# Presentation: 493337

## The cancer Biomedical Informatics Grid (caBIG):  Enabling the patient-centric molecular medicine revolution

- J. Robert Beck, M.D.
- Fox Chase Cancer Center
- R. Mark Adams, Ph.D.
- Booz Allen Hamilton

## Talk Agenda

**caBIGTM, A Cancer Center Perspective**
**Program Motivations**
**Development of the Program**
**Program Structure and Process**
**Program Timeline and Products**
**Example Program Product: C3D**
**Panel Discussion**

## Talk Agenda

**caBIGTM, A Cancer Center Perspective**
**Program Motivations**
**Development of the Program**
**Program Structure and Process**
**Program Timeline and Products**
**Example Program Product: C3D**
**Panel Discussion**

## A Focus on Interaction

## Scenario, 2008

- 	A researcher involved in a phase II clinical trial of a new molecularly targeted therapeutic for brain tumors observes that cancers derived from one specific tissue progenitor appear to be strongly affected.  The trial has been generating proteomic and microarray data.  The researcher would like to identify potential biochemical and signaling pathways that might be different between this cell type and other potential progenitors in cancer, deduce whether anything similar has been observed in other clinical trials involving agents known to affect these specific pathways, and identify any studies in model organisms involving tissues with similar pathway activity.

- Small Molecules

- Cell Type

- Pathways

- Clinical Trials

- Therapeutics

- Animal Models

- Homologous Proteins

## Today vs 2008?

- 	In 2005 such a study would involve immense manual work getting information locally and from other sites, precluding the possibility of identifying the required data and thus being unable to deduce the likely significance of the trial observation.

- However, with caBIGTM compliant components now under development, the researcher would be able to perform the analysis routinely, with data flowing through systems and analysis being automatic.  This analysis will yield biomarkers and potential drug targets gathered from multiple workspaces and make it possible to develop treatment modalities faster, less expensively, and more effective for patients.

## CTMS Workspace

- Pathology
- reports

- Discrete and manual annotation on tissues

- Mutation
- identification

- Gene expression profiling

- Analysis

**Potential Drug Targets and Biomarkers**

- Clinical Trials Tumor Samples

- 400 brain tumor tissue samples acquired

- caArray

- FunctionExpress

- Gene
- annotation

- Gene
- Pattern

- Promoter
- DB

- Pathways
- Tool

- caTissue

- caTIES

- Clinical Annotation Modules

- Proteomics LIMS

- Q5

- PIR

- Annotation

- Discovery utilizing caBIGTM
- Integrated Cancer Research Tools

- Identify up-regulated genes in specific pathways

- TrAPSS

- Identify recurring promoter elements

## Overall Goals for caBIGTMThree-year (mid-2008)

- Develop sufficient research tools and standards to have a positive impact on the cancer research community, as measured by adoption of relevant caBIG principles in project proposals.
- Ensure widespread adoption of developer standards so that funded developer projects are operating under the Gold standard of compatibility.
- Adopt and use caBIG interoperable tools and data sets within the caBIG community.
- Develop mechanisms for engaging and promoting caBIG compliant technologies and established datasets within the oncology research community.

## Overall Goals for caBIGTMFive-year (mid-2010)

- Ensure widespread adoption, dissemination, and use of caBIG interoperable tools, standards, and data sets within the larger cancer community, to include the biopharmaceutical industry, non-NCI cancer centers, and the national cancer research enterprise.
- Begin to see results of caBIG-compliant interdisciplinary and inter-institutional research affecting clinical oncology care.

## What does caBIG mean to the Cancer Centers?

- Product—in CTMS, ICR, Tissue Banking
- Support for large scale collaborative research
- No need to “go it alone” with bioinformatics or other quantitative support tools

## Clinical Trials Management:  Three Levels of Interaction Based on Institutional Readiness

**New caBIG modules**

**Existing System:**
**Change Imminent**

**exchange data**

**caBIG Open Source**
**Core Functionality**

**Interoperable**
**caBIG Community**

**No Existing System**

**C3D Adoption**

**Additional**
**Functionality**

**Existing System:**
**No Change**

**caBIG compatibility**
**efforts with vendor**

**Additional**
**Functionality**

## What does caBIG offer the Cancer Center for Clinical Trials Management?

**Cancer Center Clinical Database or C3D – available today**** **
**Adverse Event Reporting or caAERS – available 1****st**** Qtr 2006**** **
**Clinical Trial Structured Protocol Representation (BRIDG) – available (in draft) now**** **
**Key is to understand the workflows to support clinical trials and choose a starting point for use of caBIG tools**

