and Human Services (HHS)
EXPIRED
NEW RESEARCH STRATEGIES FOR EVALUATION AND ASSESSMENT OF BONE QUALITY
Release Date: December 31, 2001
RFA: RFA-AR-02-002
National Institute of Arthritis and Musculoskeletal and Skin Diseases
(http://www.niams.nih.gov/)
National Institute of Dental and Craniofacial Research
(http://www.nidr.nih.gov/)
Letter of Intent Receipt Date: February 21, 2002
Application Receipt Date: March 21, 2002
THIS RFA USES "MODULAR GRANT" AND "JUST-IN-TIME" CONCEPTS. MODULAR
INSTRUCTIONS MUST BE USED FOR RESEARCH GRANT APPLICATIONS UP TO $250,000 PER
YEAR. MODULAR BUDGET INSTRUCTIONS ARE PROVIED IN SECTION C OF THE PHS 398
(REVISION 5/2001) AVAILABLE AT
http://grants.nih.gov/grants/funding/phs398/phs398.html.
PURPOSE
The National Institute of Arthritis and Musculoskeletal and Skin Diseases
(NIAMS) invites research applications that provide novel means to assess bone
quality and elucidate the relationships among disease- and aging-related
changes in bone quality, gender-related variations in bone quality, and
increased bone fragility and fracture susceptibility. Current tools for the
precise assessment of fracture risk are limited. In order to target high
risk populations for preventive or therapeutic interventions, it is necessary
to have tools that are able to assess bone strength and quality.
Applications may be in the form of individual research projects (R01) or
exploratory/developmental research grants (R21).
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, "New Research
Strategies for Evaluation and Assessment of Bone Quality," is related to the
priority area of chronic diseases. Potential applicants may obtain a copy of
"Healthy People 2010" at http://www.health.gov/healthypeople.
ELIGIBILITY REQUIREMENTS
Applications may be submitted by domestic and foreign for-profit and non-
profit organizations, public and private, such as universities, colleges,
hospitals, laboratories, units of State and local governments, and eligible
agencies of the Federal government. Applicants also may collaborate, through
consultation or contractual agreements, with investigators at foreign
institutions. Racial/ ethnic minority individuals, women, and persons with
disabilities are encouraged to apply as Principal Investigators.
Participation in the program by investigators at minority institutions is
strongly encouraged.
MECHANISMS OF SUPPORT
The mechanisms of support will include the investigator-initiated research
project grant (R01) and the exploratory/developmental research grant (R21).
R01 Applications. The individual research grant (R01) is a specific,
circumscribed project to be performed by the named investigator(s) who has a
specific interest and competency in an area of interest to this RFA. The
total project period for an R01 application submitted in response to this RFA
may not exceed 5 years. Future unsolicited competing continuation
applications will compete with all investigator-initiated applications and be
reviewed according to the customary peer review procedures. Because the
nature and scope of the research proposed in response to this RFA may vary,
it is anticipated that the size of an R01 award will vary also. Modular
budgeting procedures apply to grants up to $250,000. Specific R01
application instructions have been modified to reflect "modular grant" and
"just-in-time" streamlining efforts. Complete instructions and information
on modular grants can be found at
http://grants.nih.gov/grants/funding/modular/modular.htm. Direct costs will
be awarded in modules of $25,000, less any overlap or other necessary
administrative adjustments. F and A costs will be awarded based on the
negotiated rates.
R21 Applications. The purpose of the R21 projects solicited under this RFA
is to gather preliminary data leading to the development of an investigator-
initiated research project (R01). Use of this mechanism is recommended by
investigators experienced in bone structure/imaging /osteoporosis research
who wish to adapt or apply novel methodologies to study bone quality. It is
also recommended for investigators with relevant expertise (e.g., imaging of
other tissues, engineers, or others) interested in developing a program for
assessment of bone quality. Exploratory/developmental research grants (R21)
may not exceed $100,000 per year (4 modules) in direct costs, not including
facilities and administrative (F&A) costs for collaborating institutions, if
any. The total project period for an R21 application submitted in response
to this RFA may not exceed 3 years. These grants are nonrenewable and
continuation of projects developed under the R21 program should be through
the traditional unsolicited (R01) grant programs. Exploratory/ developmental
studies are not intended for large-scale undertakings or to support or
supplement ongoing research. Instead, investigators are encouraged to
explore the feasibility of an innovative research question or approach that
may not be at a stage advanced enough to compete as a standard research
project grant (e.g., R01).
