# Presentation: 007652

## A Report to the National Cancer Advisory Boardfrom the Translational Research Working GroupJune 15, 2007 - Bethesda, Maryland       

Ernest Hawk, MD, MPH
NCI/OD/Office of Centers, Training & Resources

Lynn Matrisian, PhD
Vanderbilt-Ingram Comprehensive Cancer Center

William Nelson, MD, PhD
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

*                                                                   *
- Ernest Hawk, MD, MPH
- NCI/OD/Office of Centers, Training & Resources
- Lynn Matrisian, PhD
- Vanderbilt-Ingram Comprehensive Cancer Center
- William Nelson, MD, PhD
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

**Transforming Translation: ****Harnessing Discovery for Patient & Public Benefit**

**Notes:**

Luxury of understanding a disease well enough for it to be prevented
Knowledge has come about very quickly...adenomas only recognized as precursor lesions within the last 50 years
Inspiring – so much is known, and humbling – so much is unknown

## NIH Mission Statement

- “Science in pursuit of fundamental knowledge about the nature and behavior of living systems
- &
- the application of that knowledge to extend healthy life and reduce the burdens of illness and disability”

*http://www.nih.gov/about/index.html#mission.htm*

## Translational Research Working Group

- Charge:

- Evaluate the current status of NCI’s
- investment in translational research
- & envision its future in an inclusive, representative & transparent manner

## NCI’s “Bench to Bedside & Back”               Research Infrastructure & Programs

**ICMIC**

**CPTAC**

**CCNE**

**NTROI**

**NCI’s “Bench to Bedside & Back”               Research Infrastructure & Programs**

**Basic**

**Phase III/IV Trials**

**MMHC**

**Integrated **
**Systems **
**Biology**

**RAID/**
**RAPID**

**SPOREs**

**Cooperative**
**Groups**

**CCOPs**

**EDRN**

**PO1s**

**Intramural Program**

**Phase I Trials**

**Phase II Trials**

**RO1s**

**DCP/DCTD **
**Phase I/II Trials Programs**

**“****Translational Science”**

**“****Clinical Trials”**

**Cancer Centers**

**CCR**
**DCEG**
**DCB**
**DCP**
**DCCPS**
**DCTD**
**OCTR**
**OTIR**
**Cross-NCI**

**58 centers; ~$130 M/year**

**61 centers; ~$240 M/year**

## Why Convene a TRWG? Why Now?

**Major advances in **
**cancer biology**

**Translational systems**
**that cannot keep pace**

**Opportunities**

**Resources**

**Expectations**

- Time

- Magnitude

**Business as Usual?**

**UNTENABLE**

**Changing environment**
** ****Growth**
** ****Diversity**
** ****Competition**

## TRWG’s Activities

- Recruited leadership & members
- Reviewed 11 foundational documents
- Analyzed Clinical Trials Working Group process for ideas, challenges & lessons learned
- Developed web-based communication platform *(www.cancer.gov/trwg)*
- Gathered public input on key questions & proposed solutions
- Public Roundtable I (Phoenix) + web – February 2006
- Industry/foundation/society Roundtable (Philadelphia) – April 2006
- Public Roundtable II (Atlanta) + web – November 2006
- Analyzed NCI’s current investments in TR
- Portfolio analysis 			–  Process analysis
- Mapped 6 developmental pathways to clinical goals
- Constituted 6 subcommittees
- Organization & funding		–  Prioritization
- Core services			–  Project management
- Training/workforce			–  External integration

## TRWG Subcommittees

| Overall      Leadership | Organization & Funding | Core Services Coordination | Prioritization |
| --- | --- | --- | --- |
| Hawk, Ernest | Gray, Joe | Cowan, Kenneth | Tlsty, Thea |
| Matrisian, Lynn | Reid, Brian | Schnall, Mitchell | Schilsky, Richard* |
| Nelson, Bill | Bast, Robert* | Bigner, Darell | Abbruzzese, James |
|  | Caligiuri, Michael | Buetow, Kenneth | Emanuel, Peter |
|  | Cote, Richard | Doroshow, James | McGrath, Gail |
|  | Dennis, Phillip | DuBois, Raymond | McTiernan, Anne |
|  | Gomez, Jorge | Jacks, Tyler | Mohla, Suresh |
|  | Gritz, Ellen | Look, A. Thomas | Perez-Soler, Roman |
|  | Hait, William | Maslow, David | Rabkin, Charles |
|  | Kerr, David | Schlom, Jeffrey | Weiner, Louis |
|  | Scheinberg, David |  |  |
|  | Simon, Richard |  |  |
|  | Sullivan, Daniel |  |  |

