Full Text DE-92-02


NIH GUIDE, Volume 21, Number 10, March 13, 1992

RFA:  DE-92-02

P.T. 34

  Oral Diseases 
  Biomedical Research, Multidiscipl 
  Behavioral/Social Studies/Service 

National Institute of Dental Research
National Institute on Aging

Letter of Intent Receipt Date:  August 1, 1992
Application Receipt Date:  November 10, 1992


The National Institute of Dental Research (NIDR) and the National
Institute on Aging (NIA), as part of their expanding programs of
research on the oral health of older Americans, invite applications
from United States institutions for the support of Research Centers on
Oral Health in Aging (RCOHAs).  The primary goal of these centers is to
provide support for interrelated, multidisciplinary, basic biomedical
and behavioral research and clinical or epidemiological studies of oral
health in relation to aging.  The research emphasis of individual
applications may differ depending on the expertise, resources, and
interests of the applicant group.  However, unless clearly a part of a
research study, clinical treatment is not be to included.  This Request
for Applications (RFA) represents one mechanism in the implementation
of a major NIDR initiative, the Research and Action Program for
Improving the Oral Health of Older Americans and Other Adults at High
Risk.  Other mechanisms used by NIDR in spearheading this program
include clinical core centers and research and development contracts.
This RFA is for a single competition with a receipt date of November
10, 1992.  Support for this initiative will be through specialized
center grants (P50) for a period of five years, commencing as early as
September 1, 1993.  First year budgets may not exceed $500,000 in
direct costs.  It is anticipated that one or two awards may be made.


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 RFA,
Research Centers on Oral Health in Aging, 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).


Applications may be submitted by domestic for-profit and non-profit
organizations, public and private, such as universities, hospitals,
laboratories, units of State and local governments, and eligible
agencies of the Federal Government.  Foreign organizations are not
eligible to apply.  However, domestic applications may include
international components.  Applications with key personnel, such as
center directors or investigators, who are minority individuals and/or
women are encouraged.  Although an application must be submitted from
a single institution, it may include consortia arrangements with other
institutions if these arrangements are clearly delineated and formally
and officially 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 have ongoing,
independently supported research and must propose new research in the
area of oral health in aging.


RCOHAs will be supported by specialized center grants (P50) for a
period of five years, commencing as early as September 1, 1993.  This
RFA is a one-time solicitation.  Subsequent support will be contingent
upon program needs and an institution's ability to compete successfully
in response to an RFA.  In addition to support for multidisciplinary
research projects, support will be provided for core resources, the
sharing of which will facilitate the total research effort.  Each core
unit must be utilized by at least two projects.  Responsibility for the
planning, direction, and execution of the proposed research will be
solely that of the applicant.  Except as otherwise stated in this RFA,
awards will be administered under PHS grants policy as stated in the
PHS Grants Policy Statement, DHHS Publication No. (OASH) 90-50,000,
revised October 1, 1990.


Applicants may request up to $500,000 in direct costs for the first
year.  Whenever indirect costs are assigned to a subcontract and
counted as direct costs, the direct cost maximum of $500,000 may be
exceeded by the amount of the indirect costs assigned to the
subcontract.  Applications that exceed these limits will be returned
without review.  Budget increases of no more than four percent per year
may be requested for each of the subsequent four years.  Applicants are
encouraged to seek support from other public and private sector
sources, including foundations and industrial concerns, for studies
that will complement and expand the research supported by the RCOHAs.
A summary of the objectives and financial support for such studies must
be included in the application.

