Testimony
Statement by
Michaele Chamblee Christian, M.D.
Associate Director
Division of Cancer Treatment and Diagnosis, Cancer Evaluation
Therapy Program, National Cancer Institute
National Institutes Health
Dept. of Health and Human Services
on
Delivering More Innovative and Effective Treatments To make cancer a more Treatable Disease
before the
Committee on Government Reform
U.S. House of Representatives
|
May 13, 2004
Good morning. I am Dr. Michaele Chamblee Christian, Associate Director
of the Division of Cancer Treatment and Diagnosis for the Cancer Therapy
Evaluation Program, in the National Cancer Institute (NCI), within the
National Institutes of Health (NIH) and the Department of Health and Human
Services. I am a medical oncologist.
Thank you, Mr. Chairman, Representative Waxman, and distinguished Members
of the Committee, for the opportunity to discuss NCI’s efforts to
deliver innovative and effective cancer treatments to the public and the
steps being taken to turn cancer into a more treatable disease.
Recent advances across the biomedical research enterprise have set the
stage for unparalleled progress in biomedicine early in the 21st century.
Basic research has given us an understanding that cancer is a disease
process where normal cells are transformed into cancer cells through a
series of defined steps that begin with small changes in cellular DNA.
If left unchecked, these transformed cells can progress and spread to
cause the suffering and death that we recognize as the horrible burden
of cancer. Fortunately, our growing understanding of this disease process
has revealed multiple opportunities to intervene.
New intervention strategies include preventing initiation of the disease
process; early detection, when the disease is most amenable to elimination;
and arresting the process to stop the spread (metastasis) of the disease,
which is the primary reason that patients suffer unduly and die. In short,
we are rapidly learning how to modulate the cancer disease process. This
ability to intervene will ultimately eliminate some cancers and transform
others into chronic, manageable diseases that patients can live with and
not die from.
Scientific advances in genomics, nanotechnology, proteomics, immunology
and bioinformatics may soon allow us to profile a patient’s genetic,
lifestyle, and environmental risk for cancer and to be able to combine
effective prevention and early intervention strategies for those at high
risk. For example, genomic analysis of a patient’s tumor and proteomic
patterns obtained from a patient’s serum, as well as sophisticated
imaging technologies designed for molecular detection, will be used to
identify cancers at the earliest stages. Precise molecular diagnosis and
patient-specific profiling will allow physicians to predict responses
to specific interventions and provide a rational basis for tailoring treatments.
The result will be more effective and less toxic, targeted agents delivered
to patients, which will greatly change the outcome of many cancers and
which is attainable in the foreseeable future.
Given these extraordinary opportunities, the NCI is focused on accelerating
the pace of therapeutics development through better integration of its
translational research and clinical trials components and better collaboration
with our partners in academia, the community, the pharmaceutical industry,
and other federal agencies to ensure that we are optimally positioned
to address the most compelling scientific and medical challenges facing
patients with cancer.
Bringing Innovative Treatments to the Public
The National Cancer Institute (NCI) has an extensive clinical trials program
that is dedicated to developing more effective treatments for cancer patients
using novel investigational (experimental) agents and new applications
of commercially available drugs. In fact, the NCI is the largest sponsor
of cancer clinical trials in the world and works extensively with the
biotechnology and pharmaceutical industries, that are the source of many
of these new agents, to accelerate the pace and scope of development.
At any given time, the NCI has over 500 clinical trials actively enrolling
patients and several hundred more still in analysis. Over 31,000 patients
are enrolled on NCI-sponsored treatment trials each year, and many additional
patients participate in clinical trials at NCI funded cancer centers across
the country and in clinical trials sponsored by biopharmaceutical companies.
Nearly 18,000 patients participate in NCI-sponsored cancer prevention
and control studies. NCI treatment trials alone involve 3,300 clinical
sites and approximately 11,000 investigators.