**Serving on more than one subcommittee, as able*
*Blue = Co-chairs*

## TRWG Subcommittees

| Project Management | Training & Workforce | External Integration |
| --- | --- | --- |
| Lawrence, Theodore | Lyerly, H. Kim | Courtneidge, Sara |
| Limburg, Paul | Olopade, Olufunmilayo | Gordon, Gary |
| Collins, Jerry | Bast, Robert* | Alberts, David |
| Esserman, Laura | Dubinett, Steven | Anderson, Kenneth |
| Fenton, Laurie | Hong, Waun Ki | Cheever, Martin |
| Nichols, Cherie | McLeod, Howard | DiBisceglie, Adrian |
| Sellers, Thomas | Moore, Ida “Ki” | Downing, Gregory |
| Sidransky, David | Oberholtzer, John Carl | Gilmer, Tona |
| Srivastava, Sudhir | Schilsky, Richard* | Lubenow, Anne |
|  |  | Pazdur, Richard** |
|  |  | Sigal, Ellen |

**Serving on more than one subcommittee, as able*
***FDA was represented by various employees*
*Blue = Co-chairs*

## TRWG’s Definition of Translational Research

- Research that transforms scientific discoveries arising in the lab, clinic or population into new clinical tools & applications that reduce cancer incidence, morbidity & mortality

**Lab**

**Population**

**Clinic**

**New Tools & **
**New Applications**

*www.cancer.gov/trwg*

## The Translational Continuum*Refining the TRWG’s Scope of Activity

**Basic Science**
**Discovery**
**  ****Promising molecule or gene target**
**  ****Candidate protein biomarker**
**  ****Basic epidemiologic finding**

**Early Translation**
**  ****Partnerships & collaboration (academia, government, industry)**
**  ****Intervention development***
**  ****Phase I/II trials**

**Late Translation**
**  ****Phase III trials**
**  ****Regulatory approval**
**  ****Partnerships**
**  ****Production & commercialization**
**  ****Phase IV trials – approval for additional uses**
**  ****Payment mechanism(s) established to support adoption**
**  ****Health services research to support dissemination & adoption**

**Dissemination***
**  ****To community health providers**
**  ****To patients & public**

**Adoption**
**  ****Adoption of advance by providers, patients, public**
**  ****Payment mechanism(s) in place to enable adoption**

**President’s Cancer Panel, 2004-2005 Annual Report*

**Focus of TRWG**

**New drug, assay, device, *
*behavioral intervention, *
*educational materials, training*

**Interface with CTWG **
**& its Recommendations**

## Pathways to Clinical Goals

**Pathways to Clinical Goals**

*www.cancer.gov/trwg*

_**Risk Assessment**_** **
*(for screening, diagnosis, staging, response assessment, prognosis, or prediction)*
**  ****Biospecimen-based           ****(**protocols, reagents, instruments)
**  ****Image-based **
- (agents, techniques)
_**Interventions**_
**  ****Agents **
- (drugs or biologics)
**  ****Immune response modifiers**
**  ****Interventive devices**
**  ****Lifestyle alterations**

## The Convergence of Risk- & Intervention-Related Pathways in Translational Progress

**Fundamental Discovery**

**in Lab, Clinic, or **
**Population**

**Parallel**

**Translational**

**Efforts**

**Develop, Optimize, Validate**

_**Intervention**_

**1.  Agent (Drug/Biologic)**

**2.  Immune Response Modifier**

**3.  Interventive Device**

**4.  Lifestyle Alteration**

**Develop, Optimize, Validate**

**Assessment Tool for **

_**Cohort**_

** ****Selection**

**1.  Risk Assessment Device**

**2. Imaging BIomarker**

**Develop, Optimize, Validate**

**Assessment Tool for **

_**Endpoint**_**/****/**

_**Evaluation**_** of Target Effects**

**1.  Risk Assessment Device**

**2.  Imaging Biomarker**

_**Intervention, Cohort, & **_
_**Endpoint (ICE)**_** of an **
**Early Phase Clinical Trial**

## Portfolio Analysis of NCI’s Translational Research Funding in FY04

- $1.3B of $4.4B budget (~30%)
- May be overestimated by    20-40%
- 56% awarded to institutions with NCI-designated cancer centers

-   Distributed across funding mechanisms

## The Challenge of Early Translation

- How can we best assure that
- The most promising concepts enter the developmental pathways?
- Concepts that enter advance to the clinic or to productive failure?
- Progress is as rapid, efficient & effective as possible?

## Translational Research Working Group Report

- Summary Vision

*Build a focused, collaborative, multi-disciplinary enterprise, tailored to the distinctive requirements of early translational research, which transforms and strengthens this essential link *
*from discovery to patient & public benefit*

## Translational Research Working Group Report

**Key Objectives*** *
-   Improve coordination & collaboration & instill a culture of      active, goal-oriented management
-   Improve identification of the most promising opportunities through a transparent & inclusive prioritization process driven by scientific promise & clinical need
-   Tailor new & existing funding programs to facilitate progress & incentivize researcher participation
-   Enhance operational efficiency & effectiveness for individual projects and their many supporting activities

