Report of the 

Clinical Trials Working Group
	

of the 

National Cancer Advisory Board
	

Restructuring the 

National Cancer Clinical Trials 

Enterprise
	

June 2005
	
 

 

Restructuring the National Cancer Clinical Trials Enterprise 

CLINICAL TRIALS WORKING GROUP 

Chairman 

James H. Doroshow, M.D. 

Director
 

Division of Cancer Treatment and Diagnosis 

National Cancer Institute 

Bethesda, MD 

Co-Chairman 

Howard A. Fine, M.D.
 

Chief 

Neuro-Oncology Branch 

Center for Cancer Research
 

National Cancer Institute 

Bethesda, MD 

James L. Abbruzzese, M.D. 

Chairman and Professor of Medicine 

Department of Gastrointestinal 

Oncology and Digestive Diseases 

The University of Texas 

MD Anderson Cancer Center 

Houston, TX 

Martin Abeloff, M.D. 

Director 

Sidney Kimmel Comprehensive 

Cancer Center 

Johns Hopkins University 

Baltimore, MD 

Jeffrey S. Abrams, M.D. 

Chief 

Clinical Investigations Branch 

Cancer Therapy Evaluation Program 

Division of Cancer Treatment 

and Diagnosis 

National Cancer Institute 

Bethesda, MD 

Peter Adamson, M.D. 

Chief 

Division of Clinical Pharmacology 

 and Therapeutics 

The Children’s Hospital of Philadelphia 

Philadelphia, PA 

David Alberts, M.D. 

Director 

Arizona Cancer Center 

University of Arizona, Tucson 

Tucson, AZ 

Karen Antman, M.D. 

Dean and Provost 

Boston University School of Medicine 

Boston, MA 

Frederick R. Appelbaum, M.D. 

Director 

Clinical Research Division 

Fred Hutchinson Cancer 

 Research Center 

Seattle, WA 

Report of the Clinical Trials Working Group of the National Cancer Advisory Board 
 

 

 

Restructuring the National Cancer Clinical Trials Enterprise 

Steven D. Averbuch, M.D. 

Executive Director 

Clinical Research, Oncology/G.I. 

Merck Research Laboratories 

Blue Bell, PA 

Peter Bach, M.D., M.A.P.P. 

Senior Adviser 

Office of the Administrator 

Centers for Medicare and 

 Medicaid Services 

U.S. Department of Health and 

 Human Services 

Washington, DC 

Colin Begg, Ph.D. 

Chairman 

Department of Epidemiology 

and Biostatistics 

Memorial Sloan-Kettering 

Cancer Center 

New York, NY 

Kenneth H. Buetow, Ph.D. 

Director 

NCI Center for Bioinformatics 

National Cancer Institute 

Bethesda, MD 

Michaele C. Christian, M.D. 

Associate Director 

Cancer Therapy Evaluation Program 

Division of Cancer Treatment 

and Diagnosis 

National Cancer Institute 

Bethesda, MD 

Jean B. deKernion, M.D. 

Associate Dean of Clinical Research 

School of Medicine 

University of California, Los Angeles 

Los Angeles, CA 

Leslie G. Ford, M.D. 

Associate Director for Clinical Research 

Division of Cancer Prevention 

National Cancer Institute 

Bethesda, MD 

Louise B. Grochow, M.D., FACP 

Global Medical Science Director 

AstraZeneca 

Waltham, MA 

Ernest Hawk, M.D., M.P.H. 

Director
 

Office of Centers, Training, 

and Research 

National Cancer Institute 

Bethesda, MD 

David H. Johnson, M.D. 

Deputy Director 

Vanderbilt Ingram Cancer Center 

Director 

Division of Hematology/Oncology 

Vanderbilt University Medical School 

Nashville, TN 

Richard S. Kaplan, M.D. 

Acting Director 

UK National Cancer Research Network 

NCRN Coordinating Centre 

Leeds, United Kingdom 

Michael S. Katz 

Vice President, Board of Directors 

International Myeloma Foundation 

Bayside, NY 

Amy S. Langer, M.B.A. 

Breast Cancer Advocate 

Former Executive Director 

National Alliance of Breast 

Cancer Organizations (NABCO) 

New York, NY 

Report of the Clinical Trials Working Group of the National Cancer Advisory Board 
 

 

 

Restructuring the National Cancer Clinical Trials Enterprise 

Gershon Y. Locker, M.D. 

Principal Investigator 

Evanston Northwestern 

Healthcare CCOP 

Professor of Medicine 

Feinberg School of Medicine 

Northwestern University 

Evanston, IL 

Eberhard A. Mack, M.D. 

Professor 

Department of Surgery 

University of Wisconsin-Madison 

Madison, WI 

Lori Minasian, M.D. 

Chief 

Community Oncology and Prevention 

Trial Research Group 

Division of Cancer Prevention 

National Cancer Institute 

Bethesda, MD 

John E. Niederhuber, M.D. 

Professor 

Division of General Surgery 

Department of Surgery 

University of Wisconsin-Madison 

Madison, WI 

Rose Mary Padberg, R.N., M.A. 

Chief, Cancer Education 

Office of Education and 

Special Initiatives 

National Cancer Institute 

Bethesda, MD 

David R. Parkinson, M.D. 

Vice President and Head 

Clinical Oncology Therapeutic Area 

Amgen 

Thousand Oaks, CA 

Richard Pazdur, M.D. 

Director 

Office of Oncology Drug Products 

Center for Drug Evaluation 

and Research 

U.S. Food and Drug Administration 

Rockville, MD 

Edith A. Perez, M.D. 

Professor of Medicine 

Director of Cancer Clinical Study Unit 

Mayo Medical School 

Mayo Clinic 

Jacksonville, FL 

Mark J. Ratain, M.D. 

Leon O. Jacobson Professor of Medicine 

Chairman, Committee on Clinical

 Pharmacology and Pharmacogenomics 

Associate Director for Clinical Sciences 

Cancer Research Center 

University of Chicago 

Chicago, IL 

Mack Roach III, M.D. 

Professor 

Department of Radiation Oncology 

University of California, San Francisco 

San Francisco, CA 

Julia H. Rowland, Ph.D. 

Director, Office of Cancer Survivorship 

Division of Cancer Control and 

Population Sciences 

National Cancer Institute 

Bethesda, MD 

Richard Schilsky, M.D. 

Professor of Medicine 

Associate Dean for Clinical Research 

Chairman, CALGB 

University of Chicago 

Chicago, IL 

Report of the Clinical Trials Working Group of the National Cancer Advisory Board 
 

Restructuring the National Cancer Clinical Trials Enterprise 

Mitchell Schnall, M.D., Ph.D. 

Matthew J. Wilson Professor 

of Radiology 

Associate Chair of Research 

Department of Radiology 

University of Pennsylvania 

Philadelphia, PA 

Daniel Sullivan, M.D. 

Associate Director 

Cancer Imaging Program 

Division of Cancer Treatment 

and Diagnosis 

National Cancer Institute 

Bethesda, MD 

Executive Director 

Maureen R. Johnson, Ph.D. 

Special Assistant to the Director 

Office of the Director 

National Cancer Institute 

Bethesda, MD 

Sheila E. Taube, Ph.D. 

Associate Director 

Cancer Diagnosis Program 

Division of Cancer Treatment 

and Diagnosis 

National Cancer Institute 

Bethesda, MD 

James A. Zwiebel, M.D., FACP 

Associate Chief for Biologics Evaluation 

Investigational Drug Branch, CTEP 

Division of Cancer Treatment 

and Diagnosis 

National Cancer Institute 

Bethesda, MD 

Report of the Clinical Trials Working Group of the National Cancer Advisory Board 
Restructuring the National Cancer Clinical Trials Enterprise 

Table of Contents 

Executive Summary............................................................ 2

Summary Vision.................................................................. 6

Introduction ......................................................................... 9

Coordination Initiatives .................................................... 11

Prioritization/Scientific Quality Initiatives ...................... 23

Standardization Initiatives................................................ 36

Operational Efficiency Initiatives..................................... 43

Enterprise-Wide Initiatives............................................... 52

Evaluation and Outcome Measures ................................ 54

Timeline and Budget......................................................... 59

Appendices........................................................................ 64 

Appendix A

CTWG Meeting Dates ...............................................................................65 

Acknowledgments.....................................................................................66

Appendix B

Table 1: Implementation Timeline .............................................................67 

Table 2: Estimated Implementation Budget by Category ..........................75 

Table 3: Estimated Implementation Budget by Year.................................83 

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Restructuring the National Cancer Clinical Trials Enterprise 

Executive Summary 

In January 2004, Dr. Andrew von Eschenbach, Director of the National Cancer Institute 

(NCI), established the Clinical Trials Working Group (CTWG) to advise the National 

Cancer Advisory Board (NCAB) on whether and in what ways the NCI-supported 

national clinical trials enterprise should be restructured to realize the promise of 

molecular medicine for advancing oncologic clinical practice in the 21st century. The 

CTWG is a broadly constituted panel with experts from academic research institutions, 

community oncology practices, the pharmaceutical and biotechnology industries, cancer 

patient advocacy groups, NCI, the Food and Drug Administration (FDA), and the Centers 

for Medicare and Medicaid Services (CMS). 

The CTWG first reached consensus on four critical goals for designing a restructured 

national clinical trials enterprise that is not only more efficient and coordinated but 

founded on the best science. The first goal was to improve coordination and cooperation 

among the functionally diverse components of the current system, including industry and 

federal regulatory agencies. The second goal was to improve prioritization and scientific 

quality by developing an open and transparent process for the design and prioritization of 

clinical trials that are science-driven and meet the needs of patient care. The third goal 

was to improve standardization of tools and procedures for trial design, data capture, data 

sharing, and administrative functions to minimize duplication of effort, and to facilitate 

development of a shared infrastructure to support an integrated national cancer clinical 

trials network. The fourth goal was to improve operational efficiency by increasing the 

rate of patient accrual and reducing operational barriers so that trials can be initiated and 

executed in a timely, cost-effective manner. 

In addressing these goals, the CTWG proceeded through a consensus building process 

involving three sequential stages. First, the CTWG defined which specific aspects of the 

current system could and should be improved. The second stage focused on development 

of recommendations to address those improvements; these recommendations were 

presented to the NCAB on February 17, 2005. In the third stage, the CTWG defined 

specific initiatives based on those recommendations and designed implementation plans 

for their practical realization. 

The result of this broad-based, strategically-driven effort, involving all the critical 

stakeholders in the cancer clinical trials community, is the compendium of 22 initiatives 

detailed in this report on “Restructuring the National Cancer Clinical Trials Enterprise.” 

The proposed initiatives cover a wide range of specific components of the current system, 

and each addresses one of the common themes derived from the CTWG goals: 

Coordination, Prioritization/Scientific Quality, Standardization, or Operational 

Efficiency. These initiatives are designed to support a powerful and transparent clinical 

trials enterprise that integrates the individually strong components of the current system 

into a cross-disciplinary, scientifically-driven, cooperative research effort. Because this 

enterprise will also require coordinated leadership, the CTWG recommends two 

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Restructuring the National Cancer Clinical Trials Enterprise 

Enterprise-Wide initiatives addressing ongoing NCAB oversight of clinical trials and an 

integrated NCI organizational structure for clinical trials management. 

The initiatives, which are described in detail in the report, are summarized below. 

Coordination Initiatives 

	 Create a comprehensive database containing information on all NCI-funded 

clinical trials to facilitate better planning and management across clinical trial 

venues. 

 Realign NCI and academic incentives to promote collaborative team science. 

 Increase cooperation between NCI, FDA, and industry to enhance the focus and 

efficiency of oncology drug development. 

 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, and for which CMS may be able to reimburse some routine and 

investigational costs. 

Prioritization/Scientific Quality Initiatives 

	 Create an Investigational Drug Steering Committee to work with NCI to enhance 

the design and prioritization of early phase drug development trials. 

	 Create a network of Scientific Steering Committees, which leverage current 

Intergroup, Cooperative Group, Specialized Programs of Research Excellence 

(SPORE), and Cancer Center structures, to work with NCI in the design and 

prioritization of phase III trials to better allocate scarce resources, improve 

scientific quality, and reduce duplication. 

	 Increase community oncologist and patient advocate involvement in clinical trial 

design and prioritization to improve the rate of patient accrual, and better address 

practical and quality of life concerns in the design of trials. 

	 Develop a funding and prioritization process to ensure that critical correlative 

science and quality of life studies can be conducted in a timely manner in 

association with clinical trials. 

	 Develop a standards-setting process for the measurement, analysis, and reporting 

of biomarker data in association with clinical trials to enhance data comparisons, 

reduce duplication, and facilitate data submission for regulatory approval. 

	 Investigate integration of phase II trials into the overall prioritization process to 

further coordinate the national clinical trials system. 

Standardization Initiatives 

	 Create, in partnership with the extramural cancer research community, a national 

cancer clinical trials information technology infrastructure fully interoperable 

with NCI’s cancer Bioinformatics Grid to improve cost effectiveness and 

comparability of results across trials and sites. 

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Restructuring the National Cancer Clinical Trials Enterprise 

	 In consultation with industry and FDA, develop standard Case Report Forms 

incorporating Common Data Elements to improve information sharing among 

cancer researchers and optimize data requirements. 

	 Build a credentialing system for investigators and sites recognized by NCI and 

industry to allow faster trial initiation and keep the investigative community 

abreast of legal, safety, and regulatory changes. 

	 Develop commonly accepted clauses for clinical trial contracts with industry to 

reduce the lead-time needed to open trials. 

Operational Efficiency Initiatives 

	 Restructure the phase III funding model to promote rapid patient accrual rates and 

cost-effectiveness. 

 Reduce institutional barriers to timely trial initiation. 

 Increase patient and public awareness and understanding of clinical trials. 

 Increase minority patient access to clinical trials to improve the participation of 

underserved and underrepresented populations. 

	 Promote adoption of the NCI Central Institutional Review Board facilitated 

review process to reduce the time and resources needed to open trials at individual 

sites. 

Enterprise-Wide Initiatives 

 Create a Clinical Trials Oversight Subcommittee of the NCAB to advise the NCI 

Director on conduct of clinical trials across the Institute. 

 Develop a coordinated NCI organizational structure to manage the entire clinical 

trials enterprise supported by the Institute. 

No major restructuring of an ongoing enterprise such as NCI-supported cancer clinical 

trials should be undertaken without a plan to evaluate its success. Therefore, the CTWG 

has also proposed that a formal system be developed to evaluate the success of the 

restructuring effort. The evaluation system will address three important measures. The 

first measure is program management to track and evaluate implementation of the 

initiatives. The second measure is system performance to evaluate the effect of the 

restructuring on the design, prioritization, and conduct of cancer clinical trials. The third 

measure is system outcomes to assess the effect of the restructuring on increasing the 

number of useful therapies for patients and improved targeting of therapies to the patients 

most likely to benefit from them. 

Each of the initiatives is accompanied by an implementation plan including an associated 

timeline and budget. Implementation of the CTWG initiatives will require four to five 

years to complete, although the majority are targeted for implementation by the end of 

year three. Bringing the initiatives forward into routine practice will then require an 

additional two to three years. The restructuring effort is projected to cost $113M over 

five years. Projected expenses increase from $7.1M in FY06 to $20.6M in FY07 

reaching a steady state of approximately $29M annually in FY08 and beyond. Of this 

Report of the Clinical Trials Working Group of the National Cancer Advisory Board 

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Restructuring the National Cancer Clinical Trials Enterprise 

annual total, 75% is direct support to the extramural community, 10% is for the 

comprehensive clinical trials database, 10% is to operate the extramurally-driven 

prioritization process, and 5% is for the NCI management structure necessary to 

effectively guide this new enterprise. 

Implementing these initiatives will require considerable additional effort by the 

extramural clinical trials community, as well as an increased financial investment by 

NCI. But such new commitment and investment will result in an increased level of 

ownership in and responsibility for the clinical trials system by all of its stakeholders, and 

is crucial for ensuring that the large, ongoing national investment in cancer clinical trials 

achieves the goal of bringing effective new therapies to patients. By embracing this 

restructuring, NCI and the oncology community will be positioned to ensure that the 

advances in understanding the biological basis of cancer, generated by the past 40 years 

of research, make a substantive difference in reaching the NCI 2015 goal of eliminating 

suffering and death from cancer. 

Report of the Clinical Trials Working Group of the National Cancer Advisory Board 

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Restructuring the National Cancer Clinical Trials Enterprise 

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. 

Advances in molecular medicine offer enormous potential to improve cancer clinical 

practice by moving beyond the cytotoxic treatments of the past to safer and more 

effective therapies targeting the specific characteristics of a patient’s tumor. However, 

development of these targeted therapies, based on an understanding of the genetic and 

cellular mechanisms underlying specific cancers, creates several challenges for the design 

and conduct of cancer clinical trials. 

Trials driven by advances in cancer biology will require robust clinical trial designs that 

necessitate comprehensive information sharing and close collaboration among clinical 

researchers and basic and translational scientists. Moreover, the evaluation of novel 

targeted therapies, designed to be effective against cancers with a specific molecular 

profile, depends on synergistic integration of treatment protocols with modern molecular 

diagnostic and imaging techniques. Such integration will require real-time, coordinated 

participation between clinical oncologists and experts in comprehensive molecular 

analysis and bioinformatics during the conduct of trials. Therapies appropriate for only a 

subset of patients will also require a large, coordinated network of institutions and 

clinical investigators to achieve adequate and timely patient recruitment. It may be 

difficult for single institutions or even existing networks and groups to be successful on 

their own. And finally, the rapid pace of scientific progress has created an everincreasing number of novel therapies to test. Only through an open, collaborative 

prioritization system involving all the critical stakeholders can the best decisions be made 

as to which agents and disease targets warrant an investment of taxpayer dollars in 

clinical trials. 

This enormous potential for more specific cancer treatment, coupled with the complexity 

of evaluating new, highly specific agents, requires a national clinical trials enterprise that 

integrates the knowledge, insights, and skills of multiple fields into a new kind of crossdisciplinary, scientifically-driven, cooperative research endeavor. Creating such an 

endeavor will require integration of the successful, but functionally diverse, elements of 

the current clinical trials system supported by the National Cancer Institute (NCI). The 

strength of the current system is that it involves many institutions across the public, 

private, and academic sectors as well as a broad cross-section of clinical investigators and 

other healthcare professionals. The challenge is to bring these diverse institutions and 

individuals together into an integrated and efficient, but innovative and responsive, 

engine for moving therapies to patients. 

