# Presentation: 375946

## MEASURING EDRN SUCCESS USING A BUSINESS MODELOutput, Outcome, Impact

**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 in translating biomarker discovery to clinical application.

## Provided on May 9, 2006

**	****SUCCESSFUL INFRASTRUCTURE**** ****	**** BIOMARKER DISCOVERY**** ****	**** BIOMARKER VALIDATION**** ****	**** COLLABORATIONS AND PARTNERSHIPS**** ****	**** BIOMARKERS AND BIOINFORMATICS**

**Provided on May 9, 2006**

**Notes:**
EDRN became fully functional in April 2000. It was established to help discover and validate clinically useful biomarkers for cancer detection, diagnosis and risk assessment in collaboration with public and private institutions.

## EDRN Business Model

** ****Discover, develop and validate biomarkers for **
**  ****cancer detection, diagnosis and risk **
**  ****assessment**
**Conduct correlative studies/trials to validate**
**  ****biomarkers for cininical application**
**Develop quality assurance programs for **
**  ****biomarker testing and evaluation**
**Forge public-private partnerships**

**Advisors:**
**Professor Regina E. Herzlinger, Harvard **
**Business School**
**Professor David Dilts, Vanderbilt School of **
**Business and Technology**

**Notes:**
EDRN became fully functional in April 2000. It was established to help discover and validate clinically useful biomarkers for cancer detection, diagnosis and risk assessment in collaboration with public and private institutions.

## EDRN Business Model: Vertical Process Implementation

## Investigator-driven Consortium

***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 structured around four major scientific components: BDL, BRL, CEVC, and DMCC. The Steering Committee is the major oversight committee, comprised 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.

## Business Model: Stakeholders’ Input

- Source: Adapted from *Harvard Business Review, *
- May 2006, pp 58-65

- • **Investigators**
- • **Sponsors and Funders**
** **
- • **Policy Makers and Regulators**
** **
- • **Technology Developers**
** **
- • **Customer Base **

## INPUTConnecting To Stakeholders

** ****EDRN Session at AACR Annual Meetings**
** ****EDRN-FDA Annual Educational Workshop**
** ****Advocates are informed of EDRN Annual Meetings, Workshops, and **
**     ****are invited to select meetings**
**  ****Institute of Medicine-sponsored meetings: Biomarkers and Bioinformatics****       **
**  ****AACR-Sponsored Subcommittees on Biomarkers Collaborative - **
**     ****Analytical, Bioinformatics, Clinical**

- Continues...

## INPUTConnecting To Stakeholders

-  **Workshops on Public-Private Partnership; Developing Industrial Partnership; **
**     ****Developing Guidelines with the help of private sectors (see handout)**
** ****Foundations are consulting EDRN: Lustgarten on Pancreatic, Canary **
**    ****On prostate, and Colon and Lebreque on Lung; Several Joint Project Plans**
**     ****are in progress**

- Continued...

- 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).

- Continues...

## INPUTNIH Stakeholders

**EDRN-SPORE-PLCO Collaboration on Ovarian Biomarkers**
**EDRN-SPORE Lung Cancer Reference Sets assembled and are being requested under the EDRN’s Program for Rapid Independent Diagnostic Evaluation (PRIDE).**
**EDRN-NIH’s WHI Proteomics Collaboration on Colon Cancer Phase I completed, several biomarkers from Preclinical Samples identified and presented at EDRN-WHI Investigators’ Jamboree on July 17-18, 2007**
**Interfacing Mouse Models with Human Biomarker Development Meeting Held on July 16-17, 2007 in collaboration with MMHCC**
** ****Industrial Participation in Discovery and Validation; MOU with Agilent and **
**       ****Affymetrix are supporting ‘Incubator Projects’**

- Continued...

## Examples: Biotechnologies and Diagnostic 

**Examples: Biotechnologies and Diagnostic **
**Companies**

## Advances in Biomarker Science

**OUTPUT**
**Advances in Biomarker Science**

**   ****More than 465 papers published on new **
**       ****biomarkers**
**   ****Seminal discoveries and study foundations**

- Continues...

**Notes:**
EDRN investigators have published more than 300 papers, more than 25% are in journals with impact factors 30 or greater. On the next slide I have listed some of the seminal discoveries that EDRN has made in the past six years.

## Discovery

**   ****Gene fusion in prostate cancer; first ever report**
**       ****for a major epithelial tumor  (Chinnaiyan)**
**   ****Auto-antibodies as biomarkers for lung and **
**      ****prostate cancers (Hanash, Chinnaiyan, Tainsky)**
**  ** **Pioneering work in glycoproteins (Tim Block)**
**   ****Mitochondrial mutations as cancer biomarkers in **
**      ****bladder cancer (Sidransky)**

**OUTPUT**
**Discovery**

**Notes:**
I would like to emphasize the study on findings of gene fusion in prostate and bladder cancer. This is the first major report of gene fusion of EGR, ETV1 and TMPRSS genes. ERG and ETV1 fusion has been reported in Ewing Sarcoma. Our partner NIST is nor evaluating this finding and trying to develop Q-dot based staining for fusion detection.

## OUTPUTPublication

**Up to 10% publications in journal with impact factors ranging from 10 to 40, such as Science, JAMA, Nature, NEJM, PNAS, JNCI**
**40% in cancer-specific journals with impact factors ranging from 3 to 10, such as CR, CCR, CEBP**
**30% in specialized journals and other journals, such as J. Urol., **
**     ****Am. J. Gastro., etc.**
**20% in other interdisciplinary journals**
**Source: EDRN database**

- Continues...