## Common Themes of TRWG Initiatives

***  ******A - Coordinated Management***
-   Facilitate TR through a flexible, integrated NCI organizational approach
-   Achieve a shared understanding of the nature and scope of TR activity
-   Set priorities through a systematic and transparent process involving all stakeholders
***  ******B - Tailored Funding Programs***
-   Refine existing programs to promote translational success
-   Create new programs for prioritized projects and to promote industry collaboration
***  ******C - Operational Effectiveness***
-   Provide key project management resources
-   Coordinate supporting core services
-   Promote collaborations among NCI, academia, industry and foundations
-   Enhance training and career incentives

## Dr. Matrisian

## Coordinated ManagementRecommended Initiative A1

*** ******Establish a coordinated NCI-wide organizational approach to manage the diverse early translational research portfolio, reduce fragmentation and redundancy, and ensure that resources are focused on the most important and promising opportunities.***
- Scope of Clinical Trials Advisory Committee (CTAC) extended to provide external oversight to translational research
- Translational Research Operations Committee including NCI Divisions, Centers and Offices to provide internal management structure
- Translational Research Support Office created within Coordinating Center for Clinical Trials to provide operational support
- CTAC Special Working Groups established to address Minority and Underserved Populations and Rare and Pediatric Cancers

## Coordinated Management (Initiative A1)

**Coordinated Management***** (Initiative A1)***

_**Relationship of Proposed TRWG Coordinated Management Entities**_

**Clinical Trials Advisory Committee**

**NCI Director**

**Translational Research Operations Committee**

**Coordinating Center for Clinical Trials**
**Translational Research Support Office**

***“******Oversight”***

***Advisory***

***Chair***

***Direct Report***

***Support***

***Support***

*Extramural group*

*Intramural group*

*New entity*

***Advisory***

***Support***

**Special Working Groups**
** ****Minority & underserved populations**
** ****Rare & pediatric cancers**

## Coordinated ManagementRecommended Initiative A2

***Designate a specific portion of the NCI budget for early translational research to facilitate coordinated management, long-term planning, and prioritization among opportunities and approaches as well as to demonstrate NCI’s commitment to translational research.***
- Target to be established by Clinical Trials Advisory Committee – anticipated to be in 25-35% range
- Budget to encompass four early translational research components
- Solicited (RFA/PA-directed) programs
- Unsolicited, investigator-initiated awards identified as translational by new coding system
- New funding programs recommended by TRWG Report
- Operational expenses associated with implementing TRWG Initiatives

## Coordinated ManagementRecommended Initiative A3

*** ******Develop a set of award codes that accurately captures the nature and scope of the early translational research portfolio to enable a complete, shared understanding of NCI’s total investment, help identify gaps and opportunities, and demonstrate the extent of translational activity to the public.***
- New award codes to reflect key elements of the six TRWG developmental pathways to clinical goals
- New codes to be integrated with existing NCI coding and portfolio analysis systems
- Seek input on best practices from other federal agencies (e.g. DOD) with relevant coding systems

## Coding Grant 

**Decision to proceed**

**Supporting tools**

**Creation of modality**

**Preclinical development**

**Clinical trials**

**Coding Grant **
**Applications to the Translational Research Developmental Pathways:**

## Coordinated ManagementRecommended Initiative A4

***Create a transparent, inclusive prioritization process to identify the most promising early translational research opportunities based on scientific quality, technical feasibility and expected clinical or public health impact.***
- Process to be managed by a Translational Research Prioritization Working Group of the Clinical Trials Advisory Committee
- Prioritization process to be carried out annually in a systematic and transparent manner
- Process will identify specific targets for new special awards while also informing existing translational research funding initiatives

## Coordinated Management(Initiative A4)

_**Relationship of Proposed Prioritization Process with Coordinated Management Entities**_

**Clinical Trials Advisory Committee**

**NCI Director**

**Translational Research Operations Committee**

**Coordinating Center for Clinical Trials**
**Translational Research Support Office**

**Translational Research Prioritization Working Group**

***“******Oversight”***

***Advisory***

***Advisory***

***Chair***

***Direct Report***

***Support***

***Support***

***Support***

*Extramural group*

*Intramural group*

*New entity*

## Current Approach

- NCI-initiated solicitations
- Generated within Branches/Divisions
- Scientific premise, portfolio analysis, proposed budget, evaluation metrics
- Approved by Executive Committee
- Approved by BSA/BSC
- Second-level review & award concurrence by NCAB
- Investigator-initiated projects
- Peer-review’s project-specific scientific priority score
- Mild programmatic discretion at the Branch or Divisional level
- Second-level review & concurrence by NCAB

**Recommended Prioritization Process**

**Inform existing NCI initiatives**

**Proposed Additional Approach**

**Translational Research Prioritization Working Group**

**Broad public input (RFI)**

**10 ideas chosen for detailed analysis**
** ****scientific validity**
** ****feasibility**
** ****clinical need**
** ****public (vs. a private sector) priority**

**5 concept packages**

**Public comment**

**2-3 Special**
** ****Awards**

## Tailored Funding ProgramsRecommended Initiative B1

***Modify guidelines for multi-project collaborative early translational research awards to focus research on advancing specific opportunities along a developmental pathway toward patient benefit, and to reward collaborative team science.***
- Incorporate project milestones
- Require a development/commercialization strategy
- Promote and reward collaborations
- Allow budgetary flexibility for projects that meet milestones
- Review panels to include industry scientists, non-academic health professionals, program managers from foundations and patient advocates as well as academic translational researchers

