Introduction to the
Operational Data Model
(ODM)
CDISC European Italian-Speaking
User Group Meeting
Milano, 16 November 2007
Dr. Philippe Verplancke
XClinical GmbH
“End-to-end” process (overview)
CRO
Sponsor
ODM
Archive
B
B
LA
LA
Investigator
ODM
ODM
SDTM
ADaM
ODM
Define.XML
OD
M
Subject
LABs
Archive
2
“End-to-end” process (detail)
EDC
CDM
ODM
Operational
Database;
Normalized,
vertical
ODM
Export
Trial Design
Extraction,
Transformation,
Loading
Shared
value-level
ODM metadata
Standard
Analysis
SDTM
ADaM
Analysis &
Submission
Database;
Denormalized
partially horizontal
What is the ODM?
• ODM is a standard for representing clinical
trials data - CRF data as well as data
tabulations (SDTM) - to support data
interchange and archive.
• Specification of an XML standard for
describing clinical trials data that is vendor
neutral, platform independent & ensures 21
CFR Part 11 compliance (audit trailing,
electronic signatures, etc.)
4
Why XML?
•
•
•
•
Well suited for clinical data software systems
Vendor neutral
Platform independent, flexible
Designed for interchange of data between
heterogeneous systems
• Files can be automatically checked for
syntactical, structural and semantic
correctness (with XML schemas)
• Easy to transform in PDF and other formats
5
ODM Advantages
• Single format provides all components needed to
describe clinical research data with attribution
requirements mandated by regulatory agencies.
• Reduces the number of unique file formats a
clinical application needs to support.
• The ODM provides features that can improve the
integrity and reliability of clinical data interchange.
• Flexibility in design means ODM can be adapted to
any clinical research application where clinical data
is needed.
6
History
CDISC Volunteer
Group
1997
CDISC
Europe
DIA SIAC
Formed
CDISC
Incorporated
1998
2000
1999
ODM
Certification
Program
Define.XML
guidance
CDISC
Japan
2001
ODM V1.0
SDTM into
guidance
2002
ODM V1.1
2003
2004
ODM V1.2
2005
2006
ODM V1.3
7
ODM Certification Program
• Was introduced by CDISC in September 2006 at
the 3rd Interchange Meeting in Bethesda
• Independent testing procedures aimed at
eliminating variability in ODM toolsets and at
ensuring consistency in interoperability between
ODM implementations
• The first official certification logos for full
compliance with ODM were received by XClinical
(EDC system “MARVIN”) and Datalabs (acquired
by Clinphone)
8
ODM Use Cases (1/2)
• 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
9
ODM Use Cases (2/2)
• Automatic set up of EDC / CDM systems
• Data Acquisition
– eCRF
– ePRO
– EHR
• eSource
• Submission of CRF raw data (ODM XML files)
• Submission of SDTM data (ODM XML files
instead of SAS transport files)
10
Use Case: Data Interchange
A
t
i
a
t
d
a
u
D
ODMA
a
XML at
D
a
et
M
B
• One of the original use cases for the model
• Ability to interchange Metadata and / or
Clinical Data
11
ODM: MetaData
Site Details
Site No.:_______
Subject's Characteristics
Number:_______
Sex:
M []
F[]
Height: _________ cm
M
D
a
t
e
a
t
a
ODM
XML
Weight: _________ kg
12
ODM Metadata XML elements
Study
MetaDataVersion
Protocol
StudyEventDef
FormDef
ItemGroupDef
ItemDef
13
ODM: Data
Site Details
Site No.:___5___
Subject's Characteristics
Number:__12___
Sex:
M [Y]
F[]
D
a
t
a
ODM
XML
Height: ___156__ cm
Weight: ___87.2___ kg
14
ODM Data XML elements
ClinicalData
SubjectData
StudyEventData
FormData
ItemGroupData
ItemData
15
Clinical Data Keys
@ StudyOID
attributes
ClinicalData
@ SubjectKey
attributes
SubjectData
@ StudyEventOID
attributes
@ StudyEventRepeatKey
StudyEventData
@ FormOID
attributes
@ FormRepeatKey
FormData
@ ItemGroupOID
attributes
ItemGroupData
@ ItemGroupRepeatKey
@ ItemOID
attributes
ItemData
16
Example traditional data file
• Traditional Approach
Site Details
Site No.:___5___
Subject's Characteristics
Number:__12___
Sex:
M [Y]
Data
12,5,M,87.2,156
F[]
Height: ___156___ cm
Weight: ___87.2___ kg
17
Example ODM data file
• ODM
<ItemGroupDef OID="IG_COMMON" Repeating="No" SASDatasetName="COMMON" Name="Common" Domain="DM">
<ItemRef ItemOID="I_SITE" Mandatory="Yes" OrderNumber="1"/>
Metadata
<ItemRef ItemOID="I_SUBJECTID" Mandatory="Yes" OrderNumber="2"/>
<ItemRef ItemOID="I_SEX" Mandatory="Yes" OrderNumber="3"/>
</ItemGroupDef>
<ItemGroupDef OID="IG_PE" Repeating="No" SASDatasetName="PHYEXBAS" Name="Physical Exam" Domain="VS">
<ItemRef ItemOID="I_HEIGHT" Mandatory="Yes" OrderNumber="1"/>
<ItemRef ItemOID="I_WEIGHT" Mandatory="Yes" OrderNumber="2"/>
</ItemGroupDef>
…….
