Full Text AR-93-006

SYSTEMIC LUPUS ERYTHEMATOSUS IN WOMEN AND MINORITIES

NIH GUIDE, Volume 22, Number 1, January 8, 1993

RFA:  AR-93-006

P.T. 34, FF, II

Keywords: 
  Autoimmunity 
  Biology, Cellular 
  Biology, Molecular 
  Epidemiology 
  Biochemical Markers 


National Institute of Arthritis and Musculoskeletal and Skin Diseases

Letter of Intent Receipt Date:  March 5, 1993
Application Receipt Date:  April 8, 1993

PURPOSE

The National Institute of Arthritis and Musculoskeletal and Skin
Diseases (NIAMS) invites applications for research projects aimed at
identifying the biological and social factors that contribute to the
disproportionate prevalence of systemic lupus erythematosus (SLE) in
women and minority populations.

The goal of this Request for Applications (RFA) is to promote
research that will improve our knowledge of the genetic, cellular,
molecular, and environmental elements that predispose to and initiate
immune responses that lead to tissue damage and clinical
manifestation of SLE.  These studies include the analysis of their
possible interaction and synergy, and the identification and
characterization of critical epidemiological, biological, and genetic
markers that may be used for diagnosis, prognosis or that may be
subject to manipulation as a means of affecting disease outcome in
women and minority patients.

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,
Systemic Lupus Erythematosus in Women and Minorities, is related to
the priority area of chronic disabling conditions.  Potential
applicants may obtain a copy of "Healthy People 2000" (Full Report:
Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report:
Stock No. 017-001-00473-1) through the Superintendent of Documents,
Government Printing Office, Washington, DC 20402-9325 (telephone
202-783-3238).

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic 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.
Minority individuals and women are encouraged to submit applications
as Principal Investigators.  Foreign institutions are not eligible
for First Independent Research Support and Transition (FIRST) (R29)
awards.

MECHANISM OF SUPPORT

The mechanisms of support for this RFA will be the National
Institutes of Health (NIH) research project grant (R01) and the FIRST
(R29) award.  Responsibility for the planning, direction, and
execution of the proposed research 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, 1993.  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 vary also.  In addition
to the requirements stated in this RFA, awards will be administered
under PHS grants policy as stated in the Public Health Service Grants
Policy Statement, DHHS Publication No. (OASH) 90-50-000, revised
October 1, 1991.  This RFA is a one-time solicitation.  Future
unsolicited competing continuation applications will compete with all
investigator-initiated applications and be reviewed according to the
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.

FUNDS AVAILABLE

The estimated funds (total costs) available for the first year of
support is $1.0 million.  Approximately four to six awards are
anticipated.  Funding will depend on receiving applications judged
highly meritorious by peer review.  The total project period for
these awards may not exceed five years.  However, this level of
support is dependent upon receipt of a sufficient number of
applications of high scientific merit.  Although this program is
provided for in the financial plans of the NIAMS, the award of a
grant pursuant to this RFA is also contingent upon the availability
of funds for this purpose.

RESEARCH OBJECTIVES

Systemic lupus erythematosus (SLE) is a serious acute and chronic
illness.  The disease disproportionately affects women primarily
between the ages of 15 and 45.  In the United States, women of
African descent are affected approximately three times as frequently
as are women of European descent.  Worldwide, similar sex ratios are
seen, and there have been unconfirmed suggestions that in the United
States persons of Hispanic, East Asian and Native American background
are affected more frequently than persons of European ancestry.

Although there are multiple genetic differences among different
ethnic and racial groups, no single genetic difference related to
susceptibility to systemic lupus erythematosus has been found.
Susceptibility to age of onset and disease severity are probably
linked to multiple genetic and environmental factors.  These factors
may vary among different populations defined by race and gender but
the data are still preliminary and incomplete.  Further, the effects
of socioeconomic status on disease susceptibility, response to
treatment and prognosis remain unknown.

Numerous investigations focusing on the hormonal events of female
puberty and child-bearing have provided clues but no definitive
answers.  These clues have led some clinicians strongly to advise
against the use of exogenous hormones (oral contraceptives and
estrogen replacement therapy) in persons with lupus, but there is no
clear documentation that this advice is appropriate.

The purpose of this RFA is to provide data that will answer some of
these questions and to promote the design and use of new approaches
to study this problem.  Appropriate research areas might include, but
are not limited to:

o  Studies elucidating the cellular, molecular and behavioral basis
for the observed differences in lupus prevalence between men and
women.

o  Studies to identify and characterize the genetic factors
associated with lupus in minority populations and the mechanisms by
which they contribute to predisposition, onset and severity of
disease.

o  Analysis of the molecular mechanisms involved in sex hormone
regulation and immune self reactivity and their role in the induction
and maintenance of disease.

o  Analysis of the contribution of non-hormonal gender factors to
disease predisposition and resistance.

o  Studies on the effects of oral contraceptives and estrogen
replacement therapies on immunological or clinical manifestations of
the disease, including corticosteroid-induced osteoporosis.

o  Identification and characterizations of the factors that influence
response to treatment by gender, ethnic group and socioeconomic
status.