## Tailored Funding ProgramsRecommended Initiative B2

***Improve processes and mechanisms for review and funding of investigator-initiated early translational research to incentivize researchers to propose such studies.***
- Analyze translational research study section membership and practices
- Pursue NIH-wide initiative to examine value of distinctive R-series and P-series mechanisms for supporting investigator-initiated translational research
*** ***

## Tailored Funding ProgramsRecommended Initiative B3

***Establish Special Translational Research Acceleration Project (STRAP) awards to advance a select number of especially promising early translational research opportunities identified through the newly created prioritization process.***
- Solicit proposals annually for specific opportunities
- $10M of new awards annually beginning in year 3 (FY2010), steady state of $50M in annual STRAP funding after 5 years
- STRAP program requirements:
- Project plan through early stage human studies
- Project management plan
- Specific development milestones and timeline
- Development/commercialization strategy
*** ***

## Proposed STRAPs Complement Existing Mechanisms

**50% BASIC**

**35% TRANSLATIONAL**

**15% CLINICAL**

- Cancer-related biology

- Fundamental biology

- R01

- R01

- R01

- R01

- R01

- R01

- R01

- R01

- R01

- R01

- R01

- Ph I/II

- R01

- R01

- R01

- STRAP

**Proposed STRAPs Complement Existing Mechanisms**

- M
- M
- H
- C

- NTROI

- STRAP

## Dr. Nelson

## Tailored Funding ProgramsRecommended Initiative B4

***Establish a program for joint NCI/industry funding of collaborative early translational research projects that integrate the complementary strengths of both parties to pursue opportunities that are more attractive as a combined effort.***
- Establish an Industry Relations Working Group to lay groundwork for negotiation of collaborative funding arrangements
- $5M of new awards annually beginning in year 4 (FY2011), steady state of $25M in annual funding after 5 years
- RFA-directed solicitation and award process
- Program requirements:
- Project plan through hand-off to industry partner
- Joint industry/academic Steering Committee
- Negotiated intellectual property/licensing plan
- Specific development milestones and timeline
*** ***

## Tailored Funding ProgramsRecommended Initiative B5

***Integrate access to GMP/GLP manufacturing and other preclinical development services more effectively with high-priority, milestone-driven early translational research projects to better address this often rate-limiting step in moving a product forward to early human testing.***
- Preclinical milestone reviews integrated with review processes for NCI developmental resources program (RAID, RAPID or DCIDE) to avoid duplicative review
- No change in current review process for investigator-initiated applications to RAID, RAPID or DCIDE
- Development experts involved in earlier milestone reviews to help identify and solve potential obstacles in toxicology, pharmacology or manufacturing

## Operational EffectivenessRecommended Initiative C1

***Build a project management system involving staff both at NCI and at extramural institutions to facilitate coordination, communication, resource identification and access, and management of milestone-based progress for multi-disciplinary, early translational research projects. ***
- Overall system coordination provided by Translational Research Support Office (TRSO)
- Project-specific management for existing programs provided by program staff  and for new STRAP and academic/industry awards by TRSO
- NCI project managers work in collaboration with institutionally-based project managers
- Formal project management training will be provided as needed

## Operational EffectivenessRecommended Initiative C2

***Coordinate core services essential for early translational research to reduce duplication and ensure that high quality services are readily accessible to all projects and investigators.***
- Identify and analyze existing core services for redundancy
- Consolidate redundant core services with emphasis on primary role of Cancer Centers as providers of core services
- Develop comprehensive, publicly-accessible database of core services
- Establish regional centers of excellence for highly technical, equipment or resource intensive core services that are inefficient to operate locally

## Operational EffectivenessRecommended Initiative C3

***Improve standardization, quality control and accessibility of annotated biospecimen repositories and their associated analytic methods to strengthen this key translational resource.***
- Reinforce standardization and specimen and data sharing efforts of the Office of Biorepositories and Biospecimen Research (OBBR) including an informed consent  template for future use of tissue
- Modify program guidelines to incorporate OBBR’s First Generation Biorepository Guidelines
- Provide funding for guideline-compliant biospecimen collection in clinical trials
- Assist OBBR in developing new approaches to creation of a national biospecimen repository network
- Develop standardized analytic methods for  biospecimens

## Operational EffectivenessRecommended Initiative C4

***Develop enhanced approaches for negotiation of intellectual property agreements and agent access to promote collaborations among industry, academia, NCI and foundations.***
- Work with Technology Transfer Branch (TTB) to coordinate development of model agreements and best practices
- Work with TTB to evaluate alternative approaches to resolving intellectual property issues such as patent pools and government-industry consortia
- Evaluate the feasibility of developing or enhancing a range of possible NCI-operated agent repositories

