Full Text DE-93-002

SPECIALIZED CARIES RESEARCH CENTERS

NIH Guide, Volume 22, Number 15, April 16, 1993

RFA:  DE-93-002

P.T. 04

Keywords: 
  Caries 
  Biomedical Research, Multidiscipl 
  Behavioral/Social Studies/Service 
  Epidemiology 
  Clinical Medicine, General 


National Institute of Dental Research

Letter of Intent Receipt Date:  September 24, 1993
Application Receipt Date:  October 21, 1993

PURPOSE

The National Institute of Dental Research (NIDR) invites applications
from United States institutions for the support of Specialized Caries
Research Centers.  The purpose of these centers is to reduce the impact
of dental caries as a public health problem by accelerating and
expanding the development of multidisciplinary basic, clinical,
epidemiological, and behavioral research as well as by promoting the
translation of research findings into improved methods that will lead
to the early diagnosis, treatment and prevention of coronal and root
caries in high risk populations.  The current solicitation requires all
applicants to propose both basic and clinical research that are
interrelated.

HEALTHY PEOPLE 2000

The Public Health Service (PHS) is committed to achieving the health
promotion and disease prevention objectives of "Healthy People 2000,"
a PHS-led national activity for setting priority areas.  This Request
for Applications (RFA), Specialized Caries Research Centers, is related
to the priority area of oral health.  Potential applicants may obtain
a copy of "Healthy People 2000" (Full Report:  Stock No.
017-001-00474-0) or "Healthy People 2000" (Summary Report:  Stock No.
017-001-00473-1) through the Superintendent of Documents, Government
Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238).

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic non-profit, public and
private organizations, such as dental or medical schools, universities
and research institutions.  Applications from foreign institutions are
not eligible.  However, applications may include international
components.  Although an application must be submitted from a single
institution, it may include consortia arrangements with other
institutions provided these arrangements are clearly delineated and
confirmed by signed statements from the responsible officials of each
institution.  To be eligible for a center grant under this program, the
potential applicant institution must propose new projects including
clinical dental caries research.

MECHANISM OF SUPPORT

Centers will be supported by specialized research center grants (P50)
for a period of five years, commencing as early as September 1, 1994.
Responsibility for the planning, direction, and execution of the
proposed project will be solely that of the applicant.  The total
project period for applications submitted in response to the present
RFA may not exceed five years.  Since this RFA is a one-time
solicitation, issuance of a subsequent request for new and competing
continuation applications will be contingent upon program needs and the
availability of funds.

Applicants may request up to $500,000 in direct costs for the first
year.  Where indirect costs are  assigned to a subcontract and counted
as direct costs on the parent grant, the direct cost maximum of
$500,000 may be exceeded by the amount of indirect costs assigned to
the subcontract. Applications that exceed these limits will be returned
without review.  Budget increases of no more than four percent may be
requested for each of the subsequent four years.

It is unlikely that the NIDR will be able to fund P01 grant
applications resulting from the amendment of unfunded applications
responding to this RFA.  A  statement of this policy is found in the
section titled "Amended Applications".

FUNDS AVAILABLE

The NIDR is currently supporting two centers with funding periods
ending in August 1994.  If a sufficient number of applications of high
scientific merit are received, it is anticipated that two awards will
be made and up to $1.5 million in total costs will be committed for the
first year of support of the entire program.  However, award of grants
for this program is contingent upon the availability of funds for this
purpose.

Applicants are encouraged to seek support from other public sources and
private sector sources, including foundations and industrial concerns,
for studies that will complement and expand the research supported by
the Centers.  Policies governing research grant programs of the
National Institutes of Health (NIH) will prevail.

RESEARCH OBJECTIVES

Background

Dental caries is a multifactorial disease involving the interaction of
microbial, environmental and host factors. The disease is characterized
by localized demineralization of susceptible tooth surfaces by acid
produced by oral microorganisms from dietary carbohydrates.  Factors
influencing the occurrence of caries include bacterial flora present in
the oral cavity, fluoride exposure, level and type of sugar
consumption, nutritional status, tooth structure, other conditions that
may compromise general health, salivary constituents, and oral hygiene.
The presence of any or all of these factors will determine whether or
not an individual will be affected as well as the nature and extent of
the disease.  While research studies have shed light on their
importance in the etiology and pathogenicity of coronal and root
caries, additional clinical studies are essential to determine those
factors that are the best biological and chemical markers of the
disease in humans.

