Full Text DE-93-001

SPECIALIZED MATERIALS SCIENCE RESEARCH CENTERS

NIH Guide, Volume 22, Number 14, April 9, 1993

RFA:  DE-93-001

P.T. 34

Keywords: 
  Biomaterials 
  Materials Composite 


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 domestic institutions for the support of Specialized Materials
Science Research Centers.  The primary goal of these centers is to
conduct research leading to the development of new or improved
biocompatible dental restorative materials as alternatives to dental
amalgam.  The centers are intended to provide an environment that
strengthens and increases productivity in basic and clinical materials
research leading to the development of novel materials and of
innovative materials processing strategies through multidisciplinary
collaborative efforts.  It is important to focus on a collaboration
between basic and clinical sciences to achieve the proposed goals.
Applications in response to this Request for Applications (RFA) may not
include research on maxillofacial and implant materials.

The overall intent of this RFA is to attract outstanding materials
science and engineering investigators, including those with no prior
experience in dental research, to the field of restorative dental
materials science and to encourage collaboration between basic
materials scientists, dental materials scientists, engineers,
toxicologists, and clinical researchers.  The research will focus on
new approaches to materials development and methodologies and allow for
correlation of new laboratory findings with clinical performance.

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 RFA,
Specialized Materials Science 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 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 from minority individuals and
women are encouraged.  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 have ongoing, independently
supported research in materials science and must propose new research
in the area with the ultimate goal of developing new or improved dental
restorative materials and methods.

MECHANISM OF SUPPORT

This RFA will use the National Institutes of Health Specialized Center
grant (P50).  This RFA is a one-time solicitation.  Subsequent support
will be contingent upon program needs and availability of funds.
Responsibility for planning, direction, and execution of the proposed
project will be solely that of the applicant institution.  However,
periodic consultation with NIDR staff will be expected.  This may take
the form of site visits.

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 allowable 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
per year may be requested for each of the subsequent four years.
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 Specialized Materials Science Research Centers.  A summary of the
objectives and financial support for such studies must be included in
the application.

FUNDS AVAILABLE

It is anticipated that two or three awards will be made and $1.5 to
$2.25 million 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
included in the financial plans of the NIDR, the award of grants
pursuant to this RFA is also contingent upon availability of funds for
this purpose.

RESEARCH OBJECTIVES

Background

The NIDR national survey of dental health of American adults, conducted
over one year and ending in March 1986, revealed that four percent of
the employed adults surveyed were missing all their teeth, and one half
had lost at least one tooth.  However, among Americans aged 65 and
older, forty-two percent were missing all their teeth, and only two
percent still had all 28 permanent teeth.  The survey also showed that
both younger and older adults continued to suffer from tooth decay.
Employed adults had an average of 23 decayed or filled coronal
surfaces, and seniors had an average of 20.  Root caries was found in
21 percent of the employed adults and in 63 percent of the seniors.
These statistics indicate that a considerable need still exists for
dental restorative treatment.

Current dental restorative materials have several shortcomings.
Longevity of restorations is to a large extent material dependent.
Amalgam is the most widely used posterior material.  Amalgam requires
removal of sound tooth structure beyond the decay in order to secure
the restoration in place, and it exhibits deficiencies such as poor
esthetic appearance and discoloration of tooth structure.  Only minor
changes occurred in the composition of amalgams until about 20 years
ago when non-gamma-2 amalgams were developed.  Since then no major
development has occurred.

Resin-based composite materials were initially developed for anterior
restorations, but materials suitable for use in small posterior
restorations also have been marketed.  Resin-based composite materials
have limited clinical applicability due to material degradation and
wear, color changes and plaque adhesion leading to recurrent caries.
Existing types of resin-based materials are not considered suitable
alternatives to amalgam, especially for large restorations.  No major
improvement has occurred to make these materials suitable for large
posterior restorations; i.e., as materials suitable for replacement of
amalgam.

Gold inlays have been used successfully for decades.  Glass ionomer
materials do not have the physical properties required for stress
bearing areas.  They also tend to disintegrate in vivo.  Indirectly
manufactured restorations such as those made from gold and ceramic
materials require extensive removal of sound tooth tissues during
cavity preparation.  Such restorations are relatively expensive.
Ceramic materials also fracture easily.  Recently, a number of ceramic
inlay materials have been developed for indirect restorations,
including CAD-CAM restorations, which can be completed at the same
appointment as the cavity preparation.

