This Program Announcement expires on July 31, 2004, unless reissued.
RESEARCH ON FLUORIDES TO IMPROVE ORAL HEALTH
Release Date: July 27, 2001
PA NUMBER: PA-01-121
National Institute of Dental and Craniofacial Research
THIS PA USES “MODULAR GRANT” AND “JUST-IN-TIME” CONCEPTS. MODULAR
INSTRUCTIONS MUST BE USED FOR RESEARCH GRANT APPLICATIONS UP TO
$250,000 PER YEAR. MODULAR BUDGET INSTRUCTIONS ARE PROVIDED IN SECTION
C OF THE PHS 398 (REVISION 5/2001) AVAILABLE AT
https://grants.nih.gov/grants/funding/phs398/phs398.html.
PURPOSE
The National Institute of Dental and Craniofacial Research (NIDCR)
invites research grant applications to support research leading to an
increase in knowledge about the use of fluorides for improving oral
health. Special emphasis is sought in the areas of the overall
metabolism of fluoride, effects of fluoride on bone and teeth, the
development of “gold standard” methods for fluoride analysis of a wide
variety of sample types, the influence of environmental factors on the
effectiveness of fluoride, including temperature, altitude, food
components, nutrients, and food additives, and the development of
biomarkers for monitoring body fluoride burden and noninvasive methods
to quantify fluorosis in vivo. In relation to the first of these
areas, a comprehensive approach is intended in order to address
bioavailability, intake and excretion and the influence of environment,
genetics, nutrition, physiology and socio-economic and cultural
diversity on the uptake, metabolism and biological and cosmetic effects
of fluoride. The second area includes recognition of the need for
practical epidemiologic studies of the current impact of water
fluoridation and other fluoride modalities on dental caries and dental
fluorosis.
HEALTHY PEOPLE 2010
The Public Health Service (PHS) is committed to achieving the health
promotion and disease prevention objectives of “Healthy People 2010,” a
PHS-led national activity for setting priority areas. This Program
Announcement, RESEARCH ON FLUORIDES TO IMPROVE ORAL HEALTH, is related
to several priority areas. Potential applicants may obtain a copy of
“Healthy People 2010” at http://www.health.gov/healthypeople/.
ELIGIBILITY REQUIREMENTS
Applications may be submitted by domestic and foreign, for-profit and
non-profit organizations, public and private, such as universities,
colleges, hospitals, laboratories, units of State and local
governments, and eligible agencies of the Federal government.
Racial/ethnic minority individuals, women, and persons with
disabilities are encouraged to apply as principal investigators.
Domestic applications may include international components. The NIDCR
encourages applications that include investigators who are
racial/ethnic minority individuals, women and persons with
disabilities. Although an application must be submitted from a single
institution, collaborative arrangements with other institutions are
strongly encouraged. Also, applications are not restricted to
traditional dental, oral and craniofacial research settings.
MECHANISM OF SUPPORT
The mechanism of support will be the individual research project grant
(R01) or the exploratory/developmental grant (R21). Responsibility for
the planning, direction, and execution of the proposed project will be
solely that of the applicant.
The objective of the exploratory/developmental mechanism (R21) is to
encourage applications to explore the feasibility of an innovative
research question or approach, which may not be justifiable through
extant research, or competitive as a standard research project grant
(R01). These are short-term awards (up to two years) with limited
funding (up to $100,000 per year for direct costs).
RESEARCH OBJECTIVES
Background
Fluoride has been recognized as the central component in strategies to
prevent dental caries, a disease that has had major health, economic
and social effects on communities worldwide. The use of fluorides in
the prevention of dental caries has been demonstrated to be one of the
most successful public health promotion measures in history. Dramatic
reductions in dental caries in children have been experienced where
fluoride has been made available through sources such as fluoridated
water, salt, toothpastes, topical rinses, gels, and dietary
supplements. Savings of approximately $40 billion have been estimated
in oral health care delivery in the USA alone in the past 40 years,
primarily as a result of the use of fluoride.
Although the incidence of caries has dramatically decreased since water
fluoridation and fluoride toothpastes have been widely applied as a
preventive measure, dental caries remains widespread and severely
affects a large segment of the population in the world. Fluoride has
shown to be effective as an anti-caries and anti-osteoporosis element.
However, the following critical issues related to its action in bone
and teeth remain unclear. 1) The minimal effective fluoride level in
human body to prevent and control dental caries without increasing the
risk of dental fluorosis is still not established. 2) The cellular and
molecular mechanism mediating anti-caries and -osteoporosis effects is
unclear. 3) The interactions between fluoride and other food components
remain undefined; for example, it has been implicated that some food
preservatives such as benzoate can potentiate fluoride effects, but its
underlying mechanism has not been fully studied. 4) Fluoride
monitoring needs more convenient and accurate “gold standard
measurement” of body fluoride burden, which can be used to determine
fluoride in environment, foods, and body fluids and tissues. This
measurement method is critical for sample analysis, real-time and
pharmacokinetic measurements. It is critical to fully understand the
mechanisms by which fluoride prevents dental caries and osteoporosis,
and to improve routines, materials and schemes of fluoride
administration. Therefore, further investigation of these issues is of
great significance.
