# Presentation: 461044

## Restructuring the 

**Restructuring the **
**National Cancer Clinical Trials Enterprise**
**A Report to the National Cancer Advisory Board**
**From the Clinical Trials Working Group**
**James H. Doroshow, M.D., Chair**
**June 7, 2005**
**Bethesda, Maryland**

## Summary Vision

***Enhance the best of all the components of the NCI-supported clinical trials system to develop a cooperative enterprise built on a strong scientific infrastructure and a broadly engaged coalition of critical stakeholders***

## Rationale for Change

- Advances in cancer biology offer enormous potential to improve cancer clinical practice
- Opportunity to move beyond cytotoxic treatments to more effective therapies targeting the specific characteristics of a patient’s tumor
- Challenge of evaluating an ever-increasing number of new, highly specific agents in molecularly-defined subsets of patients

## Requirements for Success

**Successfully restructuring the NCI-funded clinical trials enterprise to optimize patient outcome necessitates:**
- Routine incorporation of the tools of cancer biology into cancer clinical trials
- A cooperative, interdisciplinary, efficient, and functionally integrated approach to clinical trials conduct
- An implementation strategy that recognizes the high-value components of the current clinical trials system, and simultaneously challenges them to work together in fundamentally new ways

## Requirements for Success

**1. Advances in cancer biology require:**
-   Comprehensive information sharing and close collaboration among basic, translational, and clinical investigators
-   New resources for real-time integration of molecular analysis tools into clinical trials that will change medical practice
-   Coordinated networks of investigators to allow timely completion of trials for patients with specific, molecularly-defined profiles who are drawn from larger cohorts
-   Scientific prioritization to focus investment on specific new targeted agents and the best-designed, scientifically-driven clinical trials

## Requirements for Success

**2. A cooperative, interdisciplinary, and efficient clinical trials system requires:**
-   Integration of the functionally diverse elements of the current enterprise, while improving effectiveness and retaining innovation
**  **Active and ongoing involvement of community oncologists and patient advocates to develop clinical trials appropriate for patients and their treating physicians
-   Closer collaboration between NCI staff and the extramural clinical trials community in designing, prioritizing, and executing trials
-   Early and vigorous participation of industry and government regulatory agencies to speed therapeutic development

## Requirements for Success

**3. A successful implementation strategy requires:**
-   Recognition of the essential value of Cancer Centers, SPORES, Cooperative Groups, grant-supported clinical trialists, CCOPs, community oncologists, and patient advocates in the current clinical trials process
-   Simultaneous acknowledgement that real progress means challenging each component of the current system to work together in fundamentally new ways
-   Enhanced commitment by the extramural community to the increased effort and responsibility required to assist NCI more broadly in governance of the entire cancer clinical trials enterprise
-   Development of a formal system to evaluate and measure the impact of the restructuring initiatives

## Common Themes of Restructuring Plan

- Coordination
- Coordinate clinical trials research through data sharing and providing incentives for collaboration
- Prioritization/Scientific Quality
- Involve all stakeholders in design and prioritization of clinical trials that address the most important questions, using the tools of modern cancer biology
- Standardization
- Standardize IT infrastructure and clinical research tools
- Operational Efficiency
- Use resources most efficiently through improved cost-effectiveness and accrual rates, and more rapid trial initiation
- Integrated Management
- Restructure extramural and intramural oversight of NCI clinical trials

## Implementation Timeline

- Restructuring plan encompasses 22 initiatives organized by these common themes
- Implementation projected to be complete in 4-5 years
- Majority of initiatives implemented by end of year 3
- Established as routine practice by end of year 7

## Coordination Initiatives

**Establish Comprehensive Clinical Trials Database**
- (Initiate Year 1; Implement Year 3)
- Data on all NCI-supported trials, across all funding mechanisms
- Data elements
- Descriptive information on trial status
- Clinical trial results
- Links to published or presented data
- Defined access controls
- NCI  review of safety and outcome data
- Developed in concert with caBIG
**Critical Prioritization and Coordination Tool**

## Coordination Initiatives

**	****Realign NCI Reward System & Academic Incentives**
- (Implement Year 2)
- Reward collaborations among SPOREs, P01’s, early trials groups and NCI-supported multi-site clinical trials networks
- Reward Cooperative Groups and multi-site networks for participation in trials conducted throughout the NCI-supported clinical trials system
- Reward hand-offs between NCI-supported programs that move innovative clinical trials forward
- Competitive awards for mid-level, non-PI investigators who play a critical role in collaborative clinical trials