Secondary caries is a major reason for replacement of all types of
restorations, except glass ionomer materials, because of the leachable
fluoride components.  The development of alternative materials,
therefore, should pay particular attention to possible anticariogenic
properties.  The existence of materials or agents that bond permanently
to enamel and dentin would eliminate marginal leakage and thus reduce
the risk of secondary caries and enhance the longevity of restorations,
but surface characteristics are also important for plaque adhesion.

The 1991 NIH-sponsored Technology Assessment Conference on Effects and
Side Effects of Dental Restorative Materials also emphasized the need
for continued research on materials used for permanent restorations in
order to provide supporting data to ascertain that existing and future
materials are safe and effective.

Clinical studies have shown that gold inlays are much more durable than
are any of the other current restorative materials.  The median
longevity of amalgam restorations is about 8 to 10 years, while that
for posterior composites in stress bearing areas is considerably less.
Few data are available on the longevity of other posterior
restorations, but it is generally agreed that durability is of
paramount importance for the efficacy of restorations.

Biological reactions and side effects of different restorative
materials have received much attention during the last two decades.
The incidence of biological side effects to amalgam and composite
materials is similar.  Reports on side effects for glass ionomer
materials are scarce, but these materials have not been in extensive
use.  However, biological side effects to gold and ceramic materials
are extremely rare.  Despite the low incidence of side effects to all
types of dental restorative materials, the focus on the possible toxic
effects of mercury in dental amalgam has resulted in a need for the
development of alternative restorative materials. Thus, it is important
to ensure that improved or newly developed materials are not only
effective, but also safe.

Center Goals

The Specialized Materials Science Research Center program's primary
goal is to provide support for interrelated, multidisciplinary, basic
and clinical research leading to the development of new or improved
restorative dental materials and methodologies as well as to facilitate
and establish collaboration among basic materials scientists,
biomedical engineers, clinical dental researchers, and industrial
researchers.  A secondary goal is to create an environment in which
these researchers can interact to conduct studies aimed at providing an
understanding of the physical, chemical, clinical, and biological
characteristics of novel materials and technologies.  Although funds
are not provided for training, centers are expected to provide a focus
for training of scientists dedicated to the pursuit of careers in
dental materials research.  The development of the new restorative
materials should be accompanied by development of procedures and
guidelines for their optimal use.

Some examples of research on materials that satisfy the criteria for
the ideal restorative material might include, but are not limited to,
the development of:

o  Molecular and structural models of monomer/polymer based restorative
systems.

o  Materials based on biotechnological processes for the reconstruction
of carious defects; e.g., collagen-hydroxyapatite complexes that mimic
biological materials.

o  New ceramic and titanium-based alloy restorative materials.

o  New non-mercury-containing metallic direct restorative materials.

o  New materials that enhance preventive properties through materials
design, such as slow-release systems, and adhesive, anticariogenic
restorative materials, coatings or cements that will increase the
resistance of the tooth to acid dissolution or prevent attachment of
oral bacteria to the surface of the tooth or the restoration.

o  New methods for assessing surface characteristics and surface
modifications of existing materials including effects of pellicle and
plaque formation on different materials.

o  Coatings that will protect exposed dentin and the underlying pulp
from chemical and physical damage while providing stable bonds with
both the dentin and the restorative material.

o  Cost effective technologies such as computer-controlled milling or
other new technologies for both new and existing materials that cannot
be processed by conventional approaches.

o  New methods for assessing the function, durability, and
biocompatibility of promising materials.

Center Characteristics

Each Materials Science Research Center is envisioned as an identifiable
organizational unit within one institution with established bases of
ongoing materials science or as a collaborative unit bringing together
materials science experts with dental restorative materials science
experts.  The center will consist of a cluster of related research
projects, some of which will be fundamental and others will involve
clinical studies.  These various projects should not constitute a
collection of individual, unrelated investigations more appropriately
supported by individual research project or small grants.  Core
resources, such as 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.  Pilot projects and feasibility studies may be included in
the core.  Pre-clinical and clinical assessments of developments are
envisioned as part of this five-year funding period.

The center director should be an established scientist who can provide
both scientific and administrative leadership.  The director and
co-director will be responsible for organizing and operating the center
and for communicating with the NIDR on scientific and operational
matters.  It is anticipated that each center will facilitate
cooperation between its own scientists, foster collaboration and
communication with researchers from other institutions and industry,
and also provide a training environment for young investigators.  An
internal review board consisting of staff members of the center and
other non-member expert consultants should be established.  This board
will conduct initial reviews of proposed projects, assess scientific
progress, and provide general advice on organizational developments and
program planning.  In addition, an external advisory committee
consisting of members who are not associated with the applicant
institution, who will advise the director on the merits of new projects
and the progress of existing projects, should be established.

