esource, emea london, june 2006
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eSource June 7, 2006. EMEA, London Dave Iberson-Hurst, Assero Co-lead, CDISC eSDI Group © Assero Ltd & CDISC, 2006
EMEA. June 7th, 2006 2
Agenda
CDISC Background
Method & Analysis User Requirements
Scenarios Benefits
Next Steps Summary
EMEA. June 7th, 2006 3
The CDISC Mission
Clinical Data Interchange Standards Consortium
The mission of CDISC is to develop and support global, platform-independent data standards that enable information system
interoperability to improve medical research and related areas of healthcare.
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Production Standards
Board Committees • Executive • Financial Oversight • Governance • Global Strategy • Global Communications
Industry Advisory Board
CDISC Board of Directors
Implementation Services Innovation Initiatives • Production Standards Updates
(SDTM, SEND, define.xml, ODM, LAB, ADaM, Glossary)
• End-to-end Documentation • Implementation Guide/Std
Enhancement (e.g. TDM, PK, device, vaccine)
• BRIDG Modeling • SDTM-ADaM Pilot • Submission in ODM XML • eSource Data Interchange • Terminology and NIH Grants • Protocol Representation • Healthcare Link • Industry Architecture Proposal
• Education Courses • Global User Network Support • Regional CDISC Coordinating Comm.
(Japan, Europe) • U.S. Networks • Implementation Enablers (‘proto-
tools’) • Help Desk
CDISC Coordinating Committee Leaders, Japan & Europe
Technical Advisory Committee
Board and IAB Support International Operations Support Member Services New Opportunity Exploration PR/Communications Program Management Business Case Alliance Management Website/IT; Interchanges Member Services
President
CDISC Organisation
Global Operations
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History
1999 2000 2001 2002 2003 2004
SDS V2.0 (*)
ODM V1.0
ODM V1.1
SDS V3.0 (*)
ODM V1.2
2005 1998 1997
CDISC Volunteer Group
CDISC Europe
DIA SIAC Formed
CDISC Incorporated
CDISC Japan
LAB V1.0
SDTM into guidance
Define.XML guidance
SDTM V1.0 (*)
* Note: SDS became SDTM
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Standards
LABs
Sponsor
Investigator
CRO
Subject
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Standards
LABs
Sponsor
Investigator
CRO
Subject
ODM
OD
M
ODM
Archive
Archive
SDTM ADaM ODM
Define.XML
Protocol
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Protocol
Operational Data Model
LABs
Sponsor
Investigator
CRO
Subject
ODM
OD
M
ODM
Archive
Archive
SDTM ADaM ODM
Define.XML
• Exchange & Archive of clinical data
• Production Version 1.2.1 • XML Schema
EMEA. June 7th, 2006 9
Protocol
Laboratory Data Model
LABs
Sponsor
Investigator
CRO
Subject
ODM
OD
M
ODM
Archive
Archive
SDTM ADaM ODM
Define.XML
• Exchange of LAB data
• Production Version 1.0.1
• Implementations through SAS, ASCII, XML/ODM and HL7 V3 RIM message
EMEA. June 7th, 2006 10
Protocol
Study Data Tabulation Model
LABs
Sponsor
Investigator
CRO
Subject
ODM
OD
M
ODM
Archive
Archive
SDTM ADaM ODM Define.XML
• 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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Standards for the Exchange of Non-clinical Data (SEND)
LABs
Sponsor
Investigator
CRO
Subject
ODM
OD
M
ODM
Archive
Archive
SDTM ADaM ODM
Define.XML
• Non-clinical (animal) data • Based upon CDISC SDS V3.1 • Included in SDTM model now
referenced in FDA Guidance
Protocol
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Analysis Dataset Models
LABs
Sponsor
Investigator
CRO
Subject
ODM
OD
M
ODM
Archive
Archive
SDTM ADaM ODM Define.XML
• General Considerations Document and Examples of Standard Analysis Datasets for Submissions
Protocol
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Protocol Representation
LABs
Sponsor
Investigator
CRO
Subject
ODM
OD
M
ODM
Archive
Archive
SDTM ADaM ODM
Define.XML
• HL7-CDISC-NCI Collaboration • Objective to develop a standard,
structured, machine-readable clinical protocol representation
Protocol
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Terminology
LABs
Sponsor
Investigator
CRO
Subject
ODM
OD
M
ODM
Archive
Archive
SDTM ADaM ODM
Define.XML
• Covers the work of all teams
Protocol
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CDISC Projects - A Sample
• End-to-End Production Use – How are the models used end-to-end in detail
• Device Domain – SDTM Domain
• SDTM-ADaM Pilot – In conjunction with the FDA
• Submission in ODM XML – Removal of SAS Transport Files
• The Link with Healthcare – Integrating the Healthcare Enterprise (IHE)
Profile
EMEA. June 7th, 2006 16
Background
• FDA Presentation, August 2004 - Reviewers – Operational Data Model (ODM) – The Archive Use Case – Define.xml
• FDA Presentation, November 2004 - DSI – ODM – Regulations
• Suggested changes to CSUCT guidance document
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• The electronic Source Data Interchange (eSDI) initiative
• Started in November 2004 with the encouragement from the Food and Drug Administration (FDA)
eSDI Group
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eSDI Mission
Produce a document that would benefit industry and FDA by providing
recommendations for the use of the CDISC standards with associated processes that can promote the
enhanced use of eSDI within the context of the existing regulations for regulated
clinical research.
