From: kristoff@NET.BIO.NET (Dave Kristofferson)
Newsgroups: bionet.sci-resources
Subject: NIH Guide, vol. 22, no. 1, pt. 8, 8 January 1993
Date: 8 Jan 93 03:14:35 GMT
Distribution: bionet


$$XID RFA AR93005 AR-93-005 P1O1 ***************************************

RESEARCH ON CAUSAL MECHANISMS IN SYSTEMIC LUPUS ERYTHEMATOSUS

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

RFA:  AR-93-005

P.T. 34; K.W. 0715015, 0755030, 1002008, 1002019, 0710070

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 (NIAMS) and the National Institute of Allergy and Infectious
Diseases (NIAID) invite applications focused on the mechanisms and
causes of tissue injury in systemic lupus erythematosus (SLE).  The
goals of the research are to identify and analyze the factors and
mechanisms of tissue injury not only in the kidneys but in the brain
and other organs, using advanced molecular, genetic, and
immunological approaches; to develop new experimental systems to
study and test the pathogenicity of human autoantibodies and
autoreactive cells related to lupus; to elucidate the genetic factors
important in the development of the illness; and to characterize the
mechanisms involved in induction or exacerbation of disease by
environmental factors.

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), Research on Causal Mechanisms in Systemic
Lupus Erythematosus, 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.  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, 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

Up to $1,925,000 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 seven to ten 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

Systemic lupus erythematosus (SLE) is an acute and chronic illness
predominantly affecting young women, and affecting Afro-Americans
disproportionately to Americans of European descent.  This illness is
characterized by a wide array of humoral and cellular immunological
abnormalities involving both up-regulation and down-regulation of
critical elements of the immune system.  The order in which
components of immunological dysregulation occur, i.e., which is a
primary and which is secondary event, is not well understood.  In
some cases, the defective immune responses may be genetically
determined.  The occurrence of SLE is clearly related to the
inheritance of a specific HLA types and C4 complement types, but not
all persons with the characteristic genetic background are affected.
To the contrary, identical twins discordant for disease are regularly
seen, suggesting that environmental factors contribute to the
disease.  Whether these external factors induce the initial
occurrence of the disease or are responsible for subsequent flares of
the illness is unknown.

An immunological model of the illness has dominated thinking for the
past several decades.  This model invokes the occurrence of
autoantibodies (primarily to double-stranded DNA), the formation of
immune complexes consisting of these antibodies and their antigens,
the deposition of these complexes in vulnerable areas, such as the
glomerular basement membrane, inducing complement-dependent tissue
injury.  This model has not satisfactorily explained many forms of
injury seen in patients with lupus, including neurological and
cardiac pathology and coagulation abnormalities.  Other forms of
tissue injury have occasionally been identified.  These latter forms
include the activities of cytotoxic antibodies, pathological
regulation of a variety of cytokines, coagulation abnormalities
leading to non-inflammatory vascular occlusion, and other phenomena.
It is the purpose of this RFA to explore these additional causes.

The RFA requests individual research projects (R01 and R29) that
focus on questions relevant to defining the causes of the disease and
mechanisms of tissue injury in SLE.  Appropriate research areas
include, but are not limited to:

o  Design and use of new experimental systems to dissect the events
leading to immune dysregulation in human lupus and analysis of their
relative contribution to predisposition, onset and severity of
disease.

o  Development of new experimental systems of human lupus to study
pathogenicity of autoantibodies, autoreactive, accessory and
regulatory cells and factors.

o  Analysis of the fine molecular characteristics and mechanisms
involved in tissue damage by immune complexes, including new systems
to test for pathogenicity of human autoantibodies and immune
complexes.

o  Studies of immune and non-immune mechanisms involved in cardiac
and neurological pathology including development and use of new
experimental models of these manifestations in human lupus.

o  Studies of the molecular basis for specificity and pathogenicity
of cytotoxic antibodies with emphasis on the identification of
critical sites and/or activities involved in tissue injury.

o  Characterization of the genetic and molecular mechanisms involved
in cytokine dysregulation in lupus and elucidation of the mechanisms
by which cytokine dysregulation leads to tissue injury and clinical
disease.

o  Identification and characterization of the molecular components
and mechanisms that initiate vascular injury in lupus.

o  New approaches to study coagulation abnormalities including
antiphospholipid antibody and the mechanisms leading to
noninflammatory vascular occlusion and other phenomena of the
antiphospholipid antibody syndrome.

o  Studies on the molecular mechanisms involved in induction and
exacerbation of disease caused by environmental factors.

o  Studies on the environmental factors that may induce the illness
or its exacerbation.

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 asses s 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 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 statement, "submitted in response to AR-93-005,
RESEARCH ON CAUSAL MECHANISMS IN SYSTEMIC LUPUS ERYTHEMATOSUS".

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 and NIAID 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, RESEARCH ON CAUSAL
MECHANISMS IN SYSTEMIC LUPUS ERYTHEMATOSUS AR-93-005, must be typed
on line 2a of the face page of the application form and the YES box
should be checked.

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.  The National Institute of Environmental
Health Sciences has primary interest in toxicological influences of
the immune system. Applications of this description may be referred
to that Institute.

