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© 2011

CDISC: Global ApproachTo Accelerating Medical Research

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CDISC MissionTo develop and support global, platform-independent data standards that enable information system interoperability to improve medical research and related areas of healthcare

The CDISC Vision is informing patient care and safety through higher quality medical research.

improve medical research

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CDISC• Global, open, multi-disciplinary, vendor-

neutral, non-profit standards developing organization (SDO)

• Founded 1997, incorporated 2000• Member-supported (>300 members, e.g.

academia, biopharma, service / technology providers)

• Liaison A Status with ISO TC 215• Charter agreement with HL7 (2001)• Leadership of Joint Initiative Council (JIC)

for Global Harmonization of Standards• Member of ANSI-led ISO TAG• Active Coordinating Committees (3C)

Europe, Japan, China, Korea• >> 90 countries in participant database

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• CDISC has established worldwide industry standards to support the electronic acquisition, exchange, submission and archiving of clinical research data and metadata to improve data quality and streamline medical and biopharmaceutical product development and research processes

• Consensus-based development (COP-001)• Standards are freely available at www.cdisc.org• IP Policy ensures open standards

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CDISC Organization• Volunteer participants and team members

CDISC Teams: Anyone can participate 3Cs (CDISC Coordinating Committees) User Networks (regional, often language-centered)

• Technical Leadership Committee Team leaders / co-leads Oversees the standards development and project teams Works to achieve operational and strategic goals

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Research findings

to inform healthcare decisions

Information from healthcare(private, aggregated)

to enable research

• Discovery of new therapies

• Understanding diseases• Testing/comparing

therapies (CER)• Assessing efficacy• Monitoring safety• Understanding responses(genomics, biomarkers)• Public health/quality

evaluations• Post-marketing

surveillance

• Quality healthcare• Informed decisions• Personalized medicine• Patient safety and

privacy• Public health• Improved therapies• Efficiencies/reduced

costs

ResearchHealthcare

Inefficientcycle

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Organization to Support CDISC

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Board

CAB

CCC

ProjectTeams

TLC

GovFOC Strategy TAC

User N

etworks

Technical Projects

Alliances

Education and Im

plementation Services

PR/C

omm

unications

Financial; Legal; HR

Global Operations

BoardCommittees:

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ExternalFocused Review

CDISC Standards Development Process (COP-001)

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Need for Specific

Standard(s) Identified

(any stakeholder)

Proposal to Board

of Directors(via Operations)

Working Plan (timelines, deliverablescommunication mech.,

resources req’d)(Team )

Consensus (Initial)Version

Harmon-ized

Version

Team Leader IDAnd TeamFormation

(multidisciplinary)(Operations)

Review per strategy, budget

priorities

Approved

Annual Review of Released Version (comments, chg

reqsts, tests, plans)(Team)

Released(Production)Version

1.0

ReviewVersion

Stage I: Standard Definition/Team Initiation

Stage III: Education & Support

Stage IV: Standards Update & Maintenance

Stage II: Standards Development/Review/V 1.0 Release

Working Plan(timelines, deliverables,communication mech.,

resources req’d)(Team)

Consensus(Revised)Version

Respond To CommentsAnd Questions

EducationalPrograms

(EDU, Operations)

Not Approved

TLC Review

Comments to address by team

PublicReview

Comments addressed

NewReleased(Production)Version

Harmon-ized

Version

TLC Review

ExFocused Review

Public Review

asneeded

Optional

Testing

Note: Occasional bug fix releases may be issued as needed with team review only.

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Joint Initiative Council

For the global harmonization of healthcare and

related standards.

BRIDG is going through the JIC Process; it is now an HL7 and CDISC standard – one ballot left in ISO (and CEN).

