Full Text DK-92-16


NIH GUIDE, Volume 21, Number 6, February 14, 1992

RFA:  DK-92-16

P.T. 34

  Physiology, Human 
  Digestive Diseases & Disorders 

National Institute of Diabetes and Digestive and Kidney Diseases

Letter of Intent Receipt Date:  June 15, 1992
Application Receipt Date:  July 15, 1992


The Division of Digestive Diseases and Nutrition and the Division of
Diabetes, Endocrinology and Metabolism of the National Institute of
Diabetes and Digestive and Kidney Diseases (NIDDK) wish to encourage
applications that conduct basic and clinical studies into the
physiology and pathophysiology of the pancreatic ducts.


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), Basic and Clinical Studies on the Physiology
and Pathophysiology of the Pancreatic Ducts, 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 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 apply.


Support of this program will be through the NIH grant-in-aid research
project grant (R01) award. Responsibility for the planning, direction,
and execution of the proposed project will be solely that of the
applicant.  Except as otherwise stated in this announcement, awards
will be administered under PHS grants policy as stated in the PHS
Grants Policy Statement.  The total requested project period for
applications submitted in response to this RFA may not exceed five
years.  A maximum of three years may be requested for foreign awards.
The earliest possible award date will be April 1, 1993.

This RFA is a one-time solicitation.  Future unsolicited competing
continuation applications will compete with all investigator-initiated
applications and will be reviewed according to the customary NIH peer
review process.

For FY 1993, $1.0 million will be committed to fund applications
submitted in response to this RFA.  It is anticipated that five to
seven awards will be made.  However, this funding level is dependent
upon the receipt of a sufficient number of applications of high
scientific merit.  In order to help meet NIDDK goals for managing the
costs of biomedical research, applicants more than $160,000 direct
costs for the initial budget period.  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


A neglected but very important component of the pancreas, the
pancreatic ductules and duct system, was the subject of a three-day
conference held in September 1991.  Because duct cells represent only
about 10 percent of the adult exocrine pancreas, it has been difficult
to study.  Recently, investigators have been able to use tissue culture
and microdissection techniques to study duct cells in vitro.  The ion
transport, neural and hormonal regulation, and other
electrophysiological measurements of these cells can now be made in
health and disease.  Some of the common diseases of pancreatic ducts
are pancreatitis, cystic fibrosis and adenocarcinoma.  All of these
basic and clinical areas offer opportunities to expand our knowledge of
the physiology and pathophysiology of the pancreatic duct system.

Examples of potential interest, which are not meant to be directive or
inclusive, are listed below.  Studies may examine normal duct cell
development and function and the alterations that occur in disease.

o  Assessment of pancreatic duct cell development using biochemical
markers.  When during development do protodifferentiated cells acquire
adult duct cell markers?  Do different size classes of duct cells
exhibit different biochemical markers, suggestive of different
functions?  Is duct cell development altered in disorders such as
cystic fibrosis?

o  Development of the functional capacity of the duct epithelium to
secrete fluid, electrolytes, and mucin. When does this capability
appear?  What are the controlling growth factors, hormones, stromal
interactions, receptors?  When do the various components of the
stimulus-secretion coupling system appear?  When and how do disorders
such as pancreatitis and cystic fibrosis manifest?

o  Developmental potential of adult duct epithelium.  Does the duct
cell have the capacity to give rise to new acinar and/or endocrine
cells?  What circumstances unleash or preclude such a capacity?

o  Detailed characterization of primary duct cell cultures, the first
several subcultures, and putative duct cell lines.  To what extent are
primary cell cultures and cell lines good models for duct cells in

o  Establishment of a confluent monolayer culture of duct cells on
which functional measurements can be made, as in Ussing chambers.

o  Development of integrative approaches to the study of function in
living cells, e.g., by fluorescent probes, electron microscopy.  Such
approaches can be applied to normal duct cells and cells affected by
disorders of the pancreatic ducts.

o  Understand processes at the molecular level.  Are the secretin
receptors (already cloned on brain neuroblastomas) the same on
pancreatic ducts?

o  Subsets of chronic pancreatitis that are regarded as "idiopathic"
should be evaluated to test the hypothesis that autoimmune mechanisms
directed toward ductal cells play a role in the pathogenesis.


It is NIH policy that women and minorities must be included in clinical
study populations unless there is a good reason to exclude them.  The
study design must seek to identify any pertinent gender or minority
population differences.


NIH and ADAMHA policy is that applicants for NIH/ADAMHA 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 in Section 2, A-D
of the Research Plan AND summarized in Section 2, E, 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
(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

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.


Prospective applicants are asked to submit, by June 15, 1992, 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 to:

Chief, Review Branch
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
5333 Westbard Avenue, Room 605
Bethesda, MD  20892
Telephone:  (301) 496-7083


The research grant application form PHS 398 (revised 9/91)is to be used
in applying for these grants.  The form is available from most
institutional business offices 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.

The RFA label available in the PHS 398 application kit 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 2 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 four signed, exact photocopies, in one package to:

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:

Chief, Review Branch
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
5333 Westbard Avenue, Room 605
Bethesda, MD  20892

Applications must be received by July 15, 1992.  If an application is
received after that date, it will be returned to the applicant.  The
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.


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.  The
application either may be returned to the applicant, or held until the
next receipt date and reviewed in competition with all other

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.  If
the number of applications is large compared to the number of awards to
be made, the NIDDK may conduct a preliminary scientific peer review
(triage) and withdraw applications from further competition if 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 NIDDK initial review group specifically
convened for this RFA. Following study section review, the applications
will be given a secondary review by the NIDDK Advisory Council unless
not recommended for further consideration by the initial review group.

Review criteria for this RFA 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


Awards in connection with this announcement will be made to foreign
institutions only for research that is unique and can only be performed
outside of the United States.  Public Health Service policy will govern
such awards.  The anticipated date of award is April 1, 1993.


Written and telephone inquiries concerning this RFA are encouraged.

Direct inquiries regarding programmatic issues and requests for copies
of the workshop program with summaries of the presentations and
abstracts of poster presentations, are available to those considering
responding to this RFA.

Such inquiries should be directed to:

Sarah C. Kalser, Ph.D.
Pancreatic Diseases Program Director
Division Digestive Diseases and Nutrition
National Institute of Diabetes and Digestive and Kidney Diseases
5333 Westbard Avenue, Room 3A-17
Bethesda, MD  20892
Telephone:  (301) 496-7858

Inquiries relating to proposed research on cystic fibrosis should be
directed to:

Judith Fradkin, M.D.
Chief, Endocrinology and Metabolic Diseases Program Branch
Division of Diabetes, Endocrinology and Metabolism
National Institute of Diabetes and Digestive and Kidney Diseases
5333 Westbard Avenue, Room 621
Bethesda, MD  20892
Telephone:  (301) 496-7791

Inquiries regarding fiscal matters should be directed to:

Ms. Thelma Jones
Grants Management Specialist
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
5333 Westbard Avenue, Room 649
Bethesda, MD  20892
Telephone:  (301) 496-7467


Letter of Intent:       June 15, 1992
Application Receipt:    July 15, 1992
Initial Review:         Oct/Nov  1992
Second Level Review:    February 1993
Anticipated Award:      April 1, 1993


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


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