eSource, EMEA London, June 2006

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


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.


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


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


Standards

LABs

Sponsor

Investigator

CRO

Subject


Standards

LABs

Sponsor

Investigator

CRO

Subject

ODM

OD

M

ODM

Archive

Archive

SDTM ADaM ODM

Define.XML

Protocol


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


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


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


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


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


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


Terminology

LABs

Sponsor

Investigator

CRO

Subject

ODM

OD

M

ODM

Archive

Archive

SDTM ADaM ODM

Define.XML

•  Covers the work of all teams

Protocol


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


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


•  The electronic Source Data Interchange (eSDI) initiative

•  Started in November 2004 with the encouragement from the Food and Drug Administration (FDA)

eSDI Group


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.


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


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


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


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


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


Outcome

•  Checklist – A checklist that allows industry to assess any

technology and process now or in the future •  Scenarios

– Suggested ways to move forward


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?


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?


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


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.


Requirement 1 (New Text)

An instrument used to capture source data shall ensure that the data is

captured as specified within the protocol


Requirement 2

Source data shall be Accurate, Legible, Contemporaneous, Original, Attributable,

Complete and Consistent (the ALCOA and Data Integrity requirement).


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.


Requirement 4

The storage of source documents shall provide for their ready retrieval.


Requirement 5

The investigator shall store the original source document or a certified copy.


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.


Requirement 7

Source documents and data shall be protected from destruction.


Requirement 8

The source document shall allow for accurate copies to be made.


Requirement 9

Source documents shall be protected against unauthorised access.


Requirement 10

The sponsor must never have exclusive control of a source document.


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.”


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)


Requirement 11

The location of source documents and the associated source data at all points

within the capture process shall be clearly identified.


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.


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


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


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


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


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”


Recommendations (5)

Sponsor

EHR

EHR Database

Sponsor Database

•  Direct Extraction – Data extracted from the

EHR database – EHR must be 21 CFR

Part 11 Compliant


Next Steps - The Ideal Picture?

Sponsor Investigator

Source Doc

eSource System Provider


Next Steps - The Ideal Picture?

Sponsor Investigator

Source Doc

eSource System Provider

•  Create •  Read •  Update

•  Read •  Update With

Approval

•  Read


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?


Output From Work

•  12 User Requirements •  5 Scenarios •  Recommendations •  Checklist for Investigators •  Sponsor Audit Report Template


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


Information and Contacts

•  eSDI Group Leaders – Rebecca Kush

[email protected] – Dave Iberson-Hurst

[email protected]


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


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


Discussion

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