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

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MEASURING EDRN SUCCESS USING A BUSINESS
MODELOutput, Outcome, Impact

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

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Review of Updates
Provided on May 9, 2006
SUCCESSFUL INFRASTRUCTURE BIOMARKER
DISCOVERY BIOMARKER VALIDATION
COLLABORATIONS AND PARTNERSHIPS BIOMARKERS
AND BIOINFORMATICS
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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
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EDRN Business Model Vertical Process
Implementation
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Investigator-driven Consortium
An infrastructure for supporting
collaborative research on molecular, genetic and
other biomarkers in human cancer detection and
risk assessment.
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Business Model Stakeholders Input
Investigators Sponsors and Funders
Policy Makers and Regulators Technology
Developers Customer Base

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

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INPUTConnecting 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
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INPUTConnecting To Stakeholders
Continued

• 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

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
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INPUTNIH Stakeholders
Continued

• EDRN-SPORE-PLCO Collaboration on Ovarian
  Biomarkers
• EDRN-SPORE Lung Cancer Reference Sets assembled
  and are being requested under the EDRNs Program
  for Rapid Independent Diagnostic Evaluation
  (PRIDE).
• EDRN-NIHs 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

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Examples Biotechnologies and Diagnostic
Companies
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OUTPUT Advances in Biomarker Science

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

Continues
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OUTPUT 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)

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OUTPUTPublication

• 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
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OUTPUTPublication
Continued
Average Number of Publications per NCI-funded
Biomarker Grant
Source Analysis by SAIC
Continues
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OUTPUTPublication Impact factor
Continued
Average Impact Factors for Publications Resulting
from NCI Biomarker Grants That Began in FY1999
or FY2000
Continues
Source Analysis by SAIC
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OUTPUTCollaborations
Source EDRNA database
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OUTPUTPatents and Licenses
Source EDRN database
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Output Advances in Biomarker Science Patents
Continued

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

Source Analysis by SAIC
Continued
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OUTCOMESClinical Validation

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

Continues
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OUTCOMESClinical 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)

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OUTCOMESReadying 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)

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OUTCOMES 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

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IMPACTDoes 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 Big Hairy Audacious Projects, Incubator
  Projects, and timely dissemination of research
  findings.

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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.

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Challenges

• Investigators 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

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Present and Future

• EDRN already practices management philosophy
• promoted by TRWG.
• TRWG- supported Risk Device Pathways are already
  
• being supported by EDRN.
• The Networks 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.

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Thank you!
SUCCESSFUL INFRASTRUCTURE BIOMARKER
DISCOVERY BIOMARKER VALIDATION
COLLABORATIONS AND PARTNERSHIPS BIOMARKERS
AND BIOINFORMATICS