August 29, 2005

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August 29, 2005
Clinical Trial Management Systems Workspace
Update on Adverse Event SIG Activities
Joyce C. Niland, PhD Chair and
Professor, Information Sciences City of Hope
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Adverse Event SIG Update

• AE SIG Activities
• COH caAERS Activities
• Next Steps for caAERS
• Group Exercise

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caBIG Adverse Event Reporting System (caAERS)

• Creation of tools for the capture of adverse
  events that occur during clinical trials
• Reporting of these events to individuals and
  organizations responsible for the conduct of
  trialsand for patient safety
• 12 modules
• Configurable for cancer centers with minimal data
  management systems in place, and those with
  established systems
• Production release of Modules 1-4 March 2006

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caBIG Desiderata

• Open access, open source software
• Derived from common information models
• Uses standards for data exchange formats
• Data and metadata follow ISO/IEC 11179
• Consume appropriate public, open access standards
  when available

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caBIG Adverse Event Reporting System(caAERS)

• Goal
• Open source shareable software system to
  provideuniform expedited reporting of AEs across
  trials
• Challenges
• Open source software development
• Soliciting and considering nationwide input
• Incorporating national/international standards
• Interfacing with in-house and vendor-based
  systems
• Including Cancer Center, sponsor agency
  perspectives
• Project with large community of stakeholders

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Adverse Event SIG Participants

• Donna Marlatt Dartmouth
• Bill Banks Duke
• Sharon Elcombe Mayo
• Lori Wangsness Mayo
• John Speakman MSKCC
• Doug Fridsma UPCC
• Sorena Nadaf Vanderbilt
• Bob Morrell Wake Forest
• Rhoda Arzoomanian Wisconsin
• Prakash Nadkarni Yale
• Kim Klingler SAIC

• Joyce Niland Lead, COH
• Doug Stahl Co-Lead, COH
• Caroline Song COH
• Cindy Stahl COH
• Susan Pannoni COH
• Scott Finley BAH
• Brenda Duggan NCI
• Beverly Meadows NCI
• Erin Itturiaga NCI
• Diane Paul CARRA
• Ann Setser CTEP

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Dimensions Impacting caAERS
External Forces
FDA NCI DCP, DCPD, CTEP HIPAA, Sponsors Theradex P
atients PIs MDs Patients Sponsors Mo
nitors CRAs IRBs NCI
F U N C T I 0 N A L I T Y
HL7 CDISC ICH XML ISO CFR
CDUS GeMCRIS
Existing Systems
Standards
ACES
MEDRA SNOMED CDE CTCAE
AdEERS CSAERS
End Users
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Comparison of Existing AE-Related Systems ACES
AdEERS CDUS CSAERS GeMCRIS
MedWatch
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Objectives in Developing caAERS

• Simplify, standardize, and unify AE reporting
  process while making the process as efficient as
  possible
• Capture and evaluate AEs
• Route AE report internally for sign-off
• Submit data externally for regulatory reporting
• Provide automated decision support for AE coding
• Allow public entry and query of AE related
  information
• Provide for data mining of AEs aggregated in a
  national data warehouse

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Componentized Approach to caAERS
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Componentized Approach to caAERS
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Public SafetyProfiling Website
CTC RelatedLab Data
CTC RelatedQualitative Data
Clinical Trial Participants
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Safety Profiler
Grade 1- 5 AEs
Automated CTC Grading
caBIG Adverse Event System (AES)
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1
3
AE Data
Patient/Protocol Data
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Transmission to External Agencies
Internal Routingand Review
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Publication of Summary Results
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IRB
PI/CRA
PatientSelf-Reporting
DSMB Monitor
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Data Mining forRisk Patterns
Transmission to caBIG AE Data Warehouse
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AE SIG Mission and Goals
Quarter 1

• Contribute to User Requirements for AERS
• Review and Discuss Draft User Requirements
  Artifacts
• Contribute to the Identification of elements and
  demographics for a Structured Protocol
  Representation (SPR) as required for AE Data
  Capture and Reporting

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AE SIG Mission and Goals
Quarter 2

• Discuss/Resolve Issues related to AE Data
  Capture and Reporting
• Discuss/Resolve Issues related to SPR Data
  Elements required for AE Data Capture and
  Reporting and provide feedback to SPR SIG
• Validate User Requirements for AERS Modules and
  work with caAERS Team to finalize

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AE SIG Mission and Goals
Quarter 3

• Review Design Documents for caAERS Modules
• Validate caAERS Module Design against User
  Requirements
• Validate caAERS design elements related to SPR
  (communicating with SPR SIG and development team)

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AE SIG Mission and Goals
Quarter 4

• Monitor Alpha Deployment of caAERS Modules 1-4
• Review initial Test Status and Feedback from
  Adopters of the Alpha Deployment of caAERS
  Modules 1-4
• Provide User Feedback from Initial Deployment
  related to the structured protocol elements to
  the SPR SIG and development team

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Acquiring User Requirements

• Conducted interviews with groups of users
  including clinical trials management teams and
  regulatory staff at cancer centers, clinical
  trials sponsors, cooperative groups, patient
  advocates, and federal agencies
• Draft set of user requirement specifications was
  developed including business process diagrams,
  data flow scenarios, use cases, and high level
  class diagrams
• Reviewed and validated with larger community

