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Introduction to CDASH

Rhonda Facile, CDISCMelissa Binz, Wyeth

Presented by Melissa BinzDirector Central Standards Group, Wyeth

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Introduction to the CDASH StandardMonday, March 16 2009

• Welcome and Review of Agenda• CDASH History & Status • Preview of CDASH V 1.0 Document• Survey of Domains• Practical Implementation• Wrap-up and Q & A

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Clinical Data Acquisition

Standards Harmonization

Yes, it was a stretch…but it made a fine acronym!!

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Introduction to the CDASH StandardMonday, March 16 2009

• Welcome and Review of Agenda

• CDASH History & Status • Preview of CDASH V 1.0 Document• Survey of Domains• Practical Implementation• Wrap-up and Q & A

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History

Current state - FDA Description:• Plethora of data formats and conventions• Many different computer systems for data entry at their

sites (for various trials), each of which uses different data conventions

• Inefficient• Multiplies the potential for error• Makes data sharing & mining impossiblehttp://www.fda.gov/oc/initiatives/criticalpath/reports/opp_list.pdf

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History

March 16, 2004 FDA white paper:• “Innovation/Stagnation:

Challenge and Opportunity on the Critical Path to New Medical Products”

• Describes the Critical Path –to make product development morepredictable and less costly

• Publishes 76 ‘opportunities’ for improvement• #45 – Consensus on Standards for CRFshttp://www.fda.gov/oc/initiatives/criticalpath/reports/opp_list.pdf

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Project Snapshot• 16 Safety data domains

developed• Consolidated document posted

for public review in May 2008• Received over 1800 comments

from 46 companies, institutions and agencies.

• All 3 ICH regions were represented in the public comment process

– US– Europe– Japan

• CDASH V1.0 published October 1 2008

• Streamlines data collection at investigative sites - addresses Critical Path Opportunity #45

• Continuation of ACRO’sInitiative

• Started October 2006• Supported by a collaborative

group of 17 organizations• Core team of 16 members

manages.. – 11 working groups– Comprised of between 8-40

volunteers

• ~190 working group volunteers

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CDASH Purpose & Scope

To develop a set of ‘content standards’ (element name, definition, metadata) for a basic set of global industry-wide data collection fields that support clinical researchThe initial scope - ‘safety data/domains’These safety domains cut across all therapeutic areas (TA independent)Follow CDISC Operating Procedure for Standards Development (COP-001) . . . and make certain that all SDTM “required”variables are addressed AND that all CDASH collection fields map into the SDTM

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Practical Benefits

• Eliminates some of the variety in CRFs seen at sites

• Streamlines training & increases common understanding of CRF completion instructions

• Reinforces collecting only key data • Reduces collection of duplicate data -

decreasing the potential for error

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Practical Benefits (Continued)

• Minimizes data queries• Facilitates populating CRFs by eHR without re-

entry• Cuts down on study start time – for all

stakeholders• Better quality

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CDISC Standards Development Process (COP-001) Primary Stages

Stage I: Standard Definition/ApprovalMultidisciplinary Team Initiation; Working Plan Development

Stage III: Education & Support

Stage IV: Standards Update & Maintenance

Stage II: Standards Development-Consensus Model; Reviews by External Focused Group and Open Public; Harmonization and Testing throughout; V1.0 Release

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How Was CDASH Developed?

Started with Study Data Tabulation Model (SDTM)Focused on CRF Content, not CRF LayoutReferred to ACRO CRF SamplesCollected > 150 CRF samplesEvaluated commonalities/differences of CRF samplesDocumented data points included/excluded with justifications

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How Was CDASH Developed? (Continued)

• Agree on basic data collection fields• Map to SDTM • Terminology - proposals shared with the

Terminology Team• Write definitions and completion instructions for

clinical site and Sponsors• Proceed to the next step in the Consensus

Process

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CDASH Delivers Data Collection Tables, not CRFs

Data ollection Field

Variable Name

(CDASH variable

name shaded)

Definition

Case Report Form Completion Instructions

Additional Information for

Sponsors

CDASH Core

col/Study ifier

STUDYID Unique Identifier for a study within a submission.

Not applicable. This is typically pre-printed/pre-populated.

Highly Recommended

dentifier in a Study

SITEID

Or

SITENO

Unique identifier for the study site; however, SITEID is also unique within a submission.

Record your clinical site’s identifier as defined by the sponsor.

