Full Text DK-93-19

INTERSTITIAL CYSTITIS AND OTHER BLADDER DISORDERS OF WOMEN

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

RFA:  DK-93-19

P.T. 34, II

Keywords: 
  Urogenital System 
  Infectious Diseases/Agents 


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) solicits R01 grant applications for support of basic and
clinical studies focused on the normal and abnormal function of the
urinary bladder, specifically as it relates to the urinary bladder
disorders of women: interstitial cystitis, urinary tract infections,
and urinary incontinence.  The NIDDK is committed to increasing
research into the urological disorders which affect women's health.
This request is part of the initiative to promote research in all
areas of women's urological health.

HEALTHY PEOPLE 2000

The Public Health Service 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, Interstitial Cystitis and other Bladder Disorders
of Women, 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.  Except as otherwise stated in this announcement, 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 average size of an award
is anticipated to be about $200,000 per year total cost.  The
majority of applications funded from this RFA will be for the support
of new projects.  The earliest possible award date will
be September 30, 1993.

FUNDS AVAILABLE

For FY 1993, $2,500,000 will be committed by the NIDDK to fund
applications submitted in response to this RFA.  It is anticipated
that 10 to 15 awards will be made by the NIDDK.  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 must
limit their requests to not more than $160,000 direct costs for the
initial budget period.  Although this program is provided for in the
financial plan 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

Women of all ages suffer from a disproportionately high rate of
disorders of the urinary bladder.  These disorders have many features
in common:  they are usually chronic, they go through periods of
remission and exacerbation, and they have no universally effective
cure, treatment, or prevention strategy.  Although there have been
many speculative theories for the discrepancy between incidence of
bladder disorders in females and males, there have been no well-
documented research studies that focus on the basic science of the
urinary bladder in females, the differences between the development
of the bladder in the two sexes, extrinsic factors in early
development which can affect adult urinary bladder dysfunction, the
interrelationship between the most common urinary bladder disorders
of women, (i.e., interstitial cystitis, urinary tract infections, and
urinary incontinence) and how the treatment of one disorder can
affect the development of another disorder.  This announcement
solicits applications from basic science investigators in such
diverse fields as biochemistry, molecular genetics, developmental
biology, molecular and cellular biology neurophysiology, immunology,
nutrition, endocrinology, epidemiology, and pharmacology and from
clinical investigators in adult and pediatric urology, gynecology,
infectious diseases, endocrinology, psychology and psychiatry.
Examples of Research Areas  The following are examples of research
areas which are applicable to this RFA.  It is emphasized that this
is a list of suggested research areas; it includes just a few of the
topics that could be considered for investigation.  It is anticipated
that many of the successful applications will propose areas that are
not included in this list.  o  The relationship between interstitial
cystitis and urinary tract infections; epidemiological studies,
effects of infection on the bladder mucosa and subsequent mucosal
immunological abnormalities.  o  Intra- and intercellular
communication in bladder tissues.  o  The molecular biology of
bladder mucosa in the normal bladder, in the developing bladder and
in response to extrinsic factors.  o  The urethra and the development
of bladder disorders of women.  o  Comparative studies of the
molecular biology of bladder development, especially relating early
extrinsic influences to later bladder abnormalities.  o  The role of
the pelvic musculature in normal and abnormal bladder function; its
relationship to the frequency, urgency and pain symptoms of
interstitial cystitis.  o  The pelvic musculature and recurrent
urinary tract infections.  o  The molecular biology and genetics of
normal bladder urothelial turnover, factors which affect turnover,
and urothelial turnover in interstitial cystitis and urinary tract
infections.  o  Factors that affect the development of urinary
incontinence.  o  Studies of the psychological effects of chronic
bladder disorders, comparative studies of the various disorders.  o
The molecular biology of collagen synthesis in the normal and
dysfunctional bladder.  o  The effects of pregnancy on the urinary
bladder.  o  Ethnic and racial differences in bladder disorders of
women.  o  Factors in the urine that affect normal bladder function.
o  Studies comparing the bladder with other organs such as the gut to
elucidate bladder pathophysiology.  Although this RFA is focused on
bladder dysfunction in females, it does not preclude the study of
male bladder function when it is used to enhance the understanding of
female bladder function by comparative studies. For example included
in the scope of this RFA are:  o   studies that compare interstitial
cystitis with chronic abacterial prostatitis, as a means of
elucidating the pathogenesis of interstitial cystitis;  o   studies
of differential hormone effects on the developing bladder of both
sexes in relation to an adult female bladder disorder such as
interstitial cystitis, urinary tract infections or urinary
incontinence.  Program project grant applications (PO1) are not
suited to this announcement.  SPECIAL REQUIREMENTS  1.  Annual
meeting of NIDDK Women's Urological Health Investigators  Applicants
who receive an award through this announcement are expected 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 and
can be in addition to other proposed travel.  2.  Diagnostic Criteria
for Research Studies on Interstitial Cystitis and Other Clinical
Disorders  In order to ensure that patient selection for clinical
studies is uniform, the NIDDK has established Diagnostic Criteria for
research studies on Interstitial Cystitis (IC).  All Grant
Applications For Research On IC that  Use Human Subjects Must State
That The NIDDK IC Diagnostic Criteria For Research 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.  The criteria may also be obtained from the Deputy
Director, Urology Program, DKUHD, listed in this request.  This
requirement does not preclude using subjects who do not meet the
criteria for comparison studies, but those who do not meet the
criteria must be specifically identified and designated as a study
group.  The Diagnostic Criteria for other urological diseases which
are studied must also be defined in the research proposal.  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 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 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  NIDDK,
Westwood Building, Room 605 Bethesda, MD  20892  APPLICATION
PROCEDURES  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 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, Maryland 20892; Telephone: (301) 496-7277.  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 should also be
sent under separate cover to:  Dr. Robert Hammond Chief, Review
Branch NIDDK 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 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, the staff will contact the applicant to
determine whether it should be returned to the applicant, or be 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:  Ralph L. Bain, Ph.D. Deputy Director,
Urology Program The National Institute of Diabetes and Digestive and
Kidney Diseases  Westwood Building, Room 3A-05 5333 Westbard Avenue
Bethesda, MD  20892 Telephone:  (301) 496-7574 FAX:  (301) 402-0223
Inquiries regarding fiscal matters should be directed to:  Ms. Trude
McCain Grants Management Specialist Division of Extramural Activities
The National Institute of Diabetes and Digestive and Kidney Diseases
Westwood Building, Room 649 Bethesda, MD  20892 Telephone:  (301)
496-7467  SCHEDULE:  Application Receipt:   March 25, 1993 Initial
Review:        June 1993 Second Level Review:   September, 13-14,
1993 Anticipated 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.

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