From: kristoff@NET.BIO.NET (Dave Kristofferson)
Newsgroups: bionet.sci-resources
Subject: NIH Guide, vol. 22, no. 1, pt. 5, 8 January 1993
Date: 8 Jan 93 03:08:59 GMT
Distribution: bionet


$$XID RFA AR93006 AR-93-006 P1O1 ***************************************

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; K.W. 0715015, 1002004, 1002008, 0785055, 0760002

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.


$$XID RFA AR93004 AR-93-004 P1O1 ***************************************

MYCOPLASMA AND OTHER INFECTIOUS AGENTS AS A CAUSE FOR RHEUMATIC
DISEASES

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

RFA:  AR-93-004

P.T. 34; K.W. 0715170, 0715103, 0715125, 0715015, 0715126

National Institute of Arthritis and Musculoskeletal and Skin Diseases
National Institute of Allergy and Infectious 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 (NIAID) and the National Institute of Allergy and Infectious
Diseases (NIAID) invite applications for research aimed at studying
the possible causal relationship between mycoplasma and other
infections and the chronic systemic rheumatic diseases.  The goal of
the Request for Applications (RFA) is to investigate whether any of
the chronic inflammatory rheumatic diseases might be caused by
infection, and if so, which infection and by what mechanisms.

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,
Mycoplasma and Other Infectious Agents as a Cause for Rheumatic
Diseases, 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 mechanism 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.  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

Up to $925,000 for the first-year and additional approved expenses
for up to five years has been committed to fund applications
submitted in response to this RFA.  The NIAMS and the NIAID plan to
make approximately three to four and one to two awards, respectively,
in FY 1993, contingent upon receipt of highly meritorious
applications.  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.

RESEARCH OBJECTIVES

The chronic systemic rheumatic illnesses constitute an important
burden for the United States.  They disproportionately affect women
and minority populations.  These illnesses include rheumatoid
arthritis, which is estimated to affect up to two percent of all
Americans, systemic lupus erythematosus, juvenile arthritis, and
ankylosing spondylitis and Reiter's syndrome.  These illnesses share
characteristic immunologic abnormalities; pathologically they
demonstrate sterile inflammation, i.e., inflammation in which no
infectious agent has been consistently identified.  Nonetheless,
based on both anatomic pathology and on clinical characteristics,
suspicion remains that infectious agents including mycoplasma may
play an important role in the development of these illnesses.

In the recent past, several systemic rheumatic diseases have been
demonstrated to be associated with infection, though the precise
relationship between infection and the rheumatic illness is not yet
known.  The associations include that of hepatitis B infection with
systemic necrotizing vasculitis (polyarteritis nodosa), hepatitis C
infection with IgG-IgM cryoglobulinemia, and the documentation that
an epidemic form of arthritis, primarily in children, is caused by
infection with a previously unidentified spirochete Borrelia
burgdorferi.  Such findings have given impetus to the concept that
infection can, in fact, trigger rheumatic illness.  Mycoplasma has on
occasion been suspected to be a trigger, but this hypothesis remains
controversial. Autoantibodies frequently found in patients with
rheumatic illness parallel antibodies that occur in a variety of
infectious illnesses.  The identification of potential microbial
triggering agents for the reactive arthritis and for the
spondyloarthropathies and a demonstration of the potential molecular
relationships between the HLA B27 histocompatibility antigen and
certain enteric pathogens gives further support to the hypothesis
that infection triggers rheumatic diseases.

The identification of pathogenic organisms, or description of the
relationship between acute or persistent infections and chronic
rheumatic illness, will lead to dramatic changes in current concepts
of therapy and may lead as well to effective preventive measures.
This RFA, therefore, seeks research projects that will advance
knowledge in this field.

Appropriate research areas may include, but are not limited to:

o  Identification of the role of and mechanisms used by pathogenic
organisms such as mycoplasma in the induction and maintenance of
self-reactivity and immune dysregulation in rheumatic diseases.

o  Studies on the effects of infection on self antigen processing and
presentation, inflammatory cytokine and antibody production, and
function of regulatory cells in human and experimental systems of
rheumatic diseases, with emphasis on the mechanisms and molecular
events mediating those effects.

o  Analysis of the relative contribution of the organism life cycle,
products, components and the elicited host responses to the induction
and maintenance of self-reactivity, immune dysregulation and tissue
damage in rheumatic diseases.

o  Studies on the mechanisms involved in changes in the local
environment induced by the pathogenic organisms and their products
that lead to immune self-reactivity and tissue injury.

o  Development of new animal models of human chronic rheumatic
diseases to establish the role of infectious agents in the etiology
and pathogenesis of disease and to serve as models for therapeutic
intervention.

o  Studies of the molecular basis for observed associations of HLA
haplotypes and infection in rheumatic diseases and design of
molecular approaches to manipulate this interaction to affect disease
outcome.

o  Pilot studies of new forms of prevention and treatment of
rheumatic diseases using anti-microbial agents to demonstrate
feasibility for possible multicenter clinical trials.