## Coordination Initiatives

**Enhance Coordination with Federal Agencies**
- (Initiate Year 1)
- Increase cooperation between NCI, FDA, and industry in oncology clinical trials
- Expand awareness of the NCI-FDA expedited approval process to speed trial initiation
- Work with CMS to identify clinical studies that address both NCI and CMS objectives

## Prioritization/Scientific Quality Initiatives

**Establish Transparent Prioritization System **
- Create Investigational Drug Steering Committee to enhance design and prioritization of early phase drug development trials  (Implement Year 1)
- Create network of Scientific Steering Committees for design and prioritization of phase III trials                                                        (Initiate Year 1; Fully Implement Year 5)
- Leverages current Intergroup, Cooperative Group, SPORE, and Cancer Center structures
- State of the Science Meetings
- Increase community oncologist and patient advocate involvement in clinical trial design and prioritization               (Initiate Year 1)
- Investigate integration of all phase II trials into the overall prioritization process                                                                                (Initiate Year 4)

##  Prioritization/Scientific Quality Initiatives

**	****Facilitate Correlative Studies** (Initiate Year 2)
- Clinical trial-specific, molecular profile, imaging, and quality of life studies
- Priority for studies integral to the design of the trial (e.g. an entry criterion)
- Budget set-aside
- Timely prioritization and funding process
- Develop a standards-setting process for biomarker measurements in association with clinical trials

##  Standardization Initiatives

**Create Standard Clinical Research Tools**
- Establish national cancer clinical trials IT infrastructure fully interoperable with caBIG  (Initiate Year 1; Interoperable Year 5)
- In consultation with industry and FDA, develop standard Case Report Forms incorporating Common Data Elements  (Initiate Year 1; Implement Year 3)
- Build a credentialing system for investigators and sites recognized by NCI and industry  (Initiate Year 1; Implement Year 5)
- Develop commonly accepted clauses for clinical trial contracts with industry  (Initiate Year 2)

## Operational Efficiency Initiatives

**Improve Cost-Effectiveness and Accrual Rates**
- Restructure phase III funding model (Analysis Year 1; Initiate Year 2)
- Increase patient awareness and understanding of clinical trials    (Initiate Year 1)
- Increase minority patient access to clinical trials (Initiate Year 1)
**Speed Trial Initiation at Sites**
- Reduce institutional barriers to timely trial initiation  (Analysis Year 1-2; Implement Year 3)
- Promote adoption of the NCI CIRB facilitated review process (Analysis Year 1-2; Implement Year 3)

## Enterprise-Wide Initiatives

**Create Clinical Trials Oversight Subcommittee of the NCAB to advise the NCI Director on conduct of clinical trials across the Institute**

##  Enterprise-Wide Initiatives

**Develop coordinated NCI organizational structure to manage the entire clinical trials enterprise supported by the Institute**

## Initiatives: Interactive and Interdependent

_**Initiatives: Interactive and Interdependent**_

**NCI Clinical Trials Management**

**NCAB Clinical Trials **
**Subcommittee**

***Database ***
***Aligned Incentives***

***IT Infrastructure ***
***Case Report Forms ***
***Contracts***

***Community ***
***Oncologist***
***Patient Advocate ***
***Involvement  ***

***Rapid Trial***
***Completion***

***IT Infrastructure***
***Case Report Forms***

***Federal Agency   ***
***Coordination***

***IT Infrastructure***
***Case Report Forms***

**Coordination**

**Standardization**

**Prioritization**

**Efficiency**

## Estimated CTWG Implementation Budget ($M)

| Budget Category | Year 1 | Year 2 | Year 3 | Year 4 | Year 5 |
| --- | --- | --- | --- | --- | --- |
| Extramural Clinical Trials | 1.0 | 13.8 | 20.0 | 21.0 | 21.5 |
|     High Accrual Supplmts | 0.0 |   5.0 |   6.0 |   7.0 |   7.5 |
|     Correlative Studies | 0.0 |   5.0 | 10.0 | 10.0 | 10.0 |
|     Clin Investigator Awards | 0.0 |   1.0 |   1.0 |   1.0 |   1.0 |
|     SPORE/CanCtr CTSU | 0.5 |   0.8 |   1.0 |   1.0 |   1.0 |
|     Minority Supplmts | 0.5 |   2.0 |   2.0 |   2.0 |   2.0 |
| Clinical Trials Database | 1.3 |   1.8 |   3.8 |   3.8 |   2.8 |
| Prioritization System |   1.25 |   1.8 |   2.5 |   2.7 |   2.9 |
| Analysis Projects |   1.55 |     1.95 |   0.0 |   0.0 |   0.0 |
| NCI Clin Trials Mgmt/Eval | 2.0 |     1.25 |   1.7 |   1.0 |   1.5 |
| TOTAL | 7.1 | 20.6 | 28.0 | 28.5 | 28.7 |