Report of the Clinical Trials Working Group of the National Cancer Advisory Board 

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Restructuring the National Cancer Clinical Trials Enterprise 

Building a national clinical trials enterprise founded on the best science requires the 

achievement of four important goals. The first is to enhance coordination and 

cooperation by ensuring that comprehensive information on cancer clinical trials is 

readily available for all stakeholders, that collaborative team science, as well as 

individual achievement, is rewarded, and that NCI clinical trials are effectively 

coordinated with federal regulatory systems. The second is to enhance scientific quality 

and prioritization so that NCI supports the best-designed trials, addressing the most 

important questions, leveraging the most significant scientific advances. The third is to 

enhance standardization of tools and procedures for trial design, data capture, data 

sharing, and administrative functions to decrease effort and minimize duplication. The 

fourth is to enhance operational efficiency by increasing the rate of patient accrual and 

reducing operational barriers so that trials can be initiated and executed in a timely, cost 

effective manner. 

To address these challenges and goals, the Clinical Trials Working Group (CTWG) of the 

National Cancer Advisory Board (NCAB) has developed a detailed blueprint for 

“Restructuring the National Cancer Clinical Trials Enterprise” so that the translational 

power of individualized oncologic medicine can drive clinical trials research in the 21st 

century. The strategy developed by the CTWG focuses on leveraging the unique 

strengths of the current clinical trials enterprise. It is a strategy that specifically 

recognizes the role of NCI-designated Cancer Centers as the primary institutional home 

for a large number of cancer clinical investigators, the strength of Specialized Programs 

of Research Excellence (SPOREs) in disease-oriented translational studies, the critical 

need for investigator-initiated clinical trials supported by Program Project (P01) and R01 

Grants, the stable clinical trials infrastructure provided by the Cooperative Groups, and 

the ability of Community Clinical Oncology Programs (CCOPs) and other community 

oncologists to provide clinical trials in a local environment. The proposed restructuring 

preserves and strengthens all of these existing components of the NCI clinical trials 

system, but asks them to work together in fundamentally different ways. 

Cooperative Groups, Cancer Centers, SPOREs, and individual investigators will be asked 

to participate collaboratively in a joint enterprise guided by scientific priorities and 

informed by input from basic and translational scientists, community oncologists, and 

patient advocates. Sharing of data and ideas, and the development of true team science 

will become a new standard of excellence alongside individual and institutional 

achievement. NCI staff and extramural investigators will be asked to develop a closer 

relationship based on an open sharing of ideas that will enhance the design of cancer 

clinical trials. Industry and government regulatory agencies will also be asked to become 

active participants in the collaborative enterprise. And finally, the extramural community 

will be called upon to make a significant commitment to assist in the governance of the 

new enterprise, working side by side with NCI to set new policies, procedures, and 

standards, and guide prioritization and decision-making. 

Implementing these changes will require considerable effort by all stakeholders as well as 

new financial investment. But this renewed commitment and the associated resources are 

Report of the Clinical Trials Working Group of the National Cancer Advisory Board 

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Restructuring the National Cancer Clinical Trials Enterprise 

crucial for ensuring that the large, ongoing national investment in cancer clinical trials 

achieves the goal of bringing effective new therapies to patients. By embracing this 

restructuring, NCI and the oncology community will be positioned to ensure that the 

advances in understanding the biological basis of cancer, generated by the past 40 years 

of research, are harnessed effectively to bring measurable, meaningful benefits to patients 

as NCI pursues the goal of eliminating suffering and death from cancer by 2015. 

Report of the Clinical Trials Working Group of the National Cancer Advisory Board 

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Restructuring the National Cancer Clinical Trials Enterprise 

Introduction 

In January 2004, Dr. Andrew von Eschenbach, Director of the National Cancer Institute 

(NCI), established the Clinical Trials Working Group (CTWG) to advise the National 

Cancer Advisory Board (NCAB) on the development, conduct, infrastructure, support, 

and coordination of cancer clinical trials across the NCI. The charge to the CTWG was 

to develop recommendations and an implementation plan to optimize the NCI-supported 

clinical trials system by improving coordination and research infrastructure, by removing 

institutional and regulatory barriers that inhibit collaboration in clinical trials research, 

and by envisioning how clinical trials should be conducted utilizing the tools of 

contemporary bioinformatics and molecular medicine. The CTWG is a broadly 

constituted panel with experts from academic research institutions, community oncology 

practices, the pharmaceutical and biotechnology industries, cancer patient advocacy 

groups, NCI, the Food and Drug Administration (FDA) and the Centers for Medicare and 

Medicaid Services (CMS). The membership of the CTWG is provided at the front of this 

report. 

In approaching its objectives, the CTWG built on extensive prior analysis and 

recommendations for improving the NCI-supported cancer clinical trials system 

developed by the 1997 “Report of the NCI Clinical Trials Program Review Group” 

(Armitage Report) and the subsequent 1998 “Report of the National Cancer Institute 

Clinical Trials Implementation Committee,” as well as several feedback reports on the 

success of these efforts. In addition, the CTWG examined in detail the 2003 report of the 

P30/P50 ad hoc working group, “Advancing Translational Cancer Research: A Vision of 

the Cancer Center and SPORE Programs of the Future” so that the critical role of both the 

Specialized Programs of Research Excellence (SPOREs) and NCI-designated Cancer 

Centers in the cancer clinical trials process would be part of the framework for its 

restructuring effort. In this way, the overall organization of the current NCI-funded 

clinical trials system was reviewed, providing the essential background for the work of 

the CTWG. 

The CTWG conducted seven face-to-face meetings and ten group conference calls from 

January 2004 through May 2005. Meeting dates and acknowledgments appear in 

Appendix A. In addition, the CTWG subcommittees responsible for the development of 

the formal recommendations and implementation plans conducted a substantial number 

of additional conference calls among themselves and with ad hoc experts to refine their 

proposals. Furthermore, during this process, the extramural community provided 

substantive, real-time input into the development of the CTWG’s recommendations 

through its response to questions about draft recommendations posted on a CTWG 

internet-based forum that elicited over 2200 responses. 

The CTWG reached consensus through three sequential stages. The first stage was to 

define which aspects of the current system should be improved. The second stage was to 

develop recommendations for addressing those improvements; these recommendations 

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Restructuring the National Cancer Clinical Trials Enterprise 

were presented to the NCAB on February 17, 2005. The third stage was to define new 

initiatives based on these recommendations and to design implementation plans that are 

innovative, yet practical, and which harness the best of the current clinical trials system. 

The result of this consensus building process is the 22 initiatives detailed in this report on 

“Restructuring the National Cancer Clinical Trials Enterprise.” The proposed initiatives 

are organized into five categories: Coordination, Prioritization/Scientific Quality, 

Standardization, Operational Efficiency, and Enterprise-Wide. 

The Coordination Initiatives are directed at enhanced information sharing, incentives for 

collaborative team science, and coordination of regulatory processes. The 

Prioritization/Scientific Quality Initiatives establish new processes for the design and 

prioritization of clinical trials, and for facilitating the conduct of correlative science and 

other ancillary studies. The Standardization Initiatives promote development of 

standardized tools and procedures to minimize duplication and reduce the effort required 

to initiate and conduct clinical trials. The Operational Efficiency Initiatives focus on 

improving patient accrual rates and reducing operational barriers to speed both the 

initiation and conduct of clinical trials. The Enterprise-Wide Initiatives address 

restructuring the management and oversight of NCI’s clinical trials program both from 

within the NCI and in partnership with the extramural community. 

In each section, the initiatives are organized into two categories. New Initiatives propose 

a fundamental and significant change in the operation of the current NCI clinical trials 

system. Enhancement Initiatives include those initiatives that propose an expansion or 

enhancement of an activity already underway within the Institute. Each initiative 

includes an implementation plan as well as an associated timeline and budget. The 

timelines and budgets are presented in a consolidated Timeline and Budget section. 

No major restructuring effort should be undertaken without establishing a mechanism for 

evaluating its success. Accordingly, the report includes a section on Evaluation and 

Outcomes that outlines the process recommended by the CTWG for evaluating the 

success of the restructuring effort. 

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Restructuring the National Cancer Clinical Trials Enterprise 

Coordination Initiatives 

Introduction: 

The CTWG addressed three key dimensions of coordination: enhanced information 

sharing, alignment of incentives to facilitate improved collaboration, and coordination of 

regulatory strategies and procedures with the scientific enterprise. Improvement in all 

these areas is essential to achieve the ultimate goal of delivering important new cancer 

therapies to patients more quickly. 

The CTWG envisions an enhanced cancer clinical trials enterprise in which increased 

participation by the extramural community in the prioritization process more effectively 

focuses resources on those trials judged most likely to facilitate advances in treatment. 

The success of this strengthened prioritization process depends on a shared foundation of 

comprehensive, up-to-date information about the status of cancer clinical trials. 

The productivity of the national cancer clinical trials enterprise will also depend 

increasingly on collaborative team science. However, the incentives implicit in NCI’s 

current modes of evaluating program accomplishment, making grant or contract renewal 

decisions, and allocating funds are not fully congruent with the needs of collaborative 

science. The cancer clinical trials enterprise has always benefited enormously from the 

pro bono spirit shared by cancer investigators who are dedicated to improving the lives of 

cancer patients. The system will function more effectively in the future if NCI can assure 

that institutional and professional rewards will accrue to those who participate 

collaboratively in the enterprise as a whole. 

Finally, both the FDA and CMS are intimately involved in the process by which new 

treatments are brought to market, and adopted and utilized by physicians. Close and 

continuous interaction between NCI and these partners will facilitate the development 

and utilization of new cancer therapies, while at the same time protecting patient safety. 

For the nation’s cancer clinical trials system to fulfill its promise, the supporting 

information systems, incentive structures and regulatory processes must be updated and 

coordinated to address the new needs and opportunities of cancer research today. The 

CTWG proposes five initiatives to achieve this goal; two of these are entirely new, and 

three will substantively enhance current or recently-developed activities. 

New Initiatives: 

1.	 Establish a comprehensive database containing regularly-updated information on 

all NCI-funded clinical trials. 

2.	 Realign NCI funding, academic recognition, and other incentives to promote 

collaborative team science and clinical trial cooperation. 

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Restructuring the National Cancer Clinical Trials Enterprise 

Enhancement Initiatives: 

1. Develop guidelines and procedures for joint participation of FDA and NCI in 

meetings, including those with industry, concerning new agents and diagnostics. 

2.	 Increase awareness of the NCI-FDA expedited concept/protocol approval process, 

including use of the FDA Special Protocol Assessment. 

3.	 In collaboration with CMS and other payers and stakeholders, establish a robust 

and transparent process for identifying clinical studies that might have routine and 

clinical costs supported using traditional reimbursement mechanisms. 

New Initiative 1:
 

Establish a comprehensive database containing regularly-updated information on 

all NCI-funded clinical trials. 

Rationale: 

An electronic database containing complete, up-to-date information about the status of all 

cancer clinical trials would be extremely valuable to the clinical trials community. 

Benefits include the following: 

	 When preparing new trial concepts and proposals, investigators could take into 

account other trials already completed or underway addressing similar questions, 

and thus eliminate unnecessary duplication of effort. 

 Prioritization would be enhanced by having available a full picture of the cancer 

clinical trials enterprise. 

 Patient accrual to trials would be enhanced because physicians and patients 

would be aware of relevant opportunities for participation in clinical trials. 

	 Potential patient harm would be reduced because toxicity and adverse events that 

are recognized in active trials would be rapidly disseminated to other 

investigators and practicing clinicians. 

	 Patients would benefit because patterns of favorable outcomes that are 

recognized in active trials would be rapidly disseminated to the clinical trials 

community. 

Among currently available public resources supported by the NCI, the one that most 

closely approximates the resource envisioned is the clinical trials database within NCI’s 

PDQ system. However, this database falls short in several important respects. 

First, PDQ’s listing is incomplete. NCI-funded trials in four sponsorship categories – 

Cancer Therapy Evaluation Program (CTEP), Cooperative Groups, the NCI intramural 

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Restructuring the National Cancer Clinical Trials Enterprise 

Center for Cancer Research (CCR), and the Division of Cancer Prevention (DCP) – are 

submitted automatically, as are those conducted by the European Organization for 

Research and Treatment of Cancer (EORTC). Submission of all other trials, including 

those performed by Cancer Centers, SPOREs, and investigators supported by the R01, 

R21, or P01 mechanisms, is voluntary. 

Moreover, the database in PDQ is intended primarily to facilitate patient recruitment, and 

therefore focuses on the information necessary to identify protocols for which a patient 

may be eligible. Accordingly, PDQ does not include the results of clinical trials. It does 

not collect either individual or summary patient-level data and does not provide a source 

of trial outcome information. It is thus of limited value to investigators designing new 

trials. 

Data on the results of certain clinical trials are currently collected by several different 

administrative units within the NCI. However, the specific data content and its format 

varies widely between these units. It is therefore not possible to electronically share data 

between NCI divisions, nor is it possible to provide electronically accessible data, even in 

anonymized, summary form, to the research community. 

Finally, none of the current NCI clinical trials databases reflect up-to-date principles of 

information systems design. They are not based on the structured data, standardized 

interfaces and modular architecture that would facilitate utilization across the entire 

cancer clinical trials enterprise. The infrastructure provided by the NCI’s cancer 

Bioinformatics Grid (caBIG) is founded on these principles and can serve as a blueprint 

for the construction of the recommended database. 

The new database will be more than a convenience. Because of its role as the sponsor of 

a large number of cancer clinical trials implemented across a wide range of venues, NCI 

is uniquely positioned to take a global view of emerging knowledge from cancer trials, 

and to identify important patterns and insights in a timely way. Routine review of safety, 

efficacy, and administrative data reported from ongoing NCI-funded clinical trials is 

essential to the timely recognition and appropriate dissemination of emerging insights on 

the safety and efficacy of new treatments, while also assuring that NCI’s resources are 

invested productively, and that its program planning and prioritization activities are based 

on the best and most recent available data. 

At present, this review of incoming data is constrained both by the absence of 

comprehensive data reporting and by limited capacity to evaluate such data critically. To 

assure patient safety and an optimal return on the nation’s investment in cancer clinical 

trials, it is imperative not only that the completeness of data reporting be assured, but that 

sufficient capacity to monitor incoming data from all sponsored trials be present. 

Implementation Plan: 

Content of the Database 

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Restructuring the National Cancer Clinical Trials Enterprise 

Studies. The database will include all NCI-funded clinical trials, regardless of drug 

development phase, type of intervention or treatment, study design, or program through 

which funding is provided. A long-term goal is to include information on trials funded 

by other public- and private-sector sponsors, including studies by other National 

Institutes of Health (NIH) institutes that have cancer-related endpoints specified 

prospectively (e.g., Women’s Health Study), and studies funded by the Department of 

Defense, the pharmaceutical industry, and private foundations. All trials entered into the 

database will be maintained in the database indefinitely, so that both active and 

completed studies will be included. 

To facilitate rapid progress on the most pressing coordination needs of the national 

cancer clinical trials enterprise, the CTWG recommends that the first priority for 

inclusion in the new database be trials of pharmacologic, biological, surgical and 

radiation interventions, beginning with phase III trials and followed by phase II and phase 

I studies. As soon as practical, the database will be extended to include comprehensive 

information on trials of supportive care, behavioral interventions, screening and 

detection. 

Data Elements. For each trial, the database will include descriptive information about 

the trial protocol and accrual status, as well as contact information for those who have 

further questions or wish to participate in the trial. All key elements of the existing PDQ 

system will be preserved, including the special overviews and summaries drafted for lay 

readers. In addition, the database will include a standard set of data elements collected 

during the trial. This data set will include all data elements currently in the NCI Clinical 

Data Update System (CDUS) comprehensive data set, the data currently shared in 

briefing books prepared for Cooperative Group meetings, summary information on 

adverse events, toxicity and efficacy, and links to any results published, presented in 

public, or issued as an advisory by Federal agencies including NCI and FDA. 

Database Functions 

Search and Reporting. The database will be equipped with software tools that allow 

searches on any field or combination of fields, using any keywords or combination of 

keywords. Searching will be facilitated with pre-defined menus of keyword options 

wherever appropriate (e.g., cancer type, treatment type, etc.). Both interactive and batchmode reporting will be supported, and predefined report templates will be available. 

Access Control. Access privileges will be defined to address the diverse needs of 

different users of the database. Three user categories are envisioned. “General” users 

(including practicing clinicians, patients, caregivers, patient advocates, and other 

interested parties) will have access to descriptive data about study protocols, accrual 

status, summary data on findings, and alerts approved for public release. Cancer clinical 

investigators will have access to “briefing book” data as well as access to all data 

available to general users. For phase III trials, primary outcome data and secondary 

outcomes that might influence trial participation will not generally be available until trial 

data are released by the Data and Safety Monitoring Board (DSMB) for the study. NCI 

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Restructuring the National Cancer Clinical Trials Enterprise 

program staff will have access to all data in the repository, including raw data as 

submitted as well as all data accessible to all other user categories. 

System Implementation 

Management Responsibility. The NCI Center for Bioinformatics (NCICB) will be 

responsible for management and oversight of system implementation. Actual 

implementation of different components of the system may be carried out by NCI staff, 

contractors or other external partners as appropriate. 

Design Principles. The database will be implemented in accordance with caBIG design 

principles and implementation standards. These standards, including the use of standard 

vocabularies and data elements, modular architecture, and standard programming and 

data exchange interfaces, will provide maximum power, flexibility and adaptability to 

meet the needs of the cancer clinical trials community both today and in the future. 

The central data repository will not necessarily reside in one physical location. If 

appropriate, other data resources internal and external to NCI can be incorporated 

through appropriate data retrieval links. However, such links will be designed to operate 

automatically and will be invisible to the user, who will perceive a single, unified 

“virtual” database. User tools will be accessed through web-based interfaces, with each 

interface designed to maximize ease of use for the intended user group. 

Implementation Task Force. NCI will establish an implementation task force of 

clinical investigators, community oncologists, biostatisticians, and patient advocates to 

provide input on data submission procedures, access privileges for different types of 

users, user interface needs, user tool specifications, and testing and revision of user tools. 