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 Branch
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 DK9315 DK-93-15 P1O1 *****************************************

PATHOGENESIS OF INFLAMMATORY BOWEL DISEASE AND CELIAC DISEASE

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

RFA:  DK-93-15

P.T. 34; K.W. 0715085, 0710070, 1002019, 1002004, 1002008, 0785055

National Institute of Diabetes and Digestive and Kidney Diseases

Letter of Intent Receipt Date: March 24, 1993
Application Receipt Date:      April 21, 1993

PURPOSE

This Request for Applications (RFA) invites new as well as
experienced investigators working in the areas of gastroenterology,
epidemiology, immunology, physiology, molecular and cell biology and
genetics to submit research project grant applications in the area of
autoimmune gastrointestinal diseases including ulcerative colitis,
Crohn's disease and celiac disease. Applications are encouraged from
any interested investigators regardless of their prior record of
grant support.

HEALTHY PEOPLE 2000

The NIH 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, Pathogenesis of
Inflammatory Bowel Disease and Celiac Disease, 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, D.C.  20402-9325 (telephone
202-783-3238).

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic and foreign, non-profit and
for-profit organizations, whether public or private, such as
universities, colleges, hospitals, laboratories, units of State or
local governments, and eligible agencies of the Federal Government.
Among a team of applicants, one institution must be proposed as the
lead organization to serve as the Grantee Institution and assume
responsibility for the fiscal and programmatic conduct of this
project.  Other members of the team should be proposed based on
individual consortium agreements (subcontracts).  The grantee
organization and any proposed consortium must have the staff and
facilities required for the proposed program. Applications from
minority individuals and women are encouraged.

MECHANISM OF SUPPORT

The support mechanisms for this research will be the individual
research grant (R01) and the First Independent Research Support and
Transition (First) Award (R29). This is a one-time solicitation.
Subsequent unsolicited competing continuation applications will
compete with all investigator-initiated applications and will be
reviewed according to customary peer review procedures.   This RFA
will provide the opportunity for investigators to establish support
for periods up to five years for meritorious research projects
designed to investigate the cause, natural history and treatment of
Inflammatory Bowel Disease and celiac disease.

This RFA is intended to support primarily new applications; however,
applications for continuation of currently funded projects will be
considered if they meet the objectives of this RFA.  R01 awards are
expected to average approximately $200,000 per year in total costs.
Note: Foreign institutions are not eligible for FIRST awards.

FUNDS AVAILABLE

The NIDDK plans to support approximately 10 to 12 applications
submitted in response to this solicitation.  Total costs of $2
million (direct and indirect costs)  for this program have been
included in the financial plans for fiscal year 1993.  The number of
awards to be made is dependent upon receipt of a sufficient number of
applications of high scientific merit and upon availability of funds.

Applicants for an R01 award must limit their request to not more than
$160,000 direct costs for the initial budget period, and normal
biomedical inflation increments in future years will be allowed.
Applicants for FIRST awards must limit their requests to $350,000
total direct costs across 5 years.  Although this program is provided
for 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.

RESEARCH OBJECTIVES

Background

Inflammatory Bowel Disease (IBD) is a general term given to two
diseases, ulcerative colitis and Crohn's disease, that together are
major causes of morbidity and mortality from gastrointestinal
disorders. It is estimated that 2 million Americans are affected by
IBD, many of them in the younger age groups.  Ulcerative colitis and
Crohn's disease have many similar clinical and pathological features
and are considered to be autoimmune in etiology. However, the
pathogenesis of IBD is complex and not well understood.  Ulcerative
colitis and Crohn's disease appear to be the result of a combination
of factors including genetic predisposition, alterations in the
mucosal immune system and exposure to unknown, triggering exogenous
factors, such as intestinal microbes, toxins, food substances or
drugs. As for most autoimmune diseases, the specific etiology and
pathogenesis of both ulcerative colitis and Crohn's disease remain
unclear. Current therapies for IBD are helpful in ameliorating the
symptoms and complications of these diseases but are, in general,
unsatisfactory and do not provide a specific cure or prevent or alter
the eventual natural history of disease in the majority of patients.

Celiac disease, also known as non-tropical sprue and gluten-sensitive
enteropathy, is another mucosal disease of the gastrointestinal tract
that is believed to be autoimmune in etiology.  Celiac disease
affects approximately a quarter million Americans and usually
presents with clinical symptoms during infancy or childhood. Celiac
disease is triggered by ingestion of gluten products from wheat, rye,
barley and possibly oats, but it also has a major genetic component.
Nevertheless, the primary pathogenesis of celiac disease remains
obscure.  It is not clear how gluten interacts with the intestinal
mucosa and induces injury, what components of gluten are responsible
for the injury, what genetic defect(s) or abnormal gene(s) predispose
to the disorder, or what other exogenous exposures induce this
condition.  Celiac disease represents a paradigm for autoimmunity and
autoimmune diseases in requiring a genetic background, immunologic
disturbance and exogenous exposure (gluten) for its expression.  At
present, the clinical features of celiac disease can be resolved by
avoidance of gluten in the diet. However, the dietary restrictions
for treatment of celiac disease are challenging and require life-long
adherence. Furthermore, there remains an increased incidence of
gastrointestinal lymphoma among patients with celiac disease.

