RESTORATION OF OROFACIAL TISSUES: A BIOMIMETIC/TISSUE ENGINEERING
APPROACH
RELEASE DATE: August 22, 2002
RFA: DE-03-004
National Institute of Dental and Craniofacial Research (NIDCR)
(http://www.nidr.nih.gov/)
LETTER OF INTENT RECEIPT DATE: October 20, 2002
APPLICATION RECEIPT DATE: November 20, 2002
THIS RFA CONTAINS THE FOLLOWING INFORMATION
o Purpose of this RFA
o Research Objectives
o Mechanisms of Support
o Funds Available
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Where to Send Inquiries
o Letter of Intent
o Submitting an Application
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations:
PURPOSE OF THIS RFA
The purpose of this RFA is to encourage biomimetics and tissue
engineering research in the areas of orofacial tissue and organ repair
and regeneration. The ultimate goal of this initiative is a systems
approach to the design and development of new biocompatible/inductive
materials that can stimulate cells and tissues to regenerate and/or
materials that can become integrated into the body. In particular,
this initiative encourages:
o biomimetic/tissue engineering approaches for the
restoration/regeneration of tooth and periodontal structures;
o tissue engineering and stem/progenitor cell approaches for the
construction of an artificial salivary gland and for the
repair/regeneration of Temporomandibular Joint (TMJ) structure; and
o use of new diagnostic imaging technologies and novel molecular
imaging probes to monitor key events during tissue repair/regeneration.
In the context of this initiative, integrative,
multidisciplinary/interdisciplinary research approaches from several
different scientific disciplines such as cell and molecular biology,
genetics, physics, engineering, computer and clinical sciences and
other relevant systems are encouraged. Applicants may propose
hypothesis-driven, discovery-driven, developmental, or design-directed
research.
RESEARCH OBJECTIVES
Background
The orofacial tissues and organs pose particularly interesting
challenges in repair/regeneration because of: i) a complex nerve supply
fine-tuned to serve special and general senses and to control muscles
of speech, respiration, mastication, and emotional expression; ii) a
rich blood supply to support high energy demands; iii) the presence of
the most complex joint in the body; and iv) a number of unique organs
and tissues: salivary glands, tongue, teeth and periodontal tissues.
Moreover, any interventions to restore these tissues must contend with
aesthetics and the importance of the face as the projected image of the
individual to the world. As we enter the 21st century, the field of
biomaterials is becoming one of the most exciting areas of materials
science and engineering. There is currently "fresh energy" in this
subject brought about by the availability of information from the
genome project, and the availability of human adult and embryonic stem
cells. Such advantages allow scientists to design and fabricate new
materials following and even improving, the work of nature to meet the
challenges of repairing and restoring orofacial tissues and organs.
This initiative encourages applications that make use of the recent
advances in biology, chemistry, physics and engineering to design
functional materials that simulate the natural biological environment
in order to facilitate:
i) restoration/regeneration of tooth and periodontal structures; ii)
construction of an artificial salivary gland; and iii)
repair/regeneration of TMJ structure. This initiative also encourages
the use of new imaging technologies and novel molecular imaging probes
that can provide in vivo imaging of the biological processes during
tissue repair and monitor treatment outcomes.
i. Restoration/regeneration of tooth and periodontal structures.
About 30% of the population age 65 and older is completely
edentulous (toothless). Standard treatment of tooth loss involves
prosthetic devices (dentures). Although these devices are initially
functional and restore the ability to chew, as the individual becomes
older they present problems with fit and aesthetics due to the loss of
underlying bone. Replacement of teeth by dental implants provides more
natural and stable function than dentures, but implants are not fully
biocompatible and must be periodically replaced by surgical procedures.
In addition, many Americans suffer from periodontal disease and missing
teeth. For example, by the age of 35 nearly every person has some
degree of gingival inflammation or periodontal disease, and 15% of the
total U.S. population has severe periodontal disease. At present,
periodontal diseases are treated primarily by surgical methods, but
restoration of normal function is generally slow, imperfect, and
temporary. Therefore, there are major clinical problems in the long-
term management of these disorders.
In the area of tooth structure, development and formation, the
NIDCR has supported years of research that now promise new strategies
for tooth repair and regeneration. Significant progress has been
achieved in our understanding of tooth formation. A major advance has
been the identification of specific signals required for development of
the tooth at the mechanistic level. A hierarchy of reciprocal tissue
signals has been identified, and the consequences of loss or excess
function are now recognized for several genes in critical pathways.