## Operational EffectivenessRecommended Initiative C5

***Increase NCI interaction and collaboration with foundations and advocacy groups to capitalize upon their complementary skills and resources for advancing early translational research.***
- Establish leadership position responsible for coordinating interactions with foundations and advocacy groups
- Implement more systematic, structured approach to interaction with foundations and advocacy groups
- Include foundation/advocacy representative in translational research Prioritization Working Group
- Explore approaches to avoiding duplicative proposal review
- Develop funding partnerships for targeted TR projects
- Work with foundations and advocacy groups to enhance outreach re tissue donation and image collection

## Operational EffectivenessRecommended Initiative C6

***Enhance training programs and career incentives to develop and maintain a committed early translational research workforce.***
- Develop Program Announcement highlighting training opportunities for early translational research
- Establish Translational Research Training Working Group to make recommendations on the training of clinician-scientists, PhD scientists and PhD nurses for TR
- Expand regulatory affairs training
- Revise funding programs and award guidelines to reward TR
- Collaborate with other organizations to adjust academic reward practices to enhance TR career support and incentives

## Principles Guiding Timeline and Budget

- Organizational and administrative initiatives should be initiated ASAP
- Prioritization process must be in place before STRAPs can commence
- Budget for administration will be kept to a minimum by leveraging existing structures
- Recommended extramural funding programs will require < 1% of the NCI budget

## TRWG Initiative Summary Timeline

## TRWG Initiative Summary Budget

## Dr. Hawk

## Context for the TRWG Recommendations

- Unrestricted mission, yet aware of current realities
- No impact on Discovery Research
- Should remain “unmanaged”
- Firmly committed to the vision
- TRWG’s assessment of the challenges (why?)
- TRWG’s goals (what?)
- Strived to identify “responsible” implementation strategies (when, who, how?), so recommendations are:
- Reasonably detailed
- Intentionally incremental
- Representative of a consensus view
- Aware that implementation plans should be flexible to adjust to the environment

## Proposed Next Steps 

- Publish the six pathways to clinical goals
- Develop translational research award codes based on pathways
- Implement communications plan for TRWG Report
- Convene an internal working group to discuss implementation strategies

## Acknowledgements

- National Cancer Institute
- Anna Barker, PhD
- Jim Doroshow, MD
- _Gary Dorfman, MD_
- Maureen Johnson, PhD
- _Jennifer Kwok_
- Anne Lubenow
- Cherie Nichols, MBA
- John Niederhuber, MD
- Henry Rodriguez, PhD, MBA
- _Lisa Stevens, PhD_
- _Jaye Viner, MD, MPH_
- Science & Technology Policy Institute
- _Oren Grad, MD, PhD_
- _Judy Hautala, PhD_
- _Maureen McArthur_
- _Alexis Wilson_
- _Brian Zuckerman, PhD_

- Science Applications International Corp.
- Jeff Zalatoris, PhD
- NOVA Research
- _Janet Braun_
- Ray Butler
- Erin Milliken, PhD
- Dana Young, JD
- Vanderbilt University
- David Dilts, PhD, MBA
_**Lynn Matrisian, PhD**_
- Vanessa Hill
- Johns Hopkins University
_**Bill Nelson, MD, PhD**_
- Jane Reese-Coulbourne, MS, MBA

***...******and the 57 Other Members of the Translational Research Working Group***

## Back-ups

## Potential Programmatic Utility of Developmental Pathways

- Experimental Design
- Efficiently plan, define, & explain
- Scientific goals and process
- Timeline
- Required resources
- Project Management
- Predict potential impediments by stage
- Measure progress
- Evaluate causes of delays/accelerations
- Guide redesign as necessary/appropriate
- Support Collaborations & “Hand-offs”
- Predict, plan, & facilitate timing & requirements re: critical interfaces
- Anticipate budgetary implications of shared T&E/resources
- Support Fiscal Management
- Toll-gated installments (reward mechanisms?)
- Demonstrate return on investment by “hitting”/exceeding target

## TRWG Products

- TR definition
- Six developmental pathways to clinical goals
- Portfolio analysis
- Review of NCI’s current TR activities
- Process analysis
- Case studies of 20 examples of translation in practice
- Draft final recommendations

## Obstacles to TR Progress – From the TRWG’s Perspective

## Obstacles to Meeting the Challenge

- Insufficient coordination & integration across NCI results in a fragmented TR effort that risks duplication & may miss important opportunities
- Absence of clearly designated funding & adequate incentives for researchers threatens the perceived importance of TR within the NCI enterprise
- Absence of a structured, consistent review & prioritization process tailored to the characteristics & goals of TR makes it difficult to direct resources to critical needs & opportunities

## Obstacles to Meeting the Challenge

- TR core services are often duplicative & inconsistently standardized, with capacity poorly matched to need
- Multidisciplinary nature of TR & the need to integrate sequential steps in complex development pathways warrants dedicated project management resources
- Insufficient collaboration & communication between basic & clinical scientists & the paucity of effective training opportunities limits the supply of experienced translational researchers
- Inadequate collaboration with industry delays appropriate developmental hand-offs