NCI has many initiatives underway to involve local healthcare providers,
both at academic centers and in community practice settings, in clinical
trials to allow patients everywhere to participate in the development
of innovative treatments. Beginning in 1999, the NCI undertook two important
pilot projects designed to increase both the speed of accrual and overall
access to its large, phase 3 treatment trials. Phase 3 trials are, in
large part, performed by the NCI’s Clinical Trials Groups. Before
1999, the Groups had traditionally limited participation in their trials
to their own membership. In a pilot project, the Cancer Trials Support
Unit (CTSU) was created to open the trials of the 8 Adult Cooperative
Groups to participation by any NCI-registered physician, whether or not
a member of the Group leading the trial. In order to make this a practical
reality, and not overburden investigators with regulatory and audit requirements
related to participation in trials led by different organizations, the
CTSU consolidated the regulatory and data management activities for all
the Cooperative Groups. This allowed the CTSU to provide access to the
majority of the Group’s Phase 3 trials in a consistent and uniform
format. The CTSU now provides all Group members access to any of the Group’s
trials, thereby adding flexibility and access to the NCI system that did
not formerly exist. To spur even greater participation in NCI-sponsored
trials, since 2002 the CTSU has permitted physicians not affiliated with
any Group to join and provide access to all trials on the CTSU menu to
their patients.
This new approach to participation in trials via the CTSU has required
substantial changes on the part of investigators and their staffs, reflected
in the use of new informatics systems and in new management processes.
There is growing evidence that this new approach is achieving its goals.
Enrollment via this mechanism has steadily increased over the past 2 years
and approximately 350 patients are currently being entered each month
by this CTSU mechanism. In addition, the potential now exists for regulatory
documents for all Group trials to be handled exclusively by the CTSU.
NCI would like to expand this effort by adding more trials to the CTSU
menu and providing more efficient, automated systems (online registration
and data management) to facilitate enrollments. This approach does permit
NCI to make its most important treatment trials widely available to patients
across the country treated by experienced physicians in any setting, whether
academic-centered or community-based, and regardless of their oncologist’s
affiliations.
A second pilot project, termed the Central Institutional Review Board
(CIRB), was developed by NCI in direct response to repeated requests from
the investigator community. The protracted paperwork and IRB review process
had to be completed separately at each of many hundreds of sites, even
though many smaller sites might enroll only 1-5 patients on a trial, particularly
for less common cancers (like Gastrointestinal Stromal Tumor [GIST]).
CIRB is created to assist with the reviews and increase researcher participation
in clinical trials. While there can be no substitute for local IRB review
for research being performed at a single institution, the CIRB primarily
reviews large, Phase 3 studies performed at hundreds of sites across the
country. By assuming the primary responsibility for review, adverse event
monitoring, and follow-up paperwork for these national protocols, the
investigators and local IRBs are spared duplicative application and review
work and the process of gaining approval to enroll the first patient on
a trial can be reduced from many weeks to as little as one to several
days. This initiative has made important strides since its inception in
2000 and now consists of over 165 participating IRBs. The NCI has developed
this project in close consultation with the HHS Office for Human Research
Protections (OHRP). The CIRB members who perform the reviews are highly
qualified oncologists, statisticians, patient/consumer advocates, pharmacists
and nurses from across the United States who have volunteered to assist
NCI by performing this task. While a formal evaluation of progress to
date is currently underway, NCI hopes to expand the initiative this year
to include 500 sites and has initiated the formation of a second Board
at the request of the Children’s Oncology Group that will focus
on reviewing pediatric multi-center trials.
In addition, NCI has major initiatives to disseminate information about
state of the art treatments into the community. For example, since 1999
NCI has supported the HMO Cancer Research Network (CRN), a consortium
of eleven research organizations affiliated with integrated healthcare
delivery systems located across the U.S. that provide healthcare to over
10 million members. The CRN is engaged in a wide variety of population-based
cancer control research ranging from exploring factors related to cancer
occurrence and prognosis to health system design issues related to optimizing
the performance of cancer prevention and screening services, to assessing
the impact of cancer treatment on the quality of life of cancer patients.
During its first funding cycle (1999-2002), with targeted support from
NCI, CRN investigated barriers and facilitating factors related to participation
of CRN physicians and members in cancer clinical trials. The results of
this study have been submitted for publication, and based on these results
CRN is currently designing an intervention trial to test organizational
methods to enhance participation in clinical trials at CRN institutions.
At the urging of NCI, in its renewal application (2003-2006) CRN will
initiate a series of “cancer diffusion studies” that will
document the rate and determinants of the dissemination of evidence-based
cancer treatments in the community care settings of the CRN healthcare
delivery organizations.
Public/Private Partnerships to Enhance Clinical Trials
NCI is continually working to expand its role in public-private partnerships
as more private-sector companies begin to develop anti-cancer drugs. Many
of the most promising new agents to treat cancer now come from the research
and development efforts of the biotechnology/pharmaceutical industry.
