Full Text AR-95-002


NIH GUIDE, Volume 23, Number 38, October 28, 1994

RFA:  AR-95-002

P.T. 34


National Institute of Arthritis and Musculoskeletal and Skin Diseases
National Institute on Aging

Letter of Intent Receipt Date:  January 20, 1995
Application Receipt Date:  February 21, 1995


The National Institute of Arthritis and Musculoskeletal and Skin
Diseases (NIAMS) and the National Institute on Aging (NIA) invite
investigators to submit grant applications for "New Horizons in
Osteoarthritis Research."   The applications may be for fully
independent research projects or for a group of independent research
projects that use the interactive research project grant (IRPG)
mechanism.  The research should be specifically targeted towards
understanding the disease processes in osteoarthritis.  This Request
for Applications (RFA) requests basic and applied research projects,
but not epidemiological or clinical treatment projects.


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,
New Horizons in Osteoarthritis Research, is related to the priority
areas of chronic disabling conditions and of older adults and
preventive services.  Potential applicants may obtain a copy of
"Healthy People 2000" (Full Report:  Stock No. 017-001-00474-0) or
"Healthy People 2000" (Summary Report:  Stock No. 017-001-00473-1)
through the Superintendent of Documents, Government Printing Office,
Washington, DC 20402-9325 (telephone 202-783-3238).


Applications may be submitted by domestic 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.
Foreign institutions are not eligible for First Independent Research
Support and Transition (FIRST) (R29) Awards.  Racial/ethnic minority
individuals, women, and persons with disabilities are encouraged to
apply as Principal Investigators.


This RFA will use the National Institutes of Health (NIH) research
project grant (R01), FIRST (R29) award, and the Interactive Research
Project Grant (IRPG).  Normal collaborative approaches, such as using
co-investigators, consultants or sub-contracts, may be utilized as
appropriate to achieve the aims of each independent research

The IRPG mechanism encourages interaction and collaboration among
independent scientists with common goals.  It is intended to bring
together research projects from investigators who wish to collaborate
but who do not require extensive shared resources.  There should be
constructive interchange of ideas, data and/or materials.  A minimum
of two independent investigators are encouraged to submit concurrent,
collaborative, cross-referenced individual regular research (R01) or
FIRST (R29) applications.  These applications must be free-standing
and contain independent hypotheses and aims.  An application that
provides only a service to other applicants is not acceptable.
Applicants may be from one or several institutions.  Detailed
information about this mechanism of support is available in the NIH
Program Announcement PA-94-086 in the NIH Guide for Grants and
Contracts, Volume 23, Number 28, July 29, 1994.

The total project period for applications submitted in response to
the present RFA may not exceed four years for R01s or five years for

Responsibility for the planning, direction, and execution of the
proposed project will be solely that of each independent applicant.
The anticipated award date is September 30, 1995.  Awards will be
administered under PHS grants policy as stated in the Public Health
Service Grants Policy Statement, DHHS Publication No. (OASH)
94-50-000 (rev. 4/1/94).

This RFA is a one-time solicitation.  Future unsolicited competing
continuation applications will compete with all
investigator-initiated applications and be reviewed according to
customary peer review procedures.

Applicants from institutions that have a General Clinical Research
Center (GCRC) funded by the NIH National Center for Research
Resources may wish to identify the GCRC as a resource for conducting
the proposed research.  If so, a letter of agreement from either the
GCRC program director or Principal Investigator could be included
within the application.


It is anticipated that six to eight awards will be made as a result
of applications for the "New Horizons in Osteoarthritis Research."
The estimated funds available for the first year of support for this
program are $1,400,000 in total costs.  Actual funding is dependent
on the receipt of a sufficient number of applications of high
scientific merit and the availability of funds for this purpose.  The
direct cost of each R01 is limited to $160,000 for the first year and
R29s are limited to $70,000 average per year.  Funding beyond the
first and subsequent years of the grant will be contingent upon
satisfactory progress during the preceding years and the availability
of funds.


The osteoarthritic diseases (OA) are the most prevalent disorders of
the joint, with radiographic evidence seen in at least 70 percent of
the population over age 65.  In 1984, the economic cost of OA was
estimated at $8 billion.  OA is a group of overlapping distinct
diseases that may have different etiologies but similar biologic,
morphologic, and clinical outcomes.  The disease processes not only
affect the articular cartilage but involve the entire joint including
the subchondral bone, ligaments, capsule, synovial membrane and
periarticular muscles.  Ultimately, the articular cartilage
degenerates with fibrillation, fissures, ulceration and full
thickness loss of the joint surface.

