CTWG report

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

Leslie G. Ford, M.D.
Associate Director for Clinical Research
Division of Cancer Prevention
National Cancer Institute
Bethesda, MD

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

Louise B. Grochow, M.D., FACP
Global Medical Science Director
AstraZeneca
Waltham, MA

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

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

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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

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

John E. Niederhuber, M.D.
Professor
Division of General Surgery
Department of Surgery
University of Wisconsin-Madison
Madison, WI

Mack Roach III, M.D.
Professor
Department of Radiation Oncology
University of California, San Francisco
San Francisco, CA

Rose Mary Padberg, R.N., M.A.
Chief, Cancer Education
Office of Education and
Special Initiatives
National Cancer Institute
Bethesda, MD

Julia H. Rowland, Ph.D.
Director, Office of Cancer Survivorship
Division of Cancer Control and
Population Sciences
National Cancer Institute
Bethesda, MD

David R. Parkinson, M.D.
Vice President and Head
Clinical Oncology Therapeutic Area
Amgen
Thousand Oaks, CA

Richard Schilsky, M.D.
Professor of Medicine
Associate Dean for Clinical Research
Chairman, CALGB
University of Chicago
Chicago, IL

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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

Sheila E. Taube, Ph.D.
Associate Director
Cancer Diagnosis Program
Division of Cancer Treatment
and Diagnosis
National Cancer Institute
Bethesda, MD

Daniel Sullivan, M.D.
Associate Director
Cancer Imaging 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

Executive Director
Maureen R. Johnson, Ph.D.
Special Assistant to the Director
Office of the Director
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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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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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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 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
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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.

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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.
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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
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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.

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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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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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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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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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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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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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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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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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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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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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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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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.
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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.
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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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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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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 Group 1 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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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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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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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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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, biomarkers 2 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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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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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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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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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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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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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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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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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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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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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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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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(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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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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(IRBs). Furthermore, since the median cost for IRB review at academic medical centers
was nearly $750,000 per year in 2002 6 , 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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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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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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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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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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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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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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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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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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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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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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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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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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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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Appendix A

Meeting Dates and Acknowledgments

CTWG Meeting Dates

2005
2004

January 21 & 27
CTWG Conference Calls

January 29 & 30
Initial Conference Calls

February 9 & 10
Face-to-face meeting of the CTWG
Chicago, Illinois

February 26 & 27
CTWG Conference Calls
April 22 & 23
CTWG Conference Calls

February 17
Subcommittee Chairs Report to the NCAB
Bethesda, Maryland

May 24
First Face-to-Face Meeting of the CTWG
Chicago, Illinois

March 3 & 4
CTWG Conference Calls
March 17 & 18
CTWG Conference Calls

August 27
Face-to-Face Meeting of the CTWG
Chicago, Illinois

March 31 & April 1
Face-to-Face Meeting of the CTWG
Chicago, Illinois

September 23 & 24
CTWG Conference Calls

April 28 & 29
Face-to-Face Meeting of the CTWG
Chicago, Illinois

October 14 & 15
CTWG Conference Calls
November 17
Face-to-face meeting of the CTWG
Chicago, Illinois

May 3
Face-to-Face Meeting of the CTWG
Bethesda, Maryland

December 9 & 10
CTWG Conference Calls

May 19 & 20
CTWG Conference Calls
June 7
Final Report to the NCAB
Bethesda, Maryland

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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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Appendix B

Table 1: Implementation Timeline

Initiative

Key Milestones and Activities

Coordination

Year 1
(Oct. 2005-Sept. 2006)
Establish implementation
task force
Begin to develop database
Define data to deposit
Determine data submission
procedures
Determine access controls
Investigate grant data
reporting requirements
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
Develop policies and
procedures for meetings
Develop non-disclosure
agreements
Begin joint meetings by July.