<ItemDef OID="I_HEIGHT" Name="Height" DataType="integer" SDSVarName="VSORRES" Length="3"
SASFieldName="HEIGHT">
<Question>
<TranslatedText xml:lang="en">Height</TranslatedText>
</Question>
<MeasurementUnitRef MeasurementUnitOID="MU_CMS"/>
Data
</ItemDef>
……...
<SubjectData SubjectKey="SUBJECT_12" TransactionType="Insert">
<StudyEventData StudyEventOID="BASELINE">
<FormData FormOID="F_BASELINE">
<AuditRecord>
<UserRef UserOID="USER_2"/>
<LocationRef LocationOID="LOCATION_2"/>
<DateTimeStamp>2005-05-23T07:30:16.000+01:00</DateTimeStamp>
<ReasonForChange>Initial Entry</ReasonForChange>
</AuditRecord>
…
<ItemGroupData ItemGroupOID="IG_PE_BASE">
<ItemData ItemOID="I_HEIGHT" Value=“156“/>
<ItemData ItemOID="I_WEIGHT" Value=“87.2“/>
</ItemGroupData>
18
Use Case: Audit & Archive
Site Details
Site No.:___5___
Subject's Characteristics
Number:__12___
Sex:
M [Y]
F[]
156
Height: ___1560__ cm ABC
1/1/2005
Weight: ___87.2___ kg
D
a
t
a
u
A
t
i
d
ODM
XML
19
ODM elements for Audit & Archive
ItemData
attributes
Archive
@ ItemOID
@ TransactionType
AuditRecord
attributes
@ Value
UserRef
LocationRef
@ EditPoint
@ IsNull
@ UsedImputationMethod
DateTimeStamp
Who
ReasonForChange
What
SourceID
When
Signature
Why
MeasurementUnitRef
Annotation
20
ODM: Administrative
Site Yellow
m
d
A
in
ODM
XML
Doctor Green
21
Use Case: Set up of EDC/CDMS
ODM
XML ata
D
a
et
M
• Use of the ODM Metadata to configure tools
• eCRF systems
– Several vendors using ODM-based mechanisms
• eDiary systems
– At least one system uses ODM for configuration
purposes
• ODM Version 1.3 developed to include additional
support
22
Association of CROs
http://www.acrohealth.org/
23
Practical Experience
1. ACRO
Standard Form
4. Annotated Form +
ODM Standard =
Standard electronic
metadata (XML)
<ODM>
<Study>
<Meta…
</Meta…
</Study>
</ODM>
3. ACRO Form +
CDISC SDTM
Standard =
Annotated Form
2. CDISC SDTM
Standard
5. Standard
electronic
metadata
configures
collection system
24
Electronic Configuration (ACRO)
25
Electronic Configuration (ACRO)
Courtesy of Assero
26
Electronic Configuration (ACRO)
Courtesy of Formedix
27
Electronic Configuration (ACRO)
Courtesy of XClinical
28
Electronic Configuration (ACRO)
Courtesy of XML4Pharma
29
Electronic Configuration (ACRO)
Courtesy of Outcome
30
Acquisition
Sponsor
EDC
Site A
EHR
Site B
Paper
Site C
31
Acquisition
• ODM allows for
integration of
multiple data
sources
Sponsor
a
t
a
D
ODM
XML
M
D
O
EDC
Site A
EHR
Site B
Paper
Site C
32
eSource
• Investigator is obliged to
– Maintain source data (accurate)
– Retain source data
– Prevent its destruction
– Allow access to inspectors
t
i
d
a
t
u
a
A
D
ODM
a
t
XML a
D
a
et
M
Sponsor
ODM Electronic
XML Source
33
ODM for Submission of CRF data
ODM
XML
M
D
e
D
a
t
a
t
a
XSLT
Transformation
a
t
a
ODM
XML
t
i
d
u
A
XSLT
Transformation
34
FR / Vol. 72, No. 48 / Tuesday, March
13, 2007
ed
t
a
Upd
35
ODM for Submission of SDTM data
• The FDA is developing an electronic
submissions review environment based on
CDISC Submission Standards
– Current environment based on 1999
eSubmissions Guidance
– Define.pdf – Metadata documentation
– SAS Transport Files – for CRTs
• Seek to gain efficiencies through use of
standard tools & implementation of Janus
