From: kristoff@NET.BIO.NET (Dave Kristofferson)
Newsgroups: bionet.sci-resources
Subject: NIH Guide, vol. 22, no. 1, pt. 7, 8 January 1993
Date: 8 Jan 93 03:11:39 GMT
Distribution: bionet


$$XID RFA EY9301 EY-93-01 P1O1 *****************************************

CLINICAL CENTERS FOR OCULAR HYPERTENSION TREATMENT STUDY

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

RFA:  EY-93-01

P.T. 34; K.W. 0715115, 1002046, 0755015

National Eye Institute

Application Receipt Date:  March 12, 1993

PURPOSE

The National Eye Institute (NEI) invites applications for cooperative
agreements to support participating clinics in the Ocular
Hypertension Treatment Study (OHTS).  The OHTS is an investigator-
initiated, randomized, multicenter, clinical trial to determine
whether medical reduction of intraocular pressure prevents or delays
the onset of glaucomatous optic nerve and/or visual field damage in
ocular hypertensive subjects.

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), Clinical Center for OHTS, is related to the
priority area of reducing significant visual impairment due to
glaucoma.  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 for-profit and non-profit
organizations, public and private, such as universities, colleges,
hospitals, private practice clinicians, health maintenance
organizations or managed health care organizations, units of State
and local governments, and eligible agencies of the Federal
Government.  Applications from minority individuals and from women
are encouraged.

MECHANISM OF SUPPORT

Awards will be made as cooperative agreements (U10). This is an
assistance mechanism of support in which there will be substantial,
ongoing involvement by NEI staff during the performance of the
clinical trial and interaction between the awardee and NEI staff
during performance of the project.  This RFA is a one-time
solicitation.

FUNDS AVAILABLE

It is expected that approximately 30 to 40 awards will be made as a
result of this RFA.  The total funds available for the first year of
support are expected to be approximately $1.9 million; however, this
support level is conditional upon the receipt of applications of
substantial and significant scientific merit.  Awards are expected to
be made in November 1993.  Although the financial plans of the NEI
provide for these projects, awards pursuant to this RFA are also
contingent upon the availability of funds.

RESEARCH OBJECTIVES

Background

Glaucoma is one of the leading causes of blindness in the United
States and other industrialized countries, and is the number one
cause of blindness in African Americans.  Moreover, glaucoma is one
of the most common causes of blindness in individuals above age 60,
one of the fastest growing groups in the U.S.  Elevated intraocular
pressure (IOP) is a key risk factor for the development of open-
angle glaucoma.  However, there is no consensus on whether early
treatment of elevated IOP prevents or delays the onset of open-angle
glaucoma.

The OHTS is an investigator-initiated activity funded by cooperative
agreements from the NEI.  Applications were received in October 1991
from Dr. Michael Kass, professor of ophthalmology at Washington
University, as the Study Chairman and Dr. Mae Gordon, assistant
professor of ophthalmology at Washington University, for the
Coordinating Center.  Initial review for scientific merit was held in
March 1992; secondary review by the National Advisory Eye Council
(NAEC) was in May 1992.  Cooperative agreements were made in
September 1992 to support these central OHTS activities.

Although the OHTS is designed to study the efficacy and safety of
early medical treatment in ocular hypertension, there will be other
benefits as well.  This study will allow one to refine and validate
estimates of risk for individual patients with ocular hypertension in
a large national sample.

African Americans have a much higher prevalence of open- angle
glaucoma than do whites.  However, there are no prospectively
obtained data on the conversion rate of African Americans with ocular
hypertension to open-angle glaucoma.  This study will include a
minimum of 400 African American ocular hypertensives, and will
provide data to determine the conversion rate of African American
ocular hypertensive subjects to open-angle glaucoma.

At the conclusion of this study, practitioners should be able to
provide reasonable estimates of risk for individual ocular
hypertensive patients and know which ocular hypertensive individuals
are most likely to benefit from early prophylactic medical treatment.