## TRWG Members – Broad Expertise

## Programmatic Representation on the TRWG (CRISP Database, 2000-2006)

**Cancer Centers (7)**
- David Alberts
- Michael Caligiuri
- Kenneth Cowan
- Raymond Dubois
- Peter Emanuel
- William Hait
- H. Kim Lyerly
**Industry (4)**
- Martin Cheever
- Sara Courtneidge
- Tona Gilmer
- Gary Gordon
**EDRN (2)**
- David Sidransky
- Sudhir Srivastava
**Advocates (3)**
- Laurie Fenton
- Gail McGrath
- Ellen Sigal

**P01s (17)**
- David Alberts
- Kenneth Anderson
- Robert Bast
- Michael Caligiuri
- Richard Cote
- Steven Dubinett
- Raymond Dubois
- Gary Gordon
- Joe Gray
- Waun Ki Hong
- Theodore Lawrence
- A. Thomas Look
- H. Kim Lyerly
- Brian Reid
- David Scheinberg
- Mitchell Schnall
- Thomas Sellers

**SPOREs (14)**
- James Abbruzzese
- Kenneth Anderson
- Robert Bast
- Darell Bigner
- Richard Cote
- Steven Dubinett
- Laura Esserman
- Joe Gray
- Waun Ki Hong
- Lynn Matrisian
- William Nelson
- Olufunmilayo Olopade
- David Sidransky
- Thea Tlsty
**Clinical Study Consortia (5)**
- David Alberts
- Michael Caligiuri
- James Doroshow
- Paul Limburg
- Richard Schilsky

## Programmatic Representation on the TRWG(CRISP Database, 2000-2006)

**R01s (30)**
- Kenneth Anderson
- Robert Bast
- Michael Caligiuri
- Martin Cheever
- Richard Cote
- Sara Courtneidge
- Adrian DiBisceglie
- James Doroshow
- Steven Dubinett
- Raymond Dubois
- Peter Emanuel
- Ellen Gritz
- William Hait
- Theodore Lawrence
- Paul Limburg
- A. Thomas Look
- H. Kim Lyerly
- Lynn Matrisian
- Anne McTiernan
- Ida “Ki” Moore
- William Nelson
- John Carl Oberholtzer

**Training/Ed (cont.)**
- Thomas Sellers (R25)
- Louis Weiner (K12)
**Federal Gov’t (17)**
- Kenneth Buetow (CB)
- Jerry Collins (DCTD)
- Phillip Dennis (CCR)
- James Doroshow (DCTD)
- Gregory Downing (OTIR)
- Jorge Gomez (OCTR)
- Ernest Hawk (OCTR)
- Anne Lubenow (OC)
- David Maslow (DEA)
- Suresh Mohla (DCB)
- Cherie Nichols (OSPA)
- John Carl Oberholtzer (OCTR)
- Richard Pazdur (FDA)
- Charles Rabkin (DCEG)
- Jeffrey Schlom (CCR)
- Richard Simon (DCTD)
- Sudhir Srivastava (DCP)
- Daniel Sullivan (DCTD)

**R01s (cont.)**
- Olufunmilayo Olopade
- Roman Perez-Soler
- Brian Reid
- David Scheinberg
- Thomas Sellers
- David Sidransky
- Thea Tlsty
- Louis Weiner
**Training/Education (15)**
- David Alberts (R25, T32)
- Robert Bast (K12, T32)
- Michael Caligiuri (T32)
- James Doroshow (K12)
- Raymond Dubois (T32)
- Peter Emanuel (T32)
- Waun Ki Hong (T32)
- H. Kim Lyerly (K12, T32)
- Lynn Matrisian (T32)
- Ida “Ki” Moore (T32)
- Olufunmilayo Olopade (T32)
- David Scheinberg (K12)
- Mitchell Schnall (T32)

## TRWG Expertise in Various Populations

- Head & Neck
- Waun Ki Hong
- David Sidransky
- Lung
- Phillip Dennis
- Steven Dubinett
- Laurie Fenton
- Waun Ki Hong
- Roman Perez-Soler
- Stomach/Esophagus
- Ernest Hawk
- Paul Limburg
- Brian Reid
- Pancreas
- James Abbruzzese
- Liver
- Adrian DiBisceglie
- Theodore Lawrence
- Charles Rabkin

- Ovary/Gyn
- David Alberts
- Robert Bast
- Thomas Sellers
- GU
- Richard Cote
- Prostate
- William Nelson
- Brain
- Darrel Bigner
- Skin
- David Alberts
- Leukemia/Lymphoma
- Michael Caligiuri
- Peter Emanuel
- A. Thomas Look
- David Scheinberg
- Myeloma
- Kenneth Anderson

**Colorectum**
- James Doroshow
- Raymond Dubois
- Ernest Hawk
- Paul Limburg
- Richard Pazdur
- Jeffrey Schlom
**Breast**
- Kenneth Cowan
- Laura Esserman
- Joe Gray
- William Hait
- H. Kim Lyerly
- Anne McTiernan
- Olufunmilayo Olopade
- Mitchell Schnall
- Thomas Sellers
- Thea Tlsty