##  Evaluation and Outcome Measures

**Establish structured evaluation system**
- Designed by experienced evaluation specialists
- Blend of qualitative/quantitative measures
- Evaluation involving clinical trial experts and structured empirical data
**Perform baseline evaluation**
**Perform periodic evaluations**
- Program management measures
- System performance measures
- System outcome measures

##  Program Management Measures

- Timely initiation of tasks
- Adherence to implementation plan
- Alternate plans developed to quickly and effectively manage implementation obstacles or design flaws
- Tasks accomplished on time or timelines revised in a realistic manner

##  System Performance Measures

**Restructure the funding model for Phase III efficacy trials to incentivize more rapid rates of patient accrual.**
-   Efficiencies in clinical trial management and administration     identified and implemented.  Evaluation at 2 and 4 years.
-   Distribution of patient accrual at high and medium accruing sites and number of sites below economically viable accrual levels.  Evaluation at 0, 3 and 6 years.
-   Cost savings achieved due to shift of patient accrual to highly accruing, more efficient sites. Evaluation at 3 and 6 years.
- 4.  Perception of clinical investigators concerning the degree to which NCI funding is structured to incentivize patient accrual.  Evaluation at 0, 3 and 6 years.

-  _**System Performance Measures**_

##  System Outcome Measures

- Trials that provide results critical for guiding new therapeutics and diagnostics development
- New biomarkers that enable better targeting of cancer therapies
- Revisions of major treatment guidelines to reflect new knowledge gained

##  Conclusion

**Fifty years ago, NCI had the foresight to initiate support for networks of investigators and institutions engaged in clinical trials who could speed the development of new cancer therapies.**
**Over the next half-century, with enhanced commitment of time and scientific expertise from extramural investigators, physicians, and advocates, as well as the new investment called for by this restructuring, it is our expectation that NCI - in collaboration with the entire clinical trials community - will lead the process of translating extraordinary advances in cancer biology into the clinical trials that materially improve the outcome of cancer patients everywhere**.

## Clinical Trials Working GroupMembership

- James H. Doroshow, M.D., Chair				Richard S. Kaplan, M.D.
- Howard Fine, M.D., Co-Chair				Michael S. Katz
- Maureen R. Johnson, Ph.D., Executive Director		Amy S. Langer, M.B.A.
- James L. Abbruzzese, M.D.1				Gershon Y. Locker, M.D.
- Martin Abeloff, M.D.					Eberhard A. Mack, M.D.
- Jeffrey S. Abrams, M.D.				Lori Minasian, M.D.
- Peter Adamson, M.D.1				John E. Niederhuber, M.D.
- David Alberts, M.D.1					Rose Mary Padberg, R.N., M.A.
- Karen Antman, M.D.					David R. Parkinson, M.D.1
- Frederick R. Appelbaum, M.D.1				Richard Pazdur, M.D.1
- Steven D. Averbuch, M.D.1				Edith A. Perez, M.D.
- Peter Bach, M.D., M.A.P.P.				Mark J. Ratain, M.D.1
- Colin Begg, Ph.D.					Mack Roach, III, M.D.
- Kenneth H. Buetow, Ph.D.				Julia H. Rowland, Ph.D.
- Michaele C. Christian, M.D.				Richard Schilsky, M.D.1
- Jean B. DeKernion, M.D.				Mitchell Schnall, M.D., Ph.D.
- Leslie G. Ford, M.D.					Daniel Sullivan, M.D.
- Louise B. Grochow, M.D.				Sheila E. Taube, Ph.D.
- Ernest Hawk, M.D., M.P.H.				James A. Zweibel, M.D.
- David H. Johnson, M.D.1
- 1Chair or Co-Chair of Subcommittee