Full Text DK-94-017


NIH GUIDE, Volume 23, Number 2, January 14, 1994

RFA: DK-94-017

P.T. 34

  Biomedical Research, Multidiscipl 
  Biology, Cellular 
  Biology, Molecular 

National Institute of Diabetes and Digestive and Kidney Diseases
National Institute of Allergy and Infectious Diseases

Letter of Intent Receipt Date:  June 16, 1994
Application Receipt Date:  July 14, 1994


The National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK), the National Institute of Allergy and Infectious Diseases
(NIAID), and the Juvenile Diabetes Foundation International (JDFI)
invite investigator- initiated program project grant applications.
These applications should incorporate an interdisciplinary research
approach: (1) to the development of innovative prevention and
treatment strategies for insulin-dependent diabetes mellitus (IDDM),
(2) to the etiology and pathogenesis of  IDDM and its complications,
and (3) to the genetic susceptibility for IDDM and the complications
of diabetes.  This solicitation is intended to stimulate the
application of advances in basic molecular biology, genetics,
immunology, cell biology, and biophysics to the study of IDDM and its

Applications will be submitted to the NIH and will be reviewed by NIH
according to usual NIH peer review procedures.  Applications judged
meritorious but not funded by the NIH may be considered by the JDFI
for funding.  Applicants wishing to have their application considered
by the JDFI must authorize the NIH to provide a copy of their
application and NIH-prepared summary statement of the initial review
to the JDFI.


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,
Diabetes Interdisciplinary Research Programs, 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


Applications may be submitted by domestic 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.


The mechanism of support will be the NIH program project grant (P01)
award.  A program project grant is for the support of a broadly-based
multidisciplinary or multifaceted research program that has a
specific major objective or central theme.  The award may support
research components and core functions.  Collectively, these
components should demonstrate essential elements of unity and
interdependence and result in a greater contribution to program goals
than if each activity were pursued individually.

Responsibility for the planning, direction, and execution of the
proposed project will be solely that of the principal investigator.
The current policies and requirements that govern the research grant
programs of the NIH or the JDFI will prevail depending on the funding
source.  Applicants should note that grants funded by the JDFI will
be subject to the indirect cost policy of JDFI.

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.  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 April 1, 1995.


For FY 1995, the NIDDK will commit $1.5 million and the NIAID will
commit $250,000 to fund applications submitted in response to this
RFA.  It is anticipated that two to three awards will be made by the
NIH.  The JDFI plans to make three awards.  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 and the NIAID, the
award of grants pursuant to this RFA is also contingent upon the
availability of funds for this purpose.

The maximum dollar request is limited to $750,000 in direct costs for
the initial budget period.  The maximum dollar request is limited to
$3.75 million in direct costs (approximately $5 million in total
costs) for the five-year budget period.


General Background

The National Diabetes Advisory Board (NDAB) in 1987 formulated a
National Long-Range Plan to Combat Diabetes. A number of significant
recommendations were made by the NDAB in this plan. One of these was
to establish Diabetes Interdisciplinary Research Programs (DIRPs) to
be supported by the NIH.  The DIRPs would promote the integration of
new research methodologies into diabetes research.  As a result of
establishing these programs, new as well as established scientists
with diabetes research commitments would be given the opportunity to
immerse themselves in new technologies at the cutting edge of modern

The NIDDK is coordinating efforts with the NIAID and the JDFI to
implement DIRPs in areas of research that appear particularly
relevant to the cure, prevention, and improved treatment of IDDM.
Toward this end, the JDFI has embarked on a major long-term capital
fund raising campaign targeted at establishing programs of excellence
in diabetes research.

Scientific Background

It has been established that IDDM is an autoimmune disease with major
genetic influences.  Much has been learned about the nature of the
immunologic process involved but many questions remain.  Informative
animal models of IDDM (i.e., BB/W rat and NOD mouse) continue to be a
central focus of research.  Specific genes in the HLA locus have been
associated with IDDM, but the molecular or genetic roles of these
genes or closely linked genes in the diabetic process have not been
clearly defined.

The Diabetes Control and Complications Trial has established the
crucial importance of metabolic control for preventing or delaying
the onset of diabetic complications. The present methods for
achieving metabolic control are arduous, expensive, and only
partially effective.  Innovative approaches for maintaining
euglycemia are essential.

There is a great deal of epidemiologic, clinical, and physiologic
information on the long-term microvascular, macrovascular, and
neurologic complications of diabetes.  There are also biochemical
theories of causation that have prompted research over the last
decade.  At this time, however, the molecular pathophysiology of
diabetic complications is still unclear.  Despite epidemiologic and
clinical evidence of genetic factors in the development of
complications, very little is known about the identity or function of
specific genes in these processes.

Recent advances in basic biomedical research have revolutionized our
ability to study complex diseases such as diabetes.  Further
application of the new capabilities of molecular biology, genetics,
immunology, cell biology, and biophysics to diabetes research are
essential.  Importantly, the increased utilization of these
technologies and approaches promises an improved understanding and
enhanced development of potential preventive and therapeutic

Scope and Objectives

It is the intention of the NIDDK, the NIAID and JDFI to further
stimulate the integration of the most current basic biomedical
research approaches into diabetes-related research.  It is expected
that this will be accomplished by bringing to the diabetes arena
those who are skilled in these approaches by the support of
meritorious, synergistic, multidisciplinary research program project
applications.  Applications should include the involvement of both
basic and applied scientists in collaborative endeavors.  The JDFI
will NOT consider studies aimed at primary prevention for this
particular RFA; however, such studies would be within the scope of
NIDDK/NIAID support (see list of examples below).