Over the past 10 years, the number of new agents being developed by industry
has grown over threefold, from 124 to 395.
The current status of working relationships between NCI and private industry
is excellent. These collaborative relationships have resulted in many
pharmaceutical agents that are highly effective in the treatment of cancers
and precancers. The Cancer Therapy Evaluation Program of the NCI, which
coordinates NCI’s clinical treatment trials, has formal relationships
with more than 60 biotechnology and pharmaceutical companies, including
34 Cooperative Research and Development Agreements (CRADAs), 54 Clinical
Trials Agreements (CTAs), and 9 Clinical Supply Agreements (CSAs). Similar
arrangements exist within the Division of Cancer Prevention, which has
26 CTAs and 37 Investigational New Drug Applications (INDs), and NCI’s
intramural research program, which also supports or conducts clinical
trials. NCI staff work closely with these corporate collaborators to ensure
that the most important medical and scientific questions are addressed
in the collaborative development of these agents and that duplication
is avoided. Companies are often narrowly focused on the development path
most likely to result in FDA approval, which may involve a single cancer
type. NCI can accelerate the pace of broader development substantially
to explore the many other cancer settings where an agent may have potentially
important uses. Examples include the collaboration between Novartis and
NCI-supported researchers that led to the development of Gleevec as a
remarkably effective treatment for chronic myelogenous leukemia and now
also for gastrointestinal stromal tumors. NCI is sponsoring clinical trials
with Gleevec in many other tumor types that express the relevant targets.
Likewise, in an ongoing partnership with Genentech, NCI-supported clinical
investigators are testing a promising molecularly targeted drug, Avastin,
in patients with a variety of different cancer types, including those
with advanced colorectal cancer who were previously treated with chemotherapy
alone. Through a collaborative relationship with Searle and Pfizer, Inc.,
researchers found that the arthritis drug Celebrex can
reduce the number of pre-cancerous colon polyps in patients with familial
adenomatous polyposis, an inherited syndrome that predisposes them to
colon cancer. NCI is exploring this important lead in a number of clinical
trials. These specific examples represent only a small fraction of the
clinical trials that NCI is supporting this year and the many industry
partnerships that are predominantly for non-marketed investigational agents.
Because of its extensive relationships with bio-pharmaceutical companies,
NCI is in the unique position of being able to broker and sponsor studies
of combinations of investigational agents owned by different companies.
It is widely believed that many of the promising new molecularly targeted
agents will demonstrate their optimal utility in combinations that inhibit
or modulate multiple targets in critical cancer cell pathways. NCI has
worked with over a dozen industry collaborators to arrange 22 trials of
novel investigational combinations to date and has commitments for additional
high-priority trials, some containing 3 or 4 novel agents. Without these
collaborations, many of these regimens would not have been evaluated until
one or more of the agents had received FDA marketing approval, potentially
resulting in years of delay. NCI continues to seek opportunities to provide
additional incentives for bio-pharmaceutical companies to collaborate
in the development of promising new agents and to further accelerate therapeutics
development in the public interest. NCI is carefully following the impact
of incentives such as the extension of exclusivity provided in the Best
Pharmaceuticals For Children Act of 2002, as one example.
NCI/FDA Collaboration
For the past year, NCI has also been working aggressively with the Food
and Drug Administration via the NCI/FDA Interagency Oncology Task Force
(IOTF) to increase collaboration and eliminate impediments to accelerated
therapeutics development. The formation of the IOTF was an important strategic
step toward achieving NCI’s challenge goal of eliminating suffering
and death from cancer by 2015; and the FDA’s goals of increasing
the availability and use of safe and effective treatments for cancer.
The goal of the IOTF is to leverage the expertise and capabilities of
both agencies in order to streamline and accelerate the overall development
of diagnostic, preventive, and therapeutic interventions for cancer.
Since its formation, the members of IOTF have identified several specific
initiatives that are directed toward optimizing drug and device development.
The NCI is working to specifically gather and synthesize the scientific
support needed by the FDA to address specific regulatory issues. The IOTF
is working through a series of specific subcommittees that are actively
engaged in the following areas:
- Joint Training and Fellowships: The IOTF is focused on significantly
increasing the number and quality of training of physicians and scientists
that are expert in clinical research, the clinical approval process, and
the translation of laboratory science into new products for cancer. To
that end, the IOTF Training Subgroup has developed a series of fellowship
programs that will allow NCI fellows to train at the FDA and has established
fellowships for personnel from both agencies to train in areas such as
oncology product research for cancer detection, treatment, and prevention.