Other

The OHTS is a randomized, multicenter clinical trial to determine
whether medical reduction of intraocular pressure (IOP) prevents or
delays the onset of glaucomatous optic nerve and/or visual field
damage in ocular hypertensive subjects.  One thousand five hundred
subjects with IOP greater than or equal to 26 mm Hg in at least one
eye (IOP greater than or equal to 21 mm Hg in the fellow eye) and
normal visual fields and optic discs in both eyes will be assigned
randomly to receive stepped medical treatment to both eyes or no
treatment to both eyes.  These subjects are considered to be at
moderate risk for the development of open-angle glaucoma.  The
subjects will be followed twice yearly with automated, threshold,
central, static Humphrey 30-2 perimetry, and yearly optic disc
photographs will be taken.  The study endpoints are progressive optic
disc cupping and/or reproducible glaucomatous visual field loss in
either eye of a patient.  All visual fields and optic disc
photographs will be read in masked fashion by central reading
centers.  It is projected that the time required to recruit the
required patients will be two years, and each patient will be
followed for a minimum of five years.  During the course of the
study, data will also be collected for an analysis of the cost
effectiveness of preventative treatment in ocular hypertension.  This
will include ascertainment of both direct costs of treatment as well
as indirect nonmonetary costs.  In addition, data will be collected
on the impact of medical treatment on the patients' quality of life.

An organization applying as a clinical center in the OHTS must
document its capability to recruit 25 or more fully eligible patients
per year (for two years) for the clinical trial.

SPECIAL REQUIREMENTS

The Principal Investigator and Clinical Coordinator will be asked to
attend a two-day training meeting to be held in St. Louis during the
first project year. Applicants are advised to include plans for this
training meeting in their budget requests.  The Principal
Investigator and Clinic Coordinator of each participating clinic will
be requested to attend an annual one-day meeting of study
investigators to be held in conjunction with the annual meeting of
the American Academy of Ophthalmology.  Applicants are advised to
include plans for meeting travel expenses in their budget requests
using the following as guidance:  The NEI will provide support for
the cost of one night's lodging and one day of per diem for the
Principal Investigator; roundtrip air fare, one night's lodging, and
one day of per diem will be provided for the Coordinator to attend
this annual meeting.

Applicants are advised to describe plans to accommodate the stated
program requirements, criteria, and NEI staff involvement (explained
below).

Terms and Conditions.  The Principal Investigator will be responsible
for all aspects of the day-to-day operations of his/her clinical
center and the local implementation of the study protocol.  He/She
will have the primary responsibility to identify and recruit eligible
patients. He/She will be responsible for the follow up of each
patient enrolled in the clinical trial and submitting the required
data to the Coordinating Center.

The Principal Investigator will retain custody of and have primary
rights to the data developed under the cooperative agreement, subject
to Government rights of access, consistent with current DHHS, PHS,
and NIH policies.

The Chief of the NEIs Collaborative Clinical Research Branch (CCRB)
will participate with and assist, but not direct:

1.  The Study Chairperson and Coordinating Center Director in the
nomination and selection of the independent Data and Safety
Monitoring Committee.

2.  The Study Chairperson and, when appropriate, the Executive
Committee, in ensuring that standardized patient information
handbooks, recruitment information, press releases, and publicity
exhibits are properly prepared and implemented.

3.  The Study Chairperson in the identification of additional
clinics, if necessary, in order to enhance patient recruitment.

4.  The Executive Committee in routine performance monitoring of the
entire study including matters of quality control among various
components and in the determination of inadequate patient recruitment
or failure to comply with the protocol on the part of individual
clinics.  Clinic support can be withheld or terminated based on these
determinations.

5.  The Data and Safety Monitoring Committee as an ex officio member
and will participate in all decisions of the Committee, e.g., to
proceed from one phase of the study to the next, to implement
protocol changes, to evaluate patient recruitment issues, to approve
any ancillary studies, to plan data analysis, and to announce study
findings and the timing of release of any interim or final reports.