In consultation with the task force, NCICB will conduct interviews, focus groups, or 

other research as needed to define user-friendly interfaces for investigators and other user 

groups, and will conduct pilot testing with extramural users prior to system roll-out. 

Relationship to Other Cancer Trial Databases. The database is intended to be the 

primary clinical trials information tool provided by NCI to support investigators, 

practicing clinicians, and lay users. Once it is implemented, NCI will not invest 

resources in duplicative data repositories. However, as is the case with existing clinical 

trials data repositories, it is expected that there will be outside groups who wish to 

provide access to database content through distinctive user interfaces that address the 

needs of special audiences. Construction of the database according to caBIG principles 

will allow NCI to grant qualified outside groups the right to develop independent 

software tools that access selected data from the repository and present it through 

distinctive search and reporting interfaces, in accordance with established access policies 

and controls. 

Data Submission Procedures and Policies 

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Restructuring the National Cancer Clinical Trials Enterprise 

Data Submission Procedures. Procedures for data submission will be designed by 

NCICB in consultation with NCI program staff and representatives of the extramural 

investigator community on the implementation task force. The goal is to incorporate data 

submission into typical investigator workflows with minimal added burden such that 

investigators submit required data to NCI only once, and NCI manages distribution to all 

NCI staff who need access. In some cases, where appropriate standards for data systems 

design have been implemented locally, it may be appropriate for “submission” to occur 

via a link to a local data repository rather than through physical transmission to the 

central repository. 

Data Submission Policies. Reporting of data required for the database will be a routine 

obligation for all NCI studies, regardless of funding mechanism. For programs 

implemented via cooperative agreements, program guidelines will be updated to specify 

data reporting requirements and to define required data reporting as an allowable cost. 

For programs implemented via grants, NCI will seek counsel from appropriate authorities 

within NCI and the Office of Management and Budget (OMB) to specify a data reporting 

requirement in compliance with Federal regulations governing grants, and to assure that 

such data reporting requirements are allowable expenses. Furthermore, the CTWG 

recommends that funds be made available to accommodate the initial costs incurred for 

additional data reporting requirements prior to cooperative agreement, grant, or contract 

competitive renewal. 

NCI Review of Data 

To implement timely review of this expanded data set, new NCI oncology staff members, 

as well as expansion of existing contractor support, will be required. As the new clinical 

trials database is implemented, NCI will evaluate the potential for new software tools 

associated with the database to facilitate the required logistical support. 

New Initiative 2 

Realign NCI funding, academic recognition, and other incentives to promote 

collaborative team science and clinical trial cooperation. 

Rationale: 

It is widely recognized that current incentives within the national cancer clinical trials 

enterprise, both those implicit in NCI project selection and funding practices, and those 

implicit in academic institutions’ criteria for academic promotion and honors, do not 

encourage cooperative efforts to bring new therapies to patients. These incentives can be 

realigned in two primary ways. The first is to modify NCI competitive award 

mechanisms to give appropriate credit for participation in collaborative clinical trials and 

to provide adequate resources to all investigators participating in such trials. The second 

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Restructuring the National Cancer Clinical Trials Enterprise 

is to modify academic institutional practices to increase the value accorded to active 

participation in federally-funded clinical trials during faculty performance evaluations. 

Current patterns of academic recognition are deeply rooted in the culture and 

management practices of academic institutions, and inducing cultural change in such 

powerful, autonomous and managerially conservative institutions will be a challenge. 

While NCI does not directly control the behavior of academic institutions, nor should it, 

it is important for the Institute to catalyze the process of change by realigning those 

incentives that are within its control to send a clear message as to the importance of 

collaborative science in bringing effective new treatments to patients. 

One of the most powerful tools at NCI’s disposal is the set of criteria used to determine 

whether awards will be made or renewed. Funding decisions have enormous 

implications for an institution, both financial and otherwise. It is imperative that award 

guidelines be updated to reflect NCI’s best current understanding of the practices needed 

to advance cancer clinical research most effectively. 

Although research funding is a potent incentive at the institutional level, NCI should also 

take steps to facilitate the recognition of clinical trial participation within academic 

institutions’ career advancement mechanisms. NCI leadership should work to engage 

academic institutions in a fundamental review of the principles underlying career 

advancement policies and in defining appropriate adjustments to those policies. 

The ultimate goal is a shared culture in which investigators collaborate freely across 

disciplines, institutions, and programs wherever this is needed to most expeditiously 

advance the design and conduct of cancer clinical trials. 

Implementation Plan: 

Award Guidelines 

NCI program award guidelines and scoring systems will be revised to allocate credit for 

the behaviors needed to advance collaborative science. The objectives of these 

modifications will include the following: 

1.	 Reward collaborations among Cancer Centers, SPOREs, P01s, R01s, early clinical 

trials networks, Cooperative Groups and other NCI-supported multisite clinical trials 

networks that advance concepts from pilot studies to Phase III trials and provide 

correlative science services for large, multisite studies. 

2.	 Reward Cooperative Groups and other NCI-funded clinical trials networks for broad 

participation in multisite trials conducted throughout the NCI-supported clinical trials 

system. 

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Restructuring the National Cancer Clinical Trials Enterprise 

3.	 Reward efforts to move innovation forward through the most effective and 

expeditious means, including handoffs between various NCI-funded programs where 

appropriate. 

Funding Practices 

NCI funding practices will also be examined for opportunities to incentivize collaborative 

science. Examples might include reimbursement for SPORE and Cancer Center clinical 

trials that accrue patients through the NCI’s Cancer Trials Support Unit (CTSU), and 

travel and expense reimbursement for non-PI investigators to attend planning and 

coordination meetings for trials. 

New Forms of Recognition for Cancer Clinical Investigators 

NCI will create a new “Cancer Clinical Investigator Team Leadership Award” for midlevel clinical investigators not currently holding Principal Investigator status on an NCI 

grant. The award, which would provide funding equivalent to 10-20% salary support per 

year, will be competitive, with nominations submitted annually by Cancer Centers or 

other institutions carrying out NCI-funded clinical trials. The intent is to reward 

exceptional contributions that advance effective new treatments toward practice and 

embody the ideals of collaborative team science. NCI will also conduct informal 

consultations, focus groups, and surveys to identify additional forms of recognition that 

could be awarded by NCI and that would be valued by investigators and their institutions. 

Academic Reward Practices 

NCI and NIH leadership will work proactively with the Association of American Medical 

Colleges (AAMC), the Institute of Medicine (IOM) and other organizations to persuade 

medical school deans of the need to adjust their institutions’ incentive structures to 

reward collaborative clinical research. 

Enhancement Initiative 1:
 

Develop guidelines and procedures for joint participation of FDA and NCI in 

meetings, including those with industry, concerning new agents and diagnostics. 

Rationale: 

The great need for improved cancer therapies, the long and expensive research and 

development process for new drugs, and the large number of candidate drugs generated 

by advances in fundamental research make it imperative to reduce inefficiencies in the 

process by which new drugs are tested and approved for marketing. 

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Restructuring the National Cancer Clinical Trials Enterprise 

Improved interaction between NCI, industry, and FDA would save time, effort and 

resources in bringing new cancer therapeutic agents to market. Beneficial outcomes 

would include clinical trial strategies and protocols that better meet FDA standards, 

higher quality FDA submissions based on results from NCI-funded trials, and greater 

focus of NCI-funded clinical research on drug candidates that are likely to meet FDA 

requirements for marketing approval. 

In 2003, NCI and FDA created a framework for enhanced collaboration in the 

Interagency Oncology Task Force. The Task Force has been addressing a range of issues 

of mutual interest, most notably strengthening the infrastructure for cancer clinical trials 

and new drug evaluation. The CTWG initiative seeks to build on this foundation and 

further promote interaction between NCI, FDA, and industry in the development of new 

agents, with the goal of improving the focus, efficiency, and timeliness of oncology drug 

development. 

Implementation Plan: 

FDA-industry meetings. NCI representatives will be included in meetings for all agents 

for which NCI has a Clinical Trial Agreement (CTA) or a Cooperative Research and 

Development Agreement (CRADA) with the sponsor, and sponsors will be encouraged to 

include NCI representatives in meetings even when NCI does not have a CTA or 

CRADA. 

NCI Drug Development Group meetings. Special liaison representatives from FDA 

will be included to better inform the FDA about new agents that are in the earliest stage 

of preclinical development by the NCI. 

NCI meetings with industry to review new agents. Sponsors will be encouraged to 

include FDA representatives in these meetings. 

Operating procedures and guidelines for joint meeting participation will be developed. A 

key requirement is to create policies and procedures that promote free and open sharing 

of knowledge and insights, while assuring industry that proprietary information will 

remain confidential and that interactions with FDA will not prejudice later regulatory 

proceedings. It will also be necessary to assure that FDA can continue to respond to any 

new, safety-critical information in accordance with its mandate. 

These proposals have already been placed on the agenda of the FDA and the Interagency 

Oncology Task Force for review and refinement. Plans are underway to obtain broad 

input from the pharmaceutical and biotechnology industries as well. FDA and industry 

support is necessary to assure that joint FDA/NCI meeting participation enhances the 

drug development process rather than complicates it to no material benefit. 

It should be noted that the new guidelines are not meant to be rigid. Industry will always 

retain the right to decline broader involvement when such involvement is felt to be 

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Restructuring the National Cancer Clinical Trials Enterprise 

inappropriate, and NCI and FDA will, as always, need to prioritize the use of available 

staff time. However, the intent is to establish the proposed broader meeting participation 

as the standard. 

Enhancement Initiative 2:
 

Increase awareness of the NCI-FDA expedited concept/protocol approval process, 

including use of the FDA Special Protocol Assessment. 

Rationale: 

For NCI-funded trials that could lead to a licensed indication, the NCI and FDA have 

developed a process whereby a concept, once approved by NCI, will receive a rapid 

review (two to three weeks maximum) by the FDA. Based upon this initial FDA review, 

a series of informational exchanges ensue between the FDA and those conducting the 

trial (the Cooperative Group, company-sponsor, and NCI) until a consensus is reached on 

a trial design that will meet FDA requirements for registration. Following this consensus, 

the protocol is developed using NCI’s expedited protocol development process, and the 

company sponsor, if it so chooses, can also submit the protocol to the FDA for a Special 

Protocol Assessment (SPA). 

An approved SPA documents the FDA’s binding agreement that the design and planned 

analysis of a study adequately addresses the objectives in support of a regulatory 

submission (for phase III Cooperative Group trials, this is usually an efficacy claim). 

Although the SPA process is available to all industry sponsors, the FDA has agreed to 

work with NCI to complete the review of NCI Cooperative Group trials in an even more 

rapid fashion since the Agency will have reviewed the trial at the concept stage. This 

process allows the Cooperative Group, its industry partners, and the NCI to proceed 

expeditiously in preparation of a final protocol document without the risk of belated 

disapproval by the FDA. 

Unfortunately, this approach is not well known throughout the pharmaceutical and 

biotechnology industries and is currently underutilized. 

Implementation Plan: 

NCI will develop and implement a communication campaign to enhance industry 

awareness of this expedited process. NCI will consult with FDA to identify any changes 

in agency guidelines or other documentation that would increase awareness, and will 

work with industry to identify outreach mechanisms likely to be most productive. 

Approaches could include special seminars or workshops, perhaps in conjunction with 

existing scientific meetings, articles in professional publications, printed materials, and 

one-to-one outreach aimed at clinical research leaders in industry. 

Report of the Clinical Trials Working Group of the National Cancer Advisory Board 

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Restructuring the National Cancer Clinical Trials Enterprise 

Enhancement Initiative 3:
 

In collaboration with CMS and other payers and stakeholders, establish a robust 

and transparent process for identifying clinical studies that might have routine and 

clinical costs supported using traditional reimbursement mechanisms. 

Rationale: 

It is essential to improve the efficiency not only of the clinical research enterprise but 

also of the regulatory and reimbursement frameworks within which it operates. Ideally, 

these interacting processes will become fully synergistic toward the goal of making 

beneficial new technologies rapidly available and appropriately used. 

The pace of clinical evaluation can only match the pace of biomedical discovery if 

models are developed to conduct large scale, real-time clinical research throughout the 

health care delivery system. Availability of CMS funds for reimbursement of some welldefined and routine clinical care costs in cancer clinical trials will decrease barriers to 

patient enrollment, enhance the generalizability of the conclusions, and help make 

additional studies possible. Working together with other stakeholders, CMS and NCI can 

identify a portfolio of clinical research studies that are prioritized, designed, and 

implemented to be responsive to the information needs of decision makers (patients, 

clinicians, and policymakers). Formal CMS involvement under well-defined rules in 

collaboration with NCI may encourage industry to invest in additional clinical studies 

that can leverage these benefits. 

CMS-NCI collaboration can increase the number of studies designed with questions of 

routine practice in mind, and can increase the speed with which critical reimbursement 

decisions are made and effective new therapies enter broad clinical practice. 

Implementation Plan: 

CMS-NCI discussions are ongoing with respect to Medicare reimbursement for the costs 

of routine and investigational clinical costs in nine specific NCI-supported trials 

exploring off-label drug treatments for colorectal cancer and with respect to possible 

coverage for fluorodeoxyglucose-positron emission tomography (FDG-PET) in cancer 

care in the context of well-designed prospective clinical studies. CMS and NCI are also 

currently in discussions concerning specific activities to develop a generalizable 

conceptual framework for identifying studies that may be appropriate candidates for 

“coverage with evidence development” and to create study designs that address both 

CMS and NCI objectives. Discussions are also ongoing concerning mechanisms for 

engagement of stakeholders and payers beyond CMS to establish processes for 

identifying and prioritizing studies that are appropriate targets for collaboration. 

Report of the Clinical Trials Working Group of the National Cancer Advisory Board 

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Restructuring the National Cancer Clinical Trials Enterprise 

Prioritization/Scientific Quality Initiatives 

Introduction: 

Enhanced scientific quality and prioritization of clinical trials is potentially the most 

important goal for the redesigned NCI clinical trials enterprise. The need for efficient use 

of resources and the urgency of making new therapies available to patients requires that 

NCI sponsor the best-designed trials, addressing the most important questions, leveraging 

the most significant scientific advances. Achieving this goal requires that design and 

prioritization of clinical trials be improved and that the tools of molecular medicine and 

other correlates of clinical response be applied in a timely, prioritized, and high quality 

manner to enhance clinical trial outcomes. 

Clinical trial design and prioritization can be enhanced in several ways. The first is by a 

proactive examination of strategic directions for both early phase drug development trials 

and later stage studies designed to demonstrate efficacy for disease-specific management. 

The second is to establish an open, collaborative process for encouraging innovation, 

evaluating new ideas, and designing clinical trials that are not only based on the best 

science but are also attractive to patients and practicing oncologists. The third is to 

develop an efficient prioritization system that involves the broad oncology community in 

allocating available resources to support the most important clinical trials and reduce 

duplication and overlap. 

Each of these enhancements depends on greater cooperation between the NCI and 

academic researchers, community oncologists, patient advocates, other federal agencies, 

and industry. The result will be a more open and transparent process for the design, 

prioritization, and conduct of clinical trials that are both science-driven and meet the 

needs of patient care. 

Correlative science and quality of life studies have great potential to improve the value of 

clinical trials and can be integral to the design of a trial. However, current funding 

mechanisms and prioritization processes do not allow such studies to be initiated in a 

timely fashion so that they are optimally coordinated with the conduct of a clinical trial. 

An approach needs to be developed to integrate the funding and prioritization of these 

studies within the overall clinical trial prioritization process. 

To achieve the goals of more effective clinical trial design and prioritization, including 

integration of correlative science and quality of life (or outcome) studies, the CTWG 

proposes six new initiatives. Once the proposed prioritization system has been 

successfully implemented for studies of new therapies, expansion to include studies of 

new preventive agents will be investigated. 

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Restructuring the National Cancer Clinical Trials Enterprise 

New Initiatives: 

1.	 Establish an Investigational Drug Steering Committee to collaborate with NCI in 

the design and prioritization of early phase drug development trials with agents 

for which CTEP holds an IND. 

2.	 Establish a network of Scientific Steering Committees to address the design and 

prioritization of phase III trials that leverages current Intergroup, Cooperative 

Group, SPORE, and Cancer Center structures and involves the broad oncology 

community. 

3.	 Enhance patient advocate and community oncologist involvement in clinical trial 

design and prioritization through representation on Steering Committees and 

creation of patient advocate and community oncologist focus groups. 

4.	 Establish a funding mechanism and prioritization process to ensure that the most 

important correlative science and quality of life studies can be initiated in a timely 

manner in association with clinical trials. 

5.	 Establish a process for ensuring that correlative science studies conducted in 

association with clinical trials are performed according to standard protocols and 

standardized laboratory practices. 

6.	 Develop a plan for integrating prioritization of all phase II trials performed by 

Cooperative Groups, SPOREs, Cancer Centers, and P01, R01 and NCI intramural 

investigators into the processes established by the Investigational Drug Steering 

Committee and the Scientific Steering Committees. 

New Initiative 1:
 

Establish an Investigational Drug Steering Committee to collaborate with NCI in 

the design and prioritization of early phase drug development trials for which 

CTEP holds an IND. 

Rationale: 

The proposed Investigational Drug Steering Committee (IDSC) is designed to provide 

NCI with broad external scientific and clinical input for the design and prioritization of 

phase I and phase II trials with agents for which CTEP holds an IND. The goals of the 

IDSC are to enhance strategic input, increase the transparency and openness of the trial 

design and prioritization process, achieve optimal phase I and phase II trial designs for 

the most promising agents and, ultimately, increase the predictive value of early phase 

trials, resulting in the design of more successful phase III trials. 

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Restructuring the National Cancer Clinical Trials Enterprise 

Implementation Plan: 

Membership 

The IDSC will include the Principal Investigators of phase I U01 grants and phase II N01 

contracts, several senior CTEP staff members or their designees, and additional 

representatives with expertise in biostatistics, non-oncologic clinical trial and drug 

development methodologies, correlative science technologies, radiation oncology, etc., as 

well as patient advocates and community oncologists, as needed. Experts in specific 

molecular markers will be included as ad hoc members for consideration of specific 

agents. 