These programs will be initiated in 2004.
- Developing Markers of Clinical Benefit: Work in this critical
area includes the use of imaging in oncology drug development, collaborative
development of the scientific data needed to establish surrogate endpoints
for cancer clinical trials, and the potential utilization of advanced
technologies such as genomics, proteomics, nanotechnology and immune monitoring
to speed drug discovery and development, especially the regulatory phases.
The subcommittee is organizing background materials to capture the state-of-the-science
in specific types of cancer and technologies. These projects are all underway
and will engage scientific input through publications, meetings, and workshops.
- Common Bioinformatics Platforms: NCI has recently launched a
pilot program to connect the cancer research community through a new bioinformatics
platform known as the Cancer Bio-informatics Grid (caBIG). One of the
primary goals of this unprecedented effort is to improve the organization
and reporting of data derived from oncology clinical trials. Among other
projects, the NCI and the FDA are collaborating through the IOTF to utilize
this common infrastructure to implement electronic INDs. As part of their
participation in caBIG and the IOTF, the two agencies will pursue the
development of standards to support the submission of clinical data and
other electronic filings to shorten the time frame for processing and
alleviate investigator workloads.
- Process Improvement: The IOTF has undertaken a series of projects
to address specific issues or barriers that arise in the regulatory processes
of oncology drug development. These projects range from preclinical development
through the range of clinical trials required for drug approval. Among
the notable accomplishments are: the development of an NCI-FDA leadership
group that can act to address questions from NCI-supported investigators
during any phase of the regulatory review process; scientifically driven
review of the preclinical requirements for IND filings; and the development
of a more consistent process for the review of cancer prevention agents.
The IOTF meets regularly and actively addresses issues that can ultimately
speed the development of new interventions for cancer. The IOTF subcommittees
are currently framing new issues and developing resource materials that
will facilitate investigators in preparing the data needed for the regulatory
processes. In some cases, the FDA has already responded with guidance
documents (such as a recent guidance on pharmacogenomics) and process
changes, and the NCI is actively working to develop and synthesize the
science needed to make regulatory decisions.
NCI Partnerships with Academic Health Centers and Cancer Centers
Because funding and sponsoring cancer research is fundamental to NCI’s
mission, there are extensive collaborations with cancer centers and academic
health centers, both in drug discovery and development. NCI’s Rapid
Access to Intervention Development (RAID) Program is an example of a partnership
with academia to accelerate the development of the most promising new
agents from academic laboratories by providing the pre-clinical resources,
such as drug formulation and toxicology studies, that often present significant
obstacles to university laboratories that do not have the resources typically
present in pharmaceutical companies. To date, 91 new
agents have received pre-clinical support through this program and many
have entered clinical trials. The Division of Cancer Prevention has a
similar program called RAPID (Rapid Access to Prevention Intervention
Development) that has an additional 26 projects.
NCI has expanded its established working relationships with academic health
centers and cancer centers to accommodate the increasing need for collaboration
with laboratory scientists in conducting clinical trials for molecularly
targeted agents. The cellular pathways and interactions involved in these
molecular targets are extraordinarily complex and interrelated. These
complexities require scientists to develop new techniques and tests to
identify patients whose tumors contain the relevant targets and to monitor
drug effects during treatment. More than half of NCI-sponsored cancer
treatment trials initiated over the last 2 years have included correlative
studies with laboratory scientists, and this trend is being seen increasingly
in cancer prevention trials.
Clinical trials and much of the translational research that accompanies
them are carried out in a variety of specialized mechanisms including:
1) 25 early therapeutics development contracts and cooperative
agreements for Phase 1 and 2 trials, which are overwhelmingly based in
cancer centers; 2) 56 Specialized Programs of Research
Excellence (SPOREs), of which all but 3 are in cancer centers; 3) highly
specialized disease specific consortia such as the AIDS Malignancy Consortium,
and brain tumor consortia are located in cancer centers and academic health
centers; 4) the 9 Cancer Cooperative Groups that conduct almost all Phase
3 trials and the pilot trials leading to them. The Groups are extensive
national networks that include cancer centers and community sites. There
are 9 adult national cooperative groups including 4 multi-specialty/multi-modality
groups, 2 surgical groups, 1 each in gynecologic oncology, radiation oncology
and a diagnostic imaging group, as well as the Children’s Oncology
Group. Most cancer centers belong to several or many cooperative groups;
5) and the Community Clinical Oncology Program (CCOP), a large network
of community oncology practices that conducts cancer treatment, prevention
and control research and is not based primarily in academic centers, though
the coordinating research bases are cancer centers. The CCOP program has
grown rapidly over the past 10-15 years and now includes 61 individual
grants to community based clinical trials research organizations in 39
states, Washington, D.C., and Puerto Rico. CCOP accrual has risen steadily
over the past 10 years as a percentage of all Cooperative Group accrual
and accounts for about 30% of accrual to treatment trials.