EMEA. June 7th, 2006 19
Issues
• How to transition from the paper world to the ‘e-World’ in terms of audits, reviews, compliance to regulations
• No regulatory basis for Trusted Third Parties • Concern about Interim Analysis • Collection of data without adequate
psychometric validation • Inadequate validation and control of systems
used for data collection
EMEA. June 7th, 2006 20
History
• Expert Focus Groups Invited for Comment – 23rd February, Philadelphia – 7th March, Lisbon
• 1st Draft 14th March 2005 – 4th & 5th April, DIA ePRO Conference, Arlington – 11th April, SAS Users Forum
• 2nd Draft 25th May 2005 • 3rd Draft 11th August 2005 • 4th Draft 29th August 2005 • 5th Draft 16th September 2005 • 500+ individual comments • 6th Draft Q2 2006
EMEA. June 7th, 2006 21
Content
• Psychometric validation not in document – Now being looked at by a DIA group
• Interim Analysis – Small reminder of current regulations and
guidance • eSource
– Main focus of document – How standards can help
EMEA. June 7th, 2006 22
Motivation and Aims
• Motivation – Desire to solve the issue and increase adoption
• Aims – Something tangible to shoot at, detailed enough
to allow debate and be practical – Simple check list, well understood (a what not
how) – Allows all stakeholders (FDA, Sponsors, Vendors
& Investigators) to assess current and future technologies
EMEA. June 7th, 2006 23
Method
• Examine the paper process; if well executed, it meets the regulatory requirements
• What are the requirements that source documents must meet?
• What do the FDA, Sponsors and Investigators need (key requirements) from source documents?
• Consider – Regulations – Data Quality & Integrity – Subject Safety
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Outcome
• Checklist – A checklist that allows industry to assess any
technology and process now or in the future • Scenarios
– Suggested ways to move forward
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Criticism of Approach
• Criticisms – We don’t want to preserve paper – Why look at the paper process
• Fundamental Question – Why do we have source documents and data?
EMEA. June 7th, 2006 26
Fundamental Questions
• How do we ensure that the data submitted are the data captured?
• How do we ensure the data captured is accurate?
• How do we ensure the subject's safety?
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User Requirements
• 12 in total • As they stand today • Open for review, discussion and debate • The detail is in the white paper • All are mapped to regulations
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Requirement 1 (Old Text)
An instrument used to capture source data shall be an accurate representation of the protocol ensuring that the data as specified within the protocol is captured
correctly.
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Requirement 1 (New Text)
An instrument used to capture source data shall ensure that the data is
captured as specified within the protocol
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Requirement 2
Source data shall be Accurate, Legible, Contemporaneous, Original, Attributable,
Complete and Consistent (the ALCOA and Data Integrity requirement).
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Requirement 3
An audit trail shall be maintained as part of the source documents for the original creation and subsequent modification of
all source data.
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Requirement 4
The storage of source documents shall provide for their ready retrieval.
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Requirement 5
The investigator shall store the original source document or a certified copy.
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Requirement 6
The mechanism used to maintain source documents shall ensure that source data
cannot be modified without the knowledge or approval of the investigator.
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Requirement 7
Source documents and data shall be protected from destruction.
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Requirement 8
The source document shall allow for accurate copies to be made.
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Requirement 9
Source documents shall be protected against unauthorised access.
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Requirement 10
The sponsor must never have exclusive control of a source document.
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Requirement 10
The sponsor must never have exclusive control of a source document.
“Comments were also made indicating that this was not a new
requirement, but intrinsic to complying with FDA regulations
regarding clinical trials.”
