.5

SDTM IGv3.1.5

SDTM.xml v1.0

CDASH v2.0

Extended ODM PRM XML Schema

Define.xml IG Validation

Multiple Sclerosis

Diabetes

Virology-Hepatitis C

Oncology

Schizophrenia

Therapeutic Brain Injury

CardiovascularTHE CLINICAL TRIAL CHALLENGES

With the growth of industry standards, the level of complexity increases.

The expected trend is continued increase of complexity.

Therapeutic Areas

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CDISC A BUSINESS CASE BY GARTNER AND CDISC

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SAS RESPONSE

• PROC CDISC : SAS first attempt to

support CDISC standards

• SAS Clinical Standards Toolkit

• SAS Clinical Data Integration, SAS

Drug Development

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SAS

CLINICAL RESEARCH INFORMATION FLOW

EDC (Rave)

EDC (Other)Adapters / Interfaces

ePRO and others

Labs and other external sources

Raw data

Internal systems

Metadata, integration and standardization management

SAS Clinical Data Integration

External metadata (RDF, OWL, etc.)

SAS Drug Development

Data and analytics platform

SDTMADaMOthers

Real-world data Raw data

Metadata

Submission data sets

Tables, figures and listings

Pooled analyses

Patient Profiles/ Medical Review

JMP Clinical

SAS Visual

Analytics

Exploration across and beyond trials

Transparency initiatives

Adapters / Interfaces

Adapters / Interfaces

Dictionary coding(TMS)

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PROC CDISC

• Still supported in SAS 9.4, but stable• Support for reading ODM 1.2 and SDTM 3.1• Not flexible enough for custom domains, or for changing standard domains.• No library concept – everything built-in in code• Advise against deployment and replace by novel SAS technologies

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SAS CST SAS CLINICAL STANDARDS TOOLKIT

• The SAS Clinical Standards Toolkit (SAS CST) provides SAS implementation

of evolving clinical standards and provide a framework that exploits these

standards to meet common clinical research analysis and submission

requirements. • SAS CST provides support both for CDISC and non-CDISC general clinical

standards• Support for SAS table and XML files• Some Java and XLST inside to manage XML files.• SAS Clinical Standards Toolkit 1.6 : released February 2014 based on SAS

9.4

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SAS CDI SAS CLINICAL DATA INTEGRATION

• Is targeted for both SAS programmers and clinical data managers• SAS Clinical Standards Toolkit “under the hood”• SAS Clinical Data Integration capabilities now integrated in SAS Drug

Development with code that is generated in SAS CDI can be executed

straight from SAS Drug Development

SAS Clinical Data Integration is a data transformation solution designed to help companies organize, standardize and manage their clinical research data and metadata. The solution enables companies to

Integrate data from disparate sourcesIntegration with EDC systems, e.g. Medidata RaveStandardize their in-process data to industry modelsMigrate legacy data to modern standard modelsLeverage standardized data to efficiently prepare data for analysis and submission to regulatory authorities.

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SAS Life Science Analytics Framework

Data Capture to Data Analysis

CONVERSION

Compound Info Life Cycle

REPOSITORY

Detailed Data Store,

Metadata Store

Data Quality Service

Protocol Design

EDC/CDMS

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SAS LIFE SCIENCE ANALYTICS

FRAMEWORKA NEW FRAMEWORK FOR CLINICAL TRIAL ANALYTICS

Analysis & Regulatory

Controls

Workflow

Compliance

Analysis processes

Process traceability

Data Standards Repository

Study & standards metadata

Import/export metadata

Connects protocol/study

design

Manage controlled

terminology

Information Management

Mapping

Instance data standards

Integration (EDC, Safety, ePRO, etc.)

Data traceability/

lineage

Operations & Optimization

Risk based scoring and monitoring

Post marketing &

safety surveillance

Site selection/ management

Patient recruitment

Other SAS Offerings

Visual Analytics

Data Transparency

Enterprise Miner

others

Primary Platform• Shared repository• Single identity• Partner collaboration

• Licensing• Hosting model• Access & audit trail

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SAS & CDISC END-TO-END IN CDISC

Data models

Validation / Adherence

checks

SAS code generation

Macro API library and

customization

Metadata

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SAS & CDISC END-TO-END IN CDISC : SAS CST 1.6 AND SAS CDI 2.5

SDTM up to 3.2 (SDTM

1.4 IG)

SAS Clinical Data

Integration

SAS Clinical

Standards Toolkit

ODM 1.3.1support

Validate Toolkit

metadata

SDTM up to 3.2 (SDTM 3.1.4 IG)

Extract Clinical and Reference

data into SAS datasets

CRT-DDS 1.0 support

Import and export

define.xml files

ADaM support 2.1

updates

SEND 3.0 standard support

Controlled terminology

support

Full UTF-8 and S-JIS

code support

Updates to macro

framework

Define-XML 2.0 support

Import ADaM, SDTM and SEND

information from define.xml

Code runs everywhere

Incremental and granular

standards update in SAS

CDI

Custom domain promotion and

standards governance

Integration with

Medidata Rave / EDC

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DEFINE.XML ROUND TRIP

Sponsor•Creates define.xml based on study specifications

Data Management Team(CRO)•Extracts metadata from define.xml file

Data Management Team(CRO)• Implements and populates domains

Data Management Team(CRO)•Produces define.xml based on implementation

Sponsor•Extracts metadata from implemented define.xml file

Sponsor•Compares results to study specifications

DEFINE.XML

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%crtdds_read%sdtmutil_create Src Meta From

CRTDDS

%cstutil_create Tables From

Metadata

%sdtmutil_ Create Formats From

CRTDDS

READING THE DEFINE.XML

SAS representation of CRT-DDS

Code List SAS Format Catalog

zero observation Domain data sets

Source_*.sas7bdat

DEFINE.XML

SAS CLINICAL STANDARDS TOOLKIT

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READING THEDEFINE.XML

SAS CLINICAL DATA INTEGRATION

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CDI 2.4

ADAM SUPPORT

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CDI 2.4

BULK METADATA MANIPULATION

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GOAL

• SAS provides you with a complete technology and solution framework, not

just to use CDISC standards, but to manage and generate clinical standards

data with the aim to visualize, analyze, submit, and ensure high quality-

clinical data

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VISUALIZATION