There is extensive involvement of cancer centers and academic health centers
in most clinical trials mechanisms and in other activities supporting
translational research, as described above. In an effort to accelerate
clinical development and enhance collaboration and resource sharing, NCI
is currently examining new approaches to integrating the clinical research
that is conducted across these mechanisms to help ensure rapid and seamless
progression of new agents and regimens through this process. A broadly
representative Clinical Trials Working Group has been formed and includes
senior NCI staff and external experts from across the clinical research
spectrum, including academia, biopharmaceutical industry, and other federal
agencies (FDA and the Center for Medicare and Medicaid Services) that
will have an ongoing role in working together to improve the clinical
trials process. The goal is to better integrate information, resources,
and infrastructures so that the information gained in one venue is exploited
most appropriately in the others. For example, when the basic research
ongoing in an NCI-designated cancer center or SPORE identifies a new molecular
target in a specific disease, work can begin immediately on identifying
an assay to detect the target in tumor specimens from cancer patients,
on beginning clinical trials with agents that inhibit or modulate the
target, and on collecting tumor specimens from the patients on those or
other clinical trials to further examine the impact of the target and
its inhibition on the patient’s tumor. Studies can also be initiated
to examine the potential of new imaging techniques to identify these target
effects non-invasively and to begin new pre-clinical studies of the targeted
agents with other treatment approaches. One major aim of the NCI’s
current efforts to enhance cancer clinical research is to make many of
these research processes, which have been sequential in the past, and
proceed concurrently, thus enhancing the timeliness of the translation
of new laboratory findings into clinical trials.
Rates of Participation in Clinical Trials
NCI was asked to comment about the differences in adult (about 3% of newly
diagnosed cancer patients) and pediatric (about 60%) participation rates
in cancer clinical trials. The rate of enrollment of children with cancer
into clinical trials obviously far exceeds that for adults with cancer,
although the absolute numbers of adults participating in trials is far
higher. Though the reasons for this have not been systematically studied,
there are several factors that likely account for much of this difference.
Most children with cancer are treated in tertiary care centers, the majority
of which are associated with medical schools, whereas the vast majority
of adult cancer patients are treated in community practice settings. The
higher priority that academia places on research compared to the community
setting facilitates the enrollment of children with cancer into clinical
trials. Another important factor is the culture of the pediatric oncology
discipline. This culture is driven by a history of progressive improvements
in childhood cancer outcomes that has reinforced in these specialists
the belief that the best way to identify more effective treatments is
through well-designed clinical trials. A key characteristic of the pediatric
oncology culture is the willingness of researchers to collaborate in conducting
multi-institutional clinical trials, which are essential since few single
institutions see sufficient children with cancer to conduct the clinical
trials that are needed to reliably identify more effective therapies.
The remarkable efficacy of many pediatric cancer treatments and the dramatic
progress that has been achieved by application of the pediatric oncology
paradigm has created incentives for childhood cancer researchers to maintain
their high rates of participation in clinical trials in the hope of continuing
progress into the future. Because adult patients are predominantly treated
in the highly competitive community setting, NCI has focused its attention
and resources on building a far-reaching clinical trials infrastructure
that is user-friendly for community physicians.
Educating the Oncology Community and Patients about Clinical Trials
Since the NCI introduced its Clinical Trials Education Series (CTES) in
2002, the NCI’s Cancer Information Service (CIS) staff has been
training health professionals and community organizations in how to use
this excellent resource to educate patients and community groups about
clinical trials. To increase awareness and education about clinical trials
to the public and special populations, the CIS works in partnership with
local, state, and federal agencies to expand the reach of NCI programs
and services. The CIS Partnership Program strives to increase partners’
awareness that cancer is a major public health problem and that the burden
of cancer falls disproportionately on certain racial, ethnic, and socioeconomic
groups. The CIS forms partnerships with organizations to deliver information
that motivates people to improve their health and connects partner organizations
working in clinical trials education and outreach to build the capacity
of those organizations in order to further the reach of their programs
and services.
