Panel on Clinical and Community-Based Approaches to the Diagnosis,
Treatment and Prevention of Oral, Dental and Craniofacial Diseases
Final Report
Noevember 14, 2002
Sponsored by:
The National Institute of Dental and Craniofacial Research
National Institutes of Health
I. Background:
The National Institute of Dental and Craniofacial Research (NIDCR) is the primary
sponsor of biomedical and behavioral research and of research training in oral,
dental and craniofacial disease in the United States. The mission of the Institute
is to promote and improve health through research. It accomplishes this mission
by supporting research and training programs in intramural laboratories and
in an extended external community of investigators working in academic institutions
and in other research organizations. Support of extramural researchers is provided
through the programs and initiatives of the Divisions of Basic and Translational
Sciences and of Population and Health Promotion Sciences. Major programs in
the first of these Divisions include biotechnology and biomaterials, developmental
biology and mammalian genetics, epithelial cell regulation and transformation,
oral infectious diseases and immunology, AIDS and oral manifestations of immunosuppression,
pain, and autoimmune disease. The Division of Population and Health Promotion
Sciences supports programs in behavioral and social sciences research, population
sciences, clinical trials and patient oriented research and health disparities.
The Division of Intramural Research includes laboratories located on the NIH
campus in Bethesda, MD. Intramural scientists perform research in craniofacial
and skeletal diseases, craniofacial development, gene therapy, oral and pharyngeal
cancer, oral infection and immunity and pain.
Recognizing the importance of long-term scientific planning to capitalize on
the rapid and significant advances that are occurring in biomedical and behavioral
research, NIDCR established an internal study group with representatives from
all its Divisions to identify broad areas of importance for the Institute's
long-range scientific agenda. This group identified three priority areas of
emphasis:
Genomics and Proteomics of Dental, Oral and Craniofacial Diseases
Repair and Regeneration of Dental, Oral and Craniofacial Tissues
Clinical Approaches to the Diagnosis, Treatment and Prevention of Dental,
Oral and Craniofacial Disorders.
The study group recommended that panels of experts be convened to work with
the Institute to identify and catalogue potential opportunities for significant
scientific advances within these areas of emphasis. The first panel, (Genomics
and Proteomics), was held on May 22, 2002, and the second, (Repair and Regeneration),
on
September 5, 2002. The final reports and recommendations from these panels are
posted in the NIDCR web page (http://www.nidcr.nih.gov/research/long_range_research_opps.asp)
This web site includes the following reports: Panel I - Genomics and Proteomics
of Oral, Dental and Craniofacial Diseases; Panel on Training; and Panel II on
Repair and Regeneration of Dental, Oral and Craniofacial Tissues. What follows
is a summary of the deliberations and recommendations of the third panel, (Clinical
Research), held on November 14, 2002.
Background information, including a summary of the current clinical research
portfolio and summaries of the previous discussions on this topic was provided
to the panelists prior to the meeting. The panelists were asked to consider
four major issues/questions:
Which of the areas previously identified through internal discussion and
through interaction with the National Advisory Council represent the best
long-range science/research opportunities?
In what research areas are the most promising opportunities?
What type of resources will be required to successfully address these opportunities?
What approaches/initiatives are likely to create incentives for this type
of research?
II. GENERAL DISCUSSION
A. Background Information:
Dr. Martinez opened the meeting by welcoming the members of the panel and thanking
them for participating in this important activity. He reviewed the genesis of
the panel and the designation of clinical research as a primary area of interest
for NIDCR. A number of discussions, including those with the National Advisory
Council, constitute the background provided to the panelists. The Panel was
asked to address long-term research opportunities that would lead to a broad
framework NIDCR can use in planning its research initiatives. The recommendations
of all expert panels will contribute to the development of the Institute's Strategic
Plan and provide the basis for the development of annual research programs.
Dr. Dushanka Kleinman, Deputy Director of NIDCR, emphasized the importance
of clinical and translational research to the agenda of the new NIH Director
as well as to NIDCR. She summarized the background material provided to the
panelists and the series of activities/actions that NIDCR has undertaken in
the last 2-3 years to review and to enhance clinical research. Recently, new
clinical trial concepts and guidelines for clinical trial grant applications
and management have been developed and discussed with the Advisory Council.
Also, NIDCR sponsored a meeting of dental school deans in 2001 where the Director,
National Center for Research Resources, highlighted resources and programs available
for clinical research, including General Clinical Research Center (GCRC) Awards
and Centers of Biomedical Research Excellence (COBRE) Awards. Several dental
schools are currently benefiting from these programs. In addition a NIDCR Request
For Applications (RFA) was issued to improve the research capacity and infrastructure
of dental schools and a program announcement has been issued to support research
curriculum development in dental schools
Other recent activities relevant to clinical research, include the development
of initiatives to support patient registries (such as for patients with TMJ
disorders, TMJ implants and those with Sjögren's syndrome); the creation
of a special emphasis panel for the review of applications for clinical trials;
enhanced interaction with FDA; identification, with the help of the Advisory
Council, of a full range of areas of scientific opportunity and of the criteria
for selecting the areas of emphasis and establishing priorities among others.