Paper: This is typically pre-printed in the header of each CRF page for single site studies. For studies with multiple sites, this field is typically left blank so that the number can be recorded by the site.

EDC: This should be pre-populated.

If SITEID is not used, SITENO should be used to derive SITEID for SDTM, depending upon sponsor’s site identification scheme.

Highly Recommended

ect Identifier SUBJID Subject identifier for the study. Record the identifier for the subject. Paper: This is typically recorded in the header of each CRF page.

EDC: The subject identifiers may be provided to the site using a pre-populated list in the system.

Highly Recommended

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CDASH Delivers Domain Tables

Basic data to be collected..

Describes the purpose of the data collection

field

CRFCompletion Instructions

for Sites

How toimplementthe CRF

data collection variable

CDASH Core

Designations

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Collaborative Group - Role

• Provides expertise and strategic input to the CDASH Project Team.

• Contributes and/or helps identify resources as needed to enable achievement of the mission, goals and deliverables.

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Collaborative Group Members• American Medical Informatics

Association (AMIA)• Association of Clinical Research

Organizations (ACRO)• Association of Clinical Research

Professionals (ACRP)• Baylor College of Medicine• Biotechnology Industry

Organization (BIO)• Clinical Data Interchange

Standards Consortium (CDISC)• Clinical Research Forum• Critical Path Institute • Duke Clinical Research Institute

(DCRI)

• Food and Drug Administration (FDA)• NIH - NCI - caBIG• NIH - Clinical Research Policy

Analysis & Coordination Program• National Clinical Research

Resources (NCRR)• NIH - National Institute of Child

Health & Human Development (NICHD)

• National Library of Medicine (NLM)• Pharmaceutical Research and

Manufacturers Association (PhRMA)

• Society for Clinical Data Management (SCDM)

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Who Participated?

• Team Membership:StatisticiansMedical Monitors /

Clinical ScientistsRegulatory AffairsDrug SafetyData ManagersClinical Study CoordinatorsClinical Research AssociatesInvestigatorsClinical Program ManagersStatistical ProgrammersDatabase programmers

• Participants in the CDASH Initiative

Other = academic research organizations, government (NIH, NCI), hospitals, universities

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Key Collaborations

• Internal CDISC cross-team – CDISC SDS (Study Data Standards)Team– CDISC Terminology Team

• NIH-NCI-caBIG project• Healthcare Link – Integrating the Healthcare

Enterprise (IHE)– Reduces need to enter study data multiple times

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Introduction to the CDASH StandardMonday, March 16 2009

• Welcome and Review of Agenda

• CDASH History & Status

• Preview of CDASH V 1.0 Document• Survey of Domains• Practical Implementation• Wrap-up and Q & A

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CDASH Version 1.0

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CDASH V1.0 Table of ContentsSections1. Orientation

• Purpose• Organization of Document

2. CDASH Alignment with Other Standards

• SDTM• CDISC Controlled Terminology• Other Standards (Beyond CDISC)

3. Best Practice• Introduction to Best Practices • Recommended Methodologies for

Creating Data Collection Instruments • Recommended CRF Development

Workflow• FAQs on Best Practices for Creating

CRF Content and Structure

4. Overview of CDASH Domain Tables

• Introduction• Data Collection Fields Considered not

Necessary to Collect• Core Designations for Basic Data

Collection Fields/• Explanation of Table Headers

5. CDASH Domain Tables• Common Identifier Variables• Common Timing Variables

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CDASH V1.0 Table of Contents (continued)

Appendices7.1 Commonly Used CDISC Controlled Terminology 7.2 Regulatory References7.3 CDASH Project Development Process7.4 CDASH Core Team Members and Participating Companies7.5 List of Abbreviations and Glossary7.6 Acknowledgements7.7 Revision History7.8 Intellectual Property

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Introduction to the CDASH StandardMonday, March 16 2009

• Welcome and Review of Agenda

• CDASH History & Status • Preview of CDASH V 1.0 Document

• Survey of Domains• Practical Implementation• Wrap-up and Q & A

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Survey of Standards

• 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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Survey of Standards

Core Designations• Highly Recommended

A data collection field that should be on the CRF (e.g., a regulatory requirement, if applicable) (e.g. Adverse Event Term)

• Recommended/Conditional A data collection field that should be collected on the CRF for specific cases (may be recorded elsewhere in the CRF or from other data collection sources) (e.g. AE Start Time)

• Optional A data collection field that is available for use if needed(e.g. Was any AE experienced?)