The independent Data and Safety Monitoring Committee will serve as an
arbitrator for resolution of potential differences of opinion among
the investigators and NEI staff concerning the scientific conduct of
the study. This arbitration process in no way affects the rights of a
recipient to appeal selected grants administration decisions in
accordance with PHS regulations at 42 CFR Part 50, Subpart D, and HHS
regulations at 45 CFR Part 16.

These special terms of award are in addition to, and not in lieu of,
otherwise applicable OMB administrative guidelines, DHHS grant
administration regulations at 45 CFR Parts 74 and 92, as applicable,
and other DHHS, PHS, and NIH grant administration policies.

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 all applications for NIH 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, together with a rationale
for its choice.  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 Sections 1-4 of
the Research Plan AND summarized in Section 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.

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.

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 involving human subjects 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.

APPLICATION PROCEDURES

The application form PHS 398 (rev.10/91) is to be used in applying
for these cooperative agreements.  These forms are available at
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, MD 20892, telephone
301/496-7441.

The RFA label available in the PHS 398 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 title of the
application and the RFA number must be typed on line 2a of the face
page of the application.

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

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

At the time of submission, two additional copies of the application
and all appendix material must be sent to:

Janet M. Cuca, Ph.D.
Review and Special Projects Officer
National Eye Institute
Building 31, Room 6A06
Bethesda, MD  20892

Applications must be received by March 12, 1993.  If an application
is received after that date, it will be returned to the applicant
without review.

REVIEW CONSIDERATIONS

Applications will be evaluated in accordance with the criteria stated
below by an initial review group that will be convened by the Review
and Special Projects Office, NEI.  Applications will then undergo
second-level review by the National Advisory Eye Council.

In the event of a large response to this RFA, applications may be
subject to triage by a peer review group to determine their
scientific merit relative to other applications.  The NEI will remove
from further consideration those applications judged by the triage
process to be noncompetitive for award and notify the applicant and
institutional official.  Those applications judged to be competitive
will undergo further review.

The factors considered in evaluating responses to this RFA will be:

1.  Experimental Design:  adequacy of the participating clinic's
procedures for patient recruitment and patient retention and
followup, data collection and data management, quality control of
clinical examinations, training and certification of personnel, and
testing and monitoring of study procedures;

2.  Personnel:  qualifications of all key personnel (whether
compensated from the grant or not), including their experience and
track record in clinical trials (NEI-supported and other);

3.  Resources and Facilities:  sources and numbers of fully-eligible
patients, of patients with related disorders, and of eligible
patients likely to have participated in the study who were seen over
a recent one-year period; documentation of intended collaborations;
the clinic's recruitment and retention track record in clinical
trials; and, the physical facilities and equipment available for the
study; and,

4.  Budget:  appropriateness and reasonableness of all items
requested relative to the overall scope of the study, the potential
for patient recruitment, and the budget justifications provided in
the application.

These competitive applications will undergo initial review by the
Vision Research Review Committee on June 21-22, 1993, and receive
second-level review by the National Advisory Eye Council at its
September 9-10, 1993, meeting.

AWARD CRITERIA

The anticipated date of award is November 1993.

Funding decisions will be made on the basis of scientific and
technical merit as determined by peer review, program needs, and the
availability of funds.  The total cost of each application will also
be taken into consideration.

INQUIRIES

Written and telephone inquiries concerning this RFA are encouraged.
The opportunity to clarify any issues or questions from potential
applicants is welcome.  Potential applicants are requested to write
or telephone Dr. Richard L. Mowery to receive copies of selected
chapters from the OHTS Manual of Procedures that will be helpful in
preparing an application for submission.