It is anticipated that one or two awards will be made and at least
$750,000 in total cost will be committed for the first year of support
for the entire program, if a sufficient number of applications of high
scientific merit are received.  Although this program is provided for
in the financial plans of the NIDR, the award of grants pursuant to
this RFA is also contingent upon the availability of funds for this



In the last 10 years, there has been a considerable increase in
research associated with aging.  This has been principally stimulated
by general increases in the life span and by demographic studies that
predict a markedly increasing proportion of elderly individuals as the
21st century approaches.  For example, in the United States it is
expected that, by year 2030, one out of every five persons will be 65
years of age or older.  Such population shifts clearly will have major
effects on all facets of society, including health care.  Accordingly,
many clinical disciplines, including dentistry, have begun to evaluate
the functional status of elderly patients.  These studies have
accomplished several things.  Perhaps most importantly, they have shown
that aging and disease are different.  Many of the classical
stereotypes associated with growing old have been shown to be the
results of disease or the treatment of disease.  These studies also
have begun to define problems that clinicians will increasingly face
with elderly patients, problems that may place excessive demands on
current care providers, many of whom lack geriatric training or
appropriate resources.

There are relatively few studies that provide large-scale descriptions
of oral health status in the elderly.  These studies are from either
Western Europe or the United States and are mostly cross-sectional in
design.  At least two longitudinal studies exist, however, that examine
oral health.  Most studies have tended to concentrate on dental and
periodontal health status.  From these studies, there appear to be
clear trends among elderly persons to retain an increasing number of
teeth and thus to experience less edentulousness.  However, available
data also suggest that older individuals generally suffer from more
severe periodontal diseases than do young adults, and root caries is
becoming an increasing problem.

Some workers have conducted assessments of less commonly studied oral
functions such as salivary secretion, taste, smell (to which taste is
inextricably linked), nonchemical oral senses, oral motor performance
(such as mastication, swallowing and speech), and mucosal integrity.
These studies demonstrate that there are no alterations in the ability
of parotid glands to secrete saliva among different aged persons, but
the effect of age on submandibular/sublingual gland function remains
equivocal.  Most modern studies of gustatory function have generally
concluded that alterations associated with aging are modest and quality
specific.  These changes do not appear to influence nutritional status.
Conversely, there are several studies that demonstrate significant
reductions in olfactory performance with age and such alterations may
have given rise to many of the suggestions that food enjoyment is
reduced in the elderly.  Some studies also have indicated that there
are reductions in oral motor function with age, including changes in
masticatory performance, speech, and the oral phase of swallowing.

Generally, other aspects of oral physiology in the elderly have
received little investigative attention.  Thus, there is virtually no
data on the lubricator, antimicrobial and remineralizing functions of
saliva in the elderly; negligible information on the integrity of the
mucosal barrier and non-chemical oral senses; and, most importantly,
almost no information relating subjective complaints to objective
measurements of these many functional concerns.  There is a great need
to describe oral physiological status across the life span in healthy
persons, free of overt disease and medication, as well as to provide
such descriptions in patients with defined diseases and therapeutic

In part, the current lack of data reflects past limitations of
diagnostic tools.  At present, there are a number of methods, suitable
for use in population studies, that have been developed to assess the
broad spectrum of oral physiological functions mentioned.  They need
merely to be applied.  If changes are identified among the elderly, it
will be important to determine if they are of biological or only
statistical significance.  These data would be valuable for health care
planners in anticipating the treatment needs of this increasing segment
of society.

The NIDR and the NIA, as part of an expanding program in gerontologic
oral health research, encourage the submission of applications for the
support of RCOHAs.  This program was initiated in 1987 by an RFA that
resulted in one RCOHA being funded.  The present RFA announces the
first recompetition, in modified form, of the original RCOHA program.


The RCOHA program's primary goal is to provide support for
interrelated, multidisciplinary, basic biomedical and behavioral
studies as well as clinical and/or epidemiological research in the
broad area of oral health in relation to aging.  The secondary goal is
to create centers of excellence that will attract investigators of high
quality to this field of endeavor, provide challenging opportunities
for research training at all levels of career development, and serve as
magnet organizations to foster productive research-related
relationships with other institutions.