Leukemia and Lymphoma Society chapters across the U.S. and NCI grantees
known as the Special Populations Networks (SPNs) have been active participants
in clinical trials education by involvement in train-the-trainer sessions
offered by the CIS to become familiar with the CTES materials so that
they can use the materials to inform their communities. The purpose of
the SPNs is to build relationships between large research institutions
and community-based programs and find ways of addressing important questions
about the burden of cancer in minority communities. In particular, the
SPNs and the CIS collaborate to increase awareness of and accrual to clinical
trials.
The NCI’s Cancer Information Service interacts directly with cancer
patients and their families through its toll free number (1-800-4-CANCER),
through the Internet using real-time instant messaging technology (LiveHelp
in NCI’s web site cancer.gov), and by e-mail (through NCI’s
Web site, http://www.cancer.gov).
One of the most common reasons that patients, their families, and health
professionals contact the CIS is for information about clinical trials.
When appropriate, CIS proactively offers information on clinical trials
to individuals seeking information on treatment options and conducts a
customized search of NCI’s database of clinical trials. The clinical
trials search is provided directly to the patient so that they can discuss
the trials with their physician. Accompanying clinical trials patient
education booklets and materials are also offered to the individual.
The NCI also provides extensive internet access to information. The NCI’s
Web site (http://www.cancer.gov) provides
the public with access to the PDQ database, consisting of cancer treatment
summaries and cancer clinical trials, including approximately 2,000 cancer
clinical trials open to patient accrual. These include trials sponsored
by NCI, as well as those submitted by the pharmaceutical industry. The
information summaries are developed through peer review and application
of levels of evidence. A parallel summary is written for the lay public;
both the health professional and patient versions are also available in
Spanish. This registry is easily accessed through NCI’s Web site,
where users are able to narrow their search based on multiple parameters,
including disease characteristics and geographic location. The Web site
provides contextual material about clinical trial participation, to help
users easily find information to help them make informed decisions regarding
cancer treatment. The Web site is currently being redesigned to make it
even easier for the public to find the information they need, including
easier access to information regarding cancer treatment and clinical trials.
Improving the Clinical Trial Process
The Clinical Trials Working Group (CTWG) will attempt to better integrate
the many diverse components of NCI’s vast clinical trials program
to ensure that the most important scientific questions are being addressed
expeditiously, that duplication is avoided, resources are optimally distributed,
and the structures in place are appropriate for 21st century science and
technology.
Regarding increasing funding for the clinical trial cooperative groups
to levels approved by peer review, it is important to note that the total
funding for the cooperative groups rose by over 60% during the period
FY98-03 to peer-review-recommended full funding at that time, and the
amount of funding to cover the costs associated with enrolling a patient
in a trial more than doubled from less than $1000 at most sites to $2000
at all sites currently. The cooperative groups, albeit extremely important,
are only one component of the complex clinical trials system described
above. While they are responsible for accrual to crucial definitive Phase
3 studies which enroll the largest number of patients overall, they are
also the largest individual grants in NCI’s portfolio. The Clinical
Trials Groups undergo peer review once every 6 years. At this review,
both major accomplishments of the past 6 years and general scientific
plans for the next 6 years are presented along with a budget to support
these planned efforts. However, the specific number of clinical trials
that will actually be conducted is not predictable, nor is the size of
each trial or its accrual rate known at the time of peer review. Since
these two factors are critical determinants of the funding, administrative
support, and resources required to complete the research agenda, the annual
budget of each Group fluctuates. Each Phase 3 trial costs anywhere from
$2 million to $10 million, depending on its size. Therefore, the budget
approved at the time of peer review is seen as a future projection based
on an optimal set of provisional plans. Not all these plans will come
to fruition for multiple reasons – some are duplicative of other
efforts not known to peer reviewers at the time or review, and, not infrequently,
unanticipated scientific developments and opportunities occur. Therefore,
on an annual basis, NCI staff assesses the actual needs of each Group,
prioritizes studies among the various Cooperative Groups, and allocates
funds to each Group based on the total pool of available resources. While
peer review does a good job of assessing the infrastructure and track
record for these large cooperative groups, it is not able to assess the
relative merits and prioritization of all of a group’s proposed
research projects against the available NCI resources. NCI staff attempt
to look across all the existing projects, research priorities, and proposed
projects to make that assessment. The CTWG will enhance that process by
suggesting areas where resources can be conserved and re-aligned to get
the highest priority research done most efficiently, thereby accelerating
the delivery of promising new treatments to patients.