Comprehensive
clinical trials
database

Align incentives to
reward
collaboration

Joint FDA/NCI
meetings

Year 2
(Oct. 2006-Sept. 2007)
Continue to develop database
Create report templates
Expand NCI database review
capacity
Adjust grant data reporting
requirements

Year 3
(Oct. 2007- Sept. 2008)
Run pilot test with
extramural users
Database fully implemented
by March
Routine submission of all
trial data in place by
September

Years 4 – 5
(Oct. 2008-Sept. 2010)

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

Continue to interact with
medical school
deans/AAMC/ IOM

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Develop communication plan Initiate awareness campaign
Enhance industry
awareness of
NCI/FDA expedited
review process
Collaborate with
CMS on study
funding

Begin to establish process to
select studies

Evaluate the campaign’s
effectiveness

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)
 Establish Investigational
Drug Steering
Committee
 Organize first strategic
meeting
 Begin routine
prioritization activities
by June
 Establish initial Scientific
Steering Committees
 Convene initial State-ofthe-Science meetings
 Convene initial
community
oncologist/patient
advocate focus groups

Investigational drug
trial prioritization

Phase III trial
prioritization

 Establish additional
Scientific Steering
Committees
 Convene additional Stateof-the-Science meetings
 Convene additional focus
groups

Year 3
(Oct. 2007- Sept. 2008)

Years 4 - 5
(Oct. 2008-Sept. 2010)

 Evaluate prioritization
system
 Begin expanded
prioritization system
implementation if
successful

 Complete implementation
of expanded
prioritization system

 Routine database
submission by
September
 Evaluate feasibility of

 Begin integrated
prioritization if feasible

 Establish Steering
Committees

Community
Oncologist/Patient
Advocate Steering
Committees
Phase II trial
integration

Year 2
(Oct. 2006-Sept. 2007)

 Begin presentations at
State-of-the-Science
meetings

 Begin data submission to
database

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integrating prioritization
Correlative science /
quality of life
funding

Correlative science
standards

 Define criteria for study
prioritization
 Establish budget
 Define technology
categories

 Criteria for prioritization
established by October
 Budget established by
October
 Initiate funding
 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

FDA/industry
concurrence on
standard CRF
library

Year 1
(Oct. 2005-Sept. 2006)
 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
 Begin to
harmonize/expand NCI
standard CRFs with
industry and FDA
involvement

Credentialing
system

 Create Task Force
 Develop credentialing
criteria

caBIG
interoperability

Year 2
(Oct. 2006-Sept. 2007)
 Create web-based trial
initiation tool

Year 3
(Oct. 2007- Sept. 2008)
 Complete internal NCI IT
system harmonization

 Complete development of
standard CRFs with
industry/FDA
concurrence

 Implementation of
standard CRFs by
September
 Begin annual review and
update

 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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Years 4 – 5
(Oct. 2008-Sept. 2010)
Overall IT interoperability of
NCI-funded clinical trials
system achieved by
September 2010

 Complete system to
credential investigators
and sites by January,
2009
 Create registry

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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 Promote use of contract
clauses by industry and
clinical trial sites

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)
 Analyze phase III clinical
trial costs

Restructure phase
III clinical trials
funding model

 Initiate analysis
Identify institutional
barriers that delay
trial initiation
Increase
patient/public
awareness of clinical
trials

Increase minority
outreach
Reduce IRB
administrative
burden

 Establish interactions
between OC and OESI
and clinical investigators
 Establish interactions
between OC and OESI
and patient advocacy
groups
 Implement additional
funding for minority
outreach programs
 Initiate analysis of barriers
to CIRB adoption

Year 2
Year 3
(Oct. 2006-Sept. 2007)
(Oct. 2007- Sept. 2008)
 Analysis completed by
March
 Restructure funding model
based on analysis
 Begin to increase funding
for high accruing sites
 Analysis completed by
 Develop solutions for
September
reducing barriers
 Begin to implement
solutions

 Analysis completed by
March
 Develop approaches to
enhance CIRB adoption

 Implement approaches to
enhance CIRB adoption

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Years 4 – 5
(Oct. 2008-Sept. 2010)

