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CDISC End-to-End

UK User Group MeetingGSK, Stockley Park24th October 2007

Dave Iberson-HurstCDISC VP Technical Strategy© CDISC 2007

Dave Iberson-Hurst

• CDISC VP Technical Strategy– Co-lead Technical Advisory Committee (TAC)

– Co-Lead Technical Leadership Committee (TLC)

• European CDISC Coordinating Committee (E3C)

• ODM Team Lead

• Co-lead, electronic Source Data Interchange Group (eSDI)

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dibersonhurst@cdisc.org

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Agenda

• Review of the Models

• The CDISC Road Map

• CDISC Operational Road Map Environment

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Review of the Models

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Protocol & BRIDG

Overview

LABs

Sponsor

Investigator

CRO

Subject

ODM

ODM

Archive

Archive

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Protocol

Operational Data Model

LABs

Sponsor

Investigator

CRO

Subject

ODM

ODM

Archive

Archive

• Exchange & Archive of

clinical data

• Production Version 1.3

• XML Schema

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Original Use Cases

• Data Interchange – Transfer of information between two or more parties than maintains the integrity of the contents of the data.

• Data Archive – Long term storage of files that are no longer in active use

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Other Use Cases

• Set up of systems

• Acquisition

– eCRF

– ePRO

– EHR

• eSource

• Trial Registry

• Submission

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Protocol & BRIDG

Laboratory Data Model

LABs

Sponsor

Investigator

CRO

Subject

ODM

ODM

Archive

Archive

• Exchange of LAB data

• Production Version 1.0.1

• Implementations through SAS, ASCII, XML/ODM and HL7 V3 RIM message

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Use Case

• Support the bulk transfer of laboratory data

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Protocol & BRIDG

Study Data Tabulation Model

LABs

Sponsor

Investigator

CRO

Subject

ODM

ODM

Archive

Archive

• Submission data (Case Report

Tabulations; analysis data)

• Production Version 1.1

• Referenced as a specification in

FDA Guidance - 21 July 2004

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Analysis Dataset Models

LABs

Sponsor

Investigator

CRO

Subject

ODM

ODM

Archive

Archive• Analysis Data Model Version 2.0,

August 2006

Protocol & BRIDG

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Terminology

• Data Tabulations = SDTM data

• Analysis Datasets = ADaM data

• Two sets of data, both are representations of the clinical trial data

• Each with a specific purpose

Source: Susan Kenny, Inspire Pharmaceuticals Inc

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SDTM & Analysis Datasets

• SDTM:– observations from a clinical trial

– are particularly useful in medical officer evaluation of safety (with appropriate tools)

• ANALYSIS DATASETS:– restructured and contain additional

information (derived variables, flags, comments, etc.)

– analysis-ready

Source: Susan Kenny, Inspire Pharmaceuticals Inc

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Protocol Representation

LABs

Sponsor

Investigator

CRO

Subject

ODM

ODM

Archive

Archive

• HL7-CDISC-NCI Collaboration

• Objective to develop a standard,

structured, machine-readable clinical

protocol representation

Protocol & BRIDG

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Protocol Use Case

1. To support CDISC Study Data Tabulation Model (SDTM)

-Trial Design -Planned Assessments

-Planned Interventions -Inclusion/Exclusion criteria

-Statistical Analysis Plan

2. To support study tracking databases, e.g. EudraCT, clinicaltrials.gov, the protocol/trial tracking aspect of trial registry or results databases, or databases that support

project management tools (includes SDTM Study

Summary)

3. To support the development of the clinical trial protocol

document

Source: Protocol Team, CDISC

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BRIDG

LABs

Sponsor

Investigator

CRO

Subject

ODM

ODM

Archive

Archive

Protocol & BRIDG

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Protocol & BRIDG

Terminology

LABs

Sponsor

Investigator

CRO

Subject

ODM

ODM

Archive

Archive

• Covers the work of all teams

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EVS = NCI Enterprise

Vocabulary Services

RCRIM

Source: Andreas Gromen, Schering AG (Bayer)

Terminology Collaboration

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High Level Outline

Protocol

Set Up

Execute

Analysis

Submission

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Conventions

SDTM Tabulations

= CDISC Standard (content)

ODM = CDISC Standard (physical form) used to transport the content using World Wide Web Consortium (W3C) XML Standard