Breakthroughs in understanding enamel, dentin and cementum formation
have also occurred. Moreover, new relevant genes and structural
proteins have been discovered, and research has been accelerated by
information from the human and mouse genome projects. Besides
identifying crucial genes and their expression at different times of
tooth structure development, scientists are starting to decipher the
mechanisms of inorganic templating that direct mineral crystal
formation and the final form of natural composites. To mimic the
properties or structures of these natural materials for efficient
repair or replacement of teeth and bone, scientists will need to
develop efficient biomimetics-based designs.
Effective repair/restoration of teeth and periodontal tissues
requires balanced connective tissue growth, coverage by epithelium, and
formation of an effective tissue seal with teeth at the gum line.
Substantial advances in our understanding of cell adhesion and the
extracellular matrix molecules that support and regulate nearly all
cells provide many potential approaches to designing biomimetics.
Examples include scaffolds that mimic extracellular matrix
architecture, adhesives and anti-adhesives specific for individual
tissues, and controlled-release depots for molecules that regulate
growth, tissue rearrangement, and differentiated function.
ii. Construction of an Artificial Salivary Gland
Loss of salivary gland parenchyma and consequent inability to
make saliva affects an individual's quality of life. Currently, there
is no effective treatment for this condition. Saliva is a remarkable,
multipurpose fluid whose presence most of us take for granted. Yet
each year, it is estimated that about 40,000 people suffer a loss of
salivary gland function as a result of radiation treatment for head and
neck cancer. Although the treatment may save and prolong life, it can
permanently damage salivary glands located in the field of radiation.
In addition, it is estimated that more than one million Americans
(primarily women) are afflicted with Sjögren's syndrome, an autoimmune
disease whose symptoms include dry mouth and dry eyes. Whether
salivary glands are irreparably damaged by a disease such as Sjögren's
syndrome, or by treatment such as radiation for head and neck cancer,
the resulting loss of saliva flow markedly impairs the quality of life.
Without adequate saliva, patients may experience difficulty speaking,
chewing and swallowing. They may also experience rampant tooth decay,
mucosal infections such as candidiasis, loss of taste, and considerable
oral discomfort. This initiative encourages the application of state-
of-the-art methodologies including the use of adult and embryonic stem
cells for the regeneration of the salivary gland parenchyma and
restoration of its secretory function.
iii. Development of New Therapeutic Strategies for TMJ Repair and
Regeneration.
Epidemiological data suggest that approximately 10.8 million
American adults experience symptoms associated with Temporomandibular
Joint Disorders (TMJDs). Anatomically, the TMJ consists of the
mandibular condyle, the mandibular fossa and articular eminence of the
temporal bone, the muscles of mastication and the associated connective
tissues, including the articular disk. Abnormalities of each of these
structures have been implicated with TMJDs and, in many cases, these
structures need to be repaired or regenerated. Bone, connective tissue,
and muscle are potentially repairable through the use of mesenchymal
stem cells. Pluripotential stem cells have the inherent ability to be
transformed into many different types of tissue, depending on the
growth environment to which they are subjected. Current evidence
suggests that stem cell-mediated repair of a damaged structure is best
performed relatively soon after the initiating event. Presumably, the
differentiation of stem cells into the phenotype(s) of the injured
tissues is due to the presence of soluble factors (e.g., growth
factors, chemokines, etc) that are released from the injured tissues.
Recent work with autologous mesenchymal stem cells in animal models,
both with and without scaffolds, has demonstrated the ability of these
cells to transform into the component tissues of a joint to effect
repair of experimentally induced defects. Mesenchymal stem cells can be
harvested from bone marrow as well as from fat via liposuction. The
latter represents an easily obtainable source of autologous stem cells
for therapeutic needs.
As mentioned earlier, muscles not only control facial expressions
but are also key components of the TMJ. Muscle is a highly ordered
structure, composed of tubes of basal lamina in which differentiated
myocytes reside. Through a complex system of neuromuscular junctions,
each myocyte is synaptically connected to the central nervous system to
effect volitional motor control. The matrix scaffolding of a skeletal
muscle is extraordinarily complex and crucially important if functional
neuromuscular junctions are to be replicated. In order to design
synthetic or naturally derived matrices that promote formation of
functional facial musculature, advances in understanding muscle matrix
formation are necessary. Therefore, research should be directed toward
understanding the basal lamina of skeletal muscle, followed by
engineering a matrix that allows regeneration of normal muscle fibers
from the stem cells that exist in adult skeletal muscle.