Responsibilities 

Strategic Input. In association with the semi-annual CTEP Investigational Drug Branch 

meetings, the IDSC will organize open, structured discussions of scientific and clinical 

strategic directions in drug development. The discussions will focus on critical new 

questions for early stage clinical trials, including emerging technologies, gaps in the drug 

development pipeline, new therapeutic opportunities, correlative science strategies, and 

advances in clinical trial methodology. Based on these discussions, the IDSC will 

provide input to CTEP regarding future scientific and clinical strategic directions. 

Clinical Development Plans. Prior to Letter of Intent (LOI) solicitation, the IDSC will 

provide input regarding Clinical Development Plans prepared by CTEP staff for all new 

drugs and selected current drugs. As Clinical Development Plans evolve over time, the 

IDSC will provide continued input. 

Strategic LOI Evaluation. Periodically the IDSC will assess, from a strategic 

perspective, CTEP-approved LOIs as well as unsolicited LOIs that were rejected to 

determine whether the Clinical Development Plan for an agent should be modified. 

When requested by CTEP, the IDSC will provide input on unsolicited LOI’s to assist in 

CTEP decision-making. 

Expert Opinion. When requested, the IDSC will address specific scientific and/or 

clinical questions with regard to early stage clinical trials, provide input to the NCI Drug 

Development Group1

 concerning a decision to move a specific agent into clinical 

development, and provide input regarding the resolution of investigator appeals of CTEP 

LOI decisions. 

1

 The NCI Drug Development Group is responsible for prioritizing use of NCI resources for preclinical and 

clinical development of new agents. 

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Restructuring the National Cancer Clinical Trials Enterprise 

New Initiative 2: 

Establish a network of Scientific Steering Committees to address design and 

prioritization of phase III trials that leverages current Intergroup, Cooperative 

Group, SPORE, and Cancer Center structures and involves the broad oncology 

community. 

Rationale: 

The proposed prioritization system for phase III trials is designed to promote an open, 

collaborative process for setting clinical trial priorities and reducing trial duplication and 

overlap. The goals of this system are to ensure a well-informed evaluation of strategic 

directions; to coordinate and integrate the best ideas arising from Cooperative Groups, 

Cancer Centers, SPOREs, P01s, R01s, Community Clinical Oncology Programs 

(CCOPs), and NCI intramural investigators; and to stimulate greater involvement by 

practicing oncologists, patient advocates, and NCI staff early in the process of trial design 

and prioritization. The result should be more rapid and cost-effective development of 

successful new therapies due to an efficient prioritization process that is closely 

integrated with both the established Cooperative Group clinical trial implementation 

system and the translational clinical research activities currently conducted by Cancer 

Center, SPORE, P01, R01, and NCI intramural investigators. 

Implementation Plan: 

Overall Approach 

The proposed implementation plan is designed to leverage existing Intergroup, 

Cooperative Group, SPORE, and Cancer Center structures by creating Scientific Steering 

Committees for each major disease area as well as for pediatric oncology and symptom 

management/supportive care. All phase III concepts and protocols funded by NCI, 

regardless of mechanism (i.e., Cooperative Group, SPORE, Cancer Center, P01, etc.), 

will be prioritized through this process. Implementation will be staggered with the 

process being implemented for a limited number of diseases in the first two years. Since 

this represents a significant restructuring of the process for selecting phase III trials, a 

formal evaluation will be conducted two years after the process has been implemented for 

the initial disease categories. If the initial implementation is judged successful, the 

process will be extended to most diseases within four years. 

The proposed prioritization process differs in important respects from the Concept 

Evaluation Panels established in response to the 1997 Armitage Report. The Concept 

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Restructuring the National Cancer Clinical Trials Enterprise 

Evaluation Panels functioned as an arms-length external peer review process for phase III 

concepts proposed by the Cooperative Groups. The process was designed to ensure that 

the studies were of high scientific and clinical merit, and focused on the evaluation of 

fully developed concepts for phase III studies. The Panels were not organized to develop 

and refine a concept from an elemental stage, based on an open and collaborative sharing 

of ideas among peers. The Scientific Steering Committees, in contrast, are designed not 

only to provide robust peer review of proposed concepts, but also to facilitate the sharing 

of ideas among a broad range of clinical investigators, basic and translational scientists, 

NCI staff, community oncologists and patient advocates in the development of those 

concepts. The result should be scientifically rigorous phase III concepts that have been 

optimized through the collaborative effort and expertise of an extramural clinical trials 

community empowered to create the best-designed trials asking the most important 

questions. 

Scientific Steering Committees 

The Scientific Steering Committees will replace the existing Intergroup structures and 

serve to rationalize and facilitate a large number of current meetings and other formal and 

informal interactions that occur in the context of Cooperative Groups, Cancer Centers, 

SPOREs, P01s, etc. These existing interactions often involve clinical investigators, basic 

and translational scientists, community oncologists, patient advocates and NCI staff but, 

because of fragmentation and overlap, they may fail to provide an effective forum for 

setting priorities. In contrast, the Scientific Steering Committees will provide an 

organized, inclusive, and open forum for consideration of new ideas in the context of 

evolving scientific and clinical priorities, and the opportunity for integration of those 

ideas into more robust phase III trials. The importance and value of this approach is 

demonstrated by recent initiatives from the Gastrointestinal Intergroup to establish 

similar structures to guide new ideas and scientific advances efficiently into phase III trial 

designs. Although the initial Scientific Steering Committee organization is around 

disease sites, the prioritization system could evolve, if appropriate, to focus around 

specific molecular targets or therapeutic approaches. 

Membership. Each Scientific Steering Committee will have approximately 8-20 

members with size correlated with the number of phase III concepts likely to be 

developed. 

1.	 Membership will include Cooperative Group Disease Committee Chairs and 

clinical, basic, and translational investigators from Cooperative Groups, CCOPs, 

SPOREs, P01s, R01s, Cancer Centers, and the NCI intramural program who are 

experts in the relevant disease. The Pediatric Oncology Committee will include 

members of the Children’s Oncology Group, the Pediatric Brain Tumor 

Consortium and other pediatric oncology investigators, and the Symptom 

Management Committee will include several CCOP representatives. 

2.	 All Scientific Steering Committees will have at least one community oncologist 

and one patient advocate. If the group is large, additional community oncologists 

and patient advocates will be appointed. Community oncologist representatives 

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Restructuring the National Cancer Clinical Trials Enterprise 

will be investigators from CCOPs or Cooperative Group affiliates and will have 

significant experience treating the target disease. 

3.	 NCI staff members will include the Clinical Investigations Branch staff member 

responsible for the disease category, the Branch Chief and a biostatistician from 

the Biostatistics Research Branch. Other NCI staff such as members of the 

Investigational Drug Branch, the Cancer Diagnosis Program, the Radiation 

Oncology Sciences Program, and the Cancer Imaging Program will be included as 

ad hoc members for consideration of specific concepts. 

4.	 Appropriate correlative science and quality of life experts will be included as ad 

hoc members for consideration of specific concepts. 

5.	 As appropriate for specific agents, representatives from industry, CMS, and/or the 

Investigational Drug Steering Committee (or other experts in early therapeutics 

development) will be invited to participate. 

Responsibilities. 

1.	 The Scientific Steering Committees will organize periodic, invited State-of-theScience Meetings to identify critical questions and unmet needs, to prioritize key 

strategies and future concepts to test, and to facilitate innovation. Meetings will 

be informal and confidential to encourage discussion of newly-breaking results 

and ideas and to facilitate brainstorming. Attendees will include a broad range of 

clinical, basic, and translational investigators whose work is relevant to the 

specific disease as well as community oncologists and other oncology health care 

providers, patient advocates, and senior strategic thinkers from throughout 

oncology. Status and results of selected phase II trials would be a special feature 

at each meeting. Based on these meetings, the Committees will disseminate key 

strategic priorities for future trials to the relevant oncology communities. 

2.	 The Scientific Steering Committees will develop phase III concepts from an 

elemental stage, as well as evaluate and refine ideas for phase III trials developed 

by Cooperative Group Disease Committees or investigators from Cancer Centers, 

SPOREs, P01s, etc. Based on these deliberations, the Committee will recommend 

which concepts should proceed to the protocol stage. 

3.	 Concepts recommended by the Scientific Steering Committees will be submitted 

to NCI through the lead Cooperative Group for that concept. If the concept 

originated outside the Cooperative Group structure, the originating investigator 

will be the Principal Investigator (PI) and a Cooperative Group investigator will 

be a co-PI on the protocol. 

4.	 Given the active participation of NCI staff throughout Committee deliberations, it 

is expected that the majority of concepts will be reviewed by an expedited 

process. If Committee deliberations indicate significant scientific or clinical 

concerns about the concept, NCI could conduct a formal scientific quality review. 

NCI will review all concepts recommended by the various Committees from a 

broad programmatic and budget perspective including prioritization across 

diseases. 

5.	 Once the concept is approved by NCI, a protocol will be prepared by the lead 

Cooperative Group for submission to NCI. The Scientific Steering Committee 

will receive the final protocol for comment before NCI provides its approval. 

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6.	 The Scientific Steering Committees will monitor implementation of national 

phase III trials through the Cooperative Group and Cancer Trials Support Unit 

(CTSU) structures and periodically evaluate trial status in terms of accrual, 

unforeseen implementation issues, etc. 

New Initiative 3:
 

Enhance patient advocate and community oncologist involvement in clinical trial 

design and prioritization through representation on Steering Committees and 

creation of patient advocate and community oncologist focus groups. 

Rationale: 

The current process for design and prioritization of NCI-funded clinical trials involves a 

certain degree of participation by community oncologists and patient advocates. 

However, their participation is by no means uniform. Enhancing the involvement of 

community oncologists and patient advocates has several potential benefits. It will 

facilitate the development of clinical protocols that are attractive for patient enrollment 

and are feasible in the community setting. It will also promote development of trial 

designs that address the questions facing patients and physicians when making treatment 

decisions. Ultimately, it will result in the development of new therapies that are useful 

and practical for patients and their treating oncologists and have outcomes that improve 

patient care. 

Implementation Plan: 

Representation on Scientific Steering Committees 

Each Scientific Steering Committee will have at least one community oncologist and one 

patient advocate member in attendance at each meeting. If the Committee is large, 

additional community oncologists and patient advocates will be appointed to maintain 

adequate representation. 

Focus Groups 

1.	 Each Scientific Steering Committee will convene periodic patient and community 

oncologist focus groups to solicit general input and promote efficient trial accrual. 

For orphan diseases, a combined focus group will be convened. It is expected that 

these focus groups will also serve as a source for future members of the Scientific 

Steering Committees. 

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2.	 Focus group agendas will include topics such as current treatment issues facing 

patients and community physicians, important treatment questions that potentially 

could be answered by trials, clinical trial designs currently under consideration, 

and future trial designs proposed to answer new questions. 

3.	 If recommended by a patient advocate, community oncologist or other Scientific 

Steering Committee member, the Committee will ask focus group members to 

provide broader input to the design of a specific trial. Based on the relationships 

and knowledge gained from the annual meetings, this feedback can be provided in 

a timely fashion so as to not delay decision-making. 

Community Oncologist/Patient Advocate Steering Committees 

Two Steering Committees will be established, one for community oncologists and one for 

patient advocates, to provide input regarding the involvement of these constituencies in 

the NCI clinical trials enterprise. Each Steering Committee will meet annually to address 

policy issues across diseases, share best practices, and identify areas for improvement. 

Membership will include the community oncologists and patient advocates on the 

Scientific Steering Committees and, as needed, additional representatives from CCOPs 

and patient advocacy organizations. 

New Initiative 4:
 

Establish a funding mechanism and prioritization process to ensure that the most 

important correlative science and quality of life studies can be initiated in a timely 

manner in association with clinical trials. 

Rationale: 

Realizing the promise of molecular medicine will require that high quality correlative 

science studies be conducted in association with clinical trials, especially multisite phase 

III trials designed to establish clinical efficacy. However, the current mechanism for 

funding phase III trials does not readily provide for such correlative studies. Therefore, 

these studies have generally been supported through submission of a separate funding 

request. This is inefficient both in terms of timing relative to the conduct of the trial, and 

because a typical Study Section review is not structured to take into account the 

importance of the study in the context of the broader clinical trials prioritization process. 

The result is that many correlative science studies that could improve patient care are not 

being performed effectively today due to lack of funding. In addition, clinical trials of 

new agents that may be very effective in subsets of patients are often unsuccessful 

because the diagnostic/predictive tests that could identify those patients have not been 

evaluated in the context of a phase III study. There is also no efficient process for 

prioritizing and funding quality of life studies associated with phase III trials. 

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Although funds for correlative science and quality of life studies could be added to the 

Cooperative Group budgets, this may not be the best approach. The value of these 

studies is very trial-specific and a general allocation to all Cooperative Groups may not 

result in an optimal distribution of funds. Moreover, although some funding is available 

through existing CTEP, SPORE, Cancer Center, or R01/P01 sources for correlative 

studies associated with phase II trials, these funds are usually limited to a specific site, 

laboratory, or investigator. 

Therefore, it is proposed that a separate NCI budget be created and a prioritization 

process developed to expeditiously fund correlative science and quality of life studies 

associated with NCI-supported clinical trials. This prioritization will be closely 

integrated with the new clinical trials prioritization process described above. The goals 

are to fund the most important correlative science and quality of life studies, to ensure 

that clinical trial expenditures are optimized through collection of important correlative 

science data, and to avoid the delays associated with applying for traditional grant 

funding. 

Implementation Plan: 

Budget 

NCI will establish a separate budget to fund correlative science and quality of life studies 

conducted in association with NCI-funded clinical trials. The proposed mechanism will 

involve creation of a pool of funds that will be allocated by NCI based on 

recommendations from the Steering Committees and the appropriate NCI Divisions, and 

reviewed by the Clinical Trials Oversight Subcommittee of the NCAB. NCI will earmark 

specific portions of the budget for quality of life and correlative science studies, 

respectively. 

Eligible Studies 

Phase III Trials. The primary purpose of this budget is to fund studies in association 

with phase III trials when the cost of the studies is too large to be covered by Cooperative 

Group or other NCI support mechanisms in a sufficiently timely manner. Studies integral 

to the design of a clinical trial (e.g. an entry criterion) or studies that must be conducted 

in real time for the success of the trial will be especially important to support. 

Phase I and Phase II Trials. Studies conducted in association with phase I and phase II 

trials funded through CTEP, Cooperative Group, Cancer Center, SPORE, P01, R01, and 

other grant mechanisms will be eligible if the proposed studies are beyond the scope of 

the original grant or contract. 

Prioritization 

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Prioritization Criteria. NCI will convene a group of external experts in clinical 

research, biostatistics, bioinformatics, pathology, imaging, translational and correlative 

science and quality of life to assist in establishing the criteria for prioritizing study 

proposals. In addition to scientific quality, the criteria might include expected clinical 

impact, importance of studies to the overall value of the trial, cost-effectiveness, degree 

of innovation, availability of other funds, etc. NCI will apply these criteria when 

deciding which of the studies proposed by the Scientific Steering Committees and NCI 

Divisions should receive supplemental funding. The criteria will be updated periodically. 

Phase III Trials. Studies associated with phase III trials will be proposed for funding by 

the appropriate Scientific Steering Committee. For concepts containing a significant 

correlative science or quality of life component, the relevant Scientific Steering 

Committee will involve appropriate subject matter experts (e.g. pathology, imaging, 

comprehensive molecular analysis, immunohistochemistry, quality of life, etc.) in all 

deliberations concerning the concept. For trials where the correlative science is integral 

to the trial design (e.g. as an entry criterion), the scientific quality and impact of the 

correlative science study will be critical in reaching a decision to recommend the overall 

trial concept. If the study is not integral to the trial, the Committee will provide a 

separate review of the quality and importance of the correlative science or quality of life 

study for consideration by NCI when deciding on the priority for funding. 

Phase I and Phase II Trials. Correlative science and quality of life studies associated 

with phase II trials conducted under Cooperative Group, Cancer Center, SPORE, P01, 

R01 or N01 mechanisms and phase I trials conducted under the U01 mechanism will be 

proposed for supplemental funding by the relevant NCI program staff based on scientific 

quality of the study and its importance to the value of the trial. 

Funding Decisions. Based on the proposals from the Scientific Steering Committees and 

NCI Divisions, NCI will present a priority list of studies recommended for funding to the 

NCAB Clinical Trials Oversight Subcommittee (see Enterprise-Wide Initiative 1 on page 

50) for review and approval. 

Additional Funding Sources for Approved Studies 

Industry. For studies that have the potential to increase the market for a drug, biologic, 

or diagnostic product produced by industry, the Principal Investigator and NCI will work 

cooperatively to negotiate full or partial industry support for the proposed study. 

CMS/Other Payers. If a correlative science study has the potential to reduce the overall 

cost of patient care for a specific disease category, NCI will share details of the study 

with CMS and other payers and seek to negotiate reimbursement for the cost of the 

correlative studies. 

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Restructuring the National Cancer Clinical Trials Enterprise 

New Initiative 5:
 

Establish a process for ensuring that correlative science studies conducted in 

association with clinical trials are performed according to standard protocols and 

standardized laboratory practices. 

Rationale: 

In the era of evolving molecular diagnostics and targeted therapeutics, biomarkers2 will 

increasingly be used as predictive and prognostic markers to guide therapy decisions and 

as novel endpoints to assess drug effects and predict clinical benefit. Establishing 

standards for the measurement, analysis, and reporting of biomarker data will be essential 

for obtaining the robust correlative science information necessary to fully evaluate new 

targeted disease therapies. Such measurement standards will increase the ability to 

compare data across trials and laboratories, facilitate comparisons of large data sets from 

multiple trials, and reduce duplication in defining assay methods and data requirements. 

Moreover, such standards will be essential if data are to be submitted to the FDA in 

support of a label indication. 

Implementation Plan: 

Overall Approach 

NCI will develop a process for establishing standards for laboratory assays and imaging 

procedures used in correlative science studies for NCI-funded clinical trials. This process 

will involve experts in each of the applicable technologies including imaging, 

comprehensive molecular analysis, pathology, immunohistochemistry, etc. as well as 

representatives from National Institute of Standards and Technology (NIST) and 

industry. 

Defining Technology Categories for Standards 

The first task will be to determine which technology categories are appropriate for 

establishment of standards and which technologies need further development and 

refinement before meaningful standards can be elaborated. 