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Protocol

ODM

Trial Design

ODM

Trial Reg

Protocol

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Protocol

ODM

Trial Design

ODM

Trial Reg

Protocol

Prototype ODM Extension

Trial Design

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Protocol

ODM

Trial Design

ODM

Trial Reg

Protocol

Prototype ODM Extension

World Health Organisation (WHO)

Trial Registry

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Capture

ODM

CRF Data

CDMS

LAB

LAB Data

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Interchange

ODM

CRF Data Sponsor

database CDMS

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Interchange

ODM

CRF Data

SDTM Tabulations

Sponsor

database

Sponsor

database

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Analysis

AnalysisSDTM

Tabulations

Sponsor

database

ADaMDatasets

Sponsor

database

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Submission

Analysis

ODM

SDTM metadata

Reports

ODM

SDTM & ADaM data

SDTM Tabulations

ADaMDatasets

Review

database

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Submission

Analysis

ODM

SDTM metadata

Reports

ODM

SDTM & ADaM data

SDTM Tabulations

ADaMDatasets

Review

database

ODM Extension

Case Report Tabulation, Data Definition

Specification (CRT DDS aka define.xml)

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Submission

Analysis

ODM

SDTM metadata

Reports

ODM

SDTM & ADaM data

SDTM Tabulations

ADaMDatasets

Review

database New ODM Extension

ODM extension to carry SDTM and ADaM data,

currently being developed.

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The CDISC Blueprint

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ODM Extensions

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ODM

Schema

CRF Data &

Metadata

ODM

Schema

Submission

Metadata

Define.xml

extension

ODM

Schema

Trial

Design

Metadata

TDM

extension

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The CDISC Road Map

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Role of the Road Map

• A Road Map

– any plan or guide to show how something is arranged or can be accomplished

• Internal to CDISC

– Provide the overall technical plan

• External to CDISC

– Provide users of the CDISC standards with a picture

of what is being developed and when it will be

developed

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The CDISC Road Map

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The CDISC Road Map

Friday 15th July 2005

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The CDISC Road Map

Purpose:To provide a concise, common specification of all technical products

to be developed by CDISC.

Endpoint:By 2008, there will be a single CDISC standard for the full lifecycle of

a clinical trial or study from protocol representation through the

capture of source data to submission and archive, comprising a set of

fully integrated and consistent models which will form logically and

organically from our current set.

Success Criteria:• All submissions to the FDA are being made using the CDISC

standard;

• The set of CDISC models in use across the full life-cycle of clinical

trials; and

• The CDISC standard being globally adopted.

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The CDISC Road Map

Purpose:To provide a concise, common specification of all technical products

to be developed by CDISC.

Endpoint:By 2008, there will be a single CDISC standard for the full lifecycle of

a clinical trial or study from protocol representation through the

capture of source data to submission and archive, comprising a set of

fully integrated and consistent models which will form logically and

organically from our current set.

Success Criteria:• All submissions to the FDA are being made using the CDISC

standard;

• The set of CDISC models in use across the full life-cycle of clinical

trials; and

• The CDISC standard being globally adopted.

Since the Last Road Map

• CDISC Strategy has been developed

• CDISC technical landscape has changed

– Terminology

– Glossary

– Protocol

– BRIDG

– CDASH

– and a lot more

• CDISC internal processes have improved

– Technical Advisory Committee (TAC)

– Technical Leadership Committee (TLC)

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So … Key Points

• Road Map is work in progress

• Emphasis Changed

– From a “single CDISC standard”

– To a “harmonized set of CDISC standards”

• Emphasis On

– CDISC “content”

– With multiple supporting “transport” mechanisms

• We need to be clear on what we mean by

– Harmonized

– Content

– Transport

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Work In Progress

"Harmonized"

• that the concepts defined within the standard have agreed and clear definitions;

• that the relationships between those concepts are agreed;

• any terminology involved is agreed; and

• all of the concepts, relationships and terminology are modelled within and consistent with the BRIDG model.

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Work In Progress

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"Content" & "Transport"

• Content

– The information we wish to send

• Transport

– How we send the information

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www.dictionary.com

Work In Progress

The New End Point

• The primary end-point of the road map is a set of harmonized CDISC standards for the full life-cycle of a clinical trial from protocol representation through the capture of source data to submission and archive.

• It is suggested that success should be measured against three criteria:– the set of harmonized CDISC standards being globally

adopted

– the set of harmonized CDISC standards in use across the full life-cycle of clinical trials; and

– all submissions to the FDA are being made using the appropriate CDISC standards;

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Work In Progress

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The New End Point

• The primary end-point of the road map is a set of harmonized CDISC standards for the full life-cycle of a clinical trial from protocol representation through the capture of source data to submission and archive.