Imaging technologies and novel molecular imaging probes could
provide in vivo imaging of the biological processes (e.g., cell
movements, enzymatic activity and gene expression patterns) from stem
cells to the formation of the tissue. The use of such technologies
together with fluidics, optics and electronics could enable development
of noninvasive sensing systems to pinpoint key events that mark the
onset of TMJDs and could also be used to monitor treatment outcomes,
and key events in stem cell treatment.
Scope
The objectives and scope of this initiative are to support basic and
applied research for the design and development of new
biocompatible/inductive materials for the repair and regeneration of
tooth and periodontal tissues, salivary glands and TMJ structures.
Research topics might include but are not limited to the following:
o Design of biodegradable scaffolds to serve as platforms for cells to
organize tissues for repair and regeneration of teeth and periodontal
tissues. Biomimetic replacements for various collagens, fibronectin,
laminin, or proteoglycans could be created that combine activities from
several molecules, have specificity for anchoring only certain cells,
and possess inherent resistance to proteolytic enzymes.
o Definition of the structural architecture and molecular interactions
that specify organic-inorganic (biological-mineral) interfaces at all
hierarchical levels (i.e., from nanoscale to tissue scale). For
example, it is essential to establish how enamel, dentin, and cementum
proteins serve as templates for mineral deposition and the different
steps involved in the processes of biomineralization and strengthening
of tooth structures.
o Design of bio-inspired dental composite/ceramic materials through
biomimetic principles of hierarchical self-assembly. For example,
development of tooth restorative materials with nanoscale-oriented
deposition of materials, and biomimetic polymers that regulate form and
provide protection against fracture, which can mimic or surpass the
properties of tooth enamel.
o Use of biological principles to design and fabricate materials which
will accelerate connective tissue regrowth while restraining epithelial
overgrowth during repair of diseased periodontal tissues.
Subsequently, these materials should accelerate the later phases of
periodontal tissue restoration; i.e., closing the epithelial gap to the
tooth surface and subsequently forming an anti-bacterial seal.
o Application of principles of self-assembly and cell adhesion to
modify the surface chemistry of synthetic tooth replacements. For
example, development of adhesive surfaces using peptides or mimetics
that mediate selective adhesion to connective tissue or oral
epithelium, which can provide fully biocompatible attachment surfaces
for implantable materials.
o Use of biomimetic principles to develop anti-fouling and self-
cleaning coatings for oral biomaterial surfaces to prevent or disrupt
formation of biofilms and to enhance defenses against bacteria.
o Develop methods (e.g., scaffolds incorporating gradients of
regulatory factors and bioreactor control of biochemical and physical
signals) to induce salivary stem/progenitor cell differentiation and in
vitro assembly of a functional acinar unit prior to transplantation.
o Develop biodegradable synthetic polymers for gene transfer and for
continuous release of fully active molecules that function to stabilize
the salivary nascent tissue at the implant site.
o Develop effective drug delivery systems using biomimetic principles
based on salivary proteins. For example, mucins with their highly
branching oligosaccharide moieties, reminiscent of dentritic polymers
might be engineered to serve as effective drug delivery systems for
anticancer and other drugs.
o Identify, isolate, culture and characterize multipotent stem cells
from adult tissue types for repair of TMJ associated structures (i.e.,
bone, cartilage, muscle).
o Determine factors that drive individual stem cells into different
cellular phenotypes relevant to TMJ reconstruction (e.g., muscle, bone,
cartilage etc.).
o Conduct comparative studies between adult somatic cells with
pluripotential properties with the aim of defining a rigorous phenotype
of somatic stem cells that can be used in joint reconstruction.
o Develop clinically relevant small and large animal models to make
use of the concept of stem cell plasticity for TMJ reconstruction.
o Develop "smart" polymers that mimic the extracellular matrix in
serving as scaffolds for stem cell transplantation. These polymers
could also serve as reservoirs and delivery systems for regulatory
molecules such as growth factors, with the capability of releasing
precise amounts of these molecules only when subjected to local
pressure from TMJ movements.
o Use in vivo molecular imaging technologies for characterizing
molecular processes and screening drugs in genetically engineered
animal models of TMJDs, and for determining the interactions of
implantable materials with biological systems (e.g., material
biocompatibility and bioactivity in the host environment).
o Develop imaging agents, probes, and radiopharmaceuticals that
identify TMJ defects at the cellular and molecular level.