In 1999, the NIDCR held two workshops to bring together fluoride
researchers from various fields including biochemistry, nutrition,
environment, epidemiology and behavioral science, to discuss the
current scientific knowledge and to propose direction for future
fluoride research. On February 1, 1999, a group of experts was
convened to develop a research agenda related to recent fluoridation
interventions that have been introduced within the U.S. A second
workshop identified research needs for international collaborative
research on fluoride. This workshop was co-sponsored with 10 partners,
including other NIH components, the Centers for Disease Control and
Prevention (CDC), private corporations, and the International
Association for Dental Research. Research recommendations from both
workshops form the basis of this announcement.
Scope
The purpose of this PA is to encourage research leading to an increase
in knowledge about the use of fluorides for improving oral health.
Appropriate topics for investigation under this PA include, but are not
limited to studies:
- To elucidate the molecular mechanisms of the action of fluoride on
tooth and bone cells. These investigations might include the
effects of fluoride on:
o Expression of genes that play a critical role in tooth and bone
development and mineralization;
o Proteins and other factors participating in tooth and bone
development and mineralization;
o Intracellular signaling systems regulating tooth and bone
mineralization.
- To determine the relative contribution of pre-eruptive and post-
eruptive effects of fluoride on prevention of dental caries.
- To determine the target concentration of fluoride in the oral
environment to optimize the local action of fluoride for caries
prevention.
- To develop new generations of fluoride therapeutics, local delivery
systems or devices to produce long-lasting and appropriate
concentration of active fluoride compounds which provide better
efficacies, better cost-effectiveness, and an improved safety
profile. These new therapeutics will be specific for target
tissues, and present in low levels in non-target tissues.
- To investigate the interactions between fluorides and food
components, nutrients and additives, and to develop methods to
enhance the beneficial effect of fluoride.
- To investigate the influence of environmental factors including
temperature and altitude on the effectiveness of fluoride.
- To develop simple global “gold standard” measurements, which are
more accurate, rapid and convenient analyses for monitoring of
fluoride levels such as screening, pharmacokinetics, time course
determination, and other purposes in body fluids and other specimens
including blood, saliva, urine and hair.
- To ascertain the relative contribution of currently available
fluoride modalities on dental caries prevention and control and on
dental fluorosis in populations.
- To investigate skeletal fluorosis and other fluoride effects on bone
in areas with high concentrations of natural fluoride, including
identification of environmental, cultural and social factors
associated with excessive fluoride exposure, the pathogenesis of
skeletal fluorosis, and development of valid and noninvasive methods
to quantify fluorosis in vivo and to identify risk indicators or
markers for dental fluorosis.
- To measure the public health cosmetic significance of enamel
opacities/fluorosis across cultures, and to explore preventive and
therapeutic interventions for both enamel and skeletal fluorosis.
INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS
It is the policy of the NIH that women and members of minority groups
and their subpopulations must be included in all NIH supported
biomedical and behavioral research projects involving human subjects,
unless a clear and compelling rationale and justification is provided
that inclusion is inappropriate with respect to the health of the
subjects or the purpose of the research. This policy results from the
NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43).
All investigators proposing research involving human subjects should
read the “NIH Guidelines For Inclusion of Women and Minorities as
Subjects in Clinical Research,” which have been published in the
Federal Register of March 28, 1994 (FR 59 14508-14513) and in the NIH
Guide for Grants and Contracts, Vol. 23, No. 11, March 18, 1994
available on the web at the following URL address:
https://grants.nih.gov/grants/guide/notice-files/not94-100.html
INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN
SUBJECTS
It is the policy of NIH that children (i.e., individuals under the age
of 21) must be included in all human subjects research, conducted or
supported by the NIH, unless there are scientific and ethical reasons
not to include them. This policy applies to all initial (type 1)
applications submitted for receipt dates after October 1, 1998.
All investigators proposing research involving human subjects should
read the “NIH Policy and Guidelines on the Inclusion of Children as
Participants in Research Involving Human Subjects” that was published
in the NIH Guide for Grants and Contracts, March 6, 1998, and is
available at the following URL address:
https://grants.nih.gov/grants/guide/notice-files/not98-024.html.
Investigators also may obtain copies of these policies from the program
staff listed under INQUIRIES. Program staff may also provide
additional relevant information concerning the policy.