EMEA. June 7th, 2006 40
PRO Guidance Document
• FDA Guidance for Industry. – Patient-Reported Outcome Measures: Use in
Medical Product Development to Support Labeling Claims
• Lines 848 & 849 – Sponsors should also plan to avoid the following:
• Direct PRO data transmission from the PRO data collection device to the sponsor (i.e., the sponsor should not have exclusive control of the source document)
EMEA. June 7th, 2006 41
Requirement 11
The location of source documents and the associated source data at all points
within the capture process shall be clearly identified.
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Requirement 12 (Old Text)
When source data are copied, the process used shall ensure that the copy is an exact copy having all of the same
attributes and information as the original.
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Requirement 12 (New Text)
When source data are copied, the process used shall ensure that the copy
is an exact copy preserving all of the data and metadata of the original
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Recommendations (1)
• Source at Site – Electronic equivalent of paper – Must be easy (practical) for the investigator – The CDISC Operational Data Model (ODM) can
assist greatly
Sponsor
Investigator
Source Data
ODM
Sphere of investigator control
EMEA. June 7th, 2006 45
Recommendations (2)
• eSource System Provider – Works on behalf of the investigator – Must document how the 12 core requirements
are met – This document must be open to inspection by
the FDA
Sponsor
Investigator eSource System Provider
EMEA. June 7th, 2006 46
Recommendations (3)
Sponsor
EHR
ODM
Source Data
Sponsor Database
• Single Source Concept – Single entry of data
using an EHR – Data used, as required,
in both healthcare and clinical research
– Use of “ODM Store” helps facilitate compliance with the regulations
ODM
EMEA. June 7th, 2006 47
Recommendations (4)
Sponsor
EHR EHR Database
Sponsor Database
• EHR Extraction and Investigator Verification – Data extracted from the
EHR database – Investigator verifies the
data – Protects against 21 CFR
11 “creep”
EMEA. June 7th, 2006 48
Recommendations (5)
Sponsor
EHR
EHR Database
Sponsor Database
• Direct Extraction – Data extracted from the
EHR database – EHR must be 21 CFR
Part 11 Compliant
EMEA. June 7th, 2006 49
Next Steps - The Ideal Picture?
Sponsor Investigator
Source Doc
eSource System Provider
EMEA. June 7th, 2006 50
Next Steps - The Ideal Picture?
Sponsor Investigator
Source Doc
eSource System Provider
• Create • Read • Update
• Read • Update With
Approval
• Read
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Fundamental Questions
• How do we ensure that the data submitted are the data captured?
• How do we ensure the data captured is accurate?
• How do we ensure the subject's safety?
EMEA. June 7th, 2006 52
Output From Work
• 12 User Requirements • 5 Scenarios • Recommendations • Checklist for Investigators • Sponsor Audit Report Template
EMEA. June 7th, 2006 53
Summary
• The work of the eSDI group provides a clear way forward in the use of eSource
• Core requirements and recommendations provide the foundation stone for the building of true e-Clinical systems
• Draft 6 being worked on, will be released via the CDISC website, www.cdisc.org
EMEA. June 7th, 2006 54
Information and Contacts
• eSDI Group Leaders – Rebecca Kush
[email protected] – Dave Iberson-Hurst
EMEA. June 7th, 2006 55
Contributors
• Ethan Basch Memorial Sloan-Kettering Cancer Center
• Peter Black Scirex
• David Detoro Schering Plough
• Hugh Donovan Siemens
• Greg Fromell University of Pennsylvania
• Ed Helton SAS
• John Jordon Schering Plough
• Suzanne Markel-Fox GSK
• Michael Noonan Asthma Research
• Lisa Olson SEC Associates
• Shaghig Palanjian Perceptive Informatics
• Jay Pearson Merck & Co.
• David Reasner Sepracor
• Dana Stone Merck & Co.
• Mark Weiner University of Pennsylvania
• Wallace Wormley University of Pennsylvania
EMEA. June 7th, 2006 56
FDA Liaisons
• Laurie Burke Director Study Endpoints and Label Development, Office of New Drugs CDER
• Joanne Rhoads Director, Division of Scientific Investigations, CDER
• Joe Salewski Deputy Director, Division of Scientific Investigations, CDER
• Jane Scott Study Endpoints and Label Development, Office of New Drugs, CDER
• Steve Wilson Deputy Director, Division of Biometrics II, CDER
EMEA. June 7th, 2006 57
Discussion