 Continue to implement
solutions

Restructuring the National Cancer Clinical Trials Enterprise

Table 1, Continued: Implementation Timeline

Initiative

Key Milestones and Activities

Enterprise-Wide

Year 1
(Oct. 2005-Sept. 2006)
 Establish oversight
subcommittee

NCAB Clinical
Trials Oversight
Subcommittee
Restructure NCI
clinical trials
management
Evaluation and
outcome measures

Year 2
(Oct. 2006-Sept. 2007)

Year 3
(Oct. 2007- Sept. 2008)

Years 4 - 5
(Oct. 2008-Sept. 2010)

 Evaluate progress of
specific initiatives based
on implementation plan
timeline

 Evaluate progress of
specific initiatives based
on implementation plan
timeline

 Restructure NCI
management
 Develop evaluation
system
 Take baseline
measurements of
programs to be
evaluated

 Evaluate progress of
specific initiatives based
on implementation plan
timeline

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Table 2: Estimated Implementation Budget by Category

Initiative
Coordination
Create
comprehensive
clinical trials
database

Align incentives to
reward
collaboration

Develop joint
FDA/NCI meetings
Enhance industry
awareness of
NCI/FDA expedited

Expenses
Extramural
Data Reporting
Costs 7
Yr 1 $0.0M
Yr 2 $0.0M
Yr 3 $2.0M
Yr 4 $1.0M
Yr 5 $0.0M

Analysis/Development NCI Operational
Projects
Activities
Database
NCI Data Review
Develpmt/Maint
Staff
Yr 1 $1.0M
Yr 3-5 $250K/yr
Yr 2 $1.5M
Yr 3 $0.5M
Data Review
Yr 4 $1.8M
Contract
Yr 5 $1.8M
Yr 3-5 $750/yr

Meeting Support
Implementation Task
Force
Yr 1 $250K
Yr 2 $250K
Yr 3 $250K

Total
Yr 1
Yr 2
Yr 3
Yr 4
Yr 5

$1.3M
$1.8M
$3.8M
$3.8M
$2.8M

Clinical Inv. Award
Yr 2-5 $1.0M/yr
SPORE/Cancer
Center CTSU Trials
$0.5M/yr
Yr 2 $0.75M/yr
Yr 1

N/A

See Note 1

N/A

Yr 1 $0.5M
Yr 2 $1.8M
Yr 3 $2.0M
Yr 4 $2.0M
Yr 5 $2.0M

Yr 3-5 $1.0M/yr
N/A

N/A

See Note 1

N/A

See Note 1

N/A

See Note 1

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 3-4 and completely
in Yr 5.

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review process

Collaborate with
CMS on study
funding

N/A

N/A

See Note 1

Note 1: Included in NCI clinical trials management expenses (see page 74).

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N/A

See Note 1

Restructuring the National Cancer Clinical Trials Enterprise

Table 2, Continued: Estimated Implementation Budget by Category

Initiative
Prioritization
Investigational drug
trial prioritization

Expenses
Extramural

N/A

Phase III trial
prioritization
N/A

Establish
Community
Oncologist/Patient
Advocate Steering

N/A

Analysis/Development NCI Operational
Projects
Activities
Clin Trials Mgmt
Staff
N/A
Yr 1-5 $100K/yr
Other NCI Staff
Yr 1-5 $250K/yr
Clin Trls Mgmt &
Other NCI Staff
Yr 1 $200K +
N/A
$150K
Yr 2 $200K +
$300K
Yr 3-5 $400K +
$450K

N/A

Meeting Support
Investigational Drug
Steering Committee 8
Yr 1-5 $150K/yr
SOS 9 & Steering
Com 10
Yr1 2SOS/10SC
$400K
Yr2 4SOS/20SC
$800K
Yr3 6SOS/30SC
$1.1M
Yr4 8SOS/40SC
$1.3M
Yr5 10SOS/50SC
$1.5M