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Interviews and Collaboration

• As issues emerged, entered into an Issues Log and
  distributed to SIG members for discussion
• Issue resolutions documented and changes
  incorporated into the requirements specs
  (WebBoard)

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Use Case Diagrams
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Detailed Use Cases
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Use Case-Driven Data Dictionary

• Data elements derived and reconciled via use cases

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Activity Diagrams
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Validation of caAERS AE Management Triggers
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caBIG AE Reporting System (caAERS)
Occurrenceof AdverseEvent withinCancer
Center trial
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HL7 RCRIM-CDISC-caBIG Domain Analysis
ModelBiomedical Research IntegratedDomain
Group (BRIDG) Model

• Bridging the.
• Biomedical Research Standards
• HealthcareStandards

• Organizations
• Stakeholders
• Communities

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Where BRIDG Fits in World of Standards
International Conference on Harmonization (ICH)
US FDA
Japan MHW
EU EMEA
Pharmaceutical Industry EU USA
Japan EFPIA PhRMA JPMA
REGULATORY AUTHORITIES
Health Care Providers Pharmacies - NCPDP
BRIDG
Clinical Trials
Standards HL7, XML
Dictionaries MedDRA, LOINC
Models NCI, OMG
(Adapted from Rebecca Kush, CDISD)
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How do I create an application based on BRIDG?
Version 1
Version 2
Version 3
BRIDG trunk
Version 1
V 1.1
V 1.2
V 1.3
V 1.3
V 1.3
Harmonization branch
caAERs development branch
caERs 1.1
caERs 1.2
caERs 1.3
caERs 1.4
eDCI development branch
eDCI 1.1
eDCI 1.2
eDCI 1.3
eDCI 1.2
eDCI 1.3
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Biomedical Research
Integrated Domain Group (BRIDG) Model
caAERS
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How do I create an application based on BRIDG?
Version 1
Version 2
Version 3
BRIDG trunk
Version 1
V 1.1
V 1.2
V 1.3
V 1.3
V 1.3
Harmonization branch
CAERs development branch
caERs 1.1
caERs 1.2
caERs 1.3
caERs 1.4
eDCI development branch
eDCI 1.1
eDCI 1.2
eDCI 1.3
eDCI 1.2
eDCI 1.3
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Harmonization Process of Subcomponents of the
BRIDG Model
caAERS
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Expert HL7 Modeling Consultant
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Chain of Information Models

• Reference Model
• Anatomic framework model, e.g. HL7 RIM to BRIDG
• Domain Analysis Model (DAM)
• Allows domain experts to communicate with
  programmers
• Conceptual ? Abstract ? Logical DAMs
• Message Design Model
• Converts model into a messaging schema, e.g.
  Domain Message information Model (DMIM), XML
  Schema Definition
• Database Design
• Results in Conceptual, Logical, Database, and
  Physical Design Models (CDM, LDM, DDM, PDM)

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Chain of Information Models
Logical DomainAnalysis Model (LDAM)
Abstract Domain Analysis Model (ADAM)
Conceptual DomainAnalysis Model (CDAM)
Derived directly from the user requirements
specified by theUse Cases and vocabulary
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Logical Sub-Domain Analysis Model
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Harmonization with Related Projects Individual
Case Safety Report (ICSR)
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Impact on HL7 RIM Already!

• Discovered two attributes in AE domain with no
  appropriate RIM attribute within ActRelationship
  Class to describe them
• Expectedness
• Attribution
• Requires an attribute of probability (certainty
  or uncertainty)
• Needed for traceability back to the AE SIG Use
  Cases
• In early August, AMS reported that this new
  attribute had been added per this example, and
  other similar ones brought to HL7

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Activities of AE SIG Since April, 2005

• Feedback on data elements for AE management and
  reporting
• Feedback on touch points of AEs and the Study
  Calendar
• Storyboards and prioritization of remaining
  caAERS modules
• Verification and validation of caAERS requirement
  artifacts
• Specification of caAERS workflow processes

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Next Steps for caAERS Development

• Vet the caAERS LSDam with the BRIDG team
  following the HL7 meetings in September
• Complete the physical design framework (first
  draft created)

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Next Steps for caAERS Development

• Vet the caAERS LSDam with the BRIDG team
  following the HL7 meetings in September
• Complete the physical design framework (first
  draft created)

• Iterative development phase with ongoing input
  from 2 Adopter Sites
• Production level code for caAERS Modules 1-4
  by end of caBIG Year 2 (March 2006)
• Rapidly move to additional modules envisioned

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Thank You to All SIG Participants!

• With special thanks to the following SIG members
  and their fellow staff members

• Bill Banks (Duke)
• Linda Doody (DCP)
• Brenda Duggan (NCI)
• Sharon Elcombe (Mayo)
• Kim Klingler (SAIC)
• Cecil Lynch (UCD)

• Donna Marlatt (Dartmouth)
• Bev Meadows (DCP)
• Bob Morrell (Wake Forest)
• Diane Paul (CARRA)
• Ann Setser (CTEP)
• John Speakman (MSK)

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Questions?
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GroupExercise