Full Text AR-94-004

BASIC RESEARCH ON FIBROMYALGIA

NIH GUIDE, Volume 22, Number 39, October 29, 1993

RFA:  AR-94-004

P.T. 34

Keywords: 
  Muscle Disorders 
  Pathogenesis 
  Biomedical Research, Multidiscipl 
  Biology, Cellular 
  Biology, Molecular 
  Neuroendocrinology 


National Institute of Arthritis and Musculoskeletal and Skin Diseases

Letter of Intent Receipt Date:  December 15, 1993
Application Receipt Date:  February 10, 1994

PURPOSE

The National Institute of Arthritis and Musculoskeletal and Skin
Diseases (NIAMS) invites applications for basic research on the
pathogenesis of fibromyalgia (FM).  The goal of the Request for
Applications (RFA) is to promote research that will improve our
understanding of the disease and will identify critical processes and
mediators of disease that could be used to establish a rational basis
for new and effective treatments.  Multidisciplinary approaches that
combine molecular and cellular biology techniques with
neuroendocrinology, immunology, and pharmacology research are
strongly encouraged.

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,
Basic Research on Fibromyalgia, is related to the priority area of
chronic disabling conditions.  Potential applicants may obtain a copy
of "Healthy People 2000" (Summary 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 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.
Applications from minority individuals and women are encouraged.
Foreign institutions are not eligible for First Independent Research
Support and Transition (FIRST) (R29) award.

MECHANISM OF SUPPORT

This RFA will use the National Institutes of Health (NIH) individual
research grant (R01), FIRST (R29) awards, and interactive research
project grants (IRPG) mechanisms.   IRPGs are further described in
the NIH Guide, Vol. 22, No. 16, April 23, 1993.  Responsibility for
the planning, direction, and execution of the proposed project will
be solely that of the applicant.  The total project period for
applications submitted in response to the present RFA may not exceed
five years.  The anticipated award date is September 30, 1994.
Because the nature and scope of the research proposed in response to
this RFA may vary, it is anticipated that the size of an award will
also vary.  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 resources 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.

FUNDS AVAILABLE

The estimated funds (total costs) available for the first year of
support for the entire program is 1.4 million dollars.  Funding is
contingent upon receipt of scientifically meritorious applications.
The NIAMS expects to fund five to seven new awards.

RESEARCH OBJECTIVES

Background

Fibromyalgia is a disorder characterized by widespread pain and
multiple, characteristic, tender points.  Fibromyalgia is associated
with sleep disturbances, particularly non-restorative sleep, morning
stiffness, aggravation by lower temperatures and amelioration by
exercise.  The precise frequency and natural history of fibromyalgia
are unknown, but the disorder may affect about two to three percent
of the population of the United States, and the majority of affected
individuals are women.  Fibromyalgia tends to overlap with a number
of disorders, including irritable bowel and bladder syndromes,
frequent headaches, and chronic fatigue syndrome.  In 1990, the
American College of Rheumatology published classification criteria
for fibromyalgia.  These criteria provide a uniform basis for
classifying the cases and will be invaluable in conducting research
in this area.

Although progress has been made in the identification and
differential diagnosis of the disease, the lack of knowledge about
the causes and mechanisms of the disease have limited the available
treatments to empirical therapies that afford only modest clinical
improvement.  Future progress in the treatment of fibromyalgia will
require greater and detailed understanding of the molecular
pathogenetic mechanisms.  The current status and future direction of
fibromyalgia research was the subject of a Workshop sponsored by the
National Institute of Arthritis and Musculoskeletal and Skin Diseases
held on May 19, 1993.  The Workshop brought together a group of
clinicians and scientists working in the field of fibromyalgia that
developed a comprehensive list of future research activities in
fibromyalgia.  A summary of this Workshop will be published in the
Journal of Musculoskeletal Pain.  Basic research on the pathogenesis
of fibromyalgia was identified as one critical area of future
emphasis and is the focus of the current solicitation.