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, the RFA title and
number 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 or the National Allergy and Infectious
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

Dr. Howard Dickler
Chief, Clinical Immunology Branch
Division of Allergy, Immunology, and Transplantation
National Institute of Allergy and Infectious Diseases
Solar Building, Room 4A10
Bethesda, MD  20892
Telephone:  (301) 496-7104
FAX:  (301) 402-2571

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 and No. 93.855, Allergy, Immunology and Transplantation
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.


$$XID RFA DK9314 DK-93-14 P1O1 *****************************************

INNOVATIVE APPROACHES TO THE STUDY OF INTERSTITIAL CYSTITIS

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

RFA:  DK-93-14

P.T. 34; K.W. 0705075, 0755020, 0760003

National Institute of Diabetes and Digestive and Kidney Diseases

Letter of Intent Receipt Date:  February 25, 1993
Application Receipt Date:  March 25, 1993

PURPOSE

The Division of Kidney, Urologic, and Hematologic Diseases (DKUHD) of
the National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK) is soliciting grant applications for support of studies
focused on the study of interstitial cystitis, a disorder of the
bladder also known as the painful bladder syndrome.

The NIDDK is committed to increasing research into the urologic
disorders that affect women's health.  This request is part of the
initiative to promote research in all areas of women's urologic
health.

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 Request
for Applications (RFA), Innovative Approaches to the Study of
Interstitial Cystitis, is related to the priority area of diabetes
and 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 as principal
investigators.

MECHANISM OF SUPPORT

Support of this program will be through the NIH research project
grant (R01).  Responsibility for the planning, direction, and
execution of the proposed project will be solely that of the
applicant.  Awards will be administered under PHS grants policy as
stated in the PHS Grants Policy Statement.

This RFA is a one-time solicitation.  Generally, future unsolicited
competing continuation applications will compete with all
investigator-initiated applications and be reviewed according to the
customary peer review procedures.  The total requested project period
for applications submitted in response to this RFA may not exceed
five years.  The earliest possible award date will be September 30,
1993.  Applicants must limit their requests to not more than $100,000
direct costs for the initial budget period.

FUNDS AVAILABLE

For FY 1993, $1,500,000 will be committed by the NIDDK to fund
applications submitted in response to this RFA.  It is anticipated
that 10 to 12 awards will be made.  However, this funding level is
dependent upon the receipt of a sufficient number of applications of
high scientific merit.   Although this program is provided for in the
financial plans of the NIDDK, the award of grants pursuant to this
RFA is also contingent upon the availability of funds for this
purpose.

Awards made from this RFA will be for the support of new projects.

RESEARCH OBJECTIVES

Interstitial Cystitis (IC) is a chronic, painful and variably
incapacitating disorder that manifests a symptom complex consisting
of pain in the region of the urinary bladder and associated pelvic
musculature and variable motor and sensory dysfunctions of the
urinary bladder.

The purpose of this RFA is to solicit applications that propose
unique, innovative approaches to the study of interstitial cystitis
from investigators who are not currently being funded by the NIDDK
for research on interstitial cystitis.   It is not the intent to fund
research in areas that are currently being supported by the NIDDK.
Applications may be submitted for both non-human basic research and
human clinical research studies.  Examples of areas that could be
studied include:

o  the role of the pelvic floor musculature and innervation in
chronic bladder pain;

o  animal models of interstitial cystitis such as the feline urethral
syndrome;

o  the relationship between bladder endothelins and the symptoms of
interstitial cystitis;

o  release of urinary histamine as a marker for interstitial
cystitis;

o  the relationship between reflex sympathetic dystrophy and the
symptoms associated with interstitial cystitis;

o  the relationship between endometriosis and interstitial cystitis;
and

o  similarities between chronic abacterial prostatitis and
interstitial cystitis.

This list is not all inclusive and is meant solely to stimulate
interest for unique, innovative proposals for research in
interstitial cystitis from diverse investigators.  Program project
grant applications (P01) are not suited to this announcement.

Since this request is for unique, innovative studies, it is
understood that there may be limited preliminary data to support the
application.  In those cases, the applicant may wish to designate the
proposal as a pilot project and reduce the number of requested
project years, budget and scope of the project to that which is
necessary for obtaining adequate data for a more extensive,
full-scale project.

SPECIAL REQUIREMENTS

Applicants who receive an award through this announcement are
encouraged to attend a yearly meeting (convened by the NIDDK) of
investigators to discuss progress and exchange research information.
Funds to support the travel to these meetings may be included in the
proposed budget.