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 should 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 must
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' population, including
minorities.

If the required information is not contained within the application,
the review will be deferred until the information is provided.

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 will be
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 March 5, 1993, 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 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 is helpful in planning for the review of
applications.  It allows NIAMS staff to estimate the potential review
workload and to avoid possible conflicts of interest in the review.

The letter of intent is to be sent to:

Dr. Tommy Broadwater
Chief, Review Branch, Extramural Program
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Westwood Building, Room 404
Bethesda, MD  20892
Telephone:  (301) 496-0754

APPLICATION PROCEDURE

The research grant application form PHS 398 (rev. 9/91) is to be used
in applying for these grants.  Application kits are available at most
institutional offices of sponsored research and may be obtained from
the Office of Grants Inquiries, Division of Research Grants, National
Institutes of Health, Westwood Building, Room 449, Bethesda, MD
20892, telephone 301/496-7441.

The RFA label available in the application kit must be affixed to the
bottom of the face page.  Failure to use the label could result in
delayed processing of the application such that it may not reach the
review committee in time for review.  In addition, "SYSTEMIC LUPUS
ERYTHEMATOSUS IN WOMEN AND MINORITIES, AR-93-006" must be typed on
line 2a of the face page of the application form and check the YES
box.

The completed and signed, typewritten original application and three
signed, exact, clear, single-sided photocopies must be sent or
delivered in one package to:

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

At time of submission, two additional exact copies of the application
must also be sent under separate cover to:

Dr. Tommy Broadwater
Chief, Review Branch, Extramural Program
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Westwood Building, Room 404
Bethesda, MD  20892

Applications must be received by April 8, 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 RFA that is essentially
the same as one currently pending initial review, unless the
applicant withdraws the pending application.  However, it is
allowable to submit the same project as both an R01 and as a
component project of a program project (P01).  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 previously reviewed. Such applications must
not only include an introduction addressing the previous critique but
also be responsive to this RFA.

REVIEW PROCEDURES

Upon receipt, applications will be reviewed by the DRG for
completeness.  Incomplete applications will be returned to the
applicants without further consideration.  Evaluation for
responsiveness to the program requirements and criteria stated in the
RFA is an NIAMS staff function.  If the application is not responsive
to the RFA, NIAMS staff will contact the applicant to determine
whether it should be returned to the applicant or held until the next
regular receipt date and reviewed in competition with all other
unsolicited applications.

Those applications that are complete and responsive will be evaluated
in accordance with the criteria stated below for scientific and
technical merit by an appropriate peer review group convened by the
NIAMS.  Applications may be subject to triage by an NIAMS peer review
group to determine scientific merit relative to other applications
received in response to this RFA.  If the number of applications
submitted is large compared to the number of awards to be made, a
preliminary scientific peer review may be conducted and applications
withdrawn from further competition if not competitive for the award.
The NIAMS will notify the applicant and institutional official of
this action.

Those applications judged to be competitive will be reviewed for
scientific and technical merit in accordance with the usual NIH peer
review procedures by an initial review group specifically convened
for this RFA.  Following initial review, applications will receive a
second level review by the National Arthritis and Musculoskeletal and
Skin Diseases Advisory Council unless not recommended for further
consideration by the initial review group.

Review criteria for RFAs are generally similar as those for
unsolicited investigator-initiated research grant applications and
include:

o  Scientific and technical merit criteria specific to the objectives
of the RFA;

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

o  Appropriateness and adequacy of the experimental approach and
methodology proposed to conduct 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 resources necessary to perform the proposed
research;

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

o  if an application involves activities that could have an adverse
effect upon humans, animals, or the environment, the adequacy of the
proposed means for protecting against or minimizing such effects.

In addition, for foreign applications, the following criterion
applies:

o  Uniqueness of research such that it can only be performed outside
of the United States.

Schedule

Letter of Intent Receipt Date:  March 5, 1993
Application Receipt Date:       April 8, 1993
Initial Review:                 June 1993
Second Level Review:            September 9, 1993
Anticipated Date of Award:      September 30, 1993

AWARD CRITERIA

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 project as determined by peer review;
o  Availability of funds; and
o  Program balance among research areas represented in this RFA.

The anticipated date of award is September 30, 1993.

INQUIRIES

Written and telephone inquiries regarding this RFA are encouraged.
The opportunity to clarify any issues or questions from potential
applicants is welcome.

Direct inquiries regarding programmatic issues to:

Dr. Susana A. Serrate-Sztein
Director, Arthritis Program
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Westwood Building, Room 405
Bethesda, MD  20892
Telephone:  (301) 402-3340

Direct inquiries regarding fiscal matters to:

Diane M. Watson
Chief, Grants Management Branch
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Westwood Building, Room 732A
Bethesda, MD  20892
Telephone:  (301) 402-3352

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic
Assistance No. 93.846, Arthritis, Musculoskeletal and Skin Diseases
Research.  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.

.

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