Direct inquiries regarding programmatic issues to:

Dr. Richard L. Mowery
Chief, Collaborative Clinical Research Branch
National Eye Institute
Building 31, Room 6A49
Bethesda, MD  20892
Telephone:  (301) 496-5983
FAX:  (301) 402-0528

Direct inquiries regarding administrative matters to:

Gaye Lynch
Chief, Grants Management Section
National Eye Institute
Building 31, Room 6A48
Bethesda, MD  20892
Telephone:  (301) 496-5884

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic
Assistance No. 93.868.  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 Parts 74 and 92, as applicable.  This program is not subject to
the intergovernmental review requirements of Executive Order 12372 or
Health Systems Agency review.


$$XID RFA CA9310 CA-93-10 P1O1 *****************************************

SMALL GRANTS FOR CLINICAL TRIALS IN AIDS MALIGNANCIES

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

RFA:  CA-93-10

P.T. 34; K.W. 0715008, 0715035, 0755015

National Cancer Institute

Letter of Intent Receipt Date:  February 1, 1993
Application Receipt Date:  April 23, 1993

PURPOSE

The Cancer Therapy Evaluation Program of the Division of Cancer
Treatment at the National Cancer Institute (NCI) invites small grant
applications for innovative therapeutic studies in Acquired
Immunodeficiency Syndrome (AIDS) malignancies.  The studies should be
restricted to pilot or phase I or II trials with approximately 5 to
30 patients/trial.

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), Small Grants for Clinical Trials in AIDS
Malignancies, is related to the priority area of cancer and AIDS.
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

Domestic for-profit and non-profit organizations, governments and
their agencies are eligible to apply.  Foreign institutions are not
eligible to apply.  Applications can be from single institutions or
multiple institutions (collaborating institutions, consortia,
cooperative groups).  New and experienced investigators are
encouraged to apply.  Applications from minority individuals and
women are encouraged.

MECHANISM OF SUPPORT

Support of this program will be through the National Institutes of
Health (NIH) small grants mechanism (R03).  The small grants research
program provides limited funds (maximum of $48,000 direct costs per
year) for short-term (up to two years) research projects.  The R03
grants are non-renewable.  Future competing renewals (type 2s) must
be prepared and submitted as traditional research grant applications
(R01s) to be considered along with other non-solicited investigator
initiated applications reviewed by the Division of Research Grant
(DRG) study sections.  Responsibility for the planning, direction,
and execution of the proposed research will be solely that of the
applicant.  Awards will be administered under PHS grants policy as
stated in the Public Health Service Grants Policy Statement, DHHS
Publication No. (OASH) 90-50,000, revised October 1, 1990.

This RFA is a one-time solicitation for FY 93.  Applications received
after the deadline receipt date will be returned.

FUNDS AVAILABLE

Approximately $750,000 in total costs per year for two years will be
committed to fund applications submitted in response to this RFA.
This funding level is dependent on the receipt of a sufficient number
of applications of high scientific merit.  The direct cost for each
R03 is limited to $48,000 per year.  Thus it is anticipated that ten
awards will be made in FY 93.  The total project period for
applications submitted in response to the RFA may not exceed two
years.  The earliest feasible start date for the initial awards will
be September 30, 1993.  Although this program is provided for in the
financial plans of the NCI, the award of R03 grants pursuant to this
RFA is also contingent upon the availability of funds for this
purpose.

RESEARCH OBJECTIVES

Background

Congenital and acquired states of immunodeficiency increase the
incidence of high-grade B cell non-Hodgkin's lymphoma (NHL), Kaposi's
sarcoma, and certain types of epithelial malignancies. Individuals
infected with human immunodeficiency virus (HIV) have a marked
increase in the appearance of intermediate and high-grade B cell NHL
and Kaposi's sarcoma, and show trends for an increased incidence for
Hodgkin's disease, anogenital dysplasia and cancer, and basal cell
carcinoma, compared to age-matched controls.  On October 22, 1992,
the Center for Disease Control proposed the addition of invasive
cervical cancer in HIV-infected individuals to the AIDS Surveillance
case definition.