In spite of the significant decline in tooth decay in school children
and younger adults, caries remains prevalent and costly.  Surveys by
the National Institute of Dental Research show that 25 percent of
children account for 75 percent of the dental decay in children and
approximately one-half of the nation's school children suffer from the
disease.  By the time an individual has reached late adolescence or
early adulthood, 84 percent have experienced at least one carious
lesion.

Dental caries can have profound effects on one's quality of life and
may be associated with other diseases, especially in individuals whose
immune systems are compromised.  Studies also show that older Americans
are at increased risk for root surface as well as coronal caries.
Other individuals at high risk for disease include the economically
disadvantaged, many members of racial and ethnic minorities,
individuals with medical and handicapping conditions, and patients
whose treatment includes medications and radiation therapy that
compromise oral health.

Thus, additional research is needed which focuses on the early
identification of individuals at high risk for caries and the
development of methods for early diagnosis of carious lesions.  In
addition, the development of cost-effective methods to prevent dental
caries can, at the same time, improve overall oral health and reduce
the costs associated with treatment of the disease.

Recent advances in cellular and molecular biology have contributed to
our understanding of the microbial etiology and pathogenesis of dental
caries.  New technologies hold promise for early diagnosis and
prevention of tooth decay.  For example, the development of diagnostic
probes, caries vaccines and saliva substitutes using  genetic
engineering are in various stages of development.  At this time, more
research is needed to bring these new technologies into the reality of
clinical practice.

Goals of the Centers

The primary goal of the centers is to accelerate and expand the
development of basic, clinical, epidemiological and behavioral research
as well as translating research findings into improved clinical methods
which can lead to the prevention and control of coronal and root
caries.  In order to foster a synergistic environment between basic and
clinical research, all applications must include basic and clinical
projects that are interrelated in a meaningful way.  At least one of
the projects must be clinical and involve human subjects.

Examples of research areas to be addressed include, but are not limited
to:

o  Determination of the incidence and prevalence of dental caries in
high-risk populations.

o  Exploration of molecular genetic and mucosal immunologic approaches
for developing an oral caries vaccine or passive immunization to
prevent caries in humans.  Related to this would be studies using
recombinant DNA techniques to identify oral bacteria and their
products, which may be involved in induction of specific caries
immunity.

o  Clinical evaluation of oral vaccines against Streptococcus mutans in
human subjects.

o  Development of new technologies, including molecular probes, to
identify individuals at high risk for dental caries.

o  Clinical testing of anti-plaque or anti-microbial agents to prevent
caries or reverse early carious lesions as well as studies designed to
improve their delivery and efficacy in caries prevention.

o  Determination of genetic, behavioral, developmental, dietary and
nutritional factors related to dental caries susceptibility or
resistance in humans.

o  Characterization of salivary molecules involved in tooth pellicle
formation and colonization of teeth by oral bacteria leading to caries
susceptibility or resistance in humans.

o  Studies of ecologic relationships among microorganisms in dental
plaque leading to caries development as well as of the microorganisms
present in carious lesions in enamel, cementum and dentin.

o  Studies to further elucidate the role of fluoride in preventing
coronal and root decay in adults.  Included in these are studies aimed
at identifying effective means of providing fluoride to individuals at
high risk without causing fluorosis in young children.

o  Clinical studies to establish the optimal doses, timing of
administration, method of delivery and the efficacy of antimicrobials
(e.g., chlorhexidine) to reduce the levels of S. mutans and the
incidence of dental caries in patients receiving head and neck
radiation as well as in other xerostomic individuals.

o  Development of methods using sealants on enamel and cementum
surfaces to prevent or arrest incipient carious lesions.

o  Determination of the causes of the recently reported declines in
caries prevalence.

Center Characteristics

Each research center will be an identifiable unit within a larger
institution already committed to some aspects of dental caries
research.  The center will consist of a cluster of related research
subprojects, some of which will be fundamental while others will
involve clinical and small epidemiological studies.  These subprojects
must not constitute a collection of individual, unrelated
investigations more appropriately supported by individual research
project grants or small grants.  Core resources, such as animal
facilities, computer services and equipment to be shared by
investigators will be provided, although budgetary constraints preclude
expenditures for very expensive items of equipment or major
renovations.

