# Presentation: 528263

## Translating Biomarker Discovery to Clinical Application

**Sudhir Srivastava, Ph.D., M.P.H.**
**Cancer Biomarkers Research Group**

**Notes:**
Good Afternoon!
Thank you for giving the opportunity to update on the EDRN Activities over six years. EDRN has made tremendous progress n translating biomarker discovery to clinical application.

## GOALS

**Discover, develop and validate biomarkers for cancer detection, diagnosis and risk assessment**
** **
**Conduct correlative studies/trials to validate biomarkers as indicators of early cancer, pre-invasive cancer, risk, or as surrogate endpoints**
**Develop quality assurance programs for biomarker testing and evaluation**
**Forge public-private partnerships**

## INVESTIGATOR-DRIVEN 

***An “infrastructure”    for supporting collaborative research on molecular, genetic and other biomarkers in human cancer detection and risk assessment.***

**INVESTIGATOR-DRIVEN **
**CONSORTIUM**

**Notes:**
EDRN is a investigator-driven consortium of more than 200 investigators and 40 laboratories. It is structure around four major components: BDL, BRL, CEVC, and DMCC. The Steering Committee is the major oversight committee, made of the Principal Investigators. DMCC provides logistics support and conduct research in statistical methodologies and manage and analyze data for the consortium. In collaboration the JPL, our Informatics Center, they help develop informatics infrastructures.

## MANAGEMENT STRUCTURE

- Executive
- Committee

- Colon and Other
-  GI Cancers

- Breast & Ob/Gyn
- Cancers

- Lung and Upper
- Respiratory
-  Cancers

- Policy Making
- Subcommittees

- Prostate &
- Other Urologic
- Cancers

- Steering Committee

**MANAGEMENT STRUCTURE**

- Prioritization
- Technology Sharing
- Collaboration
- Communication and Workshop
- Data sharing and Informatics

**Notes:**
The EDRN Steering Committee is assisted by organ-based collaborative groups and policy making subcommittees. The EDRN Executive Committee, a subset of the SC is responsible for making decisions on validation projects, collaborative studies, release of set-aside funds and on approval of Associate Members.

## ORGANIZATIONAL SUCCESS:       A Catalyst for Innovations and Partnership

**EDRN  Business Model and Project Management Reviewed and Cited by Many Scientific Journals and Working Groups for Best Practices:**
- Informatics to Manage and Support Biomarker Research (NCI-FDA-AACR Biomarker Collaborative Working Group Reports, Institute of Medicine on Biomarker)
- Conducting Discovery and Validation Research (JNCI, J. Proteome Research)
- Collaborative Model for Biomarker Research (Nature)
- Milestones-driven Project Management that Ensure Timely Completion
- NCI Translational Research Working Group

**The EDRN structure has been cited by the National Academy of Sciences  Institute of Medicine as an effective team-based organization (*****Large Scale Biomedical Science*****, Institute of Medicine 2001); and **
**for following best practices in *****Biospecimen Resources for the Genomic and Proteomic Era *****(Rand Science and Technology Publication, 2003), and *****Cancer Informatics *****(Eds. Silva, Ball, Chute, et. al., 2002 and in *****Cancer Biomarkers*****, Institute of Medicine 2007).**

- Continues...

**Notes:**
EDRN has successfully instilled a sense of urgency among investigators to move discover from bench to the bedside. EDRN uses a novel funding approach to reward collaboration. The EDRN structure has been emulated by many programs with NCI, NIH and internationally.

## ORGANIZATIONAL SUCCESS:       A Catalyst for Innovations and Partnership

**Rewards Collaboration and Promotes Team Science (EDRN Investigator received the first-ever AACR Team Science Award: Arul Chinnaiyan).**
** **
**EDRN is as an Unexpected Catalyst for Innovation, Partnerships, and Biomarker Research Know-How (An EDRN investigator received a DOD Innovator Award on research ideas supported by EDRN).**
**Diagnostic firms, large or small, are seeking partnerships with EDRN.**

- Continued.

## ORGANIZATIONAL SUCCESS:A Model System for Translational Research

**An integrated, collaborative model that:**
**Uses a novel mechanism to reward collaboration and promotes inclusiveness through its Associate Membership Program.**
**Has developed a roadmap for **_**[biomarkers discovery and validation ](slide8.xml)**_**.**
**Has helped developed *****biomarker metrology***** to develop, design and deliver biomarker research free of chance, bias and over-fitting (Pepe et.al., Ransohoff).**
**Has championed protocol-driven, phase-approach to proteomics evaluation for cancer diagnostic.**
**Disseminates resources for extramural communities on protocols, reagents, reference sets, study designs and statistical methodologies.**

## PHASES OF BIOMARKER 

**PHASES OF BIOMARKER **
**VALIDATION**

**Notes:**
Each phase is statistically tested for its progression to the next phase. As we move further along these phases, the evidence for clinical usability of the biomarker increases.

## EDRN PROGRAM FOR RAPID INDEPENDENTDIAGNOSTIC EVALUATION (PRIDE)

**A RAID-like mechanism that:**
**Encourages extramural investigators to seek assistance from EDRN in cross-laboratory validation of their biomarker assays.**
**Helps develop and institutes quality assurance programs for biomarker testing and evaluation.**
**PRIDE announcement is published in NIH Guide yearly.**

**Notes:**
EDRN has been using a RAID- and RAPID-like mechanism to assist nonEDRN investigators to validate their biomarkers. We are now planning to publish this opportunity in the NIH Guide. EDRN’s biomarker measurement standards are being modeled on NIST’s standards for chemical reagents.

## PRESENT AND FUTURE

** ****EDRN already practices management philosophy **
**    ****promoted by TRWG. **
** ****TRWG- supported Risk Device Pathways are already **
**    ****being supported by EDRN.**
** ****The Network’s productivity, funding opportunities and **
**     ****infrastructure have fashioned a new environment for **
**     ****biomarker research.**
-   **A number of biomarker tests will be ready for submission**
**     ****to FDA, a remarkable achievement considering the history **
**     ****of **_[approval of diagnostic markers by FDA](slide11.xml)_**.**

## FDA APPROVAL OF 

- Joseph A. Ludwig*‡ and John N. Weinstein* Nature Rev. Cancer 2005

**FDA APPROVAL OF **
**CANCER BIOMARKERS**

## SIGNIFICANT NOTES

-  EDRN 4th Report Released
-     January 2008
-  EDRN 5th Annual Workshop
-     March 16-19, Bethesda, MD
-  AACR Sunrise Session on EDRN
-     April 15, 2008

## UPDATES

**UPDATES**

**  ****BIOMARKER DISCOVERY: Dr. Sam Hanash**
**  ****BIOMARKER VALIDATION: Dr. Ian Thompson**
**  ****BIOMARKER REFERENCE LABORATORIES: **
**     ****Dr. Dan Chan**
**  ****STATISTICAL AND INFORMATICS: **
**     ****Drs. Ziding Feng, Mark Thornquist, and **
**     ****Dan Crichton**

**Notes:**
I will discuss its accomplished using the following outlines. First: EDRN as a Successful Infrastructure.