REQUIRED EDUCATION IN THE PROTECTION OF HUMAN RESEARCH PARTICIPANTS
All investigators proposing research involving human subjects should
read the policy that was published in the NIH Guide for Grants an
Contracts, June 5, 2000 (Revised August 25, 2000), available at:
https://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.
PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT
The Office of Management and Budget (OMB) Circular A-110 has been
revised to provide public access to research data through the Freedom
of Information Act (FOIA) under some circumstances. Data that are (1)
first produced in a project that is supported in whole or in part with
Federal funds and (2) cited publicly and officially by a Federal agency
in support of an action that has the force and effect of law (i.e., a
regulation) may be accessed through FOIA. It is important for
applicants to understand the basic scope of
this amendment. NIH has provided guidance at:
https://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.
Applicants may wish to place data collected under this PA in a public
archive, which can provide protections for the data and manage the
distribution for an indefinite period of time. If so, the application
should include a description of the archiving plan in the study design
and include information about this in the budget justification section
of the application. In addition, applicants should think about how to
structure informed consent statements and other human subjects
procedures given the potential for wider use of data collected under
this award.
URLS IN NIH GRANT APPLICATIONS OR APPENDICES
All applications and proposals for NIH funding must be self-contained
within specified page limitations. Unless otherwise specified in an
NIH solicitation, internet addresses (URLs) should not be used to
provide information necessary to the review because reviewers are under
no obligation to view the Internet sites. Reviewers are cautioned that
their anonymity may be compromised when they directly access an
Internet site.
APPLICATION PROCEDURES
The PHS 398 research grant application instructions and forms (rev.
5/2001) at https://grants.nih.gov/grants/funding/phs398/phs398.html are
to be used in applying for these grants and will be accepted at the
standard application deadlines (https://grants.nih.gov/grants/dates.htm)
as indicated in the application kit. This version of the PHS 398 is
available in an interactive, searchable PDF format. Although applicants
are encouraged to begin using the 5/2001 revision of the PHS 398 as
soon as possible, the NIH will continue to accept applications prepared
using the 4/1998 revision until January 9, 2002. Beginning January 10,
2002, however, the NIH will return applications that are not submitted
on the 5/2001 version. For further assistance contact GrantsInfo,
Telephone 301/710-0267, Email: GrantsInfo@nih.gov.
Applicants planning to submit an investigator-initiated new (type 1),
competing continuation (type 2), competing supplement, or any
amended/revised version of the preceding grant application types
requesting $500,000 or more in direct costs for any year are advised
that he or she must contact the Institute or Center (IC) program staff
before submitting the application, i.e., as plans for the study are
being developed. Furthermore, the application must obtain agreement
from the IC staff that the IC will accept the application for
consideration for award. Finally, the applicant must identify, in a
cover letter sent with the application, the staff member and Institute
or Center who agreed to accept assignment of the application.
This policy requires an applicant to obtain agreement for acceptance of
the original application as well as any subsequent revisions. Refer to
the NIH Guide for Grants and Contracts, March 20, 1998 at
https://grants.nih.gov/grants/guide/notice-files/not98-030.html.
SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS
The modular grant concept establishes specific modules in which direct
costs may be requested as well as a maximum level for requested
budgets. Only limited budgetary information is required under this
approach. The just-in-time concept allows applicants to submit certain
information only when there is a possibility for an award. It is
anticipated that these changes will reduce the administrative burden
for the applicants, reviewers and NIH staff. The research grant
application form PHS 398 (rev. 5/2001) at
https://grants.nih.gov/grants/funding/phs398/phs398.html is to be used
in applying for these grants, with modular budget instructions provided
in Section C of the application instructions. Applicants are
permitted, however, to use the 4/1998 revision of the PHS 398 for
scheduled application receipt dates until January 9, 2002. If you are
preparing an application using the 4/1998 version, please refer to the
step-by-step instructions for Modular Grants available at
https://grants.nih.gov/grants/funding/modular/modular.htm. Additional
information about Modular Grants is also available on this site.
The title and number of the program announcement must be typed on line
2 of the face page of the application form and the YES box must be
marked.
Submit a signed, typewritten original of the application, including the
Checklist, and five signed photocopies in one package to:
CENTER FOR SCIENTIFIC REVIEW
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040, MSC 7710
BETHESDA, MD 20892-7710
BETHESDA, MD 20817 (for express/courier service)
REVIEW CONSIDERATIONS
Applications will be assigned on the basis of established PHS referral
guidelines. Applications will be evaluated for scientific and
technical merit by an appropriate scientific review group convened in
accordance with the standard NIH peer review procedures. As part of
the initial merit review, all applications will receive a written
critique and undergo a process in which only those applications deemed
to have the highest scientific merit, generally the top half of
applications under review, will be discussed, assigned a priority
score, and receive a second level review by the appropriate national
advisory council or board.
