MANAGING AND ANALYZING CLINICAL DATA
MARK 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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THE CLINICAL TRIAL CHALLENGES
…
With the growth of industry standards, the level of complexity increases.
SDTM QS
Supplements
The expected trend is continued increase of complexity.
Content Standards
Semantics
Technical Standards
Therapeutic Areas
Parkinson’s
Disease
BRIDG
v3.0.3
SDTM
v1.2
SDTM IG
v3.1.2
CDASH
v1.0
SDTM
v1.1
SDTM IG
v3.1.1
SDTM
v1.0 BRIDG
ODM
SDTM IG v1.1
v1.3
v3.1
Define.xml
v1.0
ODM
ODM
v1.2.1
v1.1
/
ODM BRIDG
ADaM
v1.2 v1.0
v2.0
2002
2005 2003 2006
2004 2007
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BRIDG
v2.1
BRIDG
v2.0
ADaM
v2.1
ADaM IG
v1.0
BRIDG
v3.0
SDTM
v3.1.2
Am.1
ADaM
Val.
Checks
v1.0
Alzheimer
v1.0
BRIDG
v3.0.2
SDM.XML
v1.0
ODM
v1.3.1
BRIDG
v3.0.1
BRIDG
v1.1.1
BRIDG
v2.2
Protocol
Model
v1.0
2008
2009
2010
ADaM
Val.
Checks
v1.1
Oncology
Diabetes
BRIDG UG v2
Define.xml v2.0
PKD
BRIDG
v3.2
SDTM
v1.4
SDTM IG
v3.1.4
Tuberculosis
Schizophrenia
ADaM MD Guide
CDASH v1.2
SDTM
v1.3
SDTM IG
v3.1.3
Therapeutic
Brain Injury
VirologyHepatitis C
Devices
ADaM
Val. Checks
v1.2
Cardiovascular
CDASH E2B
SAE IG
BRIDG v4.0
Virology
…
SDTM
Associated
Persons IG
v1.0
SEND v3.0.1
Asthma
Multiple
Sclerosis
Define.xml IG
Validation
CDASH v2.0
SDTM
v1.5
SDTM IG
v3.1.5
ADaM General
Occurrence Model
v1.0
ADaM
Integration IG
v1.0
Extended ODM
PRM XML Schema
Pain
PRM Toolset
v1.0
CDASH
v1.1
CDASH UG
v1.0
SEND
v3.0
2011
Alzheimer
v1.1
SDTM.xml v1.0
ADaM IG
v1.1
SEND v3.1
SDTM Devices IG v1.1
BRIDG
v3.1
Protocol
Concept
Guide
SDTM Device
Submission Pilot
2012
2013
2014
CDISC A BUSINESS CASE BY GARTNER AND CDISC
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SAS RESPONSE
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•
PROC CDISC : SAS first attempt to
support CDISC standards
•
SAS Clinical Standards Toolkit
•
SAS Clinical Data Integration, SAS
Drug Development
CLINICAL RESEARCH INFORMATION FLOW
SAS
Dictionary
coding
(TMS)
EDC (Rave)
EDC (Other)
Submission
data sets
SDTM
ADaM
Others
Adapters /
Interfaces
ePRO and others
Adapters /
Interfaces
Internal systems
Adapters /
Interfaces
Labs and other
external sources
Raw data
Real-world data
External metadata
(RDF, OWL, etc.)
Raw data
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SAS Clinical Data
Integration
Metadata,
integration and
standardization
management
SAS Drug
Development
Metadata
Tables, figures
and listings
Data and analytics
platform
Pooled
analyses
JMP
Clinical
Patient Profiles/
Medical Review
SAS
Visual
Analytics
Exploration across
and beyond trials
Transparency
initiatives
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
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
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Protocol Design
Data Capture to
Data Analysis
CONVERSION
Compound Info
Life Cycle
REPOSITORY
SAS Life Science Analytics Framework
EDC/CDMS
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Data Quality
Service
Detailed Data
Store,
Metadata Store
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
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Analysis &
Regulatory
Controls
Data
Standards
Repository
Workflow
Study &
standards
metadata
Information
Management
Operations &
Optimization
Other SAS
Offerings
Mapping
Risk based
scoring and
monitoring
Visual
Analytics
Compliance
Import/export
metadata
Instance data
standards
Post
marketing &
safety
surveillance
Data
Transparency
Analysis
processes
Connects
protocol/study
design
Integration
(EDC, Safety,
ePRO, etc.)
Site selection/
management
Enterprise
Miner
Process
traceability
Manage
controlled
terminology
Data
traceability/
lineage
Patient
recruitment
others
SAS & CDISC END-TO-END IN CDISC
Data models
Metadata
Macro API
library and
customization
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Validation /
Adherence
checks
SAS code
generation
SAS & CDISC END-TO-END IN CDISC : SAS CST 1.6 AND SAS CDI 2.5
SEND 3.0
standard
support
Integration
with
Medidata
Rave / EDC
Cus tom domain
promotion and
standards
govern an ce
Incremental and
granular
standards
update in SAS
CDI
SDTM up to
3.2 (SDTM
1.4 IG)
ADaM
support 2.1
updates
ODM 1.3.1
support
Extract
Clinical and
Reference
data into SAS
datasets
Validate
Toolkit
metadata
CRT-DDS 1.0
support
Import and
export
define.xml
files
Import ADaM,
SDTM and SEND
information
from define.xml
SDTM up to
3.2 (SDTM
3.1.4 IG)
Controlled
terminology
support
Define-XML
2.0 support
SAS
Clinical
Standards
Toolkit
Code runs
everywhere
SAS Clinical
Data
Integration
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Updates to
macro
framework
Full UTF-8
and S-JIS
code support
DEFINE.XML
ROUND TRIP
Sponsor
•Compares
results to
study
specifications
Sponsor
• Extracts metadata
from implemented
define.xml file
DEFINE.XML
Data Management
Team(CRO)
• Produces define.xml
based on
implementation
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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
READING THE
SAS CLINICAL STANDARDS TOOLKIT
DEFINE.XML
Source_*.sas7bdat
%crtdds_read
DEFINE.XML
%sdtmutil_create
Src Meta From
CRTDDS
%sdtmutil_ Create
Formats From
CRTDDS
SAS representation
of CRT-DDS
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%cstutil_create
Tables From
Metadata
Code List SAS
Format Catalog
zero observation
Domain data sets
READING THE SAS CLINICAL DATA INTEGRATION
DEFINE.XML
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ADAM SUPPORT
CDI 2.4
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BULK METADATA MANIPULATION
CDI 2.4
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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 qualityclinical data
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VISUALIZATION
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