Research applications should be in the broad areas of IDDM or
molecular and genetic aspects of complications of the disease.
Relevant topics listed below are examples and should not be construed
as required or limiting.

o  Development of safe and effective techniques to maintain
euglycemia by biological or mechanical means, including investigation
of the metabolic performance and biocompatibility of the technique

o  Beta cell replacement therapies:  glucose sensors, implantable
pumps, and bio-artificial pancreas

o  Genetic manipulation of beta cells or surrogate cells to replace
physiologic insulin secretion capacity that has been destroyed in

o  Immunoalteration of beta cells/islets or the immune response in an
attempt to prevent autoimmune and graft- versus-host destruction of
beta cells/islets

o  Genetic regulation of beta cell differentiation and its role in

o  Molecular mechanisms of beta cell destruction in IDDM

o  Identification and characterization of targets for the autoimmune
process in IDDM

o  IDDM prevention strategies to identify high risk individuals and
prevent the clinical onset of disease, perhaps by induction of

o  Identification and functional characterization of genes for IDDM
and IDDM-susceptibility

o  Identification and functional characterization of genes
influencing the development of long-term complications of IDDM

o  Identification of basic molecular or cellular processes leading to
complications and interventions to prevent or halt the progression of
long-term complications of diabetes


Letter of Authorization

Applicants should submit a brief letter to the NIDDK indicating
whether or not they wish their application to be considered for
funding by the JDFI.  While applicants may request that their
applications be considered only by the NIH and not by the JDFI, it is
necessary that the record indicate the applicant's consideration of
this opportunity. For those applicants who wish to have the JDFI
consider their application, all materials relating to the application
will be promptly forwarded to that organization and the summary
statements for such applications will be shared with the JDFI when
available.  The NIDDK will provide no information to the JDFI related
to applications from applicants who request that the JDFI not
consider their application.  Letters of authorization should be
prepared by the principal investigator and co-signed by the official
signing for the applicant organization.  This letter may be combined
with the Letter of Intent (see below) or may be submitted as a cover
letter accompanying the application.

In all cases, the NIDDK and the NIAID will make its funding decisions
prior to those of the JDFI.

Periodic Meetings

Upon initiation of this program, the NIDDK, the NIAID and JDFI plan
to sponsor periodic meetings to encourage exchange of information
among investigators, to foster collaborative efforts among program
grantees, and to identify resources that would enhance the
productivity of grantees.  For this purpose, applicants should
request travel funds for a two-day meeting each year, probably to be
held in Bethesda, Maryland. Applicants should also include a
statement in their applications indicating their willingness to
participate in such meetings and to cooperate with other researchers
at other diabetes interdisciplinary research program sites.



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 that is 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/offerors
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, 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
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


Prospective applicants are asked to submit, by June 16, 1994, 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 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 to:

Dr. Robert D. Hammond
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
Westwood Building, Room 605
Bethesda, MD  20892
Telephone:  (301) 594-7515


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 Information, Division of Research Grants, National Institutes
of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892,
telephone 301/710-0267.

Applicants should request a copy of the publication entitled "NIDDK
Program Projects Grants:  Administrative Guidelines."  These
guidelines contain important additional information on the suggested
format of applications and on review criteria.  Prospective
applicants may obtain these guidelines from Dr. Robert D. Hammond.

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, "Diabetes Interdisciplinary Research
Programs," and number, DK-94-017, 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

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
should also be sent under separate cover to Dr. Robert D. Hammond.

Applications must be received by July 14, 1994.  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.

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 should be included
with the application.


Upon receipt, applications will be initially 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, NIDDK staff will contact the applicant to determine
whether it should be returned to the applicant or whether 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.  It
is not anticipated that site visits will be part of the review
process; therefore, each application should be complete in itself, as
if no visit is expected.  If the number of applications is large
compared to the number of awards to be made, a preliminary scientific
peer review (triage) may be conducted.  Applications may be withdrawn
from further competition if judged to be non-competitive.  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 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 NIDDK Advisory Council and the NIAID 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  synergy of subprojects to achieve the goals of the program

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.


Awards will be based upon the following criteria:

o  priority score
o  availability of funds
o  programmatic priorities of the funding Institute

The anticipated date of award is April 1, 1995.


Written and telephone inquiries concerning this RFA are encouraged.

Inquiries regarding programmatic issues should be directed

Joan T. Harmon, Ph.D.
Diabetes Research Section
National Institute of Diabetes and Digestive and Kidney Diseases
Westwood Building, Room 622
Bethesda, MD  20892
Telephone:  (301) 594-7565
FAX:  (301) 594-9011

Elaine Collier, M.D.
Autoimmunity Section
National Institute of Allergy and Infectious Diseases
Solar Building, Room 4A20
Bethesda, MD  20892
Telephone:  (301) 496-7985
FAX:  (301) 402-2571

Inquiries regarding fiscal matters should be directed to:

Betty E. Bailey
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
Westwood Building, Room 649
Bethesda, MD  20892
Telephone:  (301) 594-7543
FAX:  (301) 594-7594


Letter of Intent:    June 16, 1994
Application Receipt: July 14, 1994
Initial Review:      October/November, 1994
Second Level Review: February, 1995
Anticipated Award:   April 1, 1995


This program is described in the Catalog of Federal Domestic
Assistance No. 93.847 and 93.855.  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


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