FUNDS AVAILABLE
It is anticipated that for FY 2002, approximately $1.2 million (total costs)
will be available for the first year of support for this initiative. The
specific number of grants to be awarded will depend upon the merit and scope
of the applications received and on the availability of funds for this
purpose. An applicant using the R01 mechanism may request a project period of
up to 5 years and a budget for direct costs of up to $250,000 per year.
Exploratory/developmental research grants using the R21 mechanism may not
exceed $100,000 per year in direct costs, not including F and A costs for
collaborating institutions, if any. Total project period for an R21
application submitted in response to this RFA may not exceed 3 years. Awards
pursuant to this RFA are contingent upon the availability of funds and the
receipt of a sufficient number of meritorious applications of interest to
NIAMS. At this time, it is not known if this RFA will be reissued.
RESEARCH OBJECTIVES
The progressive or sudden loss of bone very commonly leads to osteoporosis, a
condition characterized by increased skeletal fragility and susceptibility to
fracture. Osteoporosis and its consequences are a significant cause of
frailty, morbidity, and even mortality among the elderly. However, while
reduced bone mass is important both in contributing to and predicting an
enhanced risk of fracture, low bone mass alone is not a sufficient
explanation for osteoporotic fractures. This is exemplified by the
substantial overlap in bone density between normal individuals and those who
sustain hip and other osteoporotic fractures. Recently, gender-related
differences in fracture susceptibility have been identified that cannot be
explained by simple differences in bone size. It has become apparent that
the conceptual basis of skeletal integrity must be broadened to include, in
addition to bone mineral content, qualitative factors that may impact on bone
strength such as geometry, macro and micro-structural organization,
distribution of material within bone, biochemical composition, and the burden
of unrepaired microdamage.
This RFA is directed towards: (1) stimulating research aimed at elucidating
mechanisms of bone fragility and its measurement and (2) developing
strategies and methodologies aimed at better identifying those at risk of
osteoporosis-related fractures and in need of therapeutic intervention to
prevent such fractures. Specifically, this RFA seeks applications for basic
and clinical research to identify and evaluate the relationship between
measures of bone density and bone quality and/or strategies to modify the
bone quality to reduce skeletal fragility and decreased fracture
susceptibility. Topics of interest include, but are not limited to:
o Changes in architecture, mechanical properties, and strength of bone with
disease and aging and non-invasive means to determine these properties
o Evaluation of changes in bone matrix and mineralization and their impact
on strength and resistance to microdamage
o Assessment of the consequences of the accumulation of cortical and
trabecular microdamage and their relationship to bone strength and fracture
biomechanics
o Development and application of new technologies for bone quality
assessment to be used in monitoring craniofacial development and alveolar
bone loss.
o Development and application of techniques such as histomorphometry,
ultrasound, MRI, and QCT to evaluate changes in architecture, bone strength
and fracture susceptibility
http://odp.od.nih.gov/consensus/cons/111/111_intro.htm.
Specific Objectives
This initiative will support studies in areas that have the potential to
elucidate the nature and consequences of disease- and age-related changes in
bone quality and the relationship of such changes to increased bone fragility
and fracture susceptibility. The specific objectives of this solicitation
are to address the following questions:
o What changes in bone mineral density, bone matrix, and bone architecture
significantly affect the biomechanical properties of bone?
o Are there non-invasive, reproducible imaging markers/methodologies that
can be used to assess longitudinal, age-related, and gender-related changes
in bone quality with regard to fracture risk?
o Do these non-invasive, reproducible imaging markers/methodologies for bone
quality assessment provide a means to explain the discrepancy between bone
mineral density and fracture reduction with anti-resorptive therapy?
o How do measurement site and regional heterogeneity influence these non-
invasive, reproducible imaging markers/methodologies for assessment of
bone quality?
INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS
It is the policy of the NIH that women and members of minority groups and
their 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
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html);
a complete copy of the updated Guidelines are available at
http://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
It is the policy of the NIH that children (i.e., individuals under the age of
21) must be included in all human subjects research conducted or supported by
the NIH unless there are scientific or ethical reasons not to include them.
This policy applies to all initial (Type 1) applications submitted for
receipt dates after October 1, 1998 .
All investigators proposing research involving human subjects should read the
"NIH Policy and Guidelines" on the Inclusion of Children as Participants in
Research Involving Human Subjects that was published in the NIH Guide for
Grants and Contracts, March 6, 1998, and is available at the following URL
address: http://grants.nih.gov/grants/guide/notice-files/not98-024.html.
Investigators also may obtain copies of these policies from the program staff
listed under INQUIRIES. Program staff may also provide additional relevant
information concerning the policies.