Some examples of research areas to be addressed regarding oral health
in the elderly might include, but should not be limited to:

o  Determination of the incidence and prevalence of the major oral
diseases and conditions of the elderly, including root caries,
periodontal diseases, edentulousness, soft tissue lesions (e.g.,
candidiasis, leukoplakia, and oral cancer), xerostomia, chronic pain
conditions (e.g., tic douloureux, post-herpetic neuralgia, burning
tongue syndrome, and atypical facial pain), and osteoporosis of
alveolar bone.

o  Characterization of the risk factors and correlates of oral diseases
and conditions in elderly populations.

o  Characterization of the natural history of oral disease versus oral
health among persons who seek dental services and those who do not.
These studies should involve an assessment of the principal variables
that influence utilization of dental services by the elderly.

o  Exploration of the potential of using oral tissues as models to test
theories of aging that focus on intracellular molecular or genetic

o  Characterization of normal changes (e.g., in the population of
pluripotential stem and amplifying cells) in skin and oral mucosa in
aging, and determination of the extent to which aging affects
functional aspects of the oral mucosa with particular emphasis on
permeability, mucosal immunity, and turnover (cell replacement) rates.

o  Determination of the effects of aging on salivary flow rate and
levels of salivary components (e.g., lubricator and antimicrobial
factors; mineralizing reservoir) and their relationship with
salivary-related functional abnormalities, noting, for example, what
factors are associated with complaints of dryness, root caries or
unusual dental abrasion, presence of ulcerations, fungal or other oral
infections, disorders affecting taste or other sensory modalities, and
motor problems such as difficulties in speech or swallowing.

o  Determination of the effects of aging on salivary mucous acinar cell
function compared with serous acinar cell function, and on bacterial
attachment and subsequent colonization of oral tissues.

o  Determination of whether or not and how normal aging modifies
collagen metabolism, the structure and function of bone and cartilage
matrix molecules, dentin, and cementum proteins, the effects of
hormones, vitamins, peptide, and other endogenous factors as regulators
or modulators of cellular activities relating to mineralization, and
the vascularity of bony tissue and repair and remodeling functions.

o  Determination of alterations that may occur in the periodontal
apparatus with aging.

o  Determination of the effects of aging on chemosensory, pain,
tactile, temperature, and pressure sensation and perception.

o  Development of new and improvement of existing tools for the
assessment of oral motor function (swallowing, mastication, and speech)
in healthy and in impaired older persons.

o  Studies of the relation between diseases and disorders (e.g.,
autoimmune and neurological disorders, diabetes, and bone and joint
disease) that affect oral health in the elderly, the treatments, and
oral tissues.  For example, these studies may include determination of
the etiology and natural history of primary and secondary sicca
syndromes and development of effective treatments, determination of the
relationship between radiographically observed alveolar bone loss and
bone changes (osteoporosis) elsewhere in the body, and determination of
how clinically defined states of anxiety and depression affect oral
sensory and motor functions and perception and how these interact with
appetite, eating habits, and nutritional status to affect oral and
general health.

o  Identification of the psychological and sociocultural factors that
are associated with oral hygiene behavior over the life span and
development and evaluation of oral health promotion and disease
prevention interventions that are appropriate for the various
subpopulations (e.g., institutionalized and physically and mentally
impaired) of the elderly.

o  Development of methods to prevent root and secondary caries, new
restorative materials that are particularly amenable to the oral needs
and health conditions of the elderly, and an artificial saliva with
mucosal protective and anticaries properties that could be "slow
released" in the mouth.

o  Evaluation of the effectiveness of conservative versus surgical
treatment for periodontal diseases at different levels of disease
severity and among different subpopulations of the elderly.

o  Development of modifications of prosthetic appliances to make them
more acceptable to all categories of elderly patients and exploration
of the use of dental implants for elderly patients.


In order to foster communication, cross-fertilization, and potential
collaboration in areas of mutual interest between RCOHA investigators
and other NIDR grantees and contractors involved with research on oral
health in aging, applicants must include plans in the budget requests
and a statement in the applications about the willingness of the key
investigators to participate in a workshop to be held at the National
Institutes of Health (NIH) near the end of the second budget period.