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 AADR meetings or at the NIH
to encourage exchange of information and to stimulate collaboration
among the centers.  Expenses for these meetings are the responsibility
of the centers.

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 site 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, 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), 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 question(s) addressed 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, by September 24, 1993, a
letter of intent that includes a descriptive title of the proposed or
existing center, the name, address and telephone number of the center
director, the identities of other key personnel and the participating
institution(s) and a descriptive title of each subproject, and the
number and title of the RFA in response to which the application may be
submitted.

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 Institute 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. Joyce A. Reese 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
is 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 Grant
Inquiries, Division of Research Grants, National Institutes of Health,
5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone 301/594-
7248; and from the program administrator listed under INQUIRIES.

To identify the application as a response to this RFA, check "yes" on
item 2a of face page AA of the application and enter RFA: DE-93-001,
Specialized Materials Science 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 such that it may not
reach the review committee in time for review.

The instructions accompanying form PHS-398 must be followed as far as
possible, but some modifications 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 center, for all
years of support, should be included (use pages DD-EE, form PHS 398).
Separate detailed annual and total budgets for the entire project
period for each project and core must be presented (use pages DD-EE,
form PHS 398).  Direct and indirect costs estimates 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 center
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 center and discuss  the
background and significance of the topics being addressed.  Explain how
each project 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 center regardless of funding source.

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 project should be presented as in a research
project grant application.  That is, the instruction on pages 19-24 of
form PHS 398 should be followed.  Each project 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.
Abstracts (page BB, form PHS 398) must 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 be sent to:

H. 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

Applications will be evaluated initially for scientific and technical
merit by a special review committee convened by the NIDR Scientific
Review Office.  Prior to the initial review, a triage mechanism may be
employed to screen out applications that are noncompetitive or
nonresponsive to the RFA.  An applicant interview or site visit may be
included.  Secondary review will be conducted by the National Advisory
Dental Research Council.  Non-competitive or nonresponsive applications
and those received after October 21, 1993, or that exceed the first
year budget limit of $500,000 in direct costs will be returned to the
applicant.  Waivers of the receipt deadline and budget limitation will
not be granted.

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

o  The extent to which the center will promote advances toward the
development of novel restorative dental materials and methodologies
which could not be achieved or which would be achieved more slowly if
the component projects were funded separately.

o  The extent to which the various research and pilot projects and the
cores have been combined into an effective and cohesive program, and
the adequacy of plans to ensure efficient collaboration, interaction,
and dissemination of information among investigators.

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

o  The competence of the center investigators and their commitment to
the accomplishment of the proposed research goals.

o  The scientific merit of each proposed project, including its
significance, originality, feasibility, experimental design, and
methods, including those for data management and analysis.

o   The institutional environment, including its commitment to the
proposed center, and to multidisciplinary, collaborative research of
the highest quality.

o  The adequacy of laboratory, clinical and animal facilities to meet
the needs of the proposed studies.

o  The plans for establishing and developing the center including
collaborative efforts, for monitoring research, for reviewing changes
in research directions, and for the use of scientific advisory
processes.

o  The availability and appropriateness of study populations.

o  The scientific, technical merit and justification for requested core
resources.

o  The appropriateness of the budget and period of support for research
and pilot projects, cores, and for the entire center.

o  For competitive renewal applications, the extent to which the goals
and specific aims of the previous application have been achieved.

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 director's judgement
and may adversely affect the rating.  Component projects that are not
deemed essential to the success of the center, will be recommended for
deletion.

AWARD CRITERIA

The anticipated date of award is September 29, 1994.  Applicants should
be aware that, in addition to scientific merit, program priorities and
program balance, the total cost of the Specialized Materials Science
Research Centers to the NIDR will be considered by NlDR 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 Specialized Materials Science Research Centers.

Once funded, a center may undergo an interim review by the 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 centers grants (P50)
to amend unfunded applications and submit them as unsolicited program
project grant (P01) applications.  Alternatively, sub-projects from
unfunded P50 grant applications have been amended and submitted as
applications for other support mechanisms such as research project
grants (R01) 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 P01 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 sub-projects 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 to:

Joyce A. Reese, D.D.S., M.P.H.
Biomaterials, Pulp Biology and Dental Implants Program
National Institute of Dental Research
Westwood Building, Room 509
Bethesda, MD  20892
Telephone:  (301) 594-7648
FAX:  (301) 402-4620

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
FAX:  (301) 594-7600

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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