## Tools for Translational Research

- caBIG Compatibility Guidelines
- 3 year plan:  all tool development at Gold level
- Successful Developer-adopter relationships
- Extension to other research areas
- Imaging
- Population Science

## ICR Software Maturity Table

|  | Maturity Level | Description |
| --- | --- | --- |
| 1 | Basic research/Design | The key concepts for the system have been defined, algorithms outlined, use cases documented, requirements and specification document(s) prepared.  |
| 2 | Prototype/Proof of Principle | A semi-functional system has been implemented for the purpose of getting feedback from potential end-users on the execution of the design. |
| 3 | First working implementation (“beta”) | System has gone through at least one round of testing by end users and some feedback has been incorporated.  System is in trial use by a limited number of users.  Only intended for limited distribution by users in close contact with the development team. |
| 4 | Deployed and in use | System has gone though a thorough beta test and is deployed and in use at at least one site.  Additional sites may deploy the software with possible assistance from the development team. Initial user and developer guides are available.  Known defects are documented.   |
| 5 | Post deployment and maintenance | System is readily deployed by any interested party with no assistance from the development team.  Known defects are documented.  Mature user and developer guides are available as well as training materials.   |

## Cancer Center Roles in caBIG

**Developer (20% of centers)**
**Key is to create an environment for sharing tools with other centers**
**One of the most important issues is not to ignore the need for common data elements and vocabulary services**
**Adopter (20% of centers)**
**Key is to understand the needs at local center (and be vocal)**
**Don’t abandon other development efforts; think modular**
**When adopting tools make sure they “talk” to legacy systems**
**Working Group & Strategic Planning (60% of centers)**
**These are not “soft” roles**
**Critical to the success of the program**
**White paper development will guide caBIG successes**
**Make sure to communicate internally to all parts of the Cancer Center**

## caBIG Compatibility

- What does caBIG “compatibility” mean to CC
**caBIG is all about Interoperability**
**Key is to create tools for sharing info with other centers**
**Not an easy task due to “silo” mentality**
**CDEs and EVS enable common language and data values**
**Software design principles ensure cross compatibility of developed software**
**Extensible infrastructure**
**Expandable and modular software to plug in to existing systems so current development efforts are not wasted**
**Scalable so that efficiency is gained by software engineering**
**Ensures partnerships**
**Built on commercial software development principles**
**Encourages relationships between academia, government and industry**
**Scalable so that commercial partners can utilize “open source”**

## Talk Agenda

**caBIGTM, A Cancer Center Perspective**
**Program Motivations**
**Development of the Program**
**Program Structure and Process**
**Program Timeline and Products**
**Example Program Product: C3D**
**Panel Discussion**

## The NCI 2015 challenge goal:... eliminate suffering and death due to cancer

- “When I look into the eyes of a patient losing the battle with cancer, I say to myself, It doesn’t have to be this way.”Dr. A.C. von Eschenbach, M.D.Director, National Cancer Institute
*The Nation’s Investment in Cancer Research* (2003)

## NCI biomedical informatics

***Goal:*** A virtual web of interconnected data, individuals, and organizations redefines how:
- research is conducted
- care is provided
- patients/participants interact with the biomedical research enterprise

## Biomedical information tsunami

- overwhelming volume of data
- multitude of sources

## Informatics tower of Babel

- Each cancer research community speaks its own scientific “dialect”
- Integration critical to achieve promise of molecular medicine

## Talk Agenda

**caBIGTM, A Cancer Center Perspective**
**Program Motivations**
**Development of the Program**
**Program Structure and Process**
**Program Timeline and Products**
**Example Program Product: C3D**
**Panel Discussion**

## cancer Biomedical Informatics Grid

- Common, widely distributed infrastructure permits cancer research community to focus on innovation
- Shared vocabulary, data elements, data models facilitate information exchange
- Collection of interoperable applications developed to common standard
- Raw cancer research data is available for mining and integration

## caBIG principles

- Open source
- Open access
- Open development
- Federated

## Current caBIG community

- NCI-designated Cancer Centers (50)
- Academic Centers (integrated into broader biomedical infrastructure)
- Stand-alone (community leaders)
- Community outreach
- Government
- Industry
- International Groups
- >700 active participants

## caBIG action plan

- Establish  pilot network of NCI Cancer Center
- Groups agreeing to caBIG principles
- Mixture of capabilities
- Mixture of contributions
- Expanding collection of participants
- Establish consortium development process
- Collecting and sharing expertise
- Identifying and prioritizing community needs
- Expanding development efforts
- Moving at the speed of the internet...