Standards Documents 

If establishment of standards is appropriate for a given technology, a document will be 

developed outlining the standards that should be met for the laboratory assay or imaging 

procedure in the context of specific types of clinical trials. This will include both 

2

 The term biomarker as used here conforms to the FDA definition of biomarker as “a characteristic that is 

objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or 

pharmacologic responses to a therapeutic intervention.” Although a biomarker can serve as a surrogate 

endpoint, the terms are not synonymous. 

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procedure-specific standards (e.g., interval between contrast agent injection and scan, 

temperature for specimen processing, etc.) as well as standards for quality control, 

validation, documentation, etc. If established mechanisms for accreditation or standards 

setting exist for a particular technology [e.g., Clinical Laboratory Improvement 

Amendments (CLIA), College of American Pathology (CAP), etc.], adherence to those 

standards will be recommended. 

Annual Review and Update 

At least annually, NCI will evaluate potential changes in existing standards documents 

and determine whether additional technologies have advanced sufficiently to make 

development of standards and issuance of standards documents appropriate. 

Registry of Laboratories/Imaging Cores Meeting Required Standards 

The NCI will examine the cost and benefits of establishing a registry of laboratories 

and/or imaging cores in support of clinical trials that meet the required standards for a 

given technology. 

Adherence to Standards 

Dissemination. NCI will disseminate to the oncology, pathology, and imaging 

communities clinical trial biomarker standards developed for particular technologies. 

NCI Study Requirements. Correlative science studies in the clinical setting using 

laboratory or imaging markers or techniques for which standards are established must 

adhere to those standards or present a compelling justification for deviating from such 

standards. For studies using novel laboratory or imaging markers or techniques for which 

standards do not yet exist, the study proposal must provide a set of standards to be used in 

that trial, and explain the rationale or basis for the selected standards. 

Validated Endpoints 

NCI will continue to work with the FDA and industry through the Interagency Oncology 

Task Force to define the relevant issues and establish policies and procedures for 

validating critical drug development endpoints based on biomarkers. 

New Initiative 6: 

Develop a plan for integrating prioritization of phase II trials performed by 

Cooperative Groups, SPOREs, Cancer Centers, and P01, R01 and intramural 

investigators into the systems established by the Investigational Drug Steering 

Committee and the Scientific Steering Committees. 

Rationale: 

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Restructuring the National Cancer Clinical Trials Enterprise 

The ultimate goal is to coordinate prioritization of all clinical trials funded by NCI. Once 

a prioritization system is in place for phase III trials and early phase trials with CTEP 

agents, NCI will investigate whether it is appropriate and feasible to integrate into this 

system the prioritization of phase II trials performed by Cooperative Groups, SPOREs, 

Cancer Centers, and P01, R01 and intramural investigators. If such integration is 

pursued, it will be essential to retain the incentives for innovation and the healthy 

competition inherent in the current system. Investigator-initiated exploratory phase II 

trials remain the discovery engine that will ultimately drive change. Nevertheless, the 

clinical trials enterprise will function more effectively if these new ideas are shared and 

coordinated with the strong systems in place for moving those ideas forward toward 

clinical practice. 

Implementation Plan: 

Enhanced Communication 

The first step will be involvement of investigators conducting exploratory phase II trials 

in the activities of the Scientific Steering Committees. Reports on status and results of 

selected phase II trials will be a special feature at each State-of-the-Science Meeting. 

Enhanced Information Sharing 

As the comprehensive clinical trials database is implemented, information on these 

exploratory trials will be included to facilitate communication and avoid duplication. 

Such information sharing would also alert investigators to opportunities for combining 

small trials asking related questions into larger, more broadly meaningful trials. 

Coordinated Prioritization 

Achieving this goal will have two important prerequisites. The first is restructuring of 

the NCI approval and funding process so that exploratory phase II trials can be integrated 

into a comprehensive prioritization system. The second will be to develop prioritization 

criteria that result in increased efficiency and coordination without adversely affecting 

innovation. These criteria are likely to be different from the criteria used for prioritizing 

phase III trials or CTEP investigational drug trials. Therefore, as the prioritization 

process for phase III trials and early phase trials with CTEP agents is being implemented, 

NCI will assess whether integration of these early stage trials into a comprehensive NCI 

clinical trials prioritization system would be valuable and, if so, how such integration 

might be accomplished. This assessment will be performed in concert with the phase II 

investigator community who will then be involved in developing an implementation plan, 

if appropriate. 

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Restructuring the National Cancer Clinical Trials Enterprise 

Standardization Initiatives 

Introduction: 

Transformation of the cancer clinical trials system into an efficient enterprise that 

produces quality results in a timely fashion hinges on establishing enterprise-wide 

standardization of several important tools and procedures. Creating an interoperable 

information technology platform would facilitate the reporting, analysis, and sharing of 

data across sites and promote team science. Developing commonly accepted Common 

Data Elements and standard Case Report Forms would reduce data requirements and the 

need for investigative sites to manage a wide array of different forms and data entry 

processes. Instituting a widely recognized credentialing system for research personnel 

and sites would eliminate the need to reestablish credentials each time a trial is initiated, 

further assisting both trial sponsors and investigative sites. Significant time savings 

would also be achieved by adopting standard contract language that minimizes the need 

for recurrent intellectual property, confidentiality, and other negotiations before each 

clinical trial contract is signed. 

Standardization in each of these key areas will speed the initiation and conduct of clinical 

trials, minimize duplication, and ultimately result in a faster, more efficient clinical trials 

system. To achieve this improved standardization, the CTWG proposes four initiatives; 

three of these are new, and one proposes to significantly enhance current NCI activities. 

New Initiatives: 

1.	 Promote establishment of national clinical trial information technology 

infrastructures that are fully interoperable with NCI’s cancer Bioinformatics Grid. 

2.	 Achieve industry and FDA concurrence on standard Case Report Forms 

incorporating Common Data Elements. 

3.	 Develop a credentialing system for investigators and sites that is recognized and 

accepted by NCI, industry sponsors, clinical investigators, and clinical trial sites. 

Enhancement Initiative: 

1. Establish commonly accepted clauses for clinical trial contracts. 

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Restructuring the National Cancer Clinical Trials Enterprise 

New Initiative 1:
 

Promote establishment of national clinical trial information technology
 

infrastructures that are fully interoperable with NCI’s cancer Bioinformatics Grid. 

Rationale: 

The universal acceptance of shared standards for collection, management, and sharing of 

cancer clinical trial data would be of enormous benefit in terms of cost-effectiveness and 

comparability of results across trials and sites. Such standards would facilitate the 

development and deployment of modular information management applications that are 

interoperable among the various research stakeholders. They would also permit 

integration of the clinical research infrastructure into emerging standard electronic health 

record systems. 

NCI’s caBIG initiative, through its Clinical Trials Management Systems workspace, and 

in partnership with international standards-developing organizations (HL7, CDISC) is 

developing a comprehensive collection of standards and standards-based tools covering 

the entire clinical trial life-cycle. These tools can be available for adoption as webaccessible solutions interfaced with existing information technology (IT) infrastructures, 

or can be coupled with existing commercial software and deployed as an entire system 

for sites that lack a robust clinical trials IT architecture. The long-term goal is for all 

clinical trial sites either to migrate to the caBIG architecture or to develop interfaces and 

other required enhancements such that their IT architecture is fully interoperable with the 

caBIG standards-based architecture. 

Implementation Plan: 

The CTWG endorses the universal adoption and deployment of a common, standardsbased IT infrastructure for the management of clinical trials across the NCI-supported 

cancer enterprise that is fully interoperable with the caBIG architecture. 

Increase Clinical Investigator Input into caBIG Development 

Membership in caBIG’s Clinical Trials Management System Workspace will be 

expanded to include additional clinical investigators from Cancer Centers, Cooperative 

Groups, CCOPs, SPORES, P01s, etc. This broader representation and commitment of 

the clinical investigator community will improve the link between the caBIG 

development teams and clinical investigators to ensure that tools developed with caBIG 

standards are fully responsive to the needs of clinical researchers. Moreover, enhanced 

clinical investigator involvement will facilitate caBIG understanding and support from 

the clinical investigator community. 

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Restructuring the National Cancer Clinical Trials Enterprise 

Harmonization of Internal NCI IT Systems 

NCI will establish a timeline for harmonizing all internal NCI IT systems [i.e., CDUS, 

the Clinical Trials Monitoring Service (CTMS), CTSU, Adverse Event Expedited 

Reporting System (AdEERS), etc.] with caBIG standards. 

Interoperability Requirements 

caBIG has issued guidelines outlining the requirements necessary for a system to be 

caBIG-compliant. The caBIG management team will work with Cooperative Groups, 

SPOREs, Cancer Centers, etc., to determine the approach, timeline, and resources 

necessary for either adopting the caBIG IT systems, or making current IT systems 

interoperable with caBIG. caBIG will also assist in providing resources necessary for 

effecting caBIG interoperability. NCI will require that all sites conducting NCIsupported clinical trials outside the CTSU provide, by a to-be-determined deadline, a plan 

to become caBIG-compatible. NCI award guidelines will be modified to require a plan 

for moving to caBIG interoperability, and new RFAs/RFPs requiring informatics support 

will be reviewed for caBIG compatibility. 

Web-Based Trial Initiation Tool 

caBIG will develop and make available a web-based trial initiation portal to facilitate 

protocol activation at sites. This web-based tool will be a caBIG core module so any 

investigator can easily use it to start up phase III treatment and complex phase II trials. 

The tool will provide a schema and checklist that reminds sites of staff and services that 

must be in place to successfully implement a trial (e.g., personnel requirements, 

necessary infrastructure, IRB submission requirements, data management needs, 

procedure instructions, etc.). The content will be similar to the trial initiation materials 

provided to sites by industry sponsors. A contractor will be retained to define the content 

for the trial initiation tool, and caBIG will generate the required templates and make the 

tool available to end-users through a web-based interface. 

New Initiative 2:
 

Achieve industry and FDA concurrence on standard Case Report Forms 

incorporating Common Data Elements. 

Rationale: 

Establishing agreed upon standards for the Common Data Elements (CDEs) that should 

be captured for each trial, the vocabulary in which they are expressed, and common Case 

Report Form (CRF) templates for collecting them will reduce the effort, time, and cost of 

initiating and executing trials, minimize duplication of effort, enhance investigators’ 

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Restructuring the National Cancer Clinical Trials Enterprise 

ability to compare and analyze data across trials, and facilitate regulatory review. A 

standard CRF would eliminate the need to generate or regenerate data collection 

instruments, and the need to constantly re-train staff on their use. CRFs based on CDEs 

that utilize standard, controlled vocabularies and that are derived from standard 

information models such as HL7/CDISC will make it easier to share structured data 

electronically, improve information sharing among cancer researchers, and help to 

accelerate scientific progress. Agreement on common CRFs would also ensure that only 

the data required for a given trial is actually collected, which should reduce data 

requirements. 

Implementation Plan: 

Harmonize and Expand the Library of Existing CRFs 

NCI currently has several sets of standard phase III CRFs and is developing CRFs for 

phase II trials. Industry has preferred CRFs, which may vary from sponsor to sponsor. 

While continuing the development of its own CRF repository in collaboration with the 

clinical research community, NCI will convene a series of meetings with key 

stakeholders including industry sponsors and FDA representatives to review the current 

library of NCI and industry CRFs. The goal of this series of meetings will be to develop, 

with input from a wide audience of stakeholders, a set of harmonized CRFs that include 

core modules integrating CDEs expressed in standard vocabularies. In order to facilitate 

regulatory review, FDA involvement will be solicited at the start of the development 

process. Active industry participation will ensure that industry-specific needs are 

addressed so that the final set of standard CRFs have the potential to be widely adopted 

by both the private and public sector research communities. 

Implementation and Dissemination 

The core library of standard CRFs developed by stakeholder consensus will be accessible 

through caBIG for unrestricted use by the entire oncology community. 

Review and Update 

Following development of the standard CRFs, NCI, in collaboration with clinical 

investigators, industry, and the FDA, will conduct an annual review to determine whether 

changes are needed in the CDE modules or the existing CRFs, and whether additional 

standard CRFs should be established for other trial categories. 

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Restructuring the National Cancer Clinical Trials Enterprise 

New Initiative 3:
 

Develop a credentialing system for investigators and sites that is recognized and 

accepted by NCI, industry sponsors, clinical investigators and clinical trial sites. 

Rationale: 

The absence of an officially accepted system for credentialing clinical investigators, 

research personnel, and research sites results in a redundant system where each sponsor 

has to re-establish credentials every time a new trial is initiated, even if the investigator 

and/or site have already been credentialed by the same sponsor. A universal registry of 

credentialed investigators and sites would speed trial initiation while facilitating rapid 

communication of new regulations and changes to the clinical research community, and 

changes in the status of individual investigators and sites to sponsors. Creating a 

credentialing process and registry will result in cost savings for industry sponsors and 

clinical sites by simplifying the trial initiation process, and will help keep the 

investigative community abreast of new trends in clinical trials, including legal, safety, 

and regulatory changes. 

Implementation Plan: 

Overall Approach 

NCI will partner with relevant professional societies and trade associations [e.g., the 

American Society of Clinical Oncology (ASCO), the American Association for Cancer 

Research (AACR), the American Association of Cancer Institutes (AACI), the Oncology 

Nursing Society (ONS), the Society of Clinical Research Associates (SoCRA), the 

Association of Clinical Research Professionals (ACRP), the Pharmaceutical Research and 

Manufacturing Association (PhRMA), the Biotechnology Industry Organization (BIO), 

etc.] to create a credentialing system and registry for cancer investigators and sites. As 

appropriate, links to the clinical investigator community outside of cancer research 

should be pursued to share commonalities among credentialing criteria for research 

personnel. 

Credentialing Criteria 

NCI will form a task force composed of NCI staff and staff from interested professional 

societies and trade associations to define and establish credentialing criteria. The task 

force will also include representatives from FDA and industry, as well as clinical 

investigators and other health care professionals from the academic and community 

oncologist clinical research communities. The criteria for investigators, in addition to 

information currently collected for the 1572 form, could include the number of new 

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patients evaluated per year, number of patients enrolled onto clinical trials per year, Good 

Clinical Practice (GCP) training and experience, investigator biosketch, etc. 

Investigators will be required to keep their credentials up-to-date, and comply with any 

changes in the credentialing criteria. The criteria for sites might include staffing ratios 

and training, IT infrastructure, investigational drug pharmacy facilities and staffing, 

clinical trial and adverse event monitoring capabilities, IRB functionality, clinical trial 

volume, and clinical care facilities, among others. 

Credentialing System 

An NCI/professional society/trade association partnership will be established to develop a 

formal investigator and site credentialing system for oncology clinical trials, based on the 

criteria established by the task force. This system should incorporate information from 

professional organizations that provide certification or training programs to nurses, 

clinical research associates, pharmacists, etc., such as the ONS, SoCRA, ACRP, and 

others. The credentialing system will harmonize the data from all such professional 

societies. 

Registry 

The same NCI/professional society/trade association partnership will establish and 

maintain a database of credentialed investigators, information on credentialing of 

ancillary staff, and credentialed trial sites. As appropriate, NCI will integrate the registry 

with ongoing efforts of the Federal Investigator Registry of Biomedical Informatics 

Research Data (FIReBIRD) initiative. Once the database is available, the partnership will 

promote its use by oncology clinical trial sponsors. 

Enhancement Initiative 1: 

Establish commonly accepted clauses for clinical trial contracts. 

Rationale: 

Lack of standard contract language contributes to delays in the startup of clinical trials. 

Most academic medical centers negotiate a new contract for each new trial that is 

initiated, even though most of the issues addressed are common across trials and 

sponsors. This duplication creates large inefficiencies in the system, both in terms of 

time requirements, manpower needs, direct costs, and opportunity costs. Accepted 

standards for clinical trial contract language may help reduce the time and effort 

expended on this aspect of trial startup. 

Implementation Plan: 

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A core set of modular contract templates will be developed that can be adapted easily to a 

particular trial, that meet a high proportion of contractual requirements governing clinical 

trials, and that will be acceptable to both NCI and industry sponsors. 

NCI/Academia/Industry Conference 

NCI will convene a conference of legal and business representatives from industry 

sponsors, Cancer Centers, other academic institutions, and NCI staff to discuss existing 

contract clauses developed by NCI, and to determine what is needed to create acceptable 

language for modular contract clauses that can be used in all trial contracts. Such 

modular clauses would address intellectual property and licensing, publishing rights, 

confidentiality of data, risk and indemnification, etc. 

Standard Contract Task Force 

NCI will establish a task force to develop the concepts generated by the conference into 

standard modular clauses and templates. A limited number of modular contract templates 

should be developed that can be selected by industry sponsors, academia, and NCI. The 

task force will include legal and business representatives from NCI, Cancer Centers, 

other academic institutions and industry. Obtaining industry endorsement is crucial to 

the success of this initiative. 

Promote Use of Current Templates 

Until standard clauses are developed, NCI will promote the use of the current NCI 

standard contract clauses through posting to the NCI website to improve awareness and 

increase their utilization. 

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Restructuring the National Cancer Clinical Trials Enterprise 

Operational Efficiency Initiatives 

Introduction: 

Improving operational efficiency is essential for the cancer clinical trials system to fulfill 

its promise to deliver new treatments to patients more quickly. There are two critical 

areas in which operational efficiency could be enhanced. The first is to increase the rate 

of patient accrual so that trials can be completed in a more timely fashion. The second is 

to identify and reduce institutional barriers that prolong the time from concept approval 

to opening of patient accrual at sites. 

Opportunities for increasing the rate of patient accrual include aligning NCI funding 

more closely with the actual cost of conducting a trial, incentivizing high accruing, costefficient sites, educating patients and the public about the benefits of clinical trials, and 

improving the availability of trials to minority populations. Reducing the time required 

to start trials will require a systematic analysis of the institutional barriers that delay trial 

initiation and a reduction in current regulatory burdens. 

To achieve improved operational efficiency in each of these areas, the CTWG proposes 

the following five initiatives, two of which are new, and three that represent efforts to 

significantly improve current approaches. 

New Initiatives: 

1.	 Restructure the funding model for phase III efficacy trials to incentivize more 

rapid rates of patient accrual. 