Current leader: Bron Kisler, CDISC

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General Standards Organizations

• ISO (cont.)– CDISC is a Liaison A status to ISO TC 215 (healthcare standards)

• Possible because CDISC process conforms to ISO standards

• Allows CDISC to skip some initial steps in ISO approval

• Means CDISC standards can be approved as ISO standards

• ANSI– American National Standards Institute, US representative to ISO– CDISC standards developed with HL-7 can be ANSI-accredited

– CEN– European equivalent of ANSI

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CDISC Around the Globe

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20002008 2002

2001

2010

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Business CaseFor Using CDISC Standards

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Gartner-PhRMA-CDISC Project• Business Case for using CDISC standards• Summary:

Using CDISC standards can save significant time and cost, especially when implemented in the early stages of the study

Opportunities for an additional impact on clinical research• Increased data quality• Data Integration / enhanced re-usability• Facilitates data exchange with partners• Enable software tools• Improve team communication• Facilitate regulatory reviews and audits

Opportunity Value: Do More With Less

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Submission

Clinical Study ReportISS/ISE preparationClinical / statistical

integrated reportListings, tabulations and

other datasetseCTD file structure

12 Months

Analysis / Reporting

Data analysisSafety assessmentAnalysis table preparationClinical assessmentsReport generation

5 Months

Study Conduct

Patient recruitmentData acquisitionData exchangeSource Data Verification

(SDV)Site monitoring / auditsTransfer lab / ECG dataSite auditsDatabase QA and lockAnalysis programmingInitial statistical tablesStudy closeout / archive

Patient Participation + 4 Months

Study Start-up

Study designProtocol developmentCRF developmentDB Structure / ValidationLab/ECG specsSite/PI IdentificationSite evaluationSite initiationPatient recruitment planCritical documentsIRB approvalsTraining of team/sitesRandomization planTest article prepStatistical analysis planAnalysis table shells

5 Months

Implementation Tradeoffs: Greatest Value when Standards Implemented in Study Start-up

80% 40% 50% 40%

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CDISC Standards and Data Flow

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CDISC Standards• Glossary• SDTM - Study Data Tabulation Model• CDASH - Clinical Data Acquisition Standards

Harmonization• ADaM - Analysis Data Model• LAB - Laboratory• Terminology• TDM - Trial Design Model• Protocol Representation

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CDISC Standards• Therapeutic Area Standards• BRIDG - Biomedical Research Integrated Domain

Group Model• SHARE – Shared Health and Clinical Research

Electronic Library• ODM - Operational Data Model• RFD – Retrieve Form for Data Capture• define.XML• SEND - Standard for the Exchange of Non-clinical

Data

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www.cdisc.org

CDISC Standards – Open and Free

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Glossary

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SME View

Canonical View

HL7 R

IM View

OW

L View

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CDISC is More than Standards!

CDISC Vision

Informing patient care and safety through higher quality medical research

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Backup

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CDISC Standards• SDTM - Study Data Tabulation Model• CDASH - Clinical Data Acquisition Standards

Harmonization• ADaM - Analysis Data Model• LAB - Laboratory• Medical Devices• Terminology• TDM - Trial Design Model• Protocol Representation

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CDISC Standards• Therapeutic Area Standards• BRIDG - Biomedical Research Integrated Domain Group

Model• SHARE – Shared Health and Clinical Research Electronic

Library• ODM - Operational Data Model• RFD – Retrieve Form for Data Capture• define.XML• SEND - Standard for the Exchange of Non-clinical Data

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SDTM• Study Data Tabulation Model• Structure and content of clinical data in electronic

regulatory submissions files• Managed by the SDS team (Submission Data Standards)• The model is in Version 1.2• SDTM Implementation Guide (IG) is Version 3.1.2• FDA now accepts Version 3.1.1 and 3.1.2• Always check with reviewer before sending

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SDTM IG• Provides information on

Variable and domain naming conventions Dataset definitions for 21 subject data-related domains

and several study description domains How to create data relationships How to develop new domains How to think about and understand clinical data dataset

structures

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CDASH• Clinical Data Acquisition Standards Harmonization,

Version 1.0• ‘Content standards’ for a basic set of global industry-wide

data collection fields to support clinical research• Not CRF layouts• System-independent, open source, free• Initial scope: 16 core safety domains• Covers both paper and electronic data capture