## caBIG: a new way of doing business...

**Coordinated development**
**Active management**
**Community directed**
**Common services**

## Slide 28

## Common needs helped shape priority areas for the caBIG pilot activities 

- 0

- 5

- 10

- 15

- 20

- 25

- 30

- 35

**Clinical Data Management Tools**

- Staff Resources

**Distributed Data Sharing/Analysis Tools**

**Translational Research Tools**

**Access to Data**

**Tissue & Pathology Tools**

- Center Integration & Management

- Common Data Elements & Architecture

- Meta-Project

- Vocabulary & Ontology Tools & Databases

- Statistical Data Analysis Tools

- Visualization & Front-End Tools

- Remote/Bandwidth

**Proteomics**

**Microarray & Gene Expression Tools**

- Meeting

- LIMS

- Licensing Issues

**Pathways**

- High Performance Computing

- Integration

- Imaging Tools & Databases

- Database & Datasets

**Number of Needs Reported**

**Clinical Trial Management Systems**

**Tissue ****Banks ****& Pathology**

**Integrative Cancer Research**

## Talk Agenda

**caBIGTM, A Cancer Center Perspective**
**Program Motivations**
**Development of the Program**
**Program Structure and Process**
**Program Timeline and Products**
**Example Program Product: C3D**
**Panel Discussion**

## Slide 31

## Four Domain Workspaces and two Cross Cutting Workspaces have been launched

**DOMAIN WORKSPACE 3**
**Tissue Banks & Pathology Tools**

- provides for the integration, development, and implementation of tissue and pathology tools.

**DOMAIN WORKSPACE 2**
**Integrative Cancer Research**

- provides tools and systems to enable integration and sharing of information.

**DOMAIN WORKSPACE 1**
**Clinical Trial Management Systems**

- addresses the need for consistent, open and comprehensive tools for clinical trials  management.

**CROSS CUTTING WORKSPACE 2**
**Architecture**

- developing architectural standards and architecture necessary for other workspaces.

**CROSS CUTTING WORKSPACE 1**
**Vocabularies & Common ****Data Elements **

- responsible for evaluating, developing, and integrating systems for vocabulary and ontology content, standards, and software systems for content delivery

**DOMAIN WORKSPACE 4**
**Imaging**

- provides for the sharing and analysis of in vivo imaging data.

## Strategic Level Planning Groups

**caBIG Strategic Planning**

- Assists in identifying strategic priorities for the development and evolution of the caBIG effort.

**Training**

- Developing strategies for providing training in the use of the caBIG developed resources including on-line turtorials, workshops, training programs.

**Data Sharing and ****Intellectual Capital**

- Addresses issues related to the sharing of data, applications and infrastructure both within the consortium and in the larger cancer research community.

## The NCI’s General Contractor

- Responsible for coordination of Workspace activities
- Provides funding through contracts to participating centers
- Provides a channel for communication of guidance and priorities
- Provides a measure of participant progress (e.g., contract milestones)
- Fosters accountability and provides mechanisms for conflict resolution

- The NCI is investing resources for administration and support of the caBIG project, decreasing the burden on the participating community

## How does caBIG work?

## How can my Center Participate?

- Participation in Workspaces
- Development of Tools
- Sharing of Data
- Adoption of Tools
*etc.*
- The main mechanism is through RFPs issued by the Project on relevant topics- Workspace participation is a key way to stay abreast of relevant opportunities..

