1. Managing and Analyzing Clinical Data
Mark Lambrecht, Principal Industry Consultant, SAS
BIAS Meeting, March 14th 2014, Milan, Italy.

2. Roadmap and SAS destination
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

3. The clinical trial challenges…
SDTM Devices IG v1.1
SEND v3.1
ADaM Integration IG
v1.0
ADaM General Occurrence Model
SDTM Device
Submission Pilot
SDTM
v1.5
SDTM IG
v3.1.5
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
Cardiovascular
With the growth of industry standards, the level of complexity increases.
The expected trend is continued increase of complexity. …
SDTM
v1.4
SDTM IG
v3.1.4
Alzheimer
v1.1
Asthma
SEND v3.0.1
Protocol
Concept
Guide
BRIDG UG v2
ADaM IG
PKD
Define.xml v2.0
CDASH v1.2
BRIDG v4.0
ADaM MD Guide
CDASH E2B
SAE IG
SDTM QS
Supplements
SDTM Associated Persons IG v1.0
Parkinson’s
Disease
Virology
Content Standards
Semantics
Technical Standards
Therapeutic Areas
Pain
Tuberculosis
Devices
BRIDG
v3.1
v3.2
PRM Toolset
v1.0
CDASH UG
SDTM
v1.3
SDTM IG
v3.1.3
ADaM
Val. Checks
v1.2
BRIDG
v3.0.1
v3.0.2
v3.0.3
Protocol
Model
v1.0
ADaM
Val.
Checks
ODM
v1.3.1
Alzheimer
v1.0
SEND
v3.0
SDTM
v3.1.2
Am.1
ADaM
Val.
Checks
v1.1
CDASH
SDM.XML
BRIDG
v1.1.1
v2.0
v2.1
SDTM
v1.2
SDTM IG
v3.1.2
CDASH
v1.0
Last update: September 2013
SDTM
v1.1
SDTM IG
v3.1.1
ODM
v1.2.1
Define.xml
v1.0
BRIDG
v3.0
v2.2
ADaM
v2.1
ADaM IG
v1.0
SDTM
v1.0
SDTM IG
v3.1
ODM
v1.2
ADaM
v2.0
ODM
v1.3
BRIDG
v1.0
v1.1
ODM
v1.1 /
2002
2005
2003
2006
2004
2007
2008
2009
2010
2011
2012
2013
2014

4. CDISC
A business case by Gartner and CDISC

5. PROC CDISC : SAS first attempt to support CDISC standards
SAS response
PROC CDISC : SAS first attempt to support CDISC standards
SAS Clinical Standards Toolkit
SAS Clinical Data Integration, SAS Drug Development

6. SAS Clinical Data Integration
Clinical Research information flow
SAS
EDC (Rave)
Dictionary coding
(TMS)
External metadata
(RDF, OWL, etc.)
Submission data sets
SDTM
ADaM
Others
EDC (Other)
Metadata, integration and standardization management
SAS Clinical Data Integration
SAS Drug Development
Data and analytics platform
Adapters / Interfaces
Tables, figures and listings
ePRO and others
Adapters / Interfaces
Metadata
Pooled analyses
Internal systems
Adapters / Interfaces
Patient Profiles/ Medical Review
JMP
Clinical
SAS Visual Analytics
Exploration across and beyond trials
Labs and other external sources
Raw data
Transparency initiatives
Real-world data
Raw data

7. Still supported in SAS 9.4, but stable
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

8. Support for SAS table and XML files
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
From the documentation :

9. Integrate data from disparate sources
SAS CDI
SAS Clinical Data Integration
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 sources
Integration with EDC systems, e.g. Medidata Rave
Standardize their in-process data to industry models
Migrate legacy data to modern standard models
Leverage standardized data to efficiently prepare data for analysis and submission to regulatory authorities.
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

10. SAS Life Science Analytics Framework Protocol Design
Data Capture to Data Analysis
CONVERSION
Compound Info Life Cycle
REPOSITORY
EDC/CDMS
Data Quality Service
Detailed Data Store, Metadata Store

11. SAS Life Science Analytics Framework
A new Framework for clinical trial analytics
Primary Platform
Shared repository
Licensing
Single identity
Hosting model
Partner collaboration
Access & audit trail
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

12. SAS & CDISC End-To-End in CDISC Data models
Validation / Adherence checks
SAS code generation
Macro API library and customization
Metadata

13. SAS & CDISC
End-To-End in CDISC : SAS CST 1.6 and SAS CDI 2.5

14. Define.xml Round Trip Sponsor Compares results to study specifications
Creates define.xml based on study specifications
Sponsor
Extracts metadata from implemented define.xml file
DEFINE.XML
Data Management Team(CRO)
Extracts metadata from define.xml file
Data Management Team(CRO)
Produces define.xml based on implementation
Data Management Team(CRO)
Implements and populates domains

15. SAS Clinical Standards Toolkit
Reading the Define.xml
SAS Clinical Standards Toolkit
Source_*.sas7bdat
DEFINE.XML
%crtdds_read
%sdtmutil_create Src Meta From CRTDDS
%cstutil_create Tables From Metadata
zero observation Domain data sets
%sdtmutil_ Create Formats From CRTDDS
Code List SAS Format Catalog
SAS representation
of CRT-DDS

16. Reading The define.xml
SAS Clinical Data Integration

17. ADaM Support
CDI 2.4

18. Bulk Metadata Manipulation
CDI 2.4

19. 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

20. Visualization