## TRWG Expertise in Special Scientific Areas

**Prevention**
- David Alberts
- Adrian DiBisceglie
- Steven Dubinett
- Raymond Dubois
- Laura Esserman
- Gary Gordon
- Ellen Gritz
- Ernest Hawk
- Waun Ki Hong
- Paul Limburg
- Lynn Matrisian
- Anne McTiernan
- William Nelson
- Olufunmilayo Olopade
- Charles Rabkin
- Brian Reid
- Thomas Sellers
- David Sidransky
- Sudhir Srivastava
- Thea Tlsty
**Pediatrics**
- Peter Emanuel
- A. Thomas Look

**Drugs/Immunologics (cont.)**
- Gary Gordon
- William Hait
- Ernest Hawk
- Waun Ki Hong
- Paul Limburg
- H. Kim Lyerly
- William Nelson
- Richard Pazdur
- Roman Perez-Soler
- David Scheinberg
- Jeffrey Schlom
- Richard Schilsky
- Ellen Sigal
- Richard Simon
- Louis Weiner
**Biobehavior**
- Ellen Gritz
- Anne McTiernan
**Preclinical Models**
- Lynn Matrisian
- Suresh Mohla
- Thea Tlsty

**Survivorship**
- Ida “Ki” Moore
**Genetics**
- Kenneth Buetow
- Joe Gray
- Olufunmilayo Olopade
- William Nelson
- Charles Rabkin
- Thomas Sellers
- David Sidransky
**Imaging**
- Daniel Sullivan
- Mitchell Schnall
**Drugs/Immunologics**
- James Abbruzzese
- David Alberts
- Kenneth Anderson
- Martin Cheever
- Jerry Collins
- Michael Caligiuri
- Sara Courtneidge
- Kenneth Cowan
- James Doroshow
- Tona Gilmer

## Details of the TRWG Portfolio Analysis

## NCI Programmatic Involvement in Developmental Pathways

|                       Pathway
                           Steps

      Pathway | Early Development of Intervention | Enabling technologies (e.g., assays, repositories, models) | Refinement | Manufacturing/ Production | Early-stage trials |
| --- | --- | --- | --- | --- | --- |
| Agents (not including imaging agents) | SPORE, NCDDG, CCNE, R01, P01, Z01 | MMHCC, CPTAC, SPORE, NCDDG, CCNE, R01, P01, Z01
 | SPORE, RAID,  RAPID, NCDDG, CCNE, R01, P01, Z01
 | SPORE, RAID, RAPID, CCNE, R01, P01, Z01
 | Cancer Centers, Cooperative Groups, SPORE, DCP Phase I/II, DCTD Phase I/II, R01, P01, Z01
 |
| Immune Response Modifiers | SPORE, NCDDG, CCNE, R01, P01, Z01
 | MMHCC, SPORE, NCDDG, CPTAC, CCNE, R01, P01, Z01
 | SPORE, RAID, RAPID, NCDDG, CCNE, R01, P01, Z01
 | SPORE, RAID, RAPID, R01, P01, Z01
 | Cancer Centers, Cooperative Groups, SPORE, DCTD Phase I/II, R01, P01, Z01
 |
| Risk Assessment Devices (Biomarkers) | SPORE, EDRN, CPTAC, CCNE, R01, P01, Z01
 | MMHCC, EDRN, CPTAC, CCNE, R01, P01, Z01
 | SPORE, EDRN, CCNE, R01, P01, Z01
 | SPORE, CCNE, R01, P01, Z01
 | SPORE, EDRN, R01, P01, Z01
 |
| Risk Assessment Devices (Imaging, Imaging Agents, and Imaging Devices) | SPORE, ICMIC, NTROI, CCNE, R01, P01, Z01
 | MMHCC, CPTAC, ICMIC, NTROI, CCNE, R01, P01, Z01
 | SPORE, ICMIC, NTROI, DCIDE, CCNE, R01, P01, Z01 | SPORE, ICMIC, NTROI, DCIDE, CCNE, R01, P02, Z01 | Cancer Centers, CIP Quick Trials, SPORE, ICMIC, NTROI, R01, P01, Z01 |
| Interventive Devices | SPORE, CCNE, R01, P01, Z01
 | MMHCC, CPTAC, SPORE, CCNE, R01, P01, Z01
 | SPORE, CCNE, R01, P01, Z01
 | SPORE, R01, P01, Z01
 | SPORE, Cancer Centers, Cooperative Groups, R01, P01, Z01
 |
| Lifestyle Interventions | SPORE, R01, P01, Z01
 | MMHCC, MMHCC, SPORE, R01, P01, Z01
 | SPORE, R01, P01, Z01
 | SPORE, R01, P01, Z01
 | Cancer Centers, SPORE, Cooperative Groups, R01, P01, Z01
 |