## How can my Center get Funding?

- Your Center may be already funded- as are 50 Designated Cancer Centers nationwide
- The caBIGTM Point of Contact for your organization is a key resource
- Those with projects that may be of interest to the program are encouraged to participate in the Workspaces, and be on the project mailing lists where RFPs for project activities are distributed

## How can my Center benefit from caBIGTM Tools?

- Everything developed by the program is open source and freely available
- The latest versions of all the software developed as part of the project can be obtained from the caBIGTM CVS site:
- _[http://cabigcvs.nci.nih.gov/viewcvs/viewcvs.cgi/](http://cabigcvs.nci.nih.gov/viewcvs/viewcvs.cgi/)_
- Commercial-grade documentation is provided as part of the project, which will be located at the project gforge site:
- http://gforge.nci.nih.gov

## How can I get support for these tools?

**NCICB Applications Support will coordinate support for caBIGTM tools:**
- Live Support: Monday – Friday 8 am – 8 pm Eastern Time
- Telephone support is available Monday to Friday, 8 am – 8 pm Eastern Time, excluding government holidays.
- You may leave a message, send an email or submit a support request via the Web at any time.
- Email: **ncicb@pop.nci.nih.gov**
- Phone: **301-451-4384**
- Toll-free: **888-478-4423**
- Web: **http://ncicbsupport.nci.nih.gov**

## Talk Agenda

**caBIGTM, A Cancer Center Perspective**
**Program Motivations**
**Development of the Program**
**Program Structure and Process**
**Program Timeline and Products**
**Example Program Product: C3D**
**Panel Discussion**

## caBIG Deliverables

- The project is providing useful products in a variety of areas:
- Clinical Trials (C3D, caAERS, *etc.*)
- Tissue Banks and Pathology (caTISSUE, caTIES, *etc.*)
- Bioinformatics (caArray, caWorkbench, *etc.*)
- Tools are developed by, and with the direct specification of, the Cancer Center community, and reflect the needs and capabilities of that community.

## Slide 42

## Slide 43

## Slide 44

## Slide 45

## Slide 46

## A Sample of the caBIG Participant Community

**9Star Research**
**Albert Einstein**
**Ardais **
**Argonne National Laboratory**
**Burnham Institute **
**California Institute of Technology-JPL**
**City of Hope **
**Clinical Trial Information Service (CTIS)**
**Cold Spring Harbor**
**Columbia University-Herbert Irving**
**Consumer Advocates in Research **
**   ****and Related Activities (CARRA)**
**Dartmouth-Norris Cotton**
**Data Works Development**
**Department of Veterans Affairs**
**Drexel University  **
**Duke University**
**EMMES Corporation**
**First Genetic Trust**
**Food and Drug Administration**
**Fox Chase **
**Fred Hutchinson**
**GE Global Research Center**
**Georgetown University-Lombardi**
**IBM**
**Indiana University**
**Internet 2**
**Jackson Laboratory**
**Johns Hopkins-Sidney Kimmel  **
**Lawrence Berkeley National Laboratory **
**Massachusetts Institute of Technology **
**Mayo Clinic **
**Memorial Sloan Kettering**
**Meyer L. Prentis-Karmanos**
**New York University**

**Ohio State University-Arthur G. James/Richard Solove**
**Oregon Health and Science University**
**Roswell Park Cancer Institute **
**St Jude Children's Research Hospital**
**Thomas Jefferson University-Kimmel**
**Translational Genomics Research Institute**
**Tulane University School of Medicine**
**University of Alabama at Birmingham**
**University of Arizona  **
**University of California Irvine-Chao Family**
**University of California, San Francisco**
**University of California-Davis**
**University of Chicago**
**University of Colorado**
**University of Hawaii **
**University of Iowa-Holden**
**University of Michigan**
**University of Minnesota**
**University of Nebraska**
**University of North Carolina-Lineberger **
**University of Pennsylvania-Abramson**
**University of Pittsburgh**
**University of South Florida-H. Lee Moffitt **
**University of Southern California-Norris**
**University of Vermont**
**University of Wisconsin**
**Vanderbilt University-Ingram**
**Velos**
**Virginia Commonwealth University-Massey**
**Virginia Tech**
**Wake Forest University**
**Washington University-Siteman**
**Wistar**
**Yale UniversityNorthwestern University-Robert H. Lurie**

## Talk Agenda

**caBIGTM, A Cancer Center Perspective**
**Program Motivations**
**Development of the Program**
**Program Structure and Process**
**Program Timeline and Products**
**Example Program Product: C3D**
**Panel Discussion**

