# Presentation: 193982

## August 29, 2005

***Joyce C. Niland, PhD***
***Chair and Professor,***
***Information Sciences***
***City of Hope***

***Clinical Trial Management Systems Workspace:******  Update on Adverse Event SIG Activities***

## Adverse Event SIG Update 

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

## 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**

## 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

## 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

## Adverse Event SIG Participants:

- 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

- 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

## Dimensions Impacting caAERS

**Dimensions Impacting caAERS**

** **HL7 CDISC  ICH XML ISO CFR                              	        CDUS  GeMCRIS**  ****	**

- FDA
- NCI DCP,
- DCPD, CTEP
- HIPAA, Sponsors
- Theradex
- Patients
- PIs  MDs
- Patients
- Sponsors
- Monitors
- CRAs
- IRBs
- NCI

- MEDRA SNOMED CDE CTCAE                              	      AdEERS CSAERS

***Standards***

*** ******Existing***
***Systems***

***End Users***

***External Forces***

- F
- U
- N
- C
- T
- I
- 0
- N
- A
- L
- I
- T
- Y

- ACES

## Comparison of Existing AE-Related Systems:

**	****ACES****	****  AdEERS        CDUS        CSAERS         GeMCRIS         MedWatch**
**                **

## 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

## Componentized Approach to caAERS:

**Componentized Approach to caAERS:**

## Componentized Approach to caAERS:

- Clinical Trial Participants

**Componentized Approach to caAERS:**

**Grade 1- 5 AEs**

- AE Data

***Safety Profiler***

- PatientSelf-Reporting

- Patient/Protocol Data

**caBIG Adverse Event System (AES)**

- CTC RelatedLab Data

- CTC RelatedQualitative Data

- Automated CTC Grading

- Public SafetyProfiling Website

- Data Mining forRisk Patterns

- Transmission to External Agencies

- Internal Routingand Review

- DSMB Monitor

- IRB

- Transmission to
- caBIG AE Data Warehouse

- Publication of Summary  Results

- PI/CRA

**#1**

**#2**

**#4**

**#5**

**#6**

**#7**

**#8**

**#3**

**#9**

**#10**

**#11**

**#12**

## AE SIG Mission and Goals

-  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

_**Quarter 1**_

## AE SIG Mission and Goals

**AE SIG Mission and Goals**

-  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

_**Quarter 2**_

## AE SIG Mission and Goals

- Validate caAERS Module Design against User   Requirements
- Validate caAERS design elements related to SPR (communicating with SPR SIG and development team)

**AE SIG Mission and Goals**

_**Quarter 3**_

## AE SIG Mission and Goals

- 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

**AE SIG Mission and Goals**

_**Quarter 4**_

## 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

## Interviews and Collaboration

**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)

## Use Case Diagrams

**Use Case Diagrams**

## Detailed Use Cases

## Use Case-Driven Data Dictionary

**Use Case-Driven Data Dictionary**

- Data elements derived and reconciled via use cases

## Activity Diagrams

**Activity Diagrams**

## Validation of caAERS AE Management Triggers

**Validation of caAERS AE Management Triggers**

##    caBIG AE Reporting System (caAERS)

**   ****caBIG AE Reporting System (caAERS)**

***Occurrence******of Adverse******Event within******C******ancer Center***
***trial***

## HL7 RCRIM-CDISC-caBIG Domain Analysis Model:Biomedical Research IntegratedDomain Group (BRIDG) Model

- Bridging the....
-         Biomedical     Research     Standards
- HealthcareStandards

-                   Organizations
-            Stakeholders
- Communities

## Where BRIDG Fits in “World of Standards”

- Standards:
- HL7, XML

- Dictionaries:
- MedDRA, LOINC

- Clinical Trials

- International
- Conference on
- Harmonization (ICH)

- Pharmaceutical Industry
-    EU       USA      Japan
- EFPIA   PhRMA   JPMA

**Where *****BRIDG***** Fits in “World of Standards”**

- US
- FDA

- EU
- EMEA

- Japan
- MHW

*REGULATORY AUTHORITIES*

- Health Care Providers
- & Pharmacies - NCPDP

- Models:
- NCI, OMG

***BRIDG***

- (Adapted from Rebecca Kush, CDISD)

## How do I create an application based on BRIDG?

- Version 1

- Version 2

- Version 3

**BRIDG trunk**

**Harmonization**
**branch**

**caAERs **
**development**
**branch**

**eDCI development**
**branch**

- Version 1

- V 1.1

- V 1.2

- V 1.3

- V 1.3

- caERs 1.1

- caERs 1.2

- caERs 1.3

- eDCI 1.1

- eDCI 1.2

- eDCI 1.3

- caERs 1.4

- V 1.3

- eDCI 1.2

- eDCI 1.3

## Slide 27

## Slide 28

## 			           Biomedical Research Integrated	Domain Group (BRIDG) Model

- 			           **Biomedical Research Integrated****	****Domain Group (BRIDG) Model**

- caAERS

## How do I create an application based on BRIDG?

- Version 1

- Version 2

- Version 3

- BRIDG trunk

- Harmonization
- branch

- CAERs
- development
- branch

- eDCI development
- branch

- Version 1

- V 1.1

- V 1.2

- V 1.3

- V 1.3

- caERs 1.1

- caERs 1.2

- caERs 1.3

- eDCI 1.1

- eDCI 1.2

- eDCI 1.3

- caERs 1.4

- V 1.3

- eDCI 1.2

- eDCI 1.3

## caAERS

**Harmonization Process of Subcomponents of the BRIDG Model**

## Expert HL7 Modeling Consultant

**Expert HL7 Modeling Consultant**

## 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)

## Slide 34

## Chain of Information Models

**Conceptual Domain****Analysis Model (CDAM)**

**Derived directly from the user ****requirements specified by the****Use Cases and vocabulary**

**Chain of Information Models**

**Abstract Domain**** Analysis Model (ADAM)**

**Logical Domain****Analysis Model (LDAM)**

## Logical Sub-Domain

***Logical Sub-Domain***
***Analysis Model***

## Harmonization with Related Projects: Individual Case Safety Report (ICSR)

## 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

##        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

## 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)

## Slide 41

## 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

## 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)

## Questions?

## GroupExercise