Subject: RFA NIH Guide l/25/9l
From: Dot Baker <[email-masked]>
To: [email-masked]
Date: Thu, 24 Jan 91 11:04 EST

Hi Paul,
     This is the fourth of five coming today.  Please post to the
listserver as:
              RFADK-91-04.910125
 Thanks.  Dottie
 ---------------------------- Text of forwarded message -----------------------
 
BASIC AND CLINICAL RESEARCH ON THE URINARY BLADDER AND
PELVIC MUSCULATURE IN INTERSTITIAL CYSTITIS
 
RFA AVAILABLE:  DK-91-04
 
P.T. 34; K.W. 0705075, 0765035, 0710030
 
National Institute of Diabetes and Digestive and Kidney Diseases
 
Letter of Intent Date Receipt:  March 1, 1991
Application Receipt Date:  April 22, 1991
 
This Request for Applications (RFA) emphasizes the continued
interest of the National Institute of Diabetes and Digestive
and Kidney Diseases (NIDDK) in funding research studies in
all areas of the investigation of the urinary bladder and
the adjacent structures, including the pelvic musculature.
The special emphasis of these studies should address issues
that may have particular relevance to increasing our basic
understanding of the disorder of interstitial cystitis
(IC).  The NIDDK encourages investigators from diverse
clinical and basic science disciplines with a research
interest in the pathophysiology of bladder function and its
interrelationship with lower pelvic musculature to submit
applications for research that investigates such areas as
the etiology, diagnosis, pathophysiology, pathology,
surgical and non-surgical treatment, and prevention of IC.
 
INTRODUCTION
 
IC is a chronic, painful, and
variably incapacitating disorder that manifests a symptom
complex consisting of pain in the region of the urinary
bladder and associated pelvic musculature and variable
motor and sensory dysfunctions of the urinary bladder.  It
affects a significant percentage of the adult population,
predominatly women.  Although the symptom complex was
described nearly a century ago, there had been little
research into this disorder until recently, and the existing
data contain many conflicting and incongruous findings.
The factors that have inhibited advances in the
understanding of this disorder include:  the lack of specific
diagnostic criteria, the lack of specific tissue changes at
the histological level, the unpredictable and variable
remission and recrudescence of symptoms, failure of
investigation of associated pelvic musculature, the lack of
a competent animal model for the disorder, and the absence
of a multidisciplinary research approach in the
investigation of the disorder.
 
In order to assure that patient selection for clinical
studies is uniform the NIDDK has established Diagnostic
Criteria for research studies on IC that must be satisfied
for all patients enrolled in clinical research studies
supported by the NIDDK.  ALL CLINICAL GRANT APPLICATIONS
MUST STATE THAT THE NIDDK IC DIAGNOSTIC CRITERIA WILL BE
APPLIED TO PATIENTS SELECTED FOR INCLUSION IN THE RESEARCH
STUDY.  These criteria have been published in: the JOURNAL
OF UROLOGY 142(1): 139,1989 and the AMERICAN JOURNAL OF
KIDNEY DISEASES 8(4):353, 1989.  They may also be obtained
from the Director of the Urology Program, DKUHD (address below).
 
BACKGROUND INFORMATION
 
Interstitial cystitis is defined primarily by two factors:
1) the subjective symptom complex that includes lower
pelvic pain in the region of the urinary bladder, urinary
frequency and urgency; and, 2) characteristic findings seen
on cystoscopic evaluation (glomerulations).  Pathological
findings in the bladder with IC are variable and generally
nonspecific.  These findings may include
ulcerations, granulation tissue, fibrosis, and mononuclear
and mast cell infiltrates.  No microbial infectious agent
has yet been identified with the disorder.  There are
numerous therapeutic modalities utilized for symptom
resolution.  However, no agent has been shown to either
eradicate the process or to provide long-term, predictable,
symptomatic relief in controlled trials.
 
SPECIFIC OBJECTIVES AND SCOPE OF RESEARCH
 
The specific objectives of this RFA are to encourage
investigators, not now working in the field of bladder
physiology and pathophysiology, to enter the field of IC
research and to help focus the work of investigators
already in the field, on topics that will increase the
breadth and depth of knowledge about the etiology,
pathogenesis, prevention, and treatment of bladder disorders,
with special emphasis on the condition called interstitial
cystitis.  Especially encouraged are investigators with
research expertise in the basic and clinical science areas
of immunology, infectious diseases, endocrinology, cellular
and molecular biology, and bladder and muscular
neurophysiology and pharmacology.
 