**C3D is a web-based clinical data management solution.**
**The result of a partnership between NCICB, Center for Cancer Research (CCR) and the Oracle Corporation. **
**Goal is to provide the cancer research community with the infrastructure to collect and manage clinical trial data in a manner that supports reuse and efficiency in building studies that are consistent with the caBIG compatibility guidelines and requirements. **
**Originally developed for NCI's intramural research program, now available as both a web-accessible application service provider (ASP) solution hosted at the NCICB, or as a system entirely deployed at participating Cancer Centers. **
**C3D supports data standardization, reuse, sharing, and interoperability**

**Notes:**
Oracle Clinical provides support for defining the clinical trial, reusing standard templates and common data elements (CDEs), setting up electronic case report forms (eCRFs), storing data securely, and exporting data in formats compatible .
Remote Data Capture (RDC) provides a user-friendly interface that allows local and remote personnel to enter data and provides electronic confirmation of source data verification.
J-Review provides real-time reports on the clinical research data collected.

##    Where Are We Now?

- 70+ Active Oncology Studies
- 20+ Sites
- Support for NIH intramural and extramural research
- Automated CDE Migration from caDSR
- 2,000+ Patients; 120,000+ Completed eCRFs
- 700,000+ Lab Results Automatically Loaded ; Automated Grading Based on Common Toxicity Criteria (CTC)
- Regular Electronic Submissions to Monitors and Agencies

**Notes:**
List Monitors and Agencies

## Why Use C3D?

- Decrease individual protocol set up time
- Increase use of standards – data elements and CRFs
- Provide remote data capture across study sites
- Provide data collection in compliance with regulations (21CFR11)
- Automate regulatory submission – CTEP IND
- CTMS – biweekly incremental
- CDUS – quarterly cumulative
- Decrease local support costs – ASP model
- Decrease Oracle Clinical cost of ownership – both ASP and local models – share HHS level Oracle discount

**Notes:**
Cancer Central Clinical Database (C3D) is the Clinical Trials Database and a key component of NCI’s C3DS suite. Oracle Clinical serves as the foundation of the C3D by supporting clinical trial definition, data capture, multiple site reporting, data definition and usage standardization. Trial definition is based on Common Data Elements from an existing library of template Case Report Forms. Oracle Clinical’s Remote Data Capture (RDC) provides a user-friendly interface that allows local and remote data entry and electronically confirms source data verification. C3D also provides researchers with web-based tools for ad-hoc querying, reporting and analysis of clinical data. 

## What Are the Benefits of Using RDC?

- Eliminate duplicate data collection efforts.
- Study team can enter and review their own data directly from the medical record and/or the patient’s chart.
- Study team does not have to fill out paper case report forms (CRFs) and hand off them to data entry team.
- Speed up data collection time.
- You eliminate the time required to ship paper CRFs to the data entry team.
- You eliminate the time required for deciphering handwriting.
- You eliminate the telephone/email tag involved in answering questions and discrepancies between your study site and your data entry team.
- Improve data quality.
- Study team can enter and review their own data, eliminating the chance for errors due to handwriting or misunderstanding notes.
- Study team can see and resolve discrepancies quickly.

## Licensing C3D

- The license fee is a one time fee, which is a significantly discounted Oracle Clinical License fee of $3000 for each protocol builder account and $2000 for each data entry account.
- There will be an additional 22% annual maintenance.
- These licenses can be moved from one person to another if participants leave.

## The NCICB C3D Support Team – At Your Service

- Technical Director
- Global Librarian / Data Curator
- Protocol Builders
- Database Administrators
- C3D Developers
- Clinical Application Trainers
- Dedicated Application Support

**Notes:**
Technical Director – Sets Direction
Global Librarian / Data Curator – Suggests appropriate CDEs; curates new CDEs as needed
Protocol Builders – Build studies and program edit checks; provide Tier 2 level support 
Database Administrators – Maintain the system: take backups, apply patches, etc. 
C3D Developers – Create add-on applications: C3PR, CDE migration tool, lab loading, etc. 
Clinical Application Trainers – Provide training on C3D components
Dedicated Application Support – Provide phone and email support (next slide)

## Talk Agenda

**caBIGTM, A Cancer Center Perspective**
**Program Motivations**
**Development of the Program**
**Program Structure and Process**
**Program Timeline and Products**
**Example Program Product: C3D**
**Panel Discussion**