Because of the nature of the research required to stimulate the design
and development of a new generation of biomaterials, it is expected
that potential applicants will include investigators with expertise in
biology, bioengineering, physics, chemistry, bioimaging, bioinformatics
and clinical sciences.
MECHANISM OF SUPPORT
This RFA will use the NIH Research Project Grant (R01) and the
Exploratory/Developmental research grant (R21) mechanisms. As an
applicant you will be solely responsible for planning, directing, and
executing the proposed project. This RFA is a one-time solicitation.
Future unsolicited, competing-continuation applications based on this
project will compete with all investigator-initiated applications and
will be reviewed according to the customary peer review procedures.
The anticipated award date is July 30, 2003.
This RFA uses just-in-time concepts. Applications for the R01 and R21
mechanisms use the modular as well as the non-modular budgeting formats
(see https://grants.nih.gov/grants/funding/modular/modular.htm).
Specifically, for this RFA, use the modular format.
The R21 proposals should have the potential for truly groundbreaking
impact. Use of this mechanism by investigators with expertise in fields
(e.g., tissue engineering, biomimetics, imaging) other than dental,
oral and craniofacial research experience who wish to explore new
biomedical approaches to address basic and applied research questions
is encouraged. Applicants are encouraged to contact program staff for
advice about choosing the appropriate grant mechanism.
FUNDS AVAILABLE
The NIDCR intends to commit approximately $3,000,000 in FY 2003 to fund
8-10 new grants in response to this RFA. An R01 applicant may request a
project period of up to 4 years and a budget for direct costs of up to
$250,000 per year.
An R21 applicant may request a project period of up to 2 years and a
budget for direct costs of up to $125,000 per year. The R21 application
must include milestones that will be used to judge the success of the
proposed exploratory research. An R21 application should not exceed 10
pages for the research plan.
Because the nature and scope of the proposed research will vary from
application to application, it is anticipated that the size and
duration of each award will also vary.
Although the FY 2003 financial plans of the NIDCR provide support for
this program, awards pursuant to the RFA are contingent upon the
availability of funds and the receipt of a sufficient number of
meritorious applications. At this time, it is not known if this RFA
will be reissued.
ELIGIBLE INSTITUTIONS
You may submit an application if your institution has any of the
following characteristics:
o For-profit or non-profit organization
o Public or private institutions such as universities, colleges,
hospitals, and laboratories
o National laboratories
o Units of state and local governments
o Eligible agencies of the Federal government
o Domestic or foreign
INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS
Any individual with the skills, knowledge, and resources necessary to
carry out the proposed research is invited to work with their
institution to develop an application for support. Individuals from
underrepresented racial and ethnic groups as well as individuals with
disabilities are always encouraged to apply for NIH programs.
WHERE TO SEND INQUIRIES
We encourage inquiries concerning this RFA and welcome the opportunity
to answer questions from potential applicants. Inquiries may fall into
three areas: scientific/research, peer review, and financial or grants
management issues:
o Direct your questions about scientific/research issues to:
Eleni Kousvelari, DDS, D.Sc.,
Cellular & Molecular Biology, Physiology
& Biotechnology Branch
National Institute of Dental and Craniofacial Research
National Institutes of Health
Building 45 Room 4AN-18A
Bethesda, MD 20892
Telephone: (301) 594-2427
FAX: (301) 480-8318
Email: kousvelari@de45.nidr.nih.gov
o Direct your questions about peer review issues to:
H. George Hausch, Ph.D.
Acting Director, Division of Extramural Activities
National Institute of Dental and Craniofacial Research
National Institutes of Health
45 Center Drive, Room 4AN-44F
Bethesda, MD 20892-6402
Telephone: (301) 594-2904
FAX: (301) 480-8303
Email: George.Hausch@nih.gov
o Direct your questions about financial or grants management matters
to:
Mr. Hoai Doan
Grant Management Specialist
National Institutes of Dental and Craniofacial Research
National Institutes of Health
45 Center Drive, Room 4AN-32J
Bethesda, MD 20892-6402
P: (301)594-4800
F: (301)480-8301
Email: hoai.doan@nih.gov
LETTER OF INTENT
Prospective applicants are asked to submit a letter of intent that
includes the following information:
o Descriptive title of the proposed research
o Name, address, and telephone number of the Principal Investigator
o Names of other key personnel
o Participating institutions
o 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 allows NIDCR and CSR staff to estimate the potential
review workload and plan the review.