2.	 Identify the institutional barriers that prolong the time from concept approval to 

the accrual of the first patient, and develop solutions for overcoming these 

barriers. 

Enhancement Initiatives: 

1.	 Promote patient and public awareness and understanding of clinical trials. 

2.	 Expand current outreach programs to increase the recruitment of minority 

populations to cancer clinical trials. 

3.	 Develop approaches for enhancing adoption of centralized Institutional Review 

Board processes. 

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Restructuring the National Cancer Clinical Trials Enterprise 

New Initiative 1:
 

Restructure the funding model for phase III efficacy trials to incentivize more rapid 

rates of patient accrual.
 

Rationale: 

A complex and expensive infrastructure is required to conduct clinical trials in a manner 

that ensures proper human subject protection, rigorous scientific design, meticulous data 

collection, and valid biostatistical evaluation. Past analyses of cancer clinical trials 

estimated average per-case costs for investigators/sites to be from about $4,000 to about 

$6,000.3

 However, current per-case reimbursement to sites for most NCI-funded 

treatment trials is $2,000. This differential between actual clinical trial costs and current 

NCI reimbursement for patient accrual is not sustainable over the long term for either the 

Cooperative Groups or for the CCOPs. 

However, there may be certain cost inefficiencies in the current system. For example, it 

is unknown whether current models for statistical, data management, auditing, and 

administrative support are optimal, whether they are either over- or underfunded, or 

whether economies of scale might be possible or desirable. In addition, maintaining sites 

under the Cooperative Group mechanisms that accrue only a few patients per year is 

costly to the system, because fixed costs for site infrastructure, personnel, personnel 

training, auditing, and data management must be spread over small numbers of patients, 

resulting in a high per-case cost. Such sites could be managed more efficiently through 

the CTSU. 

The ultimate goal of this initiative is to increase the rate of patient accrual so that 

enrollment for clinical studies can be completed more rapidly but in a way that is cost 

efficient and preserves the funding flexibility of the present system. 

Implementation Plan: 

Financial Analysis of Phase III Trial Costs 

NCI will conduct a comprehensive financial analysis of clinical trial costs, moving 

beyond published analyses of per-case costs to analyze infrastructure costs in greater 

detail, including operations and statistical offices, regulatory activities, etc. The goal is to 

identify areas where Cooperative Groups and CCOPs are not receiving adequate 

compensation, and at the same time, identify inefficiencies where costs could be reduced. 

3

 Emanuel, E., et al. The Costs of Conducting Clinical Research, Journal of Clinical Oncology, 2003; 21: 

4145-50. 

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Restructuring the National Cancer Clinical Trials Enterprise 

An analysis of the cost savings that may be achieved from the closure of low accruing 

sites will be an integral part of this assessment. 

Evaluation of Data Quality as a Function of Patient Accrual Rate 

Poor data quality adversely affects not only trial results but also cost-effectiveness 

because of the expense of the data clean-up that may be required to salvage usable 

results. NCI will perform an analysis of data quality as a function of patient accrual rate 

to evaluate the perception that the quality of data obtained from low accruing sites lags 

behind that of sites with high patient accrual rates. The evaluation will consider not only 

the absolute rate of patient accrual but also the infrastructure (clinical research associates, 

nurses, data managers, etc.) available to support a given rate of accrual at a particular site. 

The analysis should evaluate whether, for a given support infrastructure, a patient accrual 

threshold exists at which data quality may suffer. The results will help determine criteria 

for the optimal numbers of patients that can be accrued in the context of a specific 

clinical trial support infrastructure without compromising data quality. 

New Phase III Trial Funding Model 

Based on the financial and data quality analyses, NCI will develop a new funding model 

for patient accrual sites, operations offices, and statistical centers. The model must take 

into consideration personnel requirements, the number, size and complexity of trials, and 

follow-up burden. Furthermore, the model may not be a one-size-fits-all solution for all 

Cooperative Groups and CCOPs and may require modification on a case-by-case basis 

and a degree of flexibility from year to year. The main goals are to align funding more 

closely with the actual cost of conducting a trial and to enhance cost-effectiveness. 

Several recommended principles for this new funding model are described below. 

Align Reimbursement with Trial Complexity. Not all trials are alike. Some may 

require additional follow-up or documentation due to medication side effects, and some 

may utilize complicated and prolonged therapeutic regimens requiring additional 

laboratory testing, etc. NCI will develop a process for evaluating trial complexity and 

investigate establishing a tiered reimbursement schedule that will match reimbursement 

more closely to the actual cost of running a trial. Such a tiered system will also be 

reflected in the funding of CCOP grants. 

Reduce Duplication of Administrative Functions. NCI will work with the Cooperative 

Groups to implement economies of scale, such as consolidation of administrative 

functions and auditing processes, where this is supported by the financial analysis, to 

reduce duplication and overlap. 

Incentivize High Accruing, Cost-Efficient Sites. Clinical trial sites that accrue greater 

numbers of patients will generally be more cost-efficient. An incentive system to 

increase the number of high accruing sites and phase out inefficient low accruing sites 

may thus enhance cost-effectiveness. To that end, NCI will develop a plan to provide 

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Restructuring the National Cancer Clinical Trials Enterprise 

supplements for high accruing sites to help cover infrastructure costs. Since 

infrastructure requirements increase with patient numbers, NCI will establish a range of 

supplements that correlate with varying levels of patient accrual. When patient accrual 

exceeds a certain threshold, a supplemental grant will be provided and the size of the 

supplement will increase as accrual rises. The financial and data quality analyses 

described above will assist in setting the appropriate accrual targets for various levels of 

supplemental funding. Such an approach will cause patient accrual expense to grow as 

the incentive system moves a higher proportion of accrual to the high accruing sites. 

However, there should be offsetting benefits in cost efficiency and more rapid trial 

completion. 

Establish Minimum Accrual Standards. Each Cooperative Group will propose 

minimum standards for patient accrual based on its own site characteristics and obtain 

NCI approval for that standard. This target is anticipated to be approximately ten to 

twelve patients per year. If sites fall below their targeted levels for two consecutive 

years, they will lose their Group membership. As independent sites, they could still 

access NCI-sponsored trials via the CTSU, where the current minimal accrual standard is 

five patients per year. 

Adjust CCOP Funding for High Accrual Rates. NCI expects CCOPs to accrue high 

volumes of patients. Therefore, as supplemental funding is provided for high-accruing 

Cooperative Group sites, a similar increase will be provided for CCOP participants 

accruing at similar levels, with the increase reflected in the CCOP grant award. Any 

funding available to Cooperative Group members above and beyond NCI support, such 

as industry funding to compensate for additional work related to a complex trial, will also 

be available to CCOP members without compromising their grant funding. 

New Initiative 2:
 

Identify the institutional barriers that prolong the time from concept approval to 

accrual of the first patient, and develop solutions for overcoming these barriers. 

Rationale: 

The time required to move from concept approval to accrual of the first patient for NCIsupported clinical trials is lengthy, often in excess of 18 months. Such a long delay 

impedes clinical progress; at times the clinical question is no longer relevant by the time 

the trial is started. Although specific barriers to rapid protocol activation have been 

documented at individual clinical sites, and a substantive reduction in the turnaround time 

for protocol review by NCI has been achieved, there has been no generalizable systems 

analysis that would clarify key barriers to starting a trial, and identify changes likely to 

lead to improvement. In light of the rapidity with which novel treatments for a number of 

previously-refractory malignancies are becoming available for clinical testing, the need to 

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Restructuring the National Cancer Clinical Trials Enterprise 

understand these barriers and to develop ways to overcome them has never been more 

urgent. 

Implementation Plan: 

Academic management experts knowledgeable in evaluating workflows will be engaged 

to examine the cancer clinical trial startup process operating in real-world settings. The 

goals are an in-depth understanding of the processes that constrain speedy trial initiation 

and a clear set of recommendations for relieving the bottlenecks. Such an analysis is 

ongoing at one major NCI-designated Comprehensive Cancer Center and will be 

expanded to other NCI-funded sites. 

Enhancement Initiative 1:
 

Promote patient and public awareness and understanding of clinical trials. 

Rationale: 

Many patients are unaware that they are eligible for clinical trials, and many are unaware 

of the benefits of clinical trials. To address this need, the NCI has two offices - the 

Office of Education and Special Initiatives (OESI) and the Office of Communications 

(OC) - that are actively involved in developing and promoting clinical trial education 

programs for multiple audiences as well as in providing access to specific types of 

clinical trials. However, many NCI-funded investigators do not take full advantage of 

these resources. The CTWG proposes enhanced interaction of OESI and OC staff with 

patient advocates and clinical investigators to build awareness of clinical trials. 

Implementation Plan: 

Overall Approach 

NCI staff from OESI and OC should become a bridge between NCI clinical investigators 

and the public to communicate the benefits of oncology clinical trials. 

Patient Advocacy Group Outreach 

Patient advocacy groups have been identified by patients as providing credible 

educational information on clinical trials.4

 OC and OESI staff will continue to work 

actively with the NCI Office of Liaison Activities and the patient advocacy programs 

4

 Surveys Identify Barriers to Participation in Clinical Trials, JNCI. 2000; 92: 1556-8. 

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Restructuring the National Cancer Clinical Trials Enterprise 

(i.e., the Consumer Advocates in Research and Related Activities and the Director’s 

Consumer Liaison Group) to identify ways to best involve patient advocacy groups in 

enhancing patient awareness of clinical trials. 

Scientific Steering Committee and Cooperative Group Meetings 

Semi-annual meetings with appropriate Scientific Steering Committee and Cooperative 

Group representatives will create a forum to promote NCI’s educational outreach 

programs and identify ways in which OESI and OC resources can be used to increase 

community awareness of NCI clinical trials. Regular meetings between clinical trial 

investigators and the NCI clinical trial education and promotions staff will ensure that 

educational and promotional messages target the needs of both investigators and patients 

and will help create best practices for enhancing patient awareness about clinical trials. 

Enhancement Initiative 2:
 

Expand current outreach programs to increase the recruitment of minority 

populations to cancer clinical trials. 

Rationale: 

A recent cross-sectional analysis of Cooperative Group clinical trials from 2000 through 

2002 found that racial and ethnic minorities were less likely to enroll in Cooperative 

Group cancer trials than were whites, with the proportion of African American trial 

participants declining in recent years.5

 Ethnically diverse populations in the United 

States are growing rapidly, and the incidence of specific cancers is higher in certain 

ethnic groups. For example, the incidence of colon, rectal, lung and bronchus cancers in 

Alaska Natives and African American men and women is higher than that of other ethnic 

groups, and death rates from prostate cancer among African American men are almost 

twice that of white men. It is vital that these and other minority populations be better 

represented in trials designed to address those cancers that affect them most severely. 

Implementation Plan: 

NCI will promote and expand known best practices for recruitment of minority 

populations by providing additional funds for the following proven initiatives. 

Pilot Minority Outreach/Navigator Program 

The Clinical Trials Patient Navigator (CTPN) program, established by the Cancer 

Disparities Research Partnership Program, was designed to help overcome barriers to trial 

5

 Murthy, V.H. et al., Participation in Clinical Trials, JAMA. 2004; 291: 2720-6. 

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Restructuring the National Cancer Clinical Trials Enterprise 

participation among minority populations, and initial reports suggest that these CTPNs 

are having a positive effect on recruitment and retention. NCI should continue to 

promote Patient Navigators where they have been successful in recruiting large numbers 

of minority populations to trials. 

Minority-Based Community Clinical Oncology Program (MBCCOP) 

NCI launched the Minority-Based Community Clinical Oncology Program (MBCCOP) 

in 1990 to support practicing oncologists who serve large minority populations and to 

facilitate the transfer of new technologies in treatment and cancer prevention practices to 

minority communities and their physicians. Although MBCCOPs comprise less than 20 

percent of the CCOP network grantees, they have contributed 33 percent of the CCOP’s 

minority accrual and 7 percent of the minority patients enrolled by all NCI Cooperative 

Group members and affiliates. The MBCCOPs are well positioned to mentor new 

investigators as they develop the necessary infrastructure and experience to successfully 

compete for MBCCOP funding. The NCI should fund more MBCCOPs and initiate a 

starter program to build the infrastructure necessary to compete for a MBCCOP. 

Minority Institution/Cancer Center Partnership Programs 

The Minority Institution/Cancer Center Partnership program, sponsored by the 

Comprehensive Minority Biomedical Branch of the NCI, was established to facilitate 

research, education, training, and outreach to the minority community and to minority 

researchers, with the goal of improving the participation of minorities in all aspects of 

cancer research. This approach brings together Minority-Serving Institutions and Cancer 

Centers to take advantage of their expertise in educating ethnic minorities and engaging 

in research, training, and career development activities respectively. One of the basic 

concepts of the program is to support and generate NIH/NCI peer-reviewed grant 

applications and funding for minority scientists and programs that focus on cancers that 

disproportionately affect minority populations. Three mechanisms of support should be 

made more robust with additional funding: Planning Grants for Minority 

Institution/Cancer Center Collaborations (P20 grants), Cooperative Planning Grant for 

Comprehensive Minority Institution/Cancer Center Partnership (U56 grants) and the 

Comprehensive Minority Institution/Cancer Center Partnership (U54 grants). 

Enhancement Initiative 3:
 

Develop approaches for enhancing adoption of centralized Institutional Review
 

Board processes. 

Rationale: 

Institutional review requirements for human subjects protection have become inefficient 

to implement and often delay the opening of trials. This is especially true for large, 

multisite trials, which can require review by many different Institutional Review Boards 

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Restructuring the National Cancer Clinical Trials Enterprise 

(IRBs). Furthermore, since the median cost for IRB review at academic medical centers 

was nearly $750,000 per year in 20026

, the potential for cost savings is substantial. 

In 2001, NCI created a Central Institutional Review Board (CIRB) in consultation with 

the DHHS Office of Human Research Protections (OHRP). Over the succeeding years, 

as operational efficiencies have been implemented and the benefits of CIRB use have 

become more widely appreciated, use of the CIRB has grown steadily. However, despite 

statements from both OHRP and FDA that a properly constituted centralized IRB process 

can fully meet the requirements of Federal law, and the demonstrated capability of the 

NCI CIRB process to substantially reduce local administrative burden without delaying 

startup of patient accrual, there remains resistance to the utilization of the CIRB process 

for facilitated review, largely among legal and senior research administration staff at 

major academic institutions. 

Implementation Plan: 

Barrier Analysis 

NCI will conduct a systematic analysis of barriers to acceptance of the CIRB facilitated 

review process among legal staff, senior research administration staff (including 

Research Vice-Presidents), and IRB administrators at institutions conducting NCI-funded 

clinical trials. The goal is to identify the nature of the barriers, (e.g., lack of 

understanding of OHRP and FDA guidelines, fear of liability, etc.) as well as to identify 

any remaining shortcomings in the operation of the NCI’s CIRB. Based on the findings, 

NCI will identify steps that can be taken to mitigate the concerns and enhance the rate of 

adoption of the CIRB process. Because the issues raised by CIRB are not unique to 

cancer research, NCI will work with NIH leadership, and participate as appropriate in 

initiatives by independent organizations such as the AAMC, to facilitate broader use of 

centralized IRB review. 

Cost Savings Analysis 

NCI will fund an analysis of the potential cost savings that would result from an 

institution’s use of the CIRB facilitated review process and disseminate its findings to the 

community. Evaluation of the time savings and efficiencies to be gained from utilizing 

CIRB facilitated review will be an integral part of the cost analysis. 

Promote Regional IRB Use 

NCI will encourage the use of “regional” IRBs for review of cancer clinical trials. These 

regional IRBs allow hospitals, community oncologists, or academic medical centers to 

have a protocol activated at multiple sites based on approval by a single IRB rather than 

requiring approval from multiple, site-specific IRBs. Such regional IRBs have already 

6

 Sugarman, J., et al., The Cost of Institutional Review Boards in Academic Medical Centers, N Engl J 

Med, 2005; 352: 1825-7. 

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Restructuring the National Cancer Clinical Trials Enterprise 

been developed by several CCOPs and by Cancer Centers in single urban areas. These 

regional IRBs would not replace or compete with the NCI CIRB, but would provide the 

local IRB oversight function inherent in the CIRB process and facilitate community 

physician participation in clinical trials. 

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Restructuring the National Cancer Clinical Trials Enterprise 

Enterprise-Wide Initiatives 

Introduction: 

The initiatives outlined in the preceding sections represent an enormous opportunity to 

enhance the NCI clinical trials enterprise. They will, however, require substantial 

coordination, management, and oversight to be successful in improving the quality, 

efficiency, and effectiveness of NCI clinical trials without introducing unwanted 

complexities and delays. Therefore it is essential that NCI also enhance its internal 

organizational structure to effectively address these challenges. 

Initiative 1:
 

Establish a permanent clinical trials subcommittee of the NCAB to advise the NCI 

Director on the conduct, oversight, and implementation of clinical trials across the 

Institute. 

Rationale: 

The CTWG has served as a strong catalyst for change, and was empowered and 

strengthened by broad representation of external stakeholders in the cancer clinical trials 

enterprise. To take this effort forward, it is essential that the NCAB establish a similar 

standing group of external experts to provide oversight for implementation of the 

initiatives proposed by the CTWG and to guide the enterprise into the future. 

Implementation Plan: 

A Clinical Trials Oversight Subcommittee of the NCAB will be established to advise the 

NCI Director on progress made in implementing the CTWG recommendations. The 

Subcommittee will provide oversight for the Director on a continuing basis on the 

conduct of clinical trials across the Institute. Membership will include standing members 

of the NCAB and other NCI Boards, as well as ad hoc members, so that the 

Subcommittee consists of a broad group of clinical trial experts representing extramural 

clinical investigators, community oncologists, other oncology health care providers, 

regulatory agencies, CMS, industry, and patient advocates. 

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Restructuring the National Cancer Clinical Trials Enterprise 

Initiative 2:
 

Develop a coordinated organizational structure within the NCI to manage the entire 

clinical trials enterprise supported by the Institute. 

Rationale: 

Achieving the full benefits of an enhanced system for coordination and prioritization of 

clinical trials will be difficult if the currently separate and independent management of 

clinical trials by several NCI Divisions is not more closely integrated. The goal is to 

develop a structure that leverages the scientific and managerial strengths of the Divisions 

and coordinates their efforts to build an efficient, interactive, and collaborative process 

for ensuring that the investment in clinical trials is optimal across the Institute. 