N/A

See Note 2

8

Four meetings per year; 30 members
State of Science Meeting; 50 attendees $80K/meeting
10
Scientific Steering Committee Meetings; size of Committee and number of meetings per year varies with disease
9

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Total
Yr 1
Yr 2
Yr 3
Yr 4
Yr 5
Yr 1
Yr 2
Yr 3
Yr 4
Yr 5

$500K
$500K
$500K
$500K
$500K
$0.75M
$1.3M
$2.0M
$2.2M
$2.4M

See Note 2

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
Correlative science
standards

Yr 2
Yr 3-5

$ 5M
$10M/yr

N/A

N/A

See Note 1

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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See Note 2

Yr 1
Yr 2
Yr 3
Yr 4
Yr 5

$ 0
$ 5M
$10M
$10M
$10M

See Note 1

Restructuring the National Cancer Clinical Trials Enterprise

Table 2, Continued: Estimated Implementation Budget by Category

Initiative
Standardization
Promote caBIG
interoperability

Expenses
Extramural

N/A

Analysis/Development NCI Operational
Projects
Activities
Interoperability
Analyses
Yr 1 $500K (NCI
N/A
intrnl)
Yr 2 $500K
(extramural)
Trial Initiation Tool
Yr 2 $500K

Meeting Support
Additional Clinical
Trials Workspace
Expense
Yr 1-5 $250/yr

Total
Yr 1
Yr 2
Yr 3
Yr 4
Yr 5

$750K
$1.3M
$250K
$250K
$250K

FDA/Industry
concurrence on
standard CRF
library

N/A

N/A

See Note 1

See Note 1

See Note 1

Credentialing
system 11

N/A

N/A

See Note 1

See Note 1

See Note 1

Standard clinical
trial contract
clauses

N/A

N/A

See Note 1

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 Category

Initiative

Expenses

Operational
Efficiency

Extramural

Restructure phase
III clinical trials
funding model

Identify institutional
barriers that delay
trial initiation

Increase
patient/public
awareness of clinical
trials
Increase minority
outreach

Analysis/Development NCI Operational
Projects
Activities

High Accrual
Supplemnts
Yr 1 $0.0M
Yr 2 $5.0M
Yr 3 $6.0M
Yr 4 $7.0M
Yr 5 $7.5M

Financial Analysis
Yr 1- 2 $500K/yr

Meeting Support

See Note 1

N/A

Total
Yr 1
Yr 2
Yr 3
Yr 4
Yr 5

$0.5M
$5.5M
$6.0M
$7.0M
$7.5M

N/A

Barrier Analysis
Yr 1-2 $350K/yr

See Note 1

N/A

Yr 1 $350K
Yr 2 $350K
Yr 3 $0
Yr 4 $0
Yr 5 $0

N/A

N/A

See Note 1

N/A

See Note 1

Expanded Minority
Programs
Yr 1
$0.5M
Yr 2-5 $2M/yr

N/A

N/A

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N/A

Yr 1
Yr 2
Yr 3
Yr 4
Yr 5

$0.5M
$2.0M
$2.0M
$2.0M
$2.0M

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

Note 1: Included in NCI clinical trials management expenses (see page 74).

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N/A

Yr 1 $200K
Yr 2 $100K
Yr 3 $0
Yr 4 $0
Yr 5 $0

Restructuring the National Cancer Clinical Trials Enterprise

Table 2, Continued: Estimated Implementation Budget by Category

Initiative
Enterprise-Wide
NCAB Clinical
Trials Oversight
Subcommittee
Restructure NCI
clinical trials
management

Evaluation and
outcome measures

Expenses
Extramural
N/A

N/A

N/A

Analysis/Development NCI Operational
Projects
Activities
N/A

N/A

Clinical Trials
Mgmt 12
Yr 1-5 $550K/yr

N/A

Evaluation System
Developmnt/Measurem
nt
Yr 1 $750K
Yr 2 $0
Yr 3 $500K
Yr 4 $0
Yr 5 $500K