The center director will provide strong and effective scientific and
administrative leadership.  A committee consisting of staff members and
other expert consultants who are not members of the center staff and an
external committee that includes members who are not associated with
the applicant institution will advise the director on the merits of new
projects and the progress of existing investigations.  The
multidisciplinary research necessary to achieve the center objectives
will require collaborations between cell and molecular biologists,
microbiologists, immunologists, biochemists, cariologists, clinicians,
epidemiologists, and behavioral scientists.

Some funds, not to exceed $25,000 in direct costs, may be used to
support pilot projects.  Although the center mechanism does not provide
funds for training, it is expected that the centers will provide a
training environment for young investigators supported by other public
or private funds.  Scientists, who wish to broaden their range of
activities during the award period, will be expected to obtain
additional research support from sources other than the center grant.
Center grant funds should not be used to provide 100 percent of the
salary support for investigators.  Funding for a five-year project
period, with a possibility of renewal, should provide a more stable
environment than is usually encountered when investigators are
supported entirely by individual research project grants.

Site visits to review the performance of the centers and provide
guidance to the director may be conducted periodically by NIDR staff
and nongovernment expert consultants.  Annual meetings with the center
directors and NIDR staff may be held at the American Association for
Dental Research meetings or at the NIH to encourage exchange of
information and to stimulate collaboration among the centers.  Expenses
for attendance at these meetings will be the responsibility of the
awardee institutions.

STUDY POPULATIONS

SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH
POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL
RESEARCH STUDY POPULATIONS

NIH policy is that applicants for clinical research grants and
cooperative agreements are required to include minorities and women in
study populations so that research findings can be of benefit to all
persons at risk of the disease, disorder or condition under study.
Special emphasis should be placed on the need for inclusion of
minorities and women in studies of diseases, disorders and conditions
which disproportionately affect them.  This policy is intended to apply
to males and females of all ages. If women or minorities are excluded
or inadequately represented in clinical research, particularly in
proposed population-based studies, a clear compelling rationale must be
provided.

The composition of the proposed study population must be described in
terms of gender and racial/ethnic group.  In addition, gender and
racial/ethnic issues should be addressed in developing a research
design and sample size appropriate for the scientific objectives of the
study.  This information should be included in form PHS 398 (rev. 9/91)
in items l-4 of the Research Plan and summarized in item 5, Human
Subjects.  Applicants are urged to carefully assess the feasibility of
including the broadest possible representation of minority groups.
However, NIH recognizes that it may not be feasible or appropriate in
all such projects to include representation of the full array of United
States racial, ethnic minority populations (i.e., Native Americans
including American Indians or Alaskan Natives, Asian/pacific Islanders,
Blacks, and Hispanics).  The rationale for studies on single minority
population groups should be provided.

For the purpose of this policy, clinical research is defined as human
biomedical and behavioral studies of etiology, epidemiology, prevention
and preventive strategies.  It also refers to studies involving the
diagnosis or treatment of diseases, disorders or conditions including,
but not limited to, clinical trials.

The usual NIH policies concerning research on human subjects also
apply.  Basic research or clinical studies in which human tissues
cannot be identified or linked to individuals are excluded from these
policies.  However, every effort should be made to include human
tissues from women and racial/ethnic minorities when it is important to
apply the results of the study broadly, and this should be addressed by
applicants.

For foreign awards, the policy on inclusion of women applies fully.
Since the definition of minority differs in other countries, the
applicant must discuss the relevance of research involving foreign
population groups to the United States' populations, including
minorities.

If the required information is not contained within the application,
the application will be returned.

Peer reviewers will address specifically whether the research plan in
the application conforms to these policies.  If the representation of
women or minorities in a study design is inadequate to answer the
scientific question(s) addressed AND the justification for the selected
study population is inadequate, it will be considered a scientific
weakness or deficiency in the study design and will be reflected in
assigning the priority score to the application.

All applications for clinical research submitted to the NIH are
required to address these policies.  NIH funding components will not
award grants or cooperative agreements that do not comply with these
policies.

LETTER OF INTENT

Prospective applicants are asked to submit a letter of intent by
September 24, 1993.  The letter should include a descriptive title of
the proposed center, the name, address and telephone number of the
center director, the identities of other key personnel and their
participating institution(s), a descriptive title of each sub-project,
and the number and title of this RFA.