## OUTPUTPublication

**Average Number of Publications per NCI-funded Biomarker Grant**

- Source: Analysis by SAIC

- Continued...

- Continues...

## OUTPUTPublication Impact factor

**Average Impact Factors for Publications Resulting from ****NCI Biomarker Grants That Began in FY1999 or FY2000**

- Source: Analysis by SAIC

- Continued...

- Continues...

## OUTPUTCollaborations

| Mechanism | Collaborative Studies/grant | Notes |
| --- | --- | --- |
| R01 | 1.8 | Based on Sampling of R01 grants of similar size |
| EDRN | 6.8 | 

All EDRN components included

 |

- Source: EDRNA database

## OUTPUTPatents and Licenses

| Mechanism | Patents/grant | Licenses/grant |
| --- | --- | --- |
| R01 | 0.20 | Not available |
| EDRN | 0.90 | 

0.5 

 |

- Source: EDRN database

## Output: Advances in Biomarker Science: Patents

**    ****Patents or Patent Applications Resulting from ****NCI-funded Biomarker Projects That Began in FY1999 or FY2000**

- Source: Analysis by SAIC

- Continued...

- Continued...

## OUTCOMESClinical Validation 

**More than 127 biomarkers in Phase 1 and 2**
**15 Biomarkers will be transitioning to Phase 3**
**Five Biomarkers in Phase 3**

- Continues...

## OUTCOMESClinical Validation: Examples

**MSA – Bladder cancer (prospective)**
**DCP and AFP-alpha 3 – Liver cancer (prospective)**
**Serum Mesothelin Related-Proteins (SMRP) and osteopontin – Mesothelioma (Harvey Pass)**
**Methylation Panel - Esophageal cancer (Steve Meltzer)**
**Annexin 1 and Annexin 2  – Lung (Sam Hanash)**
**CA 72-4, CA 15-3, CEA, CA 19-9, SMRP-1, OV-1.10, HE-4, Osteopontin, HK-11, HK -10, Spondin-2, Prolactin and CA-125**  -  **Ovarian (Cramer/Urban)**
**Prolactin, Osteopontin, CA 125, Leptin , IGFII, MIF – Ovarian (Gil Mor)**

## OUTCOMESReadying for Submission to FDA

**MSA – Bladder cancer (prospective) by CANGEN (510 K)**
**DCP and AFP-L3 – Liver cancer (prospective) by **
**    ****Esai/Wako (likely)**
**Early detection of prostate cancer-based on detection of PCA3 transcript in urine supernatant by Gen-Probe (510-K)**
**% proPSA in combination with PSA isoforms for early detection of prostate cancer, by Beckman-Coulter (510-K)**

## Biomarkers in Validation Pipeline

**    **

_**Samir Hanash**_
**Validation of protein markers in pancreatic cancer (A**
**panel of antigens)**
_**David Sidransky**_
**Mutations and deletions in mtDNA as markers for bladder and other **
**    ****cancers.**
**2. Meythlated DNA markers for prostate cancer**
**    ****Industrial Collaborator: OncoMethylome which holds the license**
**    ****Status: discussions**
_**Alan Partin**_
**     ****GSTP1 methylation markers in screen-detected prostate biopsy as reflex markers**
**	****	****	****	****	****	****	**

**OUTCOMES**
**Biomarkers in Validation Pipeline**

## IMPACTDoes the total exceed sum of its parts?

**EDRN has made significant contributions to biomarker research by providing guidelines on validation, reference samples, study designs, and other diagnostic attributes.**
**EDRN provides an unparalleled fully operational Network of strong scientific collaborations for translational research.**
**EDRN-supported studies insure that good biomarkers are promoted without regard to pecuniary interests and provides the best chance for promising markers to become future medical tools.**
**EDRN Adaptive Business Model approach encourages public-private partnership and team science and permits “****B****ig ****H****airy ****A****udacious ****P****rojects”, Incubator Projects, and timely dissemination of research findings.**

**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.

## Accountability

**Each laboratory or Center is site visited by external reviewers at least once in the grant cycle (5-yr).**
**EDRN was recently reviewed by an external panel composed of Drs. Bernard Levin, Barnett S. Kramer, Brian Reid, and Kenneth Cowan.**
**EDRN Date Management and Coordinating Center was reviewed by Drs. Sylvan Green, Heidi Weiss, and Sharon McWenney.**
**Reviews are taken into consideration by investigators and NCI staff for quality improvement in processes and procedures for maximizing progress and leveraging resources.**

**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.

## Challenges

** ****Investigator’s competing priorities and individualistic**
**    ****backgrounds at odd with collaborative environment. **
**    ****EDRN continues to make progress.**
** ****The work of growing a cohesive culture of sharing remains**
**    ****incomplete.  Some investigators have not recognized the **
**    ****importance of sharing their resources and expertise. **
**    ****This will require sustained efforts and monitoring.**
-  **Inordinate delays in getting IRB, MTA and IP issues **
**    ****resolved**

## 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 approval **
**     ****by FDA, a remarkable achievement considering the history **
**     ****of approval of diagnostic markers by FDA.**

## Thank you!

**	****SUCCESSFUL INFRASTRUCTURE**** ****	**** BIOMARKER DISCOVERY**** ****	**** BIOMARKER VALIDATION**** ****	**** COLLABORATIONS AND PARTNERSHIPS**** ****	**** BIOMARKERS AND BIOINFORMATICS**

**Thank you!**

**Notes:**
EDRN became fully functional in April 2000. It was established to help discover and validate clinically useful biomarkers for cancer detection, diagnosis and risk assessment in collaboration with public and private institutions.