Meeting Support
See Note 1

CTWG
Implementation 13
Yr 1 $450K
Yr 2 $400K
Yr 3 $350K
Yr 4-5 $200K/yr

See Note 1

N/A

Total
See Note 1

Yr 1
Yr 2
Yr 3
Yr 4
Yr 5

$1.0M
$950K
$900K
$750K
$750K

Yr 1 $750K
Yr 2 $0
Yr 3 $500K
Yr 4 $0
Yr 5 $500K

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 prioritization system is

expanded to all diseases. The expenses for managing the prioritization Steering Committees are not included in the total shown; these expenses are included in

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 standards, standard CRFs,

credentialing system and standard contract clauses.

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Restructuring the National Cancer Clinical Trials Enterprise

Table 3: Estimated Implementation Budget by Year

Initiative

Expenses

Coordination

Year 1 – FY06

Year 2 – FY07

Year 3 – FY08

Year 4 – FY09

Year 5 – FY10

Create
comprehensive
clinical trials
database

$1.3M

$1.8M

$3.8M

$3.8M

$2.8M

Align incentives to
reward
collaboration

$0.5M

$1.8M

$2.0M

$2.0M

$2.0M

Develop joint
FDA/NCI meetings

See Note 1

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

See Note 1

Collaborate with
CMS on study
funding
Prioritization

See Note 1

See Note 1

See Note 1

See Note 1

See Note 1

$500K

$500K

$500K

$500K

$500K

Investigational drug
trial prioritization

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Restructuring the National Cancer Clinical Trials Enterprise

Phase III trial
prioritization
Establish
Community
Oncologist/Patient
Advocate Steering
Committees
Phase II trial
integration
Correlative science /

$750K

$1.3M

$2.0M

$2.2M

$2.4M

See Note 2

See Note 2

See Note 2

See Note 2

See Note 2

See Note 2

See Note 2

See Note 2

See Note 2

See Note 2

N/A

$5M

$10M

$10M

$10M

See Note 1

See Note 1

See Note 1

See Note 1

See Note 1

quality of life
funding
Correlative science
standards

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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Restructuring the National Cancer Clinical Trials Enterprise

Table 3, Continued: Estimated Implementation Budget by Year

Initiative

Expenses

Standardization

Year 1 – FY06

Year 2 – FY07

Year 3 – FY08

Year 4 – FY09

Year 5 – FY10

caBIG
interoperability

$750K

$1.3M

$250K

$250K

$250K

FDA/Industry
concurrence on
standard CRF
library

See Note 1

See Note 1

See Note 1

See Note 1

See Note 1

Credentialing
system 14

See Note 1

See Note 1

See Note 1

See Note 1

See Note 1

Standard clinical
trial contract
clauses
Operational Efficiency

See Note 1

See Note 1

See Note 1

See Note 1

See Note 1

Restructure phase
III clinical trials
funding model

$500K

$5.5M

$6.0M

$7.0M

$7.5M

Identify institutional
barriers that delay
trial initiation

$350K

$350K

N/A

N/A

N/A

14

Assume cost of establishing credentialing system is paid by professional societies/trade associations.

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Restructuring the National Cancer Clinical Trials Enterprise

Increase
patient/public
awareness of clinical
trials

See Note 1

See Note 1

See Note 1

See Note 1

See Note 1

Increase minority
outreach

$0.5M

$2.0M

$2.0M

$2.0M

$2.0M

Reduce IRB
administrative
burden

$200K

$100K

N/A

N/A

N/A

Note 1: Included in NCI clinical trials management expenses (see page 77).

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Restructuring the National Cancer Clinical Trials Enterprise

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

See Note 1

Restructure NCI
clinical trials
management

$1.0M

$950K

$900K

$750K

$750K

Evaluation and
outcome measures

$750K

$0

$500K

$0

$500K

$7.1M

$20.6M

$28.0M

$28.5M

$28.7M

TOTAL
$112.9M
5 year Total
Note 1: Included in NCI clinical trials management expenses (this page).

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