Although a letter of intent is not required, is not binding, and does
not enter into the review of a subsequent application, the information
that it contains is helpful to the NIDR staff in planning for timely
review of applications. It allows NIDR staff to estimate the potential
workload and to avoid possible conflict of interest in review.

The letter of intent is to be addressed to Dr. Joseph E. Ciardi at the
address listed under INQUIRIES.

APPLICATION PROCEDURES

Prospective applicants are advised to communicate with program and
grants management staff of the NIDR Extramural Program as early as
possible in the planning phase of application preparation.  NIDR staff
are available to assist applicants to ensure that the objectives,
structure, and the budget format for the proposed center are
acceptable.

The research grant application form PHS 398 (rev. 9/91) is to be used
in applying for these grants.  These forms are available at most
institutional offices of sponsored research; from the Office of Grants
Inquiries, Division of Research Grants, National Institutes of Health,
5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone:
301/710-0267; and from the program administrator listed under
INQUIRIES.  To identify the application as a response to this RFA,
check "yes" on item 2a of the face page of the application and enter
RFA: DE-93-002, Specialized Caries Research Centers.  The RFA label
available in the form PHS 398 must be affixed to the bottom of the face
page of the original application.  Failure to use this label could
result in delayed processing of an application and it may not reach the
review committee in time for review.

The instructions accompanying form PHS 398 should be followed as far as
possible but some modifications will be necessary.  For example, a new
Table of Contents should be prepared giving page numbers for all items
in the application.  Pagination must be consecutive throughout the
application.  Each subproject must be identified by number and
investigator.

Separate detailed budgets for each year for the entire center, core
resources, subprojects and pilot projects should be prepared.  A
consolidated budget for the center, for all years of support, should be
included (use pages DD-EE, form PHS 398).  Direct and indirect cost
estimates must be provided.  Funds may be requested for professional,
technical, and administrative personnel, core resources, equipment,
supplies, minor renovations, consultant services, travel, publication
costs, and patient costs directly related to the research. Detailed
justification of the budget requests will be required.

Under Research Plan, describe the goals of the center and explain how
the core resources and each subproject will contribute to achieving
those goals.  Describe the administrative structure and define the
responsibilities of the director, advisory groups and individual
investigators.

Provide a summary of financial support from non-NIDR sources for
studies that will complement and expand the program supported by the
NIDR.  Explain how these studies will further the goals of the center
and make it more cost effective.

Throughout the application, provide sufficient but concise information
to facilitate an effective evaluation.  Brevity and clarity in the
presentation of the research plans and in the description of the
organizational structure, including the cores, may be considered a
reflection of the applicant's ability to achieve the objectives of the
center.  Each research subproject should be presented as in a research
project grant application.  That is to say, the instruction on pages
19-24 of form PHS 398 should be followed.  Each subproject must be
described within the 25 page limitation which applies to research
project grant applications and each pilot project must be presented in
no more than 10 pages. Describe each core in no more than 25 pages and
explain how it will relate to the projects that will utilize its
resources.  Each core unit must be utilized by at least two projects.
Page BB (Abstract) of form PHS 398 should be completed for the core
resources, each subproject, pilot project, and for the entire
application.

Submit a signed, typewritten original of the application, including the
Checklist, and three signed photocopies, in one package to:

Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
Bethesda, MD  20892**

At the time of submission, two additional copies of the application
must also be sent to:

George Hausch, Ph.D.
Scientific Review Office
National Institute of Dental Research
Westwood Building, Room 519
Bethesda, MD  20892

Applications must be received by October 21, 1993.  If an application
is received after that date, it will be returned to the applicant
without review.

REVIEW CONSIDERATIONS

All applications submitted in response to this RFA will be screened by
NIH staff upon receipt.  Applications that are incomplete or
nonresponsive, those received after August 19, 1993, or those which
exceed the first year budget limit of $500,000 in direct costs will be
returned to the applicant without further consideration.  Waivers of
the receipt deadline and budget limitation will not be granted.
However, where indirect costs are assigned to a subcontract and counted
as direct costs on the parent grant, the allowable direct cost maximum
of $500,000 may be exceeded by the amount of the indirect costs
assigned to the subcontract.