Implementation Plan: 

The NCI Director will appoint an internal committee composed of the senior leaders of 

all Divisions who are responsible for clinical trials to develop detailed recommendations 

for restructuring the internal NCI management of clinical trials to achieve the objectives 

of the CTWG initiatives and to provide ongoing integration and oversight of clinical 

trials supported by NCI. 

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Restructuring the National Cancer Clinical Trials Enterprise 

Evaluation and Outcome Measures 

Introduction: 

No major restructuring of an ongoing enterprise such as the NCI-funded cancer clinical 

trials program should be undertaken without establishing mechanisms to evaluate the 

success of the restructuring effort. Evaluation should be an integral part of program 

management, and should address both process and outcomes. Process assessment is 

important in order to have confidence that the effort is proceeding appropriately during 

its initial phase, as well as to create a basis for charting a revised course of action if 

needed. Outcomes assessment is essential to confirm that the effort is achieving its goals. 

Successful evaluation of clinical research programs presents several challenges. First, it 

is not possible to fully capture all of the important dimensions of performance using 

purely objective and quantitative measures. The outcome measures must include a 

judicious blend of qualitative and quantitative, objective and subjective measures. 

Second, the results of clinical research are necessarily somewhat unpredictable, and can 

depend to a significant degree on factors beyond the control of the participants. And 

third, clinical research is a complex system in which multiple internal and external factors 

interact in many different ways – some of which are observable, and some not – to affect 

outcomes. Thus, attribution of observed outcomes to particular program policies, 

organizational structures, or management decisions can be difficult. 

An evidence-based approach is essential. The determination of success or failure and 

decisions on any needed course corrections will not be automatic or mechanical, but a 

matter of judgment by experts in the field. However, this expert evaluation must be 

informed by systematic, structured empirical data so that there will be a shared basis for 

discussion and decision-making. The measures used do not serve as the sum total of the 

evaluation, but as essential “raw material” for a larger process of expert judgment in 

which the broad oncology research community must participate. 

The needed measures fall into three categories: 

 Program management process measures that evaluate implementation of the 

cancer clinical trials restructuring effort. 

 System performance process measures that evaluate the effect of changes in 

operational processes on the design, prioritization, and conduct of cancer clinical 

trials. 

 System outcome measures that assess the results which ultimately matter – an 

increased number of useful therapies for patients and improved targeting of 

therapies to the specific patients who will benefit. 

To evaluate the impact of the proposed restructuring, it is essential to conduct a baseline 

evaluation of the selected measures prior to implementation. Only then can the effect of 

change be recognized. It is also essential to set realistic timelines for achievement of the 

objectives so that evaluation is not attempted either too early or too late in the process. 

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Restructuring the National Cancer Clinical Trials Enterprise 

For example, certain process measures may come into play only after other processes on 

which they depend have been completed. Similarly, it may be a matter of years before it 

is reasonable to expect certain outcomes to be apparent. Nevertheless, many process 

measures can be fruitfully assessed at intervals to document the progress of the 

restructuring initiatives. 

The measures proposed below are not fully operationalized, and thus should be viewed as 

suggested topic areas rather than actual measures. In addition, as well defined measures 

do not currently exist for many of the elements of the NCI-supported cancer clinical trials 

program, establishing the specific measures will be an ongoing and iterative process. 

NCI will engage experienced evaluation specialists to assist in development of the 

definitions, survey instruments, statistical adjustments, and other tools required for the 

evaluation measures to be practical and valid and to conduct the evaluations. These 

specialists will also determine the appropriate timing for examining the various measures 

in the context of implementation timelines and the nature of the impacts envisioned. The 

specialists will conduct a baseline evaluation of the current system as soon as possible to 

provide a reliable basis for ascertaining the value of the restructuring effort. The results 

of this baseline evaluation will be analyzed to determine whether the chosen measures are 

valid or should be eliminated or revised. 

Program Management Process Measures: 

These measures will be tracked by NCI on a continuing basis, as part of its management 

of the restructuring process, and will be assessed in light of the proposed implementation 

plan and timeline. Questions to be addressed include the following: 

 Were the tasks initiated on time? 

 Did they follow the implementation plan as outlined? 

 If obstacles were encountered, were alternate plans implemented quickly and 

effectively? 

 Were the tasks accomplished on time or were timelines revised in a timely and 

realistic fashion? 

System Performance Process Measures: 

The restructuring effort has three key process objectives: 

 Improved communication and coordination, leading to more collaboration and 

cooperation in the design and conduct of cancer clinical trials. 

 Enhanced scientific quality of cancer clinical trials through a more strategically 

focused and transparent prioritization process involving the broad oncology 

community. 

 Enhanced operational efficiency to achieve more timely and cost-effective 

initiation and conduct of cancer clinical trials. 

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Restructuring the National Cancer Clinical Trials Enterprise 

To accomplish these objectives, the restructuring effort envisions implementing new 

structures, processes, and behaviors on the part of participants in the system. The system 

performance measures must therefore provide empirical evidence of whether the new 

structures and processes are being used effectively, whether the targeted behaviors are 

changing in the intended ways, and whether the impacted components and the system as 

a whole are in fact becoming more efficient, more collaborative, more transparent, and of 

higher scientific quality. Supplemental measures should also be used to assure that the 

new objectives are not achieved at the expense of other valued characteristics of the 

current cancer clinical trials system. 

Some of the system performance characteristics can be assessed via objective measures, 

while others must be assessed subjectively, through a systematic and transparent process 

of soliciting expert opinion. It is important to remember that no single measure will 

provide a conclusive indicator of success, nor a basis for attribution of cause and effect. 

Rather each measure must be combined with the others and included in a larger 

comprehensive evaluation by a broad range of critical stakeholders. 

Described below are some examples of the types of measures that might be developed by 

the evaluation experts retained to develop the evaluation process. These should not be 

considered either definitive or comprehensive, but rather illustrative of the logic to be 

applied. 

Coordination New Initiative 2 

Realign NCI funding, academic recognition, and other incentives to promote 

collaborative team science and clinical trial cooperation. 

1.	 Number of clinical trials that involve collaboration across mechanisms and 

resources (e.g., interactions among SPOREs, Cooperative Groups, Cancer 

Centers, etc.). Evaluation at 0, 2 and 5 years. 

2.	 Perception by academic clinical investigators of the degree to which NCI funding 

and recognition policies reward participation in collaborative clinical trials. 

Evaluation at 0, 2 and 5 years. 

3.	 Ongoing clinical research activities by investigators funded through new Clinical 

Investigator awards. Evaluation at 5 and 7 years. 

4.	 Credit awarded for participation in NCI sponsored collaborative clinical trials in 

promotion/tenure committee guidelines. Evaluation at 0, 5 and 7 years. 

5.	 Perception by academic clinical investigators of the value accorded at their 

institutions to participation in collaborative clinical trials. Evaluation at 0, 5 and 7 

years. 

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Restructuring the National Cancer Clinical Trials Enterprise 

Prioritization/Scientific Quality New Initiative 2 

Establish a network of Scientific Steering Committees to address design and 

prioritization of phase III efficacy trials that leverages current Intergroup, 

Cooperative Group, SPORE, and Cancer Center structures and involves the broad 

oncology community. 

1.	 Time from initiation of Phase III concept discussions to launch of trial accrual. 

Evaluation at 0, 2 and 5 years. 

2.	 Extent of duplication in NCI’s portfolio of phase III clinical trials. Evaluation at 

0, 2 and 5 years. 

3.	 Perception by extramural clinical investigators of the transparency, fairness, 

quality and efficiency of the phase III trial prioritization process. Evaluation at 0, 

2 and 5 years. 

4.	 Perception by community oncologists and patient advocates of the extent to which 

phase III protocols incorporate their input and have designs and clinical outcomes 

attractive to patients and treating physicians. Evaluation at 0, 2 and 5 years. 

5.	 Quality of phase III concepts submitted to CTEP including importance of clinical 

question addressed, degree of innovation, lack of duplication, strength of 

proposed correlative science, etc. Evaluation at 0, 2 and 5 years. 

Standardization New Initiative 1 

Promote establishment of national clinical trial information technology 

infrastructures that are fully interoperable with NCI’s cancer Bioinformatics Grid. 

1.	 Number of clinical trial management modules implemented in caBIG. Evaluation 

at 1 and 3 years. 

2.	 The extent to which the caBIG standards and tools have been implemented in the 

cancer clinical trials community. Evaluation at 2 and 5 years. 

3.	 The number of caBIG compliant systems developed by vendors to service the 

cancer clinical trials community. Evaluation at 2 and 5 years. 

4.	 Level of caBIG interoperability of IT systems for clinical trial management 

throughout the broad oncology community. Evaluation at 2 and 5 years. 

5.	 Perception of clinical investigators of the utility of caBIG in mounting and 

managing a clinical trial. Evaluation at 2 and 5 years. 

6.	 Cost and time savings achieved through IT interoperability. Evaluation at 5 and 7 

years. 

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Restructuring the National Cancer Clinical Trials Enterprise 

Operational Efficiency New Initiative 1 

Restructure the funding model for Phase III efficacy trials to incentivize more rapid 

rates of patient accrual. 

1.	 Efficiencies in clinical trial management and administration identified and 

implemented. Evaluation at 2 and 4 years. 

2.	 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. 

3.	 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 Outcome Measures: 

The most important and meaningful outcome measures for the restructuring effort are the 

degree to which the changes achieve the goal of enhanced clinical trial success and an 

enhanced number of new treatments reaching patients more quickly. The most important 

measures are the following: 

 Rate of accrual, time to completion, and cost effectiveness for NCI-supported 

phase III protocols. 

 Number of NCI-supported trials that provide results critical for guiding new 

therapeutics and diagnostics development. 

 Number of new biomarkers validated in NCI-supported trials that enable better 

targeting of cancer therapies. 

 Number of revisions of major treatment guidelines (e.g., ASCO, etc.) to reflect 

new knowledge gained from NCI-supported trials. 

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Restructuring the National Cancer Clinical Trials Enterprise 

Timeline and Budget 

Timeline: 

Implementation of the 22 initiatives recommended by the CTWG will require at least 

four to five years to complete, although the majority are projected to be implemented by 

the end of year three. Moving from initial implementation to routine practice will then 

require another two to three years. A schedule of key activities and milestones associated 

with each initiative is presented in Table 1 (see Appendix B). Major items for each year 

include the following: 

Year 1: 

Coordination Initiatives 

 Initiate development of comprehensive clinical trials database. 

 Expand the CTSU to cover SPORE and Cancer Center trials. 

 Develop policies and procedures governing joint NCI/FDA meetings concerning 

new agents; begin to conduct joint meetings. 

Prioritization/Scientific Quality Initiatives 

 Establish Investigational Drug Steering Committee for design and prioritization of 

early phase drug development trials. 

 Establish initial Scientific Steering Committees for the design and prioritization of 

phase III trials. 

 Convene initial State-of-the-Science Meetings. 

 Convene initial community oncologist and patient advocate focus groups. 

 Define criteria for prioritization of correlative science and quality of life 

proposals. 

Standardization Initiatives 

 Increase clinical investigator representation on the caBIG Clinical Trials 

Management System workspace. 

 Develop strategies to achieve clinical trial IT interoperability. 

 Initiate process of achieving industry/FDA concurrence on standard Case Report 

Forms incorporating Common Data Elements. 

 Initiate development of a credentialing system for investigators and sites. 

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Restructuring the National Cancer Clinical Trials Enterprise 

Operational Efficiency Initiatives 

 Conduct analysis of phase III clinical trial costs. 

 Initiate analysis of institutional barriers to timely trial initiation at sites. 

 Initiate regular interactions of NCI education and communications staff with 

patient advocacy groups and clinical investigators to increase patient and public 

awareness and understanding of clinical trials. 

 Implement additional funding for minority outreach programs. 

 Initiate analysis of institutional barriers to adoption of the NCI CIRB facilitated 

review process. 

Enterprise-Wide Initiatives 

 Establish NCAB Clinical Trials Oversight Subcommittee. 

 Restructure NCI clinical trials management. 

 Develop an evaluation system and implement baseline assessment. 

Year 2: 

Coordination Initiatives 

 Expand NCI clinical trials database review capacity. 

 Adjust grant data reporting requirements. 

 Modify NCI award guidelines to reward collaboration. 

 Institute new forms of NCI recognition to reward collaboration. 

 Initiate interactions with medical school deans on academic incentives. 

 Initiate awareness campaign for NCI/FDA expedited review process. 

 Establish NCI/CMS process to select studies appropriate for reimbursement. 

Prioritization/Scientific Quality Initiatives 

 Establish additional Scientific Steering Committees. 

 Convene additional State-of-the-Science Meetings. 

 Convene additional community oncologist and patient advocate focus groups. 

 Establish community oncologist and patient advocate Steering Committees. 

 Establish budget for correlative science/quality of life studies and initiate funding. 

 Create initial standards documents for measurement, analysis and reporting of 

biomarker data in association with clinical trials. 

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Restructuring the National Cancer Clinical Trials Enterprise 

Standardization Initiatives 

 Create web-based trial initiation tool in caBIG. 

 Complete development of standard Case Report Forms with industry/FDA 

concurrence. 

 Hold conference on standard clinical trial contract clauses with NCI, industry and 

clinical trial sites. 

Operational Efficiency Initiatives 

 Restructure phase III trial funding model. 

 Begin to increase funding for high accruing sites. 

 Complete analysis of institutional barriers to timely trial initiation at sites. 

 Develop approaches to enhance adoption of NCI CIRB facilitated review process. 

Enterprise-Wide Initiatives 

 Evaluate progress of specific initiatives based on implementation plan timeline. 

Year 3:
 

Coordination Initiatives 

	 Fully implement the clinical trials database with all data being routinely 

submitted.
 

Prioritization/Scientific Quality Initiatives 

 Evaluate phase III prioritization system.
 

 If successful, initiate expanded phase III prioritization system implementation.
 

 Evaluate feasibility of integrating prioritization of phase II trials.
 

Standardization Initiatives 

 Complete internal NCI IT system harmonization with caBIG. 

 Implement standard Case Report Forms. 

 Develop system to credential investigators and sites. 

 Reach agreement on standard clinical trial contract clauses with stakeholders. 

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Operational Efficiency Initiatives 

 Implement solutions for reducing institutional barriers to timely trial initiation at 

sites. 

 Implement approaches for enhancing adoption of NCI CIRB facilitated review 

process. 

Enterprise-Wide Initiatives 

 Evaluate progress of specific initiatives based on implementation plan timeline. 

Years 4-5: 

Coordination Initiatives 

 Implementation complete. 

Prioritization/Scientific Quality Initiatives 

 Complete implementation of prioritization system for all phase III trials.
 

 If judged feasible, initiate integrated prioritization of phase II trials. 

Standardization Initiatives 

 Achieve overall IT interoperability across NCI-funded cancer clinical trials 

system. 

 Create registry of credentialed investigators and sites. 

Operational Efficiency Initiatives 

 Implementation complete. 

Enterprise-Wide Initiatives 

 Evaluate progress of specific initiatives based on implementation plan timeline. 

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Restructuring the National Cancer Clinical Trials Enterprise 

Budget: 

The estimated cost for implementing the CTWG initiatives is presented in Tables 2 and 3 

(see Appendix B). Table 2 presents the costs by category – Extramural, 

Analysis/Development Projects, NCI Operational Activities, and Meeting Support. Table 

3 presents the costs by year. The incremental cost for Year 1 (FY 06) is $7.1M, 

increasing to $20.6M in Year 2 (FY07), and then reaching a steady state of approximately 

$29M annually by Year 3. 

By far the largest portion of this incremental expense ($21.5M or 75%) is provided to the 

extramural community to enhance the quality and efficiency of clinical trials. Of the 

remaining 25%, $2.8M (10%) directly supports the clinical trial database that provides 

clinical investigators, practicing oncologists, patients, and NCI staff with comprehensive, 

up-to-date information about all NCI-supported clinical trials. Another 10% ($2.9M) 

supports the enterprise-wide prioritization system, involving all the critical stakeholders, 

for ensuring that NCI supports the best-designed trials, addressing the most important 

questions and leveraging the most significant scientific advances. The final 5% ($1.5M) 

supports the management structure within NCI necessary to ensure that the initiatives are 

implemented and maintained in a manner that truly transforms the national cancer clinical 

trials enterprise. 

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Restructuring the National Cancer Clinical Trials Enterprise 

APPENDICES 

Appendix A 

CTWG Meeting Dates and Acknowledgments 

Appendix B 

Table 1: Implementation Timeline 

Table 2: Estimated Implementation Budget by Category 

Table 3: Estimated Implementation Budget by Year 

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Restructuring the National Cancer Clinical Trials Enterprise 

Appendix A 

Meeting Dates and Acknowledgments 

CTWG Meeting Dates 

2004 

January 29 & 30 

Initial Conference Calls 

February 26 & 27 

CTWG Conference Calls 

April 22 & 23 

CTWG Conference Calls 

May 24 

First Face-to-Face Meeting of the CTWG 

Chicago, Illinois 

August 27 

Face-to-Face Meeting of the CTWG 

Chicago, Illinois 

September 23 & 24 

CTWG Conference Calls 

October 14 & 15 

CTWG Conference Calls 

November 17 

Face-to-face meeting of the CTWG 

Chicago, Illinois 

December 9 & 10 

CTWG Conference Calls 

2005 

January 21 & 27 

CTWG Conference Calls 

February 9 & 10 

Face-to-face meeting of the CTWG 

Chicago, Illinois 

February 17 

Subcommittee Chairs Report to the NCAB 

Bethesda, Maryland 

March 3 & 4 

CTWG Conference Calls 

March 17 & 18 

CTWG Conference Calls 

March 31 & April 1 

Face-to-Face Meeting of the CTWG 

Chicago, Illinois 

April 28 & 29 

Face-to-Face Meeting of the CTWG 

Chicago, Illinois 

May 3 

Face-to-Face Meeting of the CTWG 

Bethesda, Maryland 

May 19 & 20 

CTWG Conference Calls 

June 7 

Final Report to the NCAB 

Bethesda, Maryland 

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Restructuring the National Cancer Clinical Trials Enterprise 

Acknowledgments 

In addition to all of the dedicated members of the Clinical Trials Working Group, there 

have been several other individuals who played very important roles facilitating the 

efforts of the CTWG, from its inception through the development of this report: 

Margaret Holmes, Ph.D., Director of NCI’s Office of Grant Program Coordination, and 

Clarissa L. Douglas, Program Coordinator in the Office of Grant Program Coordination, 

worked tirelessly to support the formation of the CTWG, its initial conference calls and 

face-to-face meetings, the evaluation of current issues facing NCI’s clinical trials 

structure, the elaboration of the CTWG’s working structure, and the initiation of the 

CTWG web site. 