**NCI Programmatic Involvement in Developmental Pathways**

## Portfolio Analysis: Key Findings

- Awards are not adequately categorized to provide meaningful, detailed quantitative assessments of translational content
- TR is funded by most NCI Divisions, Offices & Centers
- TR is funded by a range of mechanisms – individual, collaborative, & facilitated
- The majority of TR awards are to NCI-designated Cancer Centers

*www.cancer.gov/trwg*

## Portfolio Analysis: Program and Cooperative Awards

| Award Category | Translational Awards | Total Active Awards | % Translational | TR Award Funding in FY04 ($M) |
| --- | --- | --- | --- | --- |
| P01* | 107 | 207 | 51.7% | $215.0 |
| P20 | 8 | 34 | 23.5 | 3.0 |
| SPORE* (P50) | 58 | 58 | 100 | $131.7 |
| ICMIC (P50) | 7 | 7 | 100 | 15.8 |
| EDRN (U01/U24) | 28 | 28 | 100 | 21.8 |
| MMHCC (U01) | 10 | 23 | 43.5 | 8.1 |
| Other U01 | 122 | 209 | 58.4 | 98.6 |
| U19 | 5 | 18 | 27.8 | 3.7 |
| NTROI (U54) | 3 | 3 | 100 | 3.8 |
| Other U54 | 10 | 19 | 52.6 | 13.0 |
| U56 | 4 | 40 | 10.0 | 3.1 |

- *P01s and SPOREs are multi-component awards that typically include both research projects & core facilities.

## Portfolio Analysis: Drug Development Programs & Infrastructure Mechanisms

| Award Category | Translational Awards | Total Active Awards | % Translational | TR Award Funding in FY04 ($M) |
| --- | --- | --- | --- | --- |
| DDG | 18 | 18 | 100% | $11.1 |
| RAID | 45 | 45 | 100 | 16.3 |
| RAPID | 19 | 19 | 100 | 3.1 |

| Award Category | Translational Awards | Total Active Awards | % Translational | TR Award Funding in FY04 ($M) |
| --- | --- | --- | --- | --- |
| P30* | 54 | 61 | 88.5% | $212.5  |
| R24 | 8 | 43 | 18.6 | 1.5  |
| U24 | 8 | 14 | 57.1 | 6.0  |
| Extramural Cores
(P01, P30, P50) | 1,165 | 1,364 | 85.4 | N/A |

***Only Comprehensive and Clinical Cancer Centers were included here, not the Basic Cancer Centers.

## Portfolio Analysis: Individual Research, Small Business & Intramural Awards

| Funding Mechanism | Translational Awards | Total Active Awards | % Translational | TR Award Funding in FY04 ($M) |
| --- | --- | --- | --- | --- |
| R01 | 1,161 | 4,450 | 26.1% | $447.0 |
| R03 | 150 | 320 | 46.9  | 8.1 |
| R21 | 288 | 599 | 48.1 | 43.8 |
| R33 | 62 | 121 | 51.2 | 24.2 |
| R37 | 11 | 74 | 14.9 | 6.6 |
| R41 | 28 | 42 | 66.7 | 4.7 |
| R42 | 12 | 19 | 63.2 | 3.8 |
| R43 | 87 | 246 | 35.4 | 13.3 |
| R44 | 102 | 176 | 58.0  | 39.4 |
| Z01 | 257 | 630 | 40.8  | 164.4 |
|  |  |  |  |  |
| Totals* | 2,789 | 7,933 | 35.2 | 1,330.4 |

- *“Totals” show amounts for all Program and Cooperative Awards, Developmental Program Projects, Career Development Awards, Individual Research Awards, Small Business Awards, and Intramural Awards, & it excludes the amounts for the Infrastructure Mechanisms.

## Total Number of Translational Awards in FY04 (>/= 25% Relevant to these Disease Sites)

- “Other” includes P20, P30, R03, R24, R37, U19, U24, U54, and U56 awards. K-series awards and U10 awards are not included.

*www.cancer.gov/trwg*

## Total FY04 Spending for Translational Awards (>/= 25% Relevant to these Disease Sites)

- “Other” includes P20, P30, R03, R24, R37, U19, U24, U54, and U56 awards. K-series awards and U10 awards are not included.

*www.cancer.gov/trwg*

## Extramural Core Facilities Sponsored Through SPORE, P01, & P30 MechanismsFrequency Distribution

**Number of Institutions**

**Number of Core Facilities Per Institution**

- Number of Core facilities includes all Basic, Clinical, & Comprehensive Cancer Center (P30) Core facilities, and all SPORE & P01 Core facilities identified from the SPORE website, CRISP database, and abstracts.

## 
“To the individual who devotes his/her life to science nothing can give more happiness than when the results immediately find practical application. There are not two sciences. There is science and the application of science, and these two are linked as the fruit is to the tree.”

- “To the individual who devotes his/her life to science nothing can give more happiness than when the results immediately find practical application. There are not two sciences. There is science and the application of science, and these two are linked as the fruit is to the tree.”

*Louis Pasteur, 1822-95*

**Drawing Inspiration from Pasteur**