Applications that are complete and responsive may be subjected to a
triage by a peer review group to determine their scientific merit
relative to the other applications received in response to the RFA.
The NIH will withdraw from competition those applications judged to be
noncompetitive and notify the applicant and institutional business
official. Applications judged to be competitive will be further
evaluated for scientific/technical merit by a special grants review
committee convened by the NIDR Scientific Review Office.  This review
may involve an applicant interview or a site visit.  Secondary review
will be by the National Advisory Dental Research Council.

Major factors to be considered in the evaluation of applications will
include:

o  The extent to which the center will promote advances in the area of
cariology that could not be achieved or would be achieved more slowly
if the component projects were funded separately.

o  The institutional environment, its commitment to the center, and
evidence of an organizational structure that will promote
multidisciplinary, collaborative research.  The potential of the center
to provide a training environment for investigators supported by other
public or private funds.

o  The scientific merit, originality and feasibility of each
subproject, the soundness of the methodology proposed, and the
competence of the investigators.  Availability of statistical and data
analysis resources and evidence of their use in developing research
protocols.

o  The technical merit and justification for core resources requested.

o  The adequacy of laboratory and clinical facilities, and the
availability of appropriate populations in clinical studies.

o  The inclusion of clinical and basic research projects that are
interrelated with adequate plans for interaction and communication of
information and concepts among the collaborating investigators.

o  The scientific and administrative qualifications, experience and
commitment of the Director and his/her ability to provide effective
leadership.  The arrangements for an Assistant Director to administer
the center in the Director's absence and  replace the Director should
it become necessary.

o  Plans for establishing and developing the center, for monitoring
research, and for reviewing changes in research directions.  The
composition and use of internal and external advisory committees.

o  Appropriateness of the period and budget requested for each
subproject, core, pilot project and the entire center.

o  In the case of a renewal application, performance of the center
during the current period of support.

The inclusion of projects that are deemed to have little or no
scientific merit or that are deemed peripheral to the center's
objectives may be considered a reflection of the proposed center
director's judgement and may affect the overall rating. Component
projects without significant and substantial merit will not be
recommended for further consideration.  If such projects are not deemed
essential to the success of the center, they will be recommended for
deletion.

Each project deemed to have significant and substantial merit will
receive its own priority score.

AWARD CRITERIA

The earliest anticipated date of award is September 1, 1994.

Applicants should be aware that, in addition to scientific merit,
program priorities, program balance, and the total cost of the center
to the NIDR will be considered by NIDR staff and the Council in making
funding recommendations.  An additional consideration will be the
extent to which complementary projects, supported from non-NIDR funds,
will contribute to the cost effectiveness of the proposed center.

Once funded, a center may undergo an interim review by NIDR to evaluate
progress. The funding for subsequent years may be contingent on a
successful outcome of this review.

AMENDED APPLICATIONS

In the past, it has been common practice for applicants responding to
RFAs issued by the NIDR for Specialized Research Center grants (P50) to
amend unfunded applications and submit them as unsolicited program
project grant (P01) applications. Alternatively, subprojects from
unfunded P50 grant applications have been amended and submitted as
applications for other support mechanisms such as research project
grants (R01, R29) or small grants (R03).

Applicants responding to the current RFA should be aware that, because
of fiscal constraints, it is unlikely that the NIDR will be able to
fund program project grant applications resulting from the amendment of
unfunded applications.  Thus, submission of program project
applications with goals similar to those included in this RFA is
discouraged.  However, applicants are encouraged to amend promising
subprojects from unfunded P50 applications and apply for support under
other grant mechanisms.

INQUIRIES

Written and telephone inquiries concerning this RFA are encouraged.
The opportunity to clarify any issues or questions from potential
applicants is welcome.

Direct inquiries regarding programmatic issues and address the letter
of intent to:

Joseph E. Ciardi, Ph.D.
Caries, Nutrition and Fluoride Program
National Institute of Dental Research
Westwood Building, Room 509
Bethesda, MD  20892
Telephone:  (301) 594-7641
FAX:  (301) 594-7616

Inquiries regarding fiscal matters may be directed to:

Ms. Theresa Ringler
Grants Management Office
National Institute of Dental Research

Westwood Building, Room 510
Bethesda, MD  20892
Telephone:  (301) 594-7629

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.

.

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