Full Text DK-94-012

INTERSTITIAL CYSTITIS AND OTHER BLADDER DISORDERS OF WOMEN

NIH GUIDE, Volume 23, Number 3, January 21, 1994

RFA:  DK-94-012

P.T. 34, II

Keywords: 
  Urogenital System 
  Infectious Diseases/Agents 
  0715123 


National Institute of Diabetes and Digestive and Kidney Diseases

Letter of Intent Receipt Date:  March 15, 1994
Application Receipt Date:  April 26, 1994

PURPOSE

The Division of Kidney, Urologic, and Hematologic Diseases (DKUHD) of
the National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK) in association with the Office of Research in Women's Health
(ORWH), Office of the Director, NIH, solicits research 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, urinary incontinence, and the
basic bladder physiology of women.

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), Interstitial Cystitis and Other Bladder
Disorders of Women, is related to the priority area of chronic
debilitating illness.  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) award.  Responsibility for the planning, direction, and
execution of the proposed project will be solely that of the
applicant.  Awards will be administered under PHS grants policy as
stated in the PHS Grants Policy Statement.

This RFA is a one-time solicitation.  Generally, future unsolicited
competing continuation applications will compete with all
investigator-initiated applications and be reviewed according to the
customary peer review procedures.  The total requested project period
for applications submitted in response to this RFA may not exceed
five years.  The earliest possible award date will be September 30,
1994.

FUNDS AVAILABLE

For FY 1994, $2,500,000 will be committed by the NIDDK in association
with the ORWH to fund applications submitted in response to this RFA.

It is anticipated that 10 to 15 awards will be made.  However, this
funding level is dependent upon the receipt of a sufficient number of
applications of high scientific merit.  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

The DKUHD/ORWH Women's Urological Health Initiative is committed to
increasing research into the urological disorders that affect women's
health.  This request is part of that initiative.

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; go through periods of remission
and exacerbation; and have no universally effective strategy for
cure, treatment, or prevention.  Although there have been many
speculative theories about 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 in development of the
male and female bladders, extrinsic factors in early development that
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.

Purpose

The purpose of this RFA is to bring new and established investigators
from diverse scientific and clinical areas into the study of women's
urological disorders.  Collaboration between basic science and
clinical investigators in developing approaches to the study of the
urinary bladder and its disorders in women is an emphasis of this
solicitation.  Applications are especially encouraged 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,
nephrology, endocrinology, psychology, and psychiatry.

Applications from investigators currently funded for research in
women's urological health are encouraged if the application addresses
a new hypothesis.  Applications to continue an existing funded
project are not within the scope of this RFA.

Examples of Research Areas

The following are examples of research areas that are applicable to
this RFA.  It is emphasized that this list 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 recurrent
urinary tract infections; epidemiological studies, effects of
infection on the bladder epithelium and subsequent mucosal
immunological abnormalities.

o  Intra- and intercellular communication in bladder tissues.

o  The molecular biology of bladder mucosa in the normal bladder, the
developing bladder and in response to extrinsic factors.

o  Relationships between bladder epithelial and musculoskeletal
tissues.

o  The urethra and the development of bladder disorders of women.

o  Comparative studies of molecular biology of bladder development,
especially relating early extrinsic influences on latter 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 molecular biology and genetics of bladder urothelial turnover,
factors that affect turnover, urothelial turnover in interstitial
cystitis, and urinary tract infections.

o  Factors that affect the development of urinary incontinence.

o  Factors affecting solute and ion transport through bladder
epithelium.

o  The relationship between vulvovestibulitis and other female
urinary tract disorders.

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  Environmental factors in the development of interstitial cystitis
and other bladder disorders.

o  Factors in the urine that affect normal bladder function.

o  Novel approaches to the treatment of interstitial cystitis.

o  Studies comparing the bladder with other organs such as the gut to
elucidate bladder pathophysiology.

o  Pilot studies of clinical trials for the treatment of interstitial
cystitis.

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.

Studies of bladder cancer or malignant change of urothelial tissue
are not acceptable for this RFA.

Program project grant applications (PO1) are not suited to this RFA.

SPECIAL REQUIREMENTS

Annual meeting of NIDDK Women's Urological Health Investigators

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

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 under INQUIRIES.  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 that are
studied must also be defined in the research grant 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 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 asked to submit by March 15, 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 names of key personnel, the participating
institutions, and the number and title of the RFA to which the
application may be submitted.  Such letters are requested for the
purpose of obtaining an indication of the number and scope of
applications to be received.  The letter of intent is not binding, is
not a requirement for submission, and does not enter into the review
of the application.  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
Westwood Building, Room 605
Bethesda, MD  20892

APPLICATION PROCEDURES

The research grant application form PHS 398 (rev. 9/91) is to be used
in applying for these grants.  The form is available from most
institutional offices of sponsored research and from the Office of
Grants Information, Division of Research Grants, National Institutes
of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892,
telephone 301/435-0714.

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 Director, General Clinical Research
Program, National Center for Research Resources, telephone (301)
594-7945.

The RFA label available in the 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 the application such that it
may not reach the review committee in time for review.  In addition,
the RFA title and number must be typed on line 2a of the face page of
the application form and check the YES box.

Submit a signed, typewritten original of the application, including
the Checklist, and three signed, exact photocopies, in one package
to:

Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
Bethesda, MD  20892**

At time of submission, two additional copies of the application must
also be sent, under separate cover to:

Dr. Robert Hammond
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
Westwood Building, Room 605
Bethesda, MD  20892

Applications must be received by April 26, 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.

REVIEW CONSIDERATIONS

Upon receipt, applications will be initially reviewed by DRG for
completeness.  Incomplete applications will be returned to the
applicant without further consideration.  Evaluation for
responsiveness to the program requirements and criteria stated in the
RFA is an NIDDK staff function.  If the application is not responsive
to the RFA, the staff will contact the applicant to determine whether
it should be returned to the applicant, or held until the next
regular receipt date and reviewed in competition with all other
applications.

Those applications that are complete and responsive will be evaluated
in accordance with the criteria stated below for scientific/technical
merit by an appropriate peer review group convened by the NIDDK.  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 if they are judged to
be 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 further 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 second level review by the NIDDK 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
balance, and availability of funds.

The anticipated date of award is September 30, 1994.

INQUIRIES:

Written and telephone inquiries concerning this RFA are encouraged.
The opportunity to clarify any issues or questions from potential
applicants is welcome.

Direct inquiries regarding programmatic issues to:

Ralph L. Bain, Ph.D.
Division of Kidney, Urologic, and Hematologic Diseases
National Institute of Diabetes and Digestive and Kidney Disease
Westwood Building, Suite 3A-05
Bethesda, MD  20892
Telephone:  (301) 594-7556
FAX:  (301) 594-7501

Inquiries regarding fiscal matters may be directed to:

Ms. Trude McCain
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Disease
Westwood Building, Room 649
Bethesda, MD  20892
Telephone:  (301) 594-7543

Schedule

Letter of Intent Receipt Date:  March 15, 1994
Application Receipt Date:       April 26, 1994
Initial Review:                 June/July 1994
Second Level Review:            September 1994
Anticipated Date of Award:      September 30, 1994

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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