data warehouse
36
Submission components
• Submission MetaData
– Currently uses PDF mechanism – Define.PDF
– ODM version – Define.XML
• Submission Datasets
– Currently SAS XPORT Transport (XPT)
– ODM support being developed
• CRF Data and Audit Trail
– Currently paper or PDF
– CDISC ODM (pilot phase)
• Annotated CRF
– Currently PDF
– CDISC ODM (pilot phase)
Based on a Slide by Randy Levin, M.D. Director for Health and Regulatory Data Standards, FDA,
November 2004, DIA Meeting, Amsterdam
37
Submission guidances
http://www.fda.gov/cder/regulatory/ersr/ectd.htm
38
Submission guidances
• Study Data Tabulation Model (SDTM)
– Referenced in FDA Guidance as of 21 July 04
• Federal Register announcement
– Department of Health and Human Services, Semiannual Regulatory
Agenda (26818 Federal Register / Vol. 70, No. 93 / Monday, May 16,
2005 / Unified Agenda)
– “The proposal would revise our regulations to require that CSD
[Clinical Study Data] submitted for NDAs, ANDAs, BLAs, and their
supplements and amendments be provided in electronic format and
require the use of standard data structure, terminology, and code
sets.”
• Define.XML
– Referenced in FDA Guidance as of 18 March 05
• Federal Register announcement
– Federal Register / Vol. 70, No. 209 / Monday, October 31, 2005 /
The Regulatory Plan
39
Define.XML =
M
e
D
D
a
t
a
t
a
SDTM metadata in ODM
format
a
t
a
CRF
t
i
d
Au
M
e
D
a
t
a
t
a
SDTM
Define.XML
ODM XML
40
Define.XML
• Schema -- uses new ODM schema extension
methdology
– Def namespace
• Extends ItemGroupDef & ItemDef to meet all SDS
metadata requirements
• Borrows leaf/xlink mechanism from eCTD to
include external files:
– Annotated CRF
– SAS Transport Files
• Anticipates Analysis file needs – provides measure
specific metadata
41
SDS Domain MetaData in define.xml
•
•
•
•
•
•
Dataset Name – ItemGroupDef Domain
Description – ItemGroupDef Name
Location – extended attribute
Structure – extended attribute
Purpose – ItemGroupDef Purpose
Key Fields – extended attribute
42
SDS Variable MetaData in define.xml
•
•
•
•
•
•
•
Variable Name – ItemDef Name
Variable Description – Extension (def:label)
Type – ItemDef DataType
Format – ItemDef CodeListRef
Origin – ItemgDef Origin
Role – ItemRef Role
Comments – ItemDef Comment
43
SDS Value Level MetaData
VSTestCD
VSTest
VSORRES
Datatype
HGTIN
Height in inches
65
Integer
WGTLB
Weight in pounds
125
Integer
HGTCM
Height in cm
178
Float/Derived
WGTCM
Weight in kg
54
Float/Derived
BMI
BodyMassIndex
20
Float/Derived
44
SDS Value-level MetaData in define.xml
• TESTCD – ItemDef OID
• TEST – ItemDef attribute (def:label)
• etc.
45
The Next Step
M
et
D
aD
a
t
a
a
t
a
M
CRF
t
i
d
Au
et
aD
a
t
a
D
a
t
a
SDTM SDTM
Define.XML
?
ODM XML
46
ODM as the Backbone
CRO
Sponsor
ODM
Investigator
Subject
LABs
47
About the speaker
• XClinical, founded 2002, is an EDC-CDM vendor with
offices in Munich, Paris and Cambridge, US.
• Active member of CDISC
• MARVIN is our online, integrated EDC-CDM System
Ø GCP system validated, 21 CFR 11 compliant
Ø ODM certified
• ODM study composer, SDTM tabulator tool
• 44+ studies, 45.300+ patients
Thank you
• Questions?
• Contact
– [email protected]
– Tel. +49 89 4522775100