Review Criteria
The goals of NIH-supported research are to advance our understanding of
biological systems, improve the control of disease, and enhance health.
In the written comments reviewers will be asked to discuss the
following aspects of the application in order to judge the likelihood
that the proposed research will have a substantial impact on the
pursuit of these goals. Each of these criteria will be addressed and
considered in assigning the overall score, weighting them as
appropriate for each application. Note that the application does not
need to be strong in all categories to be judged likely to have major
scientific impact and thus deserve a high priority score. For example,
an investigator may propose to carry out important work that by its
nature is not innovative but is essential to move a field forward.
(1) Significance: Does this study address an important problem? If
the aims of the application are achieved, how will scientific knowledge
be advanced? What will be the effect of these studies on the concepts
or methods that drive this field?
(2) Approach: Are the conceptual framework, design, methods, and
analyses adequately developed, well-integrated, and appropriate to the
aims of the project? Does the applicant acknowledge potential problem
areas and consider alternative tactics?
(3) Innovation: Does the project employ novel concepts, approaches or
method? Are the aims original and innovative? Does the project
challenge existing paradigms or develop new methodologies or
technologies?
(4) Investigator: Is the investigator appropriately trained and well-
suited to carry out this work? Is the work proposed appropriate to the
experience level of the principal investigator and other researchers
(if any)?
(5) Environment: Does the scientific environment in which the work
will be done contribute to the probability of success? Do the proposed
experiments take advantage of unique features of the scientific
environment or employ useful collaborative arrangements? Is there
evidence of institutional support?
In addition to the above criteria, in accordance with NIH policy, all
applications will also be reviewed with respect to the following:
o The adequacy of plans to include both genders, minorities and their
subgroups, and children as appropriate for the scientific goals of the
research. Plans for the recruitment and retention of subjects will
also be evaluated.
o The reasonableness of the proposed budget and duration in relation
to the proposed research.
o The adequacy of the proposed protection for humans, animals or the
environment, to the extent they may be adversely affected by the
project proposed in the application.
AWARD CRITERIA
Award criteria that will be used to make award decisions include:
o scientific merit (as determined by peer review)
o availability of funds
o programmatic priorities.
Applications will compete for available funds with all other favorably
recommended applications. For those applications assigned to NIDCR,
applicants should be aware that, in addition to scientific merit,
program priorities and program balance, the total cost of the proposed
project and the availability of funds will be considered by the NIDCR
staff and the National Advisory Dental Research Council in making
funding recommendations. In addition, the NIDCR values complementary
funding from other public and private sources including foundations and
industrial concerns. In circumstances in which applications have
similar scientific merit, but vary in cost-competitiveness, the NIDCR
is likely to select the more cost-competitive application for funding.
INQUIRIES
Written, email and telephone inquiries concerning this PA are
encouraged. The opportunity to clarify any issues or questions from
potential applicants is welcome.
Direct inquiries regarding programmatic issues to:
Guo H. Zhang, Ph.D., M.Sc.
Program Director
Chronic Diseases Branch
Division of Extramural Research,
National Institute of Dental Research
National Institutes of Health
Building 45 (Natcher), Room 4An.18B
Bethesda, MD 20892-6402
Telephone: 301 594-0618
Fax: 301 480-8318
Email: guo.zhang@nih.gov
Direct inquiries regarding grants management issues to:
Mr. Martin R. Rubinstein
Chief, Grants Management Section
Division of Extramural Research
National Institute of Dental Research
National Institutes of Health
Building 45 (Natcher), Room 4AN-44A
Bethesda, MD 20892-6402
Telephone: 301-594-4800
Email: Martin.Rubinstein@nih.gov
AUTHORITY AND REGULATIONS
This program is described in the Catalog of Federal Domestic Assistance
No. 93.121. Awards are made under authorization of the Public Health
Service Act, Title IV, Part A (Public Law 78-410, as amended by Public
Law 99-158, 42 USC 241 and 285) and administered under PHS grants
policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This
program is not subject to the intergovernmental review requirements of
Executive Order 12372 or Health Systems Agency review.
The PHS strongly encourages all grant and contract recipients to
provide a smoke-free workplace and promote the non-use of all tobacco
products. In addition, Public Law 103-227, the Pro-Children Act of
1994, prohibits smoking in certain facilities (or in some cases, any
portion of a facility) in which regular or routine education, library,
day care, health care or early childhood development services are
provided to children. This is consistent with the PHS mission to
protect and advance the physical and mental health of the American
people.
*Original online at https://grants.nih.gov/grants/guide/pa-files/PA-01-121.html