Also, the reorganization of the extramural programs serves to highlight clinical
research and recent efforts have resulted in recruitment of outstanding experts
in clinical research and clinical trial management.
Dr. Bruce Pihlstrom, Director of the Division of Population and Health Promotion
Sciences reviewed the current portfolio in clinical research, describing the
distribution of the grants in patient-oriented research, population based studies
and clinical trials. About 30% of the supported clinical trials address periodontal
disease and its relationship to systemic disease. In response to questions,
Dr. Pihlstrom indicated that 20% of the funding for clinical trials goes to
studies on the effects of dental amalgam and 2% to oral cancer.
The current emphasis is placed on phase III clinical trials, which are, in
the NIH definition, randomized controlled trials designed to provide evidence
leading to a scientific basis for consideration of a change in policy or the
standard of care.
NIDCR has prepared new guidelines for the submission of applications dealing
with clinical trials. The application procedure was outlined by Dr. Pihlstrom.
Panel members provided a number of suggestions in relation to the duration,
funding and sequencing of applications for clinical trials. These suggestions
were considered for inclusion in the guidelines that are now posted on the NIDCR
home page (http://www.nidr.nih.gov/clinicaltrials/Clinical_Trials_Program.asp).
B. GENERAL DISCUSSION
The Panel discussed several issues that need to be addressed to ensure the
success of a long-term clinical research program. These include:
1) The necessary infrastructure for conducting patient-oriented research and
for meeting all the regulatory requirement needs to be developed and/or enhanced
in dental research institutions.
2) The capacity of the oral health research community to conduct clinical
research and to use the findings from research needs to be augmented through
enhanced training and the creation of a critical mass of investigators who are
familiar with and can manage clinical trials and community-based research methodologies.
Training should include well-constructed programs leading to a Master's degree
in Clinical Research as well as shorter certificate programs and "hands-on"
training within experienced research groups.
3) The development and maintenance of clinical research partnerships with
other components of the academic health centers, the community and other sites
need to be stimulated through the use of comprehensive award "packages"
that support multidisciplinary research teams. Partnerships can make use of
the resources of the NIH intramural program and Clinical Center and of enhanced
participation in on-going medical clinical trials.
4) The culture of dental institutions needs to be modified to increase interest
in clinical research and to enhance the acceptance of collaborative, interdisciplinary
research and of the sharing of resources.
III. SCIENCE AREAS
The Panel reaffirmed the areas of science opportunity previously identified
by the National Advisory Dental and Craniofacial Research Council. These include:
a) Prevention and diagnosis (general focus), including vaccine development
and testing; salivary diagnostics; diagnostics for periodontal diseases, caries,
and bone disorders.
b) Oral and Craniofacial conditions (specific focus), including caries, periodontal
diseases, orofacial pain, TMJ, mucosal infections, oral cancer, and infectious
diseases with oral manifestations.
c) Intervention studies that explore the oral-systemic health connection,
including the study of the oral manifestations and complications of genetic
conditions and of chronic systemic diseases and disorders such as cardiovascular
disease, pulmonary disease and diabetes, and the impact of oral disease on systemic
health, such as the link between periodontal disease and low, preterm birth.
d) Research on genetic and environmental determinants that affect oral health.
e) Restoration of form and function in oral, dental and craniofacial tissues
through tissue engineering and biomaterials research.
The Panel also made the following comments in discussing the range of opportunities
that exist in these areas:
Studies aimed at development and refinement of diagnostic measures and diagnostic
criteria for oral and craniofacial diseases and health status should be given
priority.
For both community-based studies and clinical trials testing preventive
or therapeutic interventions, diagnostic codes for oral and craniofacial
conditions need to be developed and put into use to ensure comparability
among investigators/clinicians participating in the trials. Also, the development
of quantifiable outcomes are needed, such as quantifiable clinical and radiographic
measures of patient function and disease progression. Studies on pharmacoecomics
are needed to establish the link between the clinical changes and the economic
impact.
There should be continued emphasis on studies aimed at achieving a greater
understanding of the relationship among oral and systemic conditions. One
approach can include NIDCR's encouragement and support of participation in
on-going trials and cohort studies that have potential impact on the oral
cavity. Ideally this could be incorporated at the initiation of studies. Examples
of study areas include osteoarthritis and autoimmune disorders, among others.