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. This policy announcement is found in the NIH Guide for Grants and
Contracts Announcement dated June 5, 2000, at the following website:
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.
URLS IN NIH GRANT APPLICATIONS OR APPENDICES
All applications and proposals for NIH funding must be self-contained within
specific page limitations. Unless otherwise specified in an NIH
solicitation, internet addresses (URLs) should not be used to provide
information necessary to the review because reviewers are under no obligation
to view the Internet sites. Reviewers are cautioned that their anonymity may
be compromised when they directly access an Internet site.
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:
http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.
Applicants may wish to place data collected under this RFA 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.
LETTER OF INTENT
Prospective applicants are asked to submit, by February 21, 2002, a letter of
intent that includes a descriptive title of the proposed research; the name,
address, and telephone number of the Principal Investigator; the identities
of other key personnel and participating institutions; and the number and
title of this RFA. Although a letter of intent is not required, is not
binding, does not commit the sender to submit an application, and does not
enter into the review of a subsequent application, the information that it
contains allows IC staff to estimate the potential review workload and avoid
conflict of interest in the review. The letter of intent is to be sent (e-
mail, fax or post) to Dr. Tommy Broadwater at the address listed under INQUIRIES.
APPLICATION PROCEDURES
Specific application instructions have been modified to reflect "MODULAR
GRANT" and "JUST-IN-TIME" streamlining efforts that have been adopted by the
NIH. Complete and detailed instructions and information on Modular Grant
applications have been incorporated into the PHS 398 (rev. 5/2001).
Additional information on Modular Grants can be found at
http://grants.nih.gov/grants/funding/modular/modular.htm.
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 http://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
http://grants.nih.gov/grants/funding/modular/modular.htm.
Modular grant applications will request direct costs in $25,000 modules, up
to a total direct cost request of $250,000 per year for R01 mechanisms and up
to a total direct cost of $100,000 per year for R21 mechanisms. A typical
modular grant application will request the same number of modules in each
year. The total direct costs must be requested in accordance with the
program guidelines and the modifications made to the standard PHS 398
application instructions described below:
In preparing the R21 application, the Background and Significance Section of
application should specifically state how the project represents a new
direction for the work performed at the PI's laboratory. This should include
a brief section (one page or less) entitled "Qualifications for High Risk" in
which the PI specifically addresses the following concerns:
o Innovation & Novelty: Does the proposed project represent a high degree of
innovation and novelty?
o Departure from current work: Does the proposed project specifically
overlap with work from the PI during the last five years? How does the
proposed work represent a significant departure from the PI's current line of
work?
o High risk: Explain how the high gain potential of the project, if
successful, offsets the high risk of failure.
A Preliminary Data section is not required for the R21 applications but if
included, it should not exceed one page.
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:
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf.
Submit a signed typewritten original of the application 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 and all
five sets of any appendix materials must be sent to:
Dr. Tommy L. Broadwater
Scientific Review Branch
National Institute of Arthritis and Musculoskeletal and Skin Diseases
45 Center Drive, Room 5AS-25U - MSC 6500
Bethesda, MD 20892-6500
Applications must be received by March 21, 2002. 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 the RFA that is essentially the same as on 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.
REVIEW CONSIDERATIONS
Upon receipt, applications will be reviewed for completeness by CSR and
responsiveness by NIAMS. 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 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 NIAMS in accordance with the review criteria stated below.
As part of the initial merit review, all applications will receive a written
critique and under 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, assigned a priority score, and receive a
second level review by the NIAMS 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 the application in order to judge the likelihood that the proposed
research will have a substantial impact on the pursuit of these goals. Each
of these criteria will be addressed and considered in assigning the overall
score, weighing them as appropriate for each application. Note that the
application does not need to be strong in all categories to be judged likely
to have major scientific impact and thus deserve a high priority score. For
example, an investigator may propose to carry out important work that by its
nature is not innovative but is essential to move a field forward. R21
applications will be judged by the criteria listed in the "High Risk
Arthritis and Musculoskeletal and Skin Diseases Research" solicitation,
AR-01-008, found at
http://grants.nih.gov/grants/guide/rfa-files/RFA-AR-01-008.html.
(1) Significance. Does the proposed study address an important problem? If
the aims of the application are achieved, how will scientific knowledge be
advanced? What will be the effect of these studies on the concepts or
methods that drive this field?
(2) Approach. Are the conceptual framework, design, methods, and analyses
adequately developed, well-integrated, and appropriate to the aims of the
project? Does the applicant acknowledge potential problem areas and consider
alternative tactics?