The letter of intent is to be sent by the date listed at the beginning
of this document. It is preferred that the letter of intent be sent
electronically to kousvelari@de45.nidr.nih.gov
If necessary, the letter of intent can be sent by regular mail to Dr.
Eleni Kousvelari, listed in the WHERE TO SEND INQUIRIES section of this
announcement.
SUBMITTING AN APPLICATION
Applications must be prepared using the PHS 398 research grant
application instructions and forms (rev. 5/2001). The PHS 398 is
available at https://grants.nih.gov/grants/funding/phs398/phs398.html in
an interactive format. For further assistance contact GrantsInfo,
Telephone (301) 710-0267,
Email: GrantsInfo@nih.gov.
SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS: Applications
requesting up to $250,000 per year in direct costs must be submitted in
a modular grant format. The modular grant format simplifies the
preparation of the budget in these applications by limiting the level
of budgetary detail. Applicants request direct costs in $25,000
modules. Section C of the research grant application instructions for
the PHS 398 (rev. 5/2001) at
https://grants.nih.gov/grants/funding/phs398/phs398.html includes
step-by-step guidance for preparing modular grants. Additional information
on modular grants is available at
https://grants.nih.gov/grants/funding/modular/modular.htm.
USING THE RFA LABEL: The RFA label available in the PHS 398 (rev.
5/2001) application form must be affixed to the bottom of the face page
of the application. Type the RFA number on the label. 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, the RFA title and number must be typed on line 2 of the face
page of the application form and the YES box must be marked. The RFA
label is also available at:
https://grants.nih.gov/grants/funding/phs398/label-bk.pdf.
SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten
original of the application, including the Checklist, and three 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)
At the time of submission, two additional copies of the application
must be sent to:
Dr. H. George Hausch
Division of Extramural Activities
National Institute of Dental and Craniofacial Research
National Institutes of Health
45 Center Drive, Room 4AN-44F
Bethesda, MD 20892-6402
APPLICATION PROCESSING: Applications must be received by the
application receipt date listed in the heading of this RFA. If an
application is received after that date, it will be returned to the
applicant without review.
The Center for Scientific Review (CSR) will not accept any application
in response to this RFA that is essentially the same as one currently
pending initial review, unless the applicant withdraws the pending
application. The CSR will not accept any application that is
essentially the same as one already reviewed. This does not preclude
the submission of substantial revisions of applications already
reviewed, but such applications must include an Introduction addressing
the previous critique.
PEER REVIEW PROCESS
Upon receipt, applications will be reviewed for completeness by the CSR
and responsiveness by the NIDCR. Incomplete applications will be
returned to the applicant without further consideration. And, if the
application is not responsive to the RFA, CSR staff may contact the
applicant to determine whether to return the application to the
applicant or submit it for review in competition with unsolicited
applications at the next appropriate NIH review cycle.
Applications that are complete and responsive to the RFA will be
evaluated for scientific and technical merit by an appropriate peer
review group convened by the CSR in accordance with the review criteria
stated below. As part of the initial merit review, all applications
will:
o Receive a written critique
o Undergo a process in which only those applications deemed to have the
highest scientific merit, generally the top half of the applications
under review, will be discussed and assigned a priority score
o Receive a second level review by the appropriate Institute Advisory
Council.
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 your application in order to judge the likelihood
that the proposed research will have a substantial impact on the
pursuit of these goals:
o Significance
o Approach
o Innovation
o Investigator
o Environment
The scientific review group will address and consider each of these
criteria in assigning your application's overall score, weighting them
as appropriate for each application. Your 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,
you 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 your study address an important problem? If the
aims of your application are achieved, how do they advance scientific
knowledge? What will be the effect of these studies on the concepts or
methods that drive this field? To what degree does the technology
support the needs for research on biological or disease processes?
(2) APPROACH: Are the conceptual framework, design, and methods
adequately developed, well integrated, and appropriate for the design
and development of new materials? Does the applicant acknowledge
potential problem areas and consider alternative tactics? If
appropriate, what is the time frame for developing the proposed new
materials and what is the suitability of this time frame for meeting
the community's needs? How easy will it be to use the proposed
materials? If industrial partnerships are proposed, how will they
facilitate and complement the development of new biomaterials?