The Role of www.clinicaltrials.gov
In 2000, the National Library of Medicine (NLM) launched a new Web site,
www.clinicaltrials.gov, which
aims to be a complete listing of all U.S. Government- and industry-sponsored
clinical trials, including cancer trials. The NIH, through the NLM, has
developed this site in collaboration with the Food and Drug Administration
(FDA) as a result of the FDA Modernization Act, which was passed into
law in November 1997. Although no single resource lists every cancer clinical
trial being conducted in the United States and abroad, ClinicalTrials.gov
currently contains approximately 10,200 clinical studies sponsored by
the NIH, other federal agencies, and private industry.
Studies listed in the database are conducted in all 50 States and in over
90 countries. For each trial, the website presents a description of the
purpose of the experimental trial, eligibility criteria for participation
in the trial, location of the trial, and a point of contact for those
who would like to enroll. ClinicalTrials.gov receives over 2.5 million
page views per month and hosts approximately 16,000 visitors daily. In
addition to helping patients find clinical trials in which they might
participate, this website also educates users about clinical trials research,
regulatory issues, and the meaning of informed consent. It provides links
to background and related research and allows mining of statistics related
to clinical studies.
NCI’s cancer.gov website is a disease specific portal that includes
extensive additional information about cancer, its prevention and treatment,
and other material of interest to cancer patients and professionals, as
described above. All clinical trials information in cancer.gov is downloaded
to and available through www.clinicaltrials.gov
as well.
NCI’s Commitment to the 2015 ‘Challenge Goal’
The NCI is taking steps to achieve the 2015 challenge by accelerating
the pace of progress across the entire cancer research continuum. Basic
research, which is aimed at discovering the pathways that lead
to cancer, represents the beginning of the continuum that proceeds through
development of new agents and technologies and ultimately to
the delivery of these new interventions to patients. Increasing
our knowledge of the molecular defects in cancer cells and their microenvironment
and identifying the biomarkers that characterize the cancer process will
enable the development of new targeted interventions for preventing, detecting
and treating cancer.
The NCI has identified six “mission-critical” research areas
that offer significant potential for accelerating progress across the
cancer continuum and for realizing our 2015 goal. These include: harnessing
the power of the newly emerging science of molecular epidemiology to better
identify risk populations; developing an integrative understanding of
cancer (systems) biology to discover key biomarkers and targets; facilitating
the development of strategic cancer interventions for targeted prevention,
early detection, and treatment; creating a national integrated clinical
trials system to more effectively test these interventions; overcoming
health disparities to deliver these advances to those in greatest need;
and developing a bioinformatics network to connect the cancer research
community and optimize the collection, analysis, and use of the enormous
amount of data that must be managed and shared.
A key example of progress in a mission-critical area is NCI’s launching
of the Cancer Biomedical Informatics Grid (caBIG). This pilot initiative
has the potential to transform the pace of cancer research by providing
the tools needed to share information and data, by initially connecting
50 of our NCI-designated cancer centers through an NCI-developed open
source system to become, in effect, the “World Wide Web” of
cancer research. This platform eventually will link individual cancer
researchers and research institutions across the nation, and around the
world, in an open source, federated network that will enable researchers
to share tools, standards, data, computing applications, and technologies.
This bioinformatics initiative will allow researchers to answer research
questions more rapidly and efficiently and will accelerate progress in
all aspects of cancer research.
Conclusion
NCI-supported clinical trials provide a crucial infrastructure for moving
new cancer interventions from the laboratory to studies in people with,
or at risk for, cancer and then to the health care setting. These clinical
trials have always included investigations of a broad set of interventions
– chemoprevention, chemotherapy, radiation, and surgery –
sometimes used alone and sometimes in combination. With recent advances
in deciphering the molecular changes that cause cancer, a new paradigm
of cancer treatment and prevention research is emerging and bringing with
it the promise of an exponential growth in effective cancer interventions.
Last Revised: May 17, 2004
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