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Expectations

• Highly Recommended data collection variables should always be present on the CRF

• Sponsors will need to add data collection fields as needed to meet protocol-specific and other data collection requirements (e.g. therapeutic area specific data variables and others as required per

protocol, business practice and operating procedures)

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CDASH Domain –New Ideas Physical Examination(PE)

• Use PE form to record only whether or not exam was done

• Record Baseline abnormalities on appropriate CRF:

• Medical History,• Targeted Medical History, or• Baseline Conditions

• Record Post-baseline abnormalities or baseline conditions that worsened on

• AE CRF

Inclusion/Exclusion(IE)

Use IE form to collect only the criteriaNOT MET for Inclusion/Exclusion criteria

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CDASH Domain –New Ideas

Protocol Deviations (DV) Avoid creating a protocol Deviations CRF This information can often be derived from other CRF domains or system functionalities.

Comments (CO) Avoid the creation of a General Comments CRF which collects unsolicited comments.

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Introduction to the CDASH StandardMonday, March 16 2009

• Welcome and Review of Agenda

• CDASH History & Status • Preview of CDASH V 1.0 Document• Survey of Domains

• Practical Implementations• Wrap-up and Q & A

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How could CDASH be used today?

• Use as a Content Standard– Off the shelf Case Report Form content– Describes relationship between Operational Data and

Submission Datasets– CDASH represented within a proprietary file format

• Excel, Word, Proprietary EDC system format• Potentially unstructured

• Use within Machine-Readable Metadata– CDASH represented in CDISC Operational Data Model– Vendor neutral system with an independent format– Hierarchical structure is ideal for re-usable library of

Components

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What is a CDASH-ODM Form Composed Of?

<ODM><Study>

<Meta…</Meta…

</Study></ODM>

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CDASH AE Form in ODMNo more hand building of this…

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Multi-Vendor Visualizations –PhaseForward

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Multi-Vendor Visualizations –Medidata

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Multi-Vendor Visualizations –Paper

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Implementing CDASH

• No Standards? No problem.• Existing Standards?

1. Gap Analysis – do not forget terminology!2. Negotiation

1. Internal stakeholders2. External stakeholders

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NCI “mandatory”

CDASH and caBIG:CRF Harmonization

• NCI/caBIG CRF modules will (at a minimum) include all CDASH mandatory questions

PLUS

• Additional content that is essential in the oncology space.

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CDASH“mandatory”

“Highly recommended”

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Introduction to the CDASH StandardMonday, March 16 2009

• Welcome and Review of Agenda

• CDASH History & Status • Preview of CDASH V 1.0 Document• Best Practice Recommendations• Survey of Domains• Practical Implementation

• Wrap-up and Q & A

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Focus 2009

• Develop CDASH Training Program• Collect feedback from “Early Implementers”• Develop and Publish Machine Readable Metadata• Develop basic data collection fields for Devices• Develop and Publish CDASH-Implementation Guide• Update CDASH v. 1.0• Present, publish and train the CDASH standard

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Thanks to all the volunteers who have worked to get us where we are today!

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CDASH Core Team Members• Rhonda Facile rfacile@cdisc.org• Gary Walker gary.walker@quintiles.com• Dorothy Dorotheo DDorotheo@intermune.com• David E. Tatum tatum.david@att.net• Paul Bukowiec Paul.Bukowiec@mpi.com• Trisha Simpson Trisha.Simpson@UCB-group.com• Shannon Labout shannon.labout@eu.astellas.com• Liz Nulton-Bodiford liz.m.nulton-bodiford@gsk.com• Jay Leeka Jay.Leeka@astrazeneca.com• Alec Vardy a.vardy@exelixis.net• Kim Truett Kim.Truett@kctdm.com• Holly Peterson Holly.Peterson@frx.com• Kit Howard kit@kestrelconsultants.com• Cathy Schleuning cathy.schleuning@UCB-group.com

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CDASH Core Team Members• Lorna Griffin lorna_griffin1@merck.com• Lauren Shinnaberry ShinaberryLauren@PRAIntl.com• Melissa Binz binzm@wyeth.com• Charlene Dark charlene.dark@gmail.com• Jennifer Price JPrice@pdsedc.com• Chandra Wooten Chandra.Wooten@gilead.com

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Strength through collaboration