(3) INNOVATION: Does the project address discovery or technology
development that represents innovation for the field of orofacial
tissue repair? Does the project challenge existing paradigms or employ
novel concepts, approaches, or methods? What are the innovative
applications of the proposed fundamental discovery, technology, or
tools?
(4) INVESTIGATOR: Does the principal investigator possess appropriate
experience and capabilities to direct and carry out this work? Is the
experience level of the principal investigator, other researchers, or
collaborators appropriate for the proposed effort?
(5) ENVIRONMENT: Does the scientific environment in which your 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 or collaborative agreements?
ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, your
application will also be reviewed with respect to the following:
o PROTECTIONS: 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.
o INCLUSION: The adequacy of plans to include subjects from both
genders, all racial and ethnic groups (and subgroups), and children as
appropriate for the scientific goals of the research. Plans for the
recruitment and retention of subjects will also be evaluated. (See
Inclusion Criteria included in the section on Federal Citations, below)
o BUDGET: The reasonableness of the proposed budget and the requested
period of support in relation to the proposed research.
For R21 applications, the scientific review group will evaluate the
feasibility milestones that would justify progression to a future R01.
RECEIPT AND REVIEW SCHEDULE
Letter of Intent Receipt Date: October 20, 2002
Application Receipt Date: November 20, 2002
Peer Review Date: February/March 2003
Council Review: May/June 2003
Earliest Anticipated Start Date: July 30, 2003
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.
REQUIRED FEDERAL CITATIONS
INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH: It is the
policy of the NIH that women and members of minority groups and their
sub-populations must be included in all NIH-supported clinical research
projects unless a clear and compelling justification is provided
indicating 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 clinical research should read the AMENDMENT
"NIH Guidelines for Inclusion of Women and Minorities as Subjects in
Clinical Research - Amended, October, 2001," published in the NIH Guide
for Grants and Contracts on October 9, 2001
(https://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html);
a complete copy of the updated Guidelines are available at
https://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.
The amended policy incorporates: the use of an NIH definition of
clinical research; updated racial and ethnic categories in compliance
with the new OMB standards; clarification of language governing NIH-
defined Phase III clinical trials consistent with the new PHS Form 398;
and updated roles and responsibilities of NIH staff and the extramural
community. The policy continues to require for all NIH-defined Phase
III clinical trials that: a) all applications or proposals and/or
protocols must provide a description of plans to conduct analyses, as
appropriate, to address differences by sex/gender and/or racial/ethnic
groups, including subgroups if applicable; and b) investigators must
report annual accrual and progress in conducting analyses, as
appropriate, by sex/gender and/or racial/ethnic group differences.
INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN
SUBJECTS: The NIH maintains a policy 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 is available at
https://grants.nih.gov/grants/funding/children/children.htm.
REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS: NIH
policy requires education on the protection of human subject
participants for all investigators submitting NIH proposals for
research involving human subjects. You will find this policy
announcement in the NIH Guide for Grants and Contracts Announcement,
dated June 5, 2000, at
https://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.
HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of
research on hESCs can be found at
https://grants.nih.gov/grants/stem_cells.htm and at
https://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html.
Only research using hESC lines that are registered in the NIH Human
Embryonic Stem Cell Registry will be eligible for Federal funding (see
http://escr.nih.gov). It is the responsibility of the
applicant to provide the official NIH identifier(s)for the hESC line(s)to be
used in the proposed research. Applications that do not provide this
information will be returned without review.
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 initiative 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. Furthermore, we caution reviewers that their
anonymity may be compromised when they directly access an Internet
site.
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 RFA is related to one or more of the priority areas.
Potential applicants may obtain a copy of "Healthy People 2010" at
http://www.health.gov/healthypeople.
AUTHORITY AND REGULATIONS: This program is described in the Catalog of
Federal Domestic Assistance No. 93.121 (NIDCR) and is not subject to
the intergovernmental review requirements of Executive Order 12372 or
Health Systems Agency review. Awards are made under authorization of
Sections 301 and 405 of the Public Health Service Act as amended (42
USC 241 and 284) and administered under NIH grants policies described
at https://grants.nih.gov/grants/policy/policy.htm and
under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92.
The PHS strongly encourages all grant recipients to provide a smoke-
free workplace and discourage the 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.