Direction and Leadership

Strong and effective scientific leadership must be provided.  RCOHA
directors will be responsible for the organization and operation of the
centers and for communication with NIDR on scientific and
administrative matters.  Directors will be responsible for maintaining
high quality research and for ensuring effective collaboration among
individual investigators.  It is essential that the research projects
be interrelated; they should not constitute a collection of individual
projects more appropriately supported by individual research project



NIH and ADAMHA policy is that applicants for NIH/ADAMHA clinical
research grants and cooperative agreements will be 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 should 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 the form PHS 398 in items
1-4 of the Research Plan AND summarized in item 5, Human Subjects.
Applicants/offerors are urged to asses carefully the feasibility of
including the broadest possible representation of minority groups.
However, NIH recognizes that it may not be feasible or appropriate in
all research 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, Hispanics).

The rationale for studies on single minority population groups should
be provided.

For the purpose of this policy, clinical research includes human
biomedical and behavioral studies of etiology, epidemiology, prevention
(and preventive strategies), 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.  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.

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 questions(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 NIH are required to
address these policies.  NIH funding components will not award grants
or cooperative agreements that do not comply with these policies.


Prospective applicants are asked to submit, by August 1, 1992, a letter
of intent that includes a descriptive title for the RCOHA, each project
and core, gives the name, address, and telephone number of the center
director and the identities of other key personnel and participating
institutions and departments, and identifies this RFA by number and

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 in planning for the timely review of
applications.  It allows NIDR staff to estimate the potential review
workload and to avoid possible conflict of interest in the review.

The letter of intent is to be addressed to:

G.G. Roussos, Ph.D.
Director, Salivary Research and
Oral Biology Centers Program
Extramural Program
National Institute of Dental Research
Westwood Building, Room 505
Bethesda, MD  20892
Telephone:  (301) 496-7884
FAX:  (301) 496-4180


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.  Advice and
suggestions by staff may materially assist applicants to ensure that
the RCOHA objectives and structure and the budget format are

Applications are to be prepared on form PHS 398 (rev. 9/91),
Application for PHS Grant, available at most institutional business or
grants and contracts offices and may be obtained from the Office of
Grants Inquiries, Division of Research Grants, National Institutes of
Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892 (telephone
301-496-7441).  The RFA label available in the PHS 398 application kit
must be affixed to the bottom of the face page of the original, and the
original must be placed on top of the entire package.  Failure to use
this label could result in delayed processing of the application such
that it may not reach the review committee in time for review.  In
addition, in order to identify the application as a response to this
RFA, the RFA title "Research Centers on Oral Health in Aging" and
number "DE-92-02" must be typed in item 2a of the face page of the
application form and the YES box must be checked.

The instructions accompanying form PHS 398 must be followed as far as
possible but some modification will be necessary.  For example, a new
Table of Contents must be prepared giving page numbers for all items in
the application.  Pagination must be consecutive throughout the
application.  Each project and core must be identified by number and
investigator.  A consolidated budget for the complete RCOHA for the
entire project period must be presented (use page 5, form PHS 398).
Separate detailed, annual and total budgets for the entire project
period for each project and core must be presented (use pages 4-5, form
PHS 398).  Present a table giving the budget totals for each project
and core and for the entire program, for all years of support.  Direct
and indirect costs are to be given.  Funds may be requested for
professional, technical, and administrative personnel; consultant
services; equipment; supplies; travel; patient costs directly related
to the research; minor renovations; and other costs.  Detailed
justification of the budget requests will be required.

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 RCOHA
and make it more cost-effective.  Awardees will be expected to update
this information on an annual basis.

Under Research Plan, describe the goals of the RCOHA and discuss the
background and significance of the topics being addressed.  Explain how
each project and core will contribute to achieving those goals.
Describe the administrative structure, the responsibilities of the
center director, individual investigators, advisory groups, and the
proposed mechanisms for monitoring scientific progress.  Describe the
relationship of all existing and pending institutional research
projects that may be relevant to the RCOHA regardless of funding

Each project must be presented as in a research project grant
application, that is, the instruction pages 19-24 of form PHS 398 must
be followed.  The 25-page limitation will apply to each project.
Describe the core units and explain how they will relate to the
projects that will utilize their resources.  Abstracts (page 2, form
PHS 398) must be completed for the entire application, each project,
and core.