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CDASH Content: Core Domains

• Common Identifier Variables• Common Timing Variables• Adverse Events (AE)• Concomitant Medications

(CM)• Comments (CO)• Drug Accountability (DA)• Demographics (DM)• Disposition (DS)• Protocol Deviations (DV)

• ECG (EG)• Exposure (EX) • Inclusion Exclusion (IE)• Lab Test Results (LB)• Medical History (MH)• Physical Exam (PE)• Vital Signs (VS)• Subject Characteristics (SC)• Substance Use (SU)

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CDASH Content• Data design best practices, e.g.,

Use of yes/no questions Date format

• Recommended methodologies for creating data collection instruments

• Common controlled terminology• Regulatory references for each domain

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CDASH User Guide v1.0• In development, expected publication 1Q10• Will contain

General assumptions about each domain Implementation examples ODM XML structure for data transmission Electronically-generated CRF examples Variables not included in the standard CDASH to SDTM mapping Horizontal vs vertical data structures

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ADaM• Analysis Data Model• Structure of analysis datasets for submission• Some limited information on specific fields expected• Planning to release a User Guide with more guidance on

implementing the model

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LAB• Provides specifications for electronic transfer of central lab

data• Extensions for microbiology and ECG data• A subset of the most commonly used LOINC terms

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Medical Devices• Currently in development• Will provide device-specific domains

Device properties Device tracking Device disposition Device malfunctions

• First stage addresses implantable devices and other similar devices

• Later will include imaging and diagnostics

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Terminology• Set of controlled terms used in CDISC standards• Provides the answers to the questions asked by the

fields/variables• Maintained by NCI Electronic Vocabulary Services (EVS)

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TDM• Trial/Study Design Model• Electronic representation of the schedule of activities

(planned assessments, interventions, administrative activities, and encounters)

• It’s the study schedule in searchable structured electronic format

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Protocol• Defines trial elements electronically• Allows the protocol to be described electronically and the

elements search and reused• Includes eligibility criteria, trial design elements (e.g.,

Arms, epochs), trial schedule of events, and selected fields required by regulatory authorities (e.g., date of first subject enrolled, sponsor name)

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Therapeutic Area Standards• Draft standards are available for

Cardiovascular: Acute Coronary Syndrome Pulmonary Tuberculosis

• A draft standard is being produced for basic oncology tumor measurements

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BRIDG• Biomedical Research Integrated Domain Group Model• Framework for linking and harmonizing the other

standards• Defines each field as a concept with an agreed meaning

and set of characteristics• Foundation for linking CDISC to EHR and other data

sources

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SHARE• Shared Health and Clinical Research Electronic Library• A standards authoring tool that

Facilitates gathering and comparing existing material to distill a preferred approach

Provides a repository for standard data elements Permits some associations between elements

• This is in development and has completed its first pilot

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ODM• Operational Data Model• An XML definition for transmitting CDISC data between

systems• Currently primarily on data exchange between labs and

sponsors, and the like• Extension being developed to support data exchange for

CDASH data, and data exchange of CDASH data with eHR applications

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RFD• Retrieve Form for Data Capture• Broadly, it is “a method for gathering data within a

user’s current application to meet the requirements of an external system.” (IHE Wiki)

• “RFD supports the retrieval of forms from a form source, display and completion of a form, and return of instance data from the display application to the source application” (IHE Wiki)

• CDISC: applied to the interface between eHR and Electronic Data Capture (EDC) systems

• In development

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define.XML• The metadata sent to the FDA describing the SDTM

datasets in the regulatory submission• Based primarily on the first 5 columns of the SDTM IG• Written in XML

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SEND• Standard for the Exchange of Non-clinical Data• SEND IG: An implementation of SDTM for animal

toxicology data• Currently in Phase II pilot with the FDA

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How It All Fits Together

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FDA

Controlled Terminolog

yBRIDG

SEND

CDASH

ADaM

SDTM IG

define.xml

LAB

ODM

Trial Design Model

Devices

Vendors SHARE

Protocol Representatio

n