A workshop entitled "New Horizons in Osteoarthritis" was held April
23-26, 1994, to bring together an interdisciplinary group of leading
clinicians and scientists to discuss the current knowledge and
delineate future research directions on the etiopathogenesis of OA.
The workshop was sponsored by the American Academy of Orthopaedic
Surgeons (AAOS), the National Institute of Arthritis and
Musculoskeletal and Skin Diseases (NIAMS), the National Institute on
Aging (NIA), the National Arthritis Foundation, and the Orthopaedic
Research and Education Foundation.

A book that summarizes this workshop on OA includes extensive
discussion in the areas of definition, epidemiology, classification,
cartilage changes in aging and degeneration, changes in the joint as
an organ, role of mediators and inflammation in degradative
mechanisms, repair of cartilage, monitoring of preclinical and
clinical progression, and treatment of OA.  It contains six sections
with individual chapters, which define the present state of knowledge
and identify future research directions.  This book will be published
by AAOS in February 1995.

This RFA for the "New Horizons in Osteoarthritis Research" is
intended to stimulate further scientific investigations on a broad
range of topics in this area of high public health impact.  Research
may be basic and/or applied in nature.  Epidemiological and clinical
treatment applications will not be accepted.  Applications must be
targeted to an aspect of the disease osteoarthritis rather than a
fundamental study of the biology of normal joint tissues.  As
indicated above under Mechanism of Support, applications may be in
the standard fully independent R01 and R29 format or interactive in
nature using the IRPG format.

This RFA is purposefully not restrictive in defining a narrow range
of OA topics to be studied.  Appropriate research areas may include,
but are not limited to, the following:

o  Exploration of the genetic basis for some types of OA.

o  Study of the altered metabolic control in OA of synthetic and
degradative processes in cartilage.

o  Study of the effects of altered biological and mechanical factors
on control of chondrocyte activity in OA degeneration.

o  Investigation of the interactive roles of the component structures
of the joint as an organ in the development and progression of OA.

o  Elucidation of the age-related changes in joint tissues and their
role in the development and progression of osteoarthritis.

o  Evaluation of the "point of no return" at which cartilage appears
to have diminished reparative ability and the degradation proceeds

o  Exploration of the role of inflammatory responses and their
mediators in the initiation and progression of OA.

o  Study of the nature and significance of wear debris from articular
cartilage in initiating and sustaining the degradative process.

o  Exploration of tissue engineering or other approaches for
biological repair of cartilage.

o  Development of markers of OA.


It is the policy of the NIH that women and members of minority groups
and their subpopulations must be included in all NIH supported
biomedical and behavioral research projects involving human subjects,
unless a clear and compelling rationale and justification is provided
that inclusion is inappropriate with respect to the health of the
subjects or the purpose of the research.  This new policy results
from the NIH Revitalization Act of 1993 (Section 492B of Public Law
103-43) and supersedes and strengthens the previous policies
(Concerning the Inclusion of Women in Study Populations, and
Concerning the Inclusion of Minorities in Study Populations), which
have been in effect since 1990. The new policy contains some
provisions that are substantially different from the 1990 policies.

All investigators proposing research involving human subjects should
read the "NIH Guidelines For Inclusion of Women and Minorities as
Subjects in Clinical Research," which have been published in the
Federal Register of March 28, 1994 (FR 59 14508-14513) and reprinted
in the NIH Guide for Grants and Contracts, Volume 23, Number 11,
March 18, 1994.

Investigators also may obtain copies of the policy from the program
staff listed under INQUIRIES.  Program staff may also provide
additional relevant information concerning the policy.


Prospective applicants are asked to submit, by January 20, 1995, 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, the number RFA AR-95-002, and the title "New Horizons
in Osteoarthritis Research".

Although a letter of intent is not required, is not binding, and does
not enter into the review of subsequent applications, the information
that it contains allows NIAMS and NIA staff to estimate the potential
review workload and to avoid conflict of interest in the review.

The letter of intent is to be sent to:

Dr. Tommy Broadwater
Extramural Program
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Natcher Building, Room 5AS-25E
45 Center Drive MSC 6500
Bethesda, MD  20892-6500
Telephone:  (301) 594-9979 (until 11/18/94) (301) 594-4952 (after
FAX:  (301) 480-4543


The research grant application form PHS 398 (rev. 9/91) is to be used
in applying for these grants.  These forms are available at most
institutional offices of sponsored research; from the Office of
Grants Information, Division of Research Grants, National Institutes
of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892,
telephone 301/710-0267; and from the NIH program administrator listed

The RFA label available in the PHS 398 (rev. 9/91) application form
must be affixed to the bottom of the face page of the application.
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 (New Horizons in
Osteoarthritis Research) and number must be typed on line 2a of the
face page of the application form and the YES box must be marked.