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

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:

H. George Hausch, Ph.D.
Chief, Scientific Review Office
Extramural Program
National Institute of Dental Research
Westwood Building, Room 519
Bethesda, MD  20892
Telephone:  (301) 496-7658

Applications must be received by November 10, 1992.  If an application
is received after that date, it will be returned to the applicant.


Review Procedures and Criteria

Applications will be evaluated initially for scientific and technical
merit by a special review committee convened by the NIDR Scientific
Review Office in consultation with the NIA.  Prior to the initial
review, a triage mechanism may be employed to determine competitiveness
among the applications received.  An applicant interview or site visit
may be conducted.  Secondary review will be conducted by the National
Advisory Councils of the NIDR and the NIA.  Non-competitive or non-
responsive applications and those received after November 10, 1992 or
that exceed the budget limitation will be returned to the applicant.
Waivers of the receipt deadline and budget limitation will not be

Factors to be considered in the evaluation of applications include:

o  The scientific merit of each proposed project, including its
significance, originality, feasibility, and appropriateness and
adequacy of the experimental design.

o  The combination of the various projects and core units into an
effective and cohesive program, and the adequacy of plans to ensure
efficient collaboration, interaction, and dissemination of information
among investigators.

o  The extent to which the center will promote advances leading to
improvements in the oral health of older individuals that could not be
achieved, or that would be achieved more slowly, if the component
projects were funded separately.

o  The competence of the investigators, the appropriateness of the
proposed level of effort, and commitment to the accomplishment of the
proposed research goals.

o  The availability of statistical and data analysis resources and
evidence of the use thereof in developing research protocols.

o  The scientific and administrative qualifications, experience, and
commitment of the director, including the ability to provide effective
leadership.  Provisions for selection of a replacement director if it
becomes necessary.

o  The scientific and administrative structure and provisions for
quality control during development of the application and establishment
of the center; procedures for monitoring the research; and mechanisms
for reviewing changes in research directions.  The composition and use
of internal and external advisory committees.

o  The scientific/technical merit and justification for core resources

o  The institution's commitment to the center; the adequacy of its
facilities, resources, and administrative capabilities.

o  The appropriateness of the period of support and budget requested
for each project, core, and for the entire center.  The extent to which
complementary projects, supported from non-NIDR funds, will contribute
to the cost-effectiveness of the proposed RCOHA.

o  If clinical studies are proposed, the availability and
appropriateness of study populations and the utilization of minorities
and women as study subjects.

o  Ethical aspects, including the provisions for the protection of
human subjects and for the humane treatment of animals.

Additional Information and Guidelines

The inclusion of projects that are deemed to have only adequate or no
scientific merit or that are considered peripheral to the RCOHA's
objectives may be considered a reflection of the center director's
judgement and may affect the rating of the application.  Component
projects lacking significant and substantial merit will not be
recommended for further consideration.  Projects with only adequate
merit that are not deemed essential to the success of the RCOHA may be
recommended for deletion.  Each project deemed to have significant and
substantial merit will receive a separate priority score.


The earliest anticipated date of award is September 1, 1993.

Applicants should be aware that, in addition to scientific merit,
program priorities, and program balance, the total cost of an RCOHA
will be considered by NIDR/NIA staff and the Councils in making funding
recommendations.  An additional consideration will be the extent to
which complementary projects, supported by other awards, will
contribute to the cost-effectiveness of the proposed RCOHA.

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


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 to Dr. G. G. Roussos at
the address and telephone number under LETTER OF INTENT.

Inquiries regarding fiscal matters may be directed to:

Ms. Theresa Ringler
Chief, Grants Management Office
Extramural Program
National Institute of Dental Research
Westwood Building, Room 518
Bethesda, MD  20892
Telephone:  (301) 496-7437


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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