In order to ensure that patient selection for clinical studies is
uniform, the NIDDK has established Diagnostic Criteria for research
studies on IC.  All grant applications that use human subjects must
state that the NIDDK IC diagnostic criteria will be applied to
patients selected for inclusion in the research study.  The NIDDK
research criteria have been published in: the Journal of Urology
142(1): 139, 1989 and the American Journal of Kidney Diseases 8(4)
353, 1989.  They may also be obtained from the program staff listed
under INQUIRIES.  This requirement does not preclude using subjects
who do not meet the criteria for comparison studies, but those who
meet the criteria must be specifically identified and designated as a
study group.

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 Item 4 (Research Design and Methods) of the Research
Plan AND summarized in Item 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.

If the required information is not contained within the application,
the application will be returned without review.

Peer reviewers will address specifically whether the research plan in
the application conforms to these policies.  If the representation of
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 requested, but not required, to submit a
letter of intent to apply to the RFA.  This letter should include the
name, telephone number, and mailing address of the Principal
Investigator, the names of other key personnel, and the name of the
applicant institution, and the number and title of this RFA.  Such a
letter of intent is not binding and it will not enter into the review
of any application subsequently submitted, nor is it a necessary
requirement for application.  Letters of intent are requested solely
for planning purposes.  The NIDDK staff will not provide responses to
such letters.  Letters of intent must be received no later than
February 25, 1993 and must be addressed to:

Dr. Robert Hammond
Chief, Review Branch
National Institute of Diabetes and Digestive and Kidney Diseases
Westwood Building, Room 605
Bethesda, MD  20892

APPLICATION PROCEDURES

The research grant application form PHS 398 (rev. 9/91) is to be used
in applying for these grants.  The form is available from most
institutional offices of sponsored research and from the Office of
Grants Inquiries, Division of Research Grants, National Institutes of
Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone
(301) 496-7441.

For developing programs that deal with clinical populations,
applicants may wish to consider utilization of General Clinical
Research Center (GCRC) facilities.  More information on the GCRC
program is available from Dr. Judith Vaitukaitis at the National
Center for Research Resources, telephone: (301) 496-6595.

The RFA label available in the application form must be affixed to
the bottom of the face page.  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 check the YES box.

Submit a signed, typewritten original of the application, including
the Checklist, and three signed, exact photocopies, 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 copies of the application must
also be sent under separate cover to:

Robert Hammond, Ph.D.
Chief, Review Branch
National Institute of Diabetes and Digestive and Kidney Diseases
Westwood Building, Room 605
Bethesda, MD  20892

Applications must be received by March 25, 1993.  If an application
is received after that date, it will be returned to the applicant.
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.  However, it is allowable to submit the same
project as both an R01 and as a component project of a program
project.  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 CONSIDERATIONS

Upon receipt, applications will be reviewed by the DRG for
completeness.  Incomplete applications will be returned to the
applicant without further consideration.  Evaluation for
responsiveness to the program requirements and criteria stated in the
RFA is an NIDDK staff function.  If the application is not responsive
to the RFA, the 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
applications.

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 NIDDK.
Applications may be subjected to triage by an NIDDK peer review group
to determine their scientific merit relative to other applications
received in response to this RFA.  If the number of applications 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 when they are not competitive for the award.
The NIDDK staff 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 this review, the applications will be given
a secondary review by the National Diabetes and Digestive and Kidney
Diseases Advisory Council unless not recommended for further
consideration by the initial review group.

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

o  scientific/technical merit criteria specific to the objectives of
the RFA;

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 resources necessary to perform the 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.

AWARD CRITERIA

Funding decisions will be made based on the initial review group and
national advisory council recommendations, program relevance and
availability of funds.

The anticipated date of award is September 30, 1993.

INQUIRIES

Written and telephone inquiries concerning this RFA are encouraged.
Direct inquiries regarding programmatic issues to:

Leroy M. Nyberg, Ph.D., M.D.
Director, Urology Program
Division of Kidney, Urologic, and Hematologic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
Westwood Building, Room 3A-05
Bethesda, MD  20892
Telephone:  (301) 496-7133

Inquiries regarding fiscal matters may be directed to:

Ms. Trude McCain
Grants Management Specialist
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
Westwood Building, Room 649
Bethesda, MD  20892
Telephone:  (301) 496-7467

Schedule

Letter of Intent Receipt Date:  February 25, 1993
Application Receipt Date:       March 25, 1993
Initial Review:                 June 1993
Second Level Review:            September, 13-14, 1993
Anticipated Date of Award:      September 30, 1993

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic
Assistance No. 93.849 (NIDDK).  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.