• It is suggested that success should be measured against three criteria:– the set of harmonized CDISC standards being globally

adopted

– the set of harmonized CDISC standards in use across the full life-cycle of clinical trials; and

– all submissions to the FDA are being made using the appropriate CDISC standards;

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Work In Progress

The New Principles

• Standards must be aligned (and stay aligned) with the BRIDG model.

• CDISC must strive towards a harmonized set of standards where:– SDTM/SEND, CDASH, ODM, LAB, ADaM, and Protocol define

content;

– Define.xml provides common metadata;

– the standards share controlled terminology and glossary;

– platform-independence and platform-neutrality are maintained; and

– Multiple transport formats for common content are supported.

• The BRIDG model serves as the portal to healthcare.• For a given standard, compatibility with all previous releases

of the standard is maintained.• Stability for those adopting must be assured.• Standards should support all CDISC stakeholders.• The standards should be tested within an environment that

reflects their operational deployment.

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Work In Progress

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Aligned with BRIDG

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Healthcare

HL7 RIM

BRIDG as a Portal to Healthcare

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Map

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Healthcare

HL7 RIM

Bridging the Silos

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Map

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The CDISC Operational Road

Map Environment

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• CDISC needs

– An environment for testing the production standards

– An environment for evaluating new ideas

– An environment to demonstrate the standards

working

• This will be provided by CDISC Operational Road Map Environment (CORE)

Tested within an Environment

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CORE - End-to-End Seminars

• First exercise undertaken in mid 2005

• Informal seminars run

– 2005 US Interchange

– 2006 DIA Annual

– 2006 US Interchange

– 2007 European Interchange

– 2007 US Interchange

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CORE - CDISC/FDA Pilots

• First Pilot

– Submission using SDTM & ADaM

– Used protocol and data supplied by Eli Lilly

• Second Pilot

– Safety submission

• ODM Pilot

– CRF Data as part of a submission

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• CORE is a test-bed, a permanent infrastructure utilizing the web

• It is CDISC’s testing ground

• It is CDISC’s shop window; it demonstrates to the world what CDISC can do

• It is not a pilot

• It develops nothing; it takes CDISC product and uses it and reports back

CORE - Principles

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A Familiar Environment

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HDMIHDMI

S-Video

Phono

SCART

HDMI High Definition Multimedia

Interface

SCART Syndicat des Constructeurs

d'Appareils Radiorécepteurs

et Téléviseurs

S-Video Separate Video

A Familiar Environment

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HDMIHDMI

S-Video

Phono

SCART

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Company Specific

The Clinical Trials Environment

Protocol Form

Setup &

Config

Data

Capture

Mapping Analysis Submission Review

The CT Environment - The CDISC Way

Protocol Form

Setup &

Config

Data

Capture

Mapping Analysis Submission Review

CDASHProtocol

ODM

SDTM & ADaM

LAB

XML

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CORE - The Beginning

Protocol Form

Setup &

Config

Data

Capture

Mapping Analysis Submission Review

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CORE - Removing the Silos

Protocol Form

Setup &

Config

Data

Capture

Mapping Analysis Submission Review

SDTM/ADaM Analysis

Protocol Setup, Capture & Mapping

SDTM Domains

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CORE - Next Steps

• Develop a detailed plan

– Based around use cases

• Working in cooperation with vendors

• Leveraging

– the work from the CDISC/FDA Pilots

– the work from the end-to-end seminars

• Next milestone being the CDISC Interchange in Copenhagen, April 21-25, 2008

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Summary

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The CDISC Blueprint

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CORE - Use CasesProtocol

Tool

Trial Supply Management

Tool

National Trial

Registry

Subject Recruitment

Tool(s)

International Trial Registry

LAB Environment

Data Capture Tool(s)

Archive System or Warehouse

CDMS

Analysis Tool(s)

Review Tool(s)

2 10

5

1514

Protocol Document

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1

9

13

8

3

4

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12, 26

Analysis Tool(s)

CDMS

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7

18

20, 21

CTMS

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Study Design Tool

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23,2419

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Work In Progress

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CORE - The Beginning

Protocol Form

Setup &

Config

Data

Capture

Mapping Analysis Submission Review

medidata

Summary

• Road Map will speak to the “harmonized” set of CDISC standards

• Focused around “content” and “transport”

• To remove silos

• Build and end-to-end solution

• BRIDG playing a central role

• CORE providing tangible evidence

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