The areas of research interest include, but are not limited to:

o  Development of in vivo or in vitro systems that will allow
analysis of biochemical and functional abnormalities observed in
fibromyalgia;

o  Family and genetic studies of fibromyalgia syndrome;

o  Mechanisms of neurohormonal dysregulation in fibromyalgia,
including alterations of the hypothalamic-pituitary-adrenal axis;

o  Elucidation of pathophysiological and neurochemical mechanisms
related to pain associated with fibromyalgia, including altered pain
threshold and the existence of localized tender points;

o  Studies on the mechanisms that mediate the relationship and
overlap between fibromyalgia, irritable bowel, chronic fatigue
syndrome and other chronic conditions;

o  Studies on the role of infections in the induction or aggravation
of fibromyalgia, the mechanisms of induction and the host factors
that predispose to development of symptoms;

o  Studies of sleep disturbances in fibromyalgia and their
relationship to neurochemical, endocrine, biochemical immune or
chronobiologic alterations to abnormalities of the neuroendocrine and
immune system in fibromyalgia.

This list is illustrative and not exclusive or restrictive.
Applications combining multidisciplinary approaches and applications
that include collaborations between investigators with expertise in
rheumatology and scientists with expertise in the disciplines of
pharmacology, biochemistry, cellular biology, endocrinology and
neurology are strongly encouraged.  The application of current
paradigms and technical approaches in those fields to the study of
fibromyalgia are also highly recommended.

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 NIH 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 must 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 must be addressed in developing a research
design and sample size appropriate for the scientific objectives of
the study.  This information must be included in the form PHS 398
(rev. 9/91) in Sections 1-4 of the Research Plan AND summarized in
Section 5, Human Subjects.  Applicants are urged to assess carefully
the feasibility of including the broadest possible representation of
minority groups.  However, NIH recognizes that it may not be feasible
or appropriate in all research projects to include representation of
the full array of United States racial/ethnic minority populations
(i.e., Native Americans [including American Indians or Alaskan
Natives], Asian/Pacific Islanders, Blacks, Hispanics).

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

For the purpose of this policy, clinical research 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.

For foreign awards, the policy on inclusion of women applies fully;
since the definition of minority differs in other countries, the
applicant must discuss the relevance of research involving foreign
population groups to the United States' populations, including
minorities.

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 AND the justification for the
selected study population is inadequate, it will be considered a
scientific weakness or deficiency in the study design and reflected
in assigning the priority score to the application.

All applications for clinical research submitted to NIH are required
to address these policies.  NIH funding components will not award
grants or cooperative agreements that do not comply with these
policies.

LETTER OF INTENT

Prospective applicants are asked to submit, by December 15, 1993, a
letter of intent that includes a 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 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 subsequent applications, the information
that it contains allows NIAMS 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. Susana A. S. Sztein at the
address listed under INQUIRIES.

APPLICATION PROCEDURES

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 301/435-0714.

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 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 (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 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 also be sent to:

Tommy Broadwater, Ph.D.
Review Branch
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Westwood Building, Room 406
Bethesda, MD  20892
Telephone:  (301) 594-9979
FAX:  (301) 594-9673

Applications must be received by February 10, 1993.  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 announcement 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.

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed for completeness by DRG
and responsiveness by the NIAMS staff.  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 may be triaged by an ICD peer review group on the basis
of relative competitiveness.  The NIH will withdraw from further
competition those applications judged to be non-competitive for award
and notify the applicant Principal Investigator and institutional
official.  Those applications judged to be competitive will undergo
further scientific merit review.  Those applications that are
complete and responsive will be evaluated in accordance with the
criteria stated below for scientific/technical merit by an
appropriate peer review group convened by the NIAMS.  The second
level of review will be provided by the National Arthritis and
Musculoskeletal and Skin Diseases Advisory Council.

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

o  scientific, technical, or clinical 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;

o  availability of the resources necessary to perform the research;

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

AWARD CRITERIA

The anticipated date of award is September 30, 1994.

Awards will be based upon the following criteria:

o  scientific merit
o  availability of funds
o  programmatic priorities of the funding ICD
o  responsiveness to the RFA

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 and address the letter
of intent to:

Susana A. S. Sztein, M.D.
Rheumatic Diseases Branch
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Westwood Building, Room 405
Bethesda, MD  20892
Telephone:  (301) 594-9953
FAX:  (301) 594-9673

Direct inquiries regarding fiscal matters to:

Mara DeKemper
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Westwood Building, Room 722
Bethesda, MD  20892
Telephone:  (301) 594-7508
FAX:  (301) 594-9950

Schedule

Letter of Intent Receipt Date:  December 15, 1993
Application Receipt Date:       February 10, 1993
Initial Review:                 June/July 1994
Second Level Review:            September 1994
Anticipated Award Date:         September 30, 1994

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic
Assistance No. 93.361,.  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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