Increased emphasis should be placed on investigations of oral functions
and symptoms and their management. Conditions such as "dry mouth"
can capture a broad range or oral and systemic issues for study.
The importance of supporting continual interaction between translational
research and clinical and community-based research was stressed. One suggested
approach includes providing support for taking and storing tissue and other
samples for mechanistic studies. In addition, assessing the translational
research portfolio may generate opportunities for clinical research. Inclusion
of translational research in clinical and community-based studies, where possible,
is recommended.
In terms of the types of resources that are required, the Panel acknowledged
that both human and fiscal resources, as well as institutional commitment,
are needed to address the scientific opportunities. They placed a priority
on encouraging the oral health research community to take maximum advantage
of partnering and using existing resources, and not recreating them. Examples
include the use of epidemiologists and biostatisticians who may be available
at the academic health center or the dental school. Other comments included:
There are insufficient numbers of researchers capable of conducting clinical
and community-based research. In addition to training and experience in research
methods, researchers are needed with specific expertise in areas such as prevention
and health promotion, diagnostic technology and drug development and testing,
and community-based interventions, as well as in translational research.
Support was articulated for the proposed clinical research masters program,
including suggestions for a "phased" program that could include
both part-time and full-time faculty. They acknowledged the support provided
via the K23 mechanism and also suggested that the full range of training should
be considered, ranging from certificate to doctoral programs.
Regarding human resources, the Panel members recommended that participation
in the K30 programs by oral health investigators be enhanced and recommended
highlighting the availability of the loan repayment program. The critical
role of mentors was emphasized, and the need to develop/support mentors for
this type of research was recommended.
In discussing the approaches/initiative that can create incentive for this
type of research, the Panel concluded that these are needed for both the
oral health research community as well as for other research groups within
the academic community to work with oral health researchers. The Panel recognized
that a strong rationale is needed to attract experienced partners from the
medical and social science fields to study questions related to oral health.
Similarly, dental health care practitioners need to be prepared to adopt
emerging technologies and interventions.
The value of community-based research was acknowledged; at the same time,
its inherent challenges were recognized. Of particular note is the need to
ensure that benefits derived from the research are transmitted back to the
community. In addition, the Panel recognized the importance of establishing
and maintaining partnerships between academic health researchers and community
programs and communities to foster community-based research.
Partnerships with industry should further support efforts in clinical and
community-based research. Opportunities for these partnerships include mutual
use of tissue and fluid specimens and support for institutional infrastructure
for research.
Supporting interactions among all categories of investigators and with the
practicing community was recommended. For example, Panel members recommended
that teaming basic scientists with clinical and community-based researchers
could benefit from the work of both groups. Also, the development of practitioner
networks was recommended to contribute to the expanded conduct of clinical
studies and ultimately to enhance science transfer.
The Panel also discussed other issues relative to clinical research and the
approach that NIDCR can use to promote the expansion of its research portfolio
into the areas of opportunity identified above. The Panel proposed several frameworks
for promoting this type of research. One is using a general approach that emphasizes
diagnosis, risk assessment, prevention and treatment. A second approach involves
the use of markers for specific diseases and their validation through population-based
studies. A third approach is to emphasize oral functions and to evaluate them
in terms of specific diseases and mechanisms of disease.
Proposals submitted within this matrix can be assessed by using the criteria
previously identified by the National Advisory Dental and Cranifacial Research
Council, which include:
a) uniqueness to the NIDCR mission
b) not being addressed by other funding agencies
c) capable of producing the most benefit to the public
d) capable of addressing the greatest public health need
e) that can be leveraged by other activities/funds
f) that can be improved by NIDCR participation
Additional elements of evaluation include whether the science base is ready,
whether the research community is ready and whether the proper measurements
are available. An alternative approach to stimulating clinical research is to
obtain input from stakeholders (including practitioners and patients) and to
identify broad areas of public interest.
As the areas of emphasis are developed, possible partnerships with industry
need to be considered. Incentives can be used for getting them involved in translational
research. These partnerships can involve products and their applications. Partnerships
can also be developed in terms of genomic efforts. Pharmaceutical and genomic
companies are desperate for serum, saliva or any other type of specimens for
tissues/sample banks, and partnering with them is a way to build the institutional
infrastructure.
The incredible complexity of doing clinical research and the regulatory burden
and capacity to comply have to be kept in mind, especially in multicenter trials
involving more than one IRB, academic units, General Clinical Research Centers
(GCRCs), etc. with different reporting and regulatory requirements.
National Institute of
Dental and Craniofacial Research
National Institutes of Health
Bethesda, MD 20892-2190
e-mail: nidcrinfo@mail.nih.gov
phone: 301/496-4261