Applications for the FIRST Award (R29) must include at least three
sealed letters of reference attached to the face page of the original
application.  FIRST Award (R29) applications submitted without the
required number of reference letters will be considered incomplete
and will be returned without review.

Submit a signed, typewritten original of the applications, including
a cover letter (if appropriate), the checklist, and three signed,
photocopies, in one package (including IRPGs whether or not the
applications arise from the same institution) to:

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

At the time of submission, two additional copies of the application
must also be sent to Dr. Tommy Broadwater at the address listed under

Applications must be received by February 21, 1995.  If an
application is received after that date, it will be returned to the
applicant without review.  The Division of Research Grants (DRG) 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 DRG 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.


Upon receipt, applications will be reviewed for completeness by DRG
and responsiveness by the NIAMS and NIA.  Incomplete applications
will be returned to the applicant without further consideration.  If
the application is not responsive to the RFA, NIAMS staff will
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, a process (triage) may be used
by the initial review group in which applications will be determined
to be competitive or non-competitive based on their scientific merit
relative to other applications received in response to the RFA.
Applications judged to be competitive will be discussed and assigned
a priority score.  Applications determined to be non-competitive will
be withdrawn from further consideration and the Principal
Investigator and the official signing for the applicant organization
will be notified.

Review criteria for this RFA are generally the same as those for
unsolicited research grant applications:

o  extent to which the proposed research addresses the goals of the

o  scientific, technical, or medical significance and originality of
proposed research;

o  appropriateness and adequacy of the experimental approach and
methodology proposed to carry out the research;

o  qualifications and research experience of the Principal
Investigator and staff, particularly, but not exclusively, in the
area of the proposed research;

o  availability of the resources necessary to perform the research;

o  adequacy of the mechanisms for quality control, study monitoring,
data management and reporting and data analysis;

o  appropriateness of the proposed budget and duration in relation to
the proposed research;

o  In the case of human tissue samples, adequacy of plans to include
both genders and minorities and their subgroups as appropriate for
the scientific goals of the research.

o  Adequacy of plans to include both genders andm inorities and their
subgroups as appropriate for the scientific goals of the research.
Plans for the recruitment and retention of subjects will also be

The initial review group will also examine the provisions for the
protection of human and animal subjects and the safety of the
research environment.

When appropriate, the special value of the cooperative and
interactive nature of the individual research applications and
applicants comprising an IRPG should be emphasized in each
application, under Section 7 of form PHS 398.


The anticipated date of award is September 30, 1995.

Applications will compete for available funds with all other
applications responsive to this RFA.  The following items will be
considered in making funding decisions:

o  quality of the proposed program project grants as determined by
peer review;
o  availability of funds; and
o  programmatic priorities.


Inquiries concerning this RFA are encouraged.  The opportunity to
clarify any issues or questions from potential applicants is welcome.

Direct inquiries regarding programmatic issues to:

Dr. Stephen L. Gordon
Musculoskeletal Diseases Branch
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Natcher Building, Room 5AS-251
45 Center Dr MSC 6500
Bethesda, MD  20892-6500
Telephone:  (301) 594-9951 (until 11/18/94) (301) 594-4977 (after
FAX:  (301) 480-4543

Dr. David Finkelstein
Biology of Aging Program
National Institute on Aging
Gateway Building, Suite 2C231
7201 Wisconsin Avenue
Bethesda, MD  20892
Telephone:  (301) 496-6402
FAX:  (301) 402-0010
Email:  FD6@CU.NIH.GOV

Direct inquiries regarding fiscal matters to:

Ms. Diane M. Watson
Grants Management Branch
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Natcher Building, Room 5AS-53
45 Center Dr MSC 6500
Bethesda, MD  20892-6500
Telephone:  (301) 594-9965 (until 11/18/94) (301) 594-3505 (after
FAX: (301) 480-5450

Mr. Robert Pike
Grants and Contracts Management Office
National Institute on Aging
Gateway Building, Suite 2N212
Bethesda, MD  20892
Telephone:  (301) 496-1472
FAX:  (301) 402-3672


This program is described in the Catalog of Federal Domestic
Assistance Nos. 93.846, 93.847, and 93.866.  Awards will be made
under the authority of the Public Health Service Act, Title III,
Section 301 (Public Law 410, 78th Congress, as amended, 42 USC 241
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 Public Health Service (PHS) strongly encourages all grant
recipients to provide a smoke-free workplace and promote the non-use
of all tobacco products.  This is consistent with the PHS mission to
protect and advance the physical and mental health of the American


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