(3) Innovation. Does the project employ novel concepts, approaches or
methods? Are the aims original and innovative? Does the project challenge
existing paradigms or seek to develop new methodologies or technologies?
(4) Investigator. Is the investigator appropriately trained and well suited
to carry out this work? Is the work proposed appropriate to the experience
level of the principal investigator and other researchers (if any)?
(5) Environment. Does the scientific environment in which the work will be
done contribute to the probability of success? Do the proposed experiments
take advantage of unique features of the scientific environment or employ
useful collaborative arrangements? Is there evidence of institutional support?
(6) Protection of Human Subjects. Are there adequate provisions for the
protection of human subjects? Is there sufficient attention given to the
extent they may be adversely affected by the project proposed in the
application? Applications that fail to comply with this requirement will be
designated as incomplete and will constitute grounds for the return of the
application without peer review.
In addition to the above criteria, in accordance with NIH policy, all
applications will also be reviewed with respect to the following:
o The adequacy of plans to include both genders, minorities and their
subgroups, and children as appropriate for the scientific goals of the
research and in conformance with the NIH policy. Plans for recruitment and
retention of subjects will also be evaluated.
o The adequacy of the provisions for the protection of animal subjects, the
safety of the research environment, to the extent they may be adversely
affected by the project proposed in the application.
o The appropriateness of staffing based on the requested percent effort and
the personnel budget. The direct costs budget request will be reviewed for
consistency with the proposed methods and specific aims. Any budgetary
adjustments recommended by the reviewers will be in $25,000 modules. The
duration of support will be reviewed to determine if it is appropriate to
ensure successful completion of the requested scope of the project.
SCHEDULE
Letter of Intent Date: February 21, 2002
Application Receipt Date: March 21, 2002
Council Review: September 25, 2002
Earliest Anticipated Start Date: September 30, 2002
AWARD CRITERIA
The following will be considered in making funding decisions:
o Scientific merit of the proposed project as determined by peer review
o Availability of funds
o Programmatic priorities
INQUIRIES
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 one of the following:
Gayle E. Lester, Ph.D.
Musculoskeletal Diseases Branch
National Institute of Arthritis and Musculoskeletal and Skin Diseases
45 Center Drive, Room 5AS-43C
Bethesda, MD 20892-6500
Telephone: (301) 594-5055
FAX: (301) 480-4543
Email: [email protected]
Guo Zhang, Ph.D.
Program Director
Division of Extramural Research
National Institute of Dental and Craniofacial Research
Natcher Building, Room 4AN-18C
Bethesda, MD 20892-6402
Telephone: (301) 594-0618
FAX: (301) 480-8318
Email: [email protected]
Direct inquiries regarding review issues to:
Tommy L. Broadwater, Ph.D.
Scientific Review Branch
National Institute of Arthritis and Musculoskeletal and Skin Diseases
45 Center Drive, Room 5AS-25U - MSC 6500
Bethesda, MD 20892-6500
Telephone: (301) 594-4953
FAX: (301) 480-4543
Email: [email protected]
Direct inquiries regarding fiscal matters to one of the following:
Melinda Nelson
Grants Management Branch
National Institute of Arthritis and Musculoskeletal and Skin Diseases
45 Center Drive, Room 5AS-49F, MSC 6500
Bethesda, MD 20892-6500
Telephone: (301) 594-3535
FAX: (301) 480-5450
Email: [email protected]
Mr. Martin Rubinstein
Office of Grants Management
National Institute of Dental and Craniofacial Research
Natcher Building, Room 4AN-44A
Bethesda, MD 20892-6402
Telephone: (301) 594-4800
FAX: (301) 480-8301
Email: [email protected]
AUTHORITY AND REGULATIONS
This program is described in the Catalog of Federal Domestic Assistance
No. 93.846. Awards are made under authorization of the Public Health
Service Act, Title IV, Part A (Public Law 78-410), as amended by Public
Law 99-158, 42 USC 241 and 285) and administered under PHS grants
policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This
program is not subject to the intergovernmental review requirements of
Executive Order 12372 or Health Systems Agency review.
The PHS strongly encourages all grant and contract recipients to
provide a smoke free workplace and promote the non-use of all tobacco
products. In addition, Public law 103-227, the pro-Children Act of
1994, prohibits smoking in certain facilities (or in some cases, any
portion of a facility) in which regular or routine education, library,
day care, health care or early childhood development services are
provided to children. This is consistent with the PHS mission to
protect and advance the physical and mental health of the
American people.
Weekly TOC for this Announcement
NIH Funding Opportunities and Notices
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