Areas that need investigation include, but are not limited
to, the following:
 
o  The effect of hormones and/or growth regulatory peptides
on the normal function of the bladder and in interstitial
cystitis.
 
o  The role of infectious agents in the pathogenesis of
interstitial cystitis.
 
o  The role of inflammatory mediators, including free
radicals, in the pathogenesis of interstitial cystitis.
 
o  Histological and pathological findings in bladder tissue
from patients with bladder diseases that may improve the
specificity of particular features for interstitial
cystitis, or may aid in establishing the diagnosis of
interstitial cystitis.
 
o  Comparisons of cellular calcium transport in the normal
bladder and in interstitial cystitis.
 
o  Comparisons of the neurotransmitter innervation of the
normal bladder and adjacent pelvic musculature with those of
interstitial cystitis.
 
o  The role of immunity and autoimmunity in the pathogenesis
of interstitial cystitis.
 
o  Surgical interventions in the treatment of interstitial
cystitis.
 
o  Innovative forms of therapy for interstitial cystitis.
 
o  Basic and clinical studies comparing the role of the
pelvic floor musculature in normal bladder function and in
the dysfunction associated with interstitial cystitis.
 
o  A comparison of the role of glycosaminoglycans and Tamm-
Horsefall protein (uromodulin) in normal bladder physiology
and in interstitial cystitis.
 
o  A comparison of the role of the urothelium in the normal
bladder functional states and in interstitial cystitis.
 
o  Urine constituents specifically associated with
interstitial cystitis.
 
o  Genetic factors associated with interstitial cystitis.
 
APPLICATION, REVIEW, AND FUNDING PROCEDURES
 
Response to this RFA is limited to individual research
project (R01) grant applications.  Applications must
be submitted on the revised (10/88) form PHS-398,
available in the business or research grants office at most
academic or research institutions, and from the Division of
Research Grants, National Institutes of Health.  The purpose
of this solicitation is to encourage applications from
established investigators in related areas of investigation
who are not currently funded by the NIDDK for research in
the area of interstitial cystitis.  However, applications
from all investigators will be accepted.  Applications from
women and minority investigators are encouraged.
 
SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF
NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN
CLINICAL RESEARCH STUDY POPULATIONS
 
The following is the NIH and ADAMHA policy regarding the
inclusion of women and minorities in study populations.
Applications that are responsive to this RFA will, by definition,
meet the requirement for inclusion of women.  The inclusion of
minorities must be addressed in application submitted responding
to this RFA.
 
NIH and ADAMHA policy is that applicants for NIH/ADAMHA clinical
research grants and cooperative agreements will be 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
should 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 should 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 should be addressed in
developing a research design and sample size appropriate for the
scientific objectives of the study.  This information should 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 includes 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 will be 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.
 
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 program staff function.
Applications that are judged non-responsive will be
administratively inactivated but may be submitted as
investigator-initiated research grants at the next
receipt date.
 
Applications responsive to this RFA will be reviewed for
scientific and technical merit in accordance with the usual
NIH peer review procedures by a 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.
 
Up to $1 million are available in support of this RFA.  The
specific number of grants and total amount of funds to be
awarded depends on the scientific merit of each application
and the total costs of the applications.  Because a major
intent of this request is to broaden the scope of research
on interstital cystitis and to increase the number of
investigators in the field, applicants should keep this in
mind when constructing their budgets.  Each application
should include travel funds designated for the Principal
Investigator to attend an annual NIDDK research workshop on
interstitial cystitis.
 
Applications must be received by April 22, 1991, to be
considered for review and funding through this RFA.
 
THE RFA LABEL CONTAINED IN THE APPLICATION KIT MUST BE
AFFIXED TO THE BOTTOM OF THE FACE PAGE OF THE ORIGINAL COPY
OF THIS APPLICATION.  FAILURE TO USE THIS LABEL COULD RESULT
IN DELAYED PROCESSING OF THE APPLICATION.  FOR PURPOSES OF
IDENTIFICATION AND PROCESSING, THE RFA NUMBER, DK-91-04, AND
TITLE SHOULD BE TYPED IN ITEM 2 ON THE FACE PAGE OF THE
APPLICATION.
 
The original and four copies of the application must be
sent to:
 
Division of Research Grants
Westwood Building, Room 240
National Institutes of Health
Bethesda, MD 20892**
 
Two additional copies of the application must be sent
under separate cover to:
 
Dr. Robert Hammond
Chief, Review Branch
Division of Extramural Activities, NIDDK
National Institutes of Health
Westwood Building, Room 406
Bethesda, MD 20892
 
Letter of Intent:  It is requested that the prospective
applicant submit a one-page letter of intent that
includes a
descriptive title of the research, the name address and
telephone number of the Principal Investigator, the names of
other key personnel, and identification of any other
participating institutions.  Such letters are requested for
the purpose of providing an indication of the number and
scope of applications to be expected and for advising
potential applicants on the suitability of the proposed
project to the intent of the RFA.  A letter of intent is not
binding and it will not enter into the review of subsequent
applications.  It is not a requirement for application.  The
letter of intent should be received by March 1, 1991.
 
Letters of intent and any inquiries about this RFA must be
sent to:
 
Director, Urology Program, NIDDK/DKUHD
National Institutes of Health
Federal Building, Room 102
Bethesda, MD 20892
Telephone:  (301) 496-8248
FAX:  (301) 402-0223
 
SUMMARY OF APPLICATION, REVIEW AND FUNDING DATES
 
Letter of Intent Due:  March 1, 1991
Receipt date for Application:  April 22, 1991
Initial Review:  June/July 1991
Advisory Council Review:  September 1991
Earliest Date of funding:  September 30, 1991
 
These programs are described in the catalog of Federal
Domestic Assistance No. 93,849-Kidney, Urologic and
Hematologic Diseases Research.  Awards will be made
under the authority of the Public Health Service Act, Title
III, Section 301 (Public Law 78-4110, as amended: 42 USC
241) and administered under PHS Grant Policies and Federal
Regulations 42 CFR Part 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.