The NIDDK believes that an intensified research effort into defining
the pathogenesis of IBD and celiac disease will help in the
prevention and therapy of these important gastrointestinal diseases.
The NIDDK encourages collaborative research among the multiple
disciplines of gastroenterology, immunology, epidemiology,
physiology, molecular, structural and cell biology and genetics to
help elucidate the etiology and pathogenesis of IBD and celiac
disease. The NIDDK especially encourages new investigators from
different fields of research to apply cutting edge research
technology and innovative approaches to the understanding of these
autoimmune gastrointestinal diseases. Institutions that have
demonstrated experience in both clinical and basic science research
will be considered most favorably for support.   Applications should
be directed at the information needed to fill gaps in our knowledge
concerning the etiology of ulcerative colitis, Crohn's disease and
celiac disease.

Examples of possible topics relevant to this RFA include:

o  the role of the mucosal immune system and its immunoregulation in
gastrointestinal inflammation characteristic of IBD and celiac
disease;

o  the role and status of inflammatory mediators, the cytokine system
and adhesion molecules in IBD and celiac disease;

o  the nature of the autoimmune reactions characteristic of IBD and
celiac disease including definition of the autoantigens and the fine
specificity of autoantibodies that are detected in patients with IBD
and celiac disease;

o  genetic markers and specific gene products associated with IBD and
celiac disease and in particular the molecular genetics of the major
histocompatibility complex in these disorders;

o  epithelial cell biology and its disturbance in gastrointestinal
inflammation characteristic of IBD and celiac disease;

o  the role of luminal bacterial flora and viral infections in IBD
and celiac disease; and

o  the epidemiology of IBD and celiac disease with particular
attention to special populations and risk factors for development of
these diseases as well as their complications such as sclerosing
cholangitis in ulcerative colitis and lymphoma in celiac disease.

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.  In such a case, a letter of agreement from
either the GCRC program director or Principal Investigator could be
included with the application.

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 disproportionally 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).

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 without review.  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 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
is being 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 NIDDK staff to estimate
the potential review workload and to avoid possible conflict of
interest in the review.  The letter of intent is to be sent by
February 26, 1993 to:

Robert Hammond, Ph.D.
Chief, Review Branch
National Institute of Diabetes and Digestive and Kidney Diseases
Westwood Building, Room 605
Bethesda, MD  20892
Telephone:  (301) 496-7083
FAX:  (301) 402-1277

APPLICATION PROCEDURES

The research grant application form PHS-398 (revised 9/91) must be
used in applying for these grants.  The form is available from most
institutional business offices or from the Office of Grants
Inquiries, Division of Research Grants, National Institutes of
Health, 5333 Westbard Avenue, Room 449, Bethesda, Maryland 20892;
(301) 496-7441.  Information describing the FIRST Award grant may
also be obtained from these sources.  The RFA label available in the
9/91 revision of PHS 398 application form must be affixed to the
bottom of the face page.  Failure to use this label could result in
delayed processing of your 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
Westwood Building, Room 240
National Institutes of Health
Bethesda, MD 20892

At the time of submission, two additional copies of the application
should also be sent under separate cover to Dr. Robert Hammond, at
the address shown above.

Applications must be received by April 21, 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 (or R29) 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.

For investigators applying for support through the FIRST award
mechanisms (R29), three letters of references must be submitted with
the application.  An applicant submitting a revised application in
response to this RFA must again submit reference letters.  Note:
Foreign institutions are inelgible for the R29 award.

REVIEW CONSIDERATIONS

Upon receipt, applications will be initially reviewed by the Division
of Research Grants (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, NIDDK staff will contact
the applicant to determine whether it should be returned to the
applicant, or whether it should be held until the next regular
receipt date and reviewed in competition with all other research
project 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.  In
cases where 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 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 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

The anticipated date of award is September 30, 1993.  Applications
will compete for available funds with all other recommended
applications submitted in response to this RFA.  The following will
be considered in making funding decisions:  Quality of the proposed
projects as determined by peer review, availability of funds, and
program balance and scientific interrelationships among the proposed
projects.

INQUIRIES

Written and telephone inquiries concerning this RFA are encouraged.
Inquiries regarding programmatic issues should be directed to:

Frank A. Hamilton, M.D., MPH
Mucosal and Immunology Program Director, NIDDK
Westwood Bldg, Room 3A16
National Institutes of Health
Bethesda, MD 20892            / Tel. 301 496-7821

Inquiries regarding fiscal matters should be directed to:

Mrs. Thelma Jones
Grants Management Specialist, NIDDK
Westwood Building, Room 649C
National Institutes of Health
Bethesda, MD  20892          / Telephone:  (301) 496-7467

SCHEDULE: Letter of Intent: February 26, 1993
Application Receipt:        April 21, 1993
Initial Review:             June/July 1993
Second Level Review:        September 1993
Anticipated Award:          September 30, 1993

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic
Assistance No. 93.848.  Awards are 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.