Tom Benthin was very helpful in facilitating the initial face-to-face meetings of the 

group and in providing graphic representations of these activities. 

Clint Malone from the NCI Center for Bioinformatics was exceptionally helpful in 

developing both the CTWG website and the web forums that were essential to the 

collection of input for the CTWG’s initial recommendations to the NCAB from the 

extramural community. 

Dr. David Dilts, Professor of Management at the Vanderbilt University School of 

Business, was kind enough to share his detailed analysis of the “bottlenecks” in the 

cancer clinical trials process at the Vanderbilt-Ingram Comprehensive Cancer Center 

with the entire CTWG, as well as his preliminary recommendations regarding how the 

elimination of such barriers might be approached. 

Drs. Stephen Grubbs and Shaker Dakhil, from the Delaware and Wichita CCOPs, 

respectively, provided critical insights into the essential role of community oncologists in 

the NCI-funded cancer clinical trials system; these insights had a major impact on the 

development of this report. 

Kristin Hinkle was exceptionally effective managing conference calls and the 

scheduling of face-to-face meetings for the CTWG. 

Maureen Johnson, Ph.D., Special Assistant, Office of the NCI Director, coordinated all 

of the activities of the CTWG as its Executive Director over the past nine months. There 

is no question that her extraordinary commitment to the CTWG played a fundamental 

role in the creation of the initiatives outlined in this report. 

Science and Technology Policy Institute (STPI) of the Institute for Defense 

Analyses: The critical roles of Judith Hautala, Ph.D. (Lead Coordinator), and Oren 

Grad, M.D., Ph.D., Yumi Ando, M.D., M.P.H., and Todd Falcone in the elaboration of 

this document would be difficult to overestimate. Each member of the STPI team was 

essential in moving the deliberations of the CTWG, from the development of preliminary 

recommendations to the ultimate completion of a document that outlines a series of 

initiatives with plans for their implementation. 

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Restructuring the National Cancer Clinical Trials Enterprise 

Appendix B 

Table 1: Implementation Timeline 

Initiative Key Milestones and Activities Coordination Year 1 

(Oct. 2005-Sept. 2006) 

Year 2 (Oct. 2006-Sept. 2007) 

Year 3 (Oct. 2007- Sept. 2008) 

Comprehensive clinical trials database 

Establish implementation task force Begin to develop database Define data to deposit Determine data submission procedures Determine access controls Investigate grant data reporting requirements 

Continue to develop database Create report templates Expand NCI database review capacity Adjust grant data reporting requirements 

Run pilot test with extramural users Database fully implemented by March Routine submission of all trial data in place by September 

Align incentives to reward collaboration 

Begin to modify NCI award guidelines Begin to create new forms of NCI recognition Develop strategies for medical school deans Expand CTSU to cover SPORE and Cancer Center trials 

Modify NCI award guidelines Institute new forms of NCI recognition Begin interactions with medical school deans/AAMC/IOM 

Continue to interact with medical school deans/AAMC/ IOM 

Joint FDA/NCI meetings 

Develop policies and procedures for meetings Develop non-disclosure agreements Begin joint meetings by July. 

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Enhance industry awareness of NCI/FDA expedited review process 

Develop communication plan Initiate awareness campaign Evaluate the campaign’s 

effectiveness 

Collaborate with CMS on study funding 

Begin to establish process to select studies 

Establish process to select studies 

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Table 1, Continued: Implementation Timeline 

Initiative Key Milestones and Activities Prioritization Year 1 

(Oct. 2005-Sept. 2006) 

Year 2 (Oct. 2006-Sept. 2007) 

Year 3 (Oct. 2007- Sept. 2008) 

Investigational drug trial prioritization 

 Establish Investigational 

Drug Steering Committee 

 Organize first strategic 

meeting 

 Begin routine 

prioritization activities by June 

Phase III trial prioritization 

 Establish initial Scientific 

Steering Committees 

 Convene initial State-ofthe-Science meetings  Convene initial 

community oncologist/patient advocate focus groups 

 Establish additional 

Scientific Steering Committees 

 Convene additional Stateof-the-Science meetings  Convene additional focus 

groups 

 Evaluate prioritization 

system 

 Begin expanded 

prioritization system implementation if successful 

Community Oncologist/Patient Advocate Steering Committees 

 Establish Steering 

Committees 

Phase II trial integration 

 Begin presentations at 

State-of-the-Science meetings 

 Begin data submission to 

database 

 Routine database 

submission by September 

 Evaluate feasibility of 

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Restructuring the National Cancer Clinical Trials Enterprise 

integrating prioritization 

Correlative science / quality of life funding 

 Define criteria for study 

prioritization 

 Establish budget 

 Criteria for prioritization 

established by October 

 Budget established by 

October 

 Initiate funding 

Correlative science standards 

 Define technology 

categories 

 Create initial standards 

documents 

 NCI implements 

standardization requirements for proposals 

 Begin ongoing review and 

update 

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Table 1, Continued: Implementation Timeline 

Initiative Key Milestones and Activities Standardization Year 1 

(Oct. 2005-Sept. 2006) 

Year 2 (Oct. 2006-Sept. 2007) 

Year 3 (Oct. 2007- Sept. 2008) 

caBIG interoperability 

 Increase clinical 

investigator representation on Clinical Trials Management Systems workspace 

 Develop strategy to 

harmonize internal NCI IT systems 

 Develop strategy to 

achieve overall IT interoperability of NCI funded clinical trial system 

 Create web-based trial 

initiation tool 

 Complete internal NCI IT 

system harmonization 

FDA/industry concurrence on standard CRF library 

 Begin to 

harmonize/expand NCI standard CRFs with industry and FDA involvement 

 Complete development of 

standard CRFs with industry/FDA concurrence 

 Implementation of 

standard CRFs by September 

 Begin annual review and 

update 

Credentialing system 

 Create Task Force  Develop credentialing 

criteria 

 Credentialing criteria 

developed by June 

 Begin to develop system 

to credential investigators and sites 

 Develop system to 

credential investigators and sites 

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Restructuring the National Cancer Clinical Trials Enterprise 

Standard clinical trial contract clauses 

 Conduct stakeholder 

conference 

 Develop standard contract 

clauses 

 Reach agreement on 

contract clauses with stakeholders 

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Restructuring the National Cancer Clinical Trials Enterprise 

Table 1, Continued: Implementation Timeline 

Initiative Key Milestones and Activities Operational Efficiency 

Year 1 (Oct. 2005-Sept. 2006) 

Year 2 (Oct. 2006-Sept. 2007) 

Year 3 (Oct. 2007- Sept. 2008) 

Restructure phase III clinical trials funding model 

 Analyze phase III clinical 

trial costs 

 Analysis completed by 

March 

 Restructure funding model 

based on analysis 

 Begin to increase funding 

for high accruing sites 

Identify institutional barriers that delay trial initiation 

 Initiate analysis  Analysis completed by 

September 

 Develop solutions for 

reducing barriers 

 Begin to implement 

solutions 

Increase patient/public awareness of clinical trials 

 Establish interactions 

between OC and OESI and clinical investigators 

 Establish interactions 

between OC and OESI and patient advocacy groups 

Increase minority outreach 

 Implement additional 

funding for minority outreach programs 

Reduce IRB administrative burden 

 Initiate analysis of barriers 

to CIRB adoption 

 Analysis completed by 

March 

 Develop approaches to 

enhance CIRB adoption 

 Implement approaches to 

enhance CIRB adoption 

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Table 1, Continued: Implementation Timeline 

Initiative Key Milestones and Activities Enterprise-Wide Year 1 

(Oct. 2005-Sept. 2006) 

Year 2 (Oct. 2006-Sept. 2007) 

Year 3 (Oct. 2007- Sept. 2008) 

NCAB Clinical Trials Oversight Subcommittee 

 Establish oversight  subcommittee 

Restructure NCI clinical trials management 

 Restructure NCI 

management 

Evaluation and outcome measures 

 Develop evaluation 

system 

 Take baseline 

measurements of programs to be evaluated 

 Evaluate progress of 

specific initiatives based on implementation plan timeline 

 Evaluate progress of 

specific initiatives based on implementation plan timeline 

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Restructuring the National Cancer Clinical Trials Enterprise 

Table 2: Estimated Implementation Budget by Category 

Initiative Expenses Coordination Extramural Analysis/Development Projects NCI Operational Activities Meeting Support 

Data Reporting Database NCI Data Review Implementation Ta

Create Costs7 Develpmt/Maint Staff Force 

comprehensive Yr 1 $0.0M Yr 1 $1.0M Yr 3-5 $250K/yr Yr 1 $250K clinical trials Yr 2 $0.0M Yr 2 $1.5M Yr 2 $250K database Yr 3 $2.0M 

Yr 4 $1.0M Yr 5 $0.0M 

Yr 3 $0.5M Yr 4 $1.8M Yr 5 $1.8M 

Data Review 

Contract 

Yr 3-5 $750/yr 

Yr 3 $250K 

Clinical Inv. Award 

Align incentives to Yr 2-5 $1.0M/yr reward SPORE/Cancer collaboration Center CTSU Trials N/A See Note 1 N/A 

Yr 1 

$0.5M/yr 

Yr 2 $0.75M/yr 

Yr 3-5 $1.0M/yr 

Develop joint FDA/NCI meetings 

N/A N/A See Note 1 N/A 

Enhance industry awareness of NCI/FDA expedited 

N/A N/A See Note 1 N/A 

7 Costs not covered by grants; no data reporting in Yr1-2; grants modified at renewal; therefore the costs are partially covered by grants 

in Yr 5. 

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Restructuring the National Cancer Clinical Trials Enterprise 

review process Collaborate with CMS on study funding 

N/A N/A See Note 1 N/A 

Note 1: Included in NCI clinical trials management expenses (see page 74). 

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Table 2, Continued: Estimated Implementation Budget by Catego

Initiative Expenses Prioritization Extramural Analysis/Development Projects NCI Operational Activities Meeting Support 

Clin Trials Mgmt Investigational Dru

Investigational drug Staff Steering Committe

trial prioritization N/A N/A Yr 1-5 $100K/yr Yr 1-5 $150K/y

Other NCI Staff 

Yr 1-5 $250K/yr 

Clin Trls Mgmt & SOS9& Steering 

Phase III trial Other NCI Staff Com10 prioritization Yr 1 $200K + Yr1 2SOS/10SC 

N/A N/A $150K $400K 

Yr 2 $200K + 

$300K 

Yr 3-5 $400K + 

$450K 

Yr2 4SOS/20SC 

$800K 

Yr3 6SOS/30SC 

$1.1M 

Yr4 8SOS/40SC 

$1.3M 

Yr5 10SOS/50SC 

$1.5M 

Establish Community Oncologist/Patient Advocate Steering 

N/A N/A N/A See Note 2 

8 Four meetings per year; 30 members 9 State of Science Meeting; 50 attendees $80K/meeting10Scientific Steering Committee Meetings; size of Committee and number of meetings per year varies with disease 

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Restructuring the National Cancer Clinical Trials Enterprise 

Committees Phase II trial prioritization integration 

N/A N/A See Note 2 N/A 

Correlative science / quality of life funding 

Yr 2 $ 5M 

Yr 3-5 $10M/yr 

N/A See Note 1 N/A 

Correlative science standards 

N/A N/A See Note 1 See Note 1 

Note 1: Included in NCI clinical trials management expenses (see page 74). Note 2: Included in phase III trial prioritization expenses (this page). 

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Restructuring the National Cancer Clinical Trials Enterprise 

Table 2, Continued: Estimated Implementation Budget by Catego

Initiative Expenses Standardization Extramural Analysis/Development Projects NCI Operational Activities Meeting Support Promote caBIG interoperability N/A 

Interoperability 

Analyses 

Yr 1 $500K (NCI 

intrnl) 

Yr 2 $500K 

(extramural) 

Trial Initiation Tool 

Yr 2 $500K 

N/A 

Additional Clinica

Trials Workspace 

Expense 

Yr 1-5 $250/yr 

FDA/Industry concurrence on standard CRF library 

N/A N/A See Note 1 See Note 1 

Credentialing system11 

N/A N/A See Note 1 See Note 1 

Standard clinical trial contract clauses 

N/A N/A See Note 1 See Note 1 

Note 1: Included in NCI clinical trials management expenses (see page 74). 11 Assume cost of establishing credentialing system is paid by professional societies/trade associations. 

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Table 2, Continued: Estimated Implementation Budget by Catego

Initiative Expenses Operational Efficiency Extramural Analysis/Development Projects NCI Operational Activities Meeting Support Restructure phase III clinical trials funding model 

High Accrual 

Supplemnts 

Yr 1 $0.0M Yr 2 $5.0M Yr 3 $6.0M 

Financial Analysis 

Yr 1- 2 $500K/yr 

See Note 1 N/A 

Yr 4 $7.0M Yr 5 $7.5M 

Identify institutional barriers that delay trial initiation 

N/A Barrier Analysis 

Yr 1-2 $350K/yr 

See Note 1 N/A 

Increase patient/public awareness of clinical trials 

N/A N/A See Note 1 N/A 

Increase minority outreach 

Expanded Minority 

Programs 

Yr 1 $0.5M N/A N/A N/A 

Yr 2-5 $2M/yr 

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Restructuring the National Cancer Clinical Trials Enterprise 

Reduce IRB administrative burden 

N/A 

Barrier Analysis 

Yr 1-2 $100K/yr 

Cost Savings Analysis 

Yr 1 $100K 

See Note 1 N/A 

Note 1: Included in NCI clinical trials management expenses (see page 74). 

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Table 2, Continued: Estimated Implementation Budget by Catego

Initiative Expenses Enterprise-Wide Extramural Analysis/Development Projects NCI Operational Activities Meeting Support NCAB Clinical Trials Oversight Subcommittee 

N/A N/A N/A See Note 1 

Restructure NCI clinical trials management 

N/A N/A 

Clinical Trials 

Mgmt12 

Yr 1-5 $550K/yr 

CTWG 

Implementation13 

Yr 1 $450K Yr 2 $400K Yr 3 $350K 

Yr 4-5 $200K/yr 

Evaluation and outcome measures N/A 

Evaluation System 

Developmnt/Measurem 

nt 

Yr 1 $750K 

Yr 2 $0 

Yr 3 $500K 

Yr 4 $0 

Yr 5 $500K 

See Note 1 N/A 

Note 1: Included in NCI clinical trials management expenses (this page). 12 Four professionals including clerical, office expenses, travel, etc.; an additional professional will be added in Yr 3 if the phase III prio

expanded to all diseases. The expenses for managing the prioritization Steering Committees are not included in the total shown; these e

the investigational drug trial prioritization and phase III trial prioritization expenses (See page 71). 

13 NCAB Subcommittee, Patient Advocate/Community Oncologist Steering Committees and meetings to develop correlative science s

credentialing system and standard contract clauses. 

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Table 3: Estimated Implementation Budget by Year 

Initiative Expenses Coordination Year 1 – FY06 Year 2 – FY07 Year 3 – FY08 Year 4 – FY09 Create comprehensive clinical trials database 

$1.3M $1.8M $3.8M $3.8M 

Align incentives to reward collaboration 

$0.5M $1.8M $2.0M $2.0M 

Develop joint FDA/NCI meetings 

See Note 1 See Note 1 See Note 1 See Note 1 

Enhance industry awareness of NCI/FDA expedited review process 

See Note 1 See Note 1 See Note 1 See Note 1 

Collaborate with CMS on study funding 

See Note 1 See Note 1 See Note 1 See Note 1 

Prioritization Investigational drug trial prioritization 

$500K $500K $500K $500K 

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Phase III trial prioritization 

$750K $1.3M $2.0M $2.2M 

Establish Community Oncologist/Patient Advocate Steering Committees 

See Note 2 See Note 2 See Note 2 See Note 2 

Phase II trial integration 

See Note 2 See Note 2 See Note 2 See Note 2 

Correlative science / quality of life funding 

N/A $5M $10M $10M 

Correlative science standards 

See Note 1 See Note 1 See Note 1 See Note 1 

Note 1: Included in NCI clinical trials management expenses (see page 77). Note 2: Included in phase III trial prioritization expenses (this page). 

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Table 3, Continued: Estimated Implementation Budget by Year 

Initiative Expenses Standardization Year 1 – FY06 Year 2 – FY07 Year 3 – FY08 Year 4 – FY09 caBIG interoperability 

$750K $1.3M $250K $250K 

FDA/Industry concurrence on standard CRF library 

See Note 1 See Note 1 See Note 1 See Note 1 

Credentialing system14 

See Note 1 See Note 1 See Note 1 See Note 1 

Standard clinical trial contract clauses 

See Note 1 See Note 1 See Note 1 See Note 1 

Operational Efficiency Restructure phase III clinical trials funding model 

$500K $5.5M $6.0M $7.0M 

Identify institutional barriers that delay trial initiation 

$350K $350K N/A N/A 

14 Assume cost of establishing credentialing system is paid by professional societies/trade associations. 

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Increase patient/public awareness of clinical trials 

See Note 1 See Note 1 See Note 1 See Note 1 

Increase minority outreach 

$0.5M $2.0M $2.0M $2.0M 

Reduce IRB administrative burden 

$200K $100K N/A N/A 

Note 1: Included in NCI clinical trials management expenses (see page 77). 

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Table 3, Continued: Estimated Implementation Budget by Year 

Initiative Expenses Enterprise-Wide NCAB Clinical Trials Oversight Subcommittee 

See Note 1 See Note 1 See Note 1 See Note 1 

Restructure NCI clinical trials management 

$1.0M $950K $900K $750K 

Evaluation and outcome measures 

$750K $0 $500K $0 

TOTAL 

$7.1M $20.6M $28.0M $28.5M 

5 year Total 

Note 1: Included in NCI clinical trials management expenses (this page). 

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