The tumors in HIV-infected individuals are generally aggressive and
insufficiently sensitive to conventional therapy.  The median
survival of HIV-associated NHL is less than one year and is only two
months for primary central nervous system lymphoma.  Clinical
observations suggest that Hodgkin's disease, anogenital dysplasia and
cancer, and basal cell carcinoma, have a different natural history
and therapeutic outcome compared to the disease in the general
population.  The dramatic growth rate of the tumors, combined with
the problems of myelosuppression and opportunistic infections, have
made treatment extremely difficult.  As children and adults with
HIV-infection are surviving longer due to improved retroviral and
opportunistic infection treatment, the incidence of the malignancies
are expected to rise.

Research into the pathogenesis of these tumors in the context of HIV
has shed light on potential interactions of cytokines, HIV, other
viral co-factors (i.e., human papilloma virus in squamous cell cancer
of the anogenital region, and EBV in the high-grade primary central
nervous system lymphomas), and oncogenes.  Based on the current
information on the potential interactions in the formation of these
tumors, and the lack of effective, standard regimens, the NCI is
encouraging investigators to apply novel therapies or innovative
approaches in pilot or phase I or II clinical trials.

Research Goals And Scope

The aim of this RFA is to stimulate pilot, phase I, or phase II
therapeutic clinical trials in AIDS malignancies so that new
treatment strategies and new agents are moved more rapidly into the
clinic.  The ultimate goal of the NCI is to provide more effective
management and treatment for HIV-associated malignancies in children
and adult men and women.

The project will fund single or groups of institutions to perform
innovative therapeutic studies in AIDS malignancies.  The studies
should be restricted to pilot, phase I, or II trials, with
approximately 5 to 30 patients/trial.  Examples of potential clinical
studies to consider:  (1) combinations of interferon-alpha and/or
retinoic acid in anogenital dysplasia or cancer (recent report by
Lippman and associates of a 68 percent response rate in patients with
cutaneous squamous cell cancer, and a 50 percent major response rate
in patients with locally advanced squamous cell cancer of the
cervix); (2) angiogenesis inhibitors in Kaposi's sarcoma; (3) immune
modulating therapy with IL-4 (and subsequent down-regulation of IL-6,
which may have some role in the development of NHL or Kaposi's
sarcoma), anti-B4 blocked ricin immunoconjugate in NHL, or anti-sense
to potential viral cofactors such as HPV in Kaposi's sarcoma.  The
investigators are not limited to the above studies, and any
innovative therapies with appropriate rationale are sought.

Although the major purpose of these grants is to facilitate rapid
testing of novel agents or innovative approaches, tumor tissue or
other relevant biologic fluid collection is strongly encouraged for
ongoing or future investigations of laboratory correlates.  The
interchange of ideas and tumor tissue between the recipients of the
grants will be encouraged.  The research plan should be focused on
the clinical trial proposed.  Laboratory studies addressing
correlative issues to the clinical trials may be included but are not
necessary.  Clinical studies must involve human subjects and be
designed to ultimately improve cancer treatment.  The clinical
studies must be based on a strong rationale and preclinical data
should support the underlying hypothesis.

STUDY POPULATIONS

SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH
POLICIES CONCERNING INCLUSION OF FEMALES AND MINORITIES IN CLINICAL
RESEARCH STUDY POPULATIONS

NIH policy is that applicants for NIH clinical research grants and
cooperative agreements will be required to include minorities and
females 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 females 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 females or
minorities are excluded or inadequately represented in clinical
research, particularly in proposed population-based studies, a clear
compelling rationale should be provided.  As Kaposi's sarcoma occurs
predominantly in men, the lack of female participation should be
rationally explained.

The composition of the proposed study population must be described in
terms of gender and racial/ethnic group, together with a rationale
for its choice.  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 the Research
Plan, 1-4, AND summarized in Section 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 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 females 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.

Peer reviewers will address specifically whether the research plan in
the application conforms to these policies.  If the representation of
females 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.

LETTER OF INTENT

Prospective applicants are asked to submit, by February 1, 1993, a
letter of intent that includes a descriptive title of the proposed
research, the names and addresses of the Principal Investigators, the
names of other investigators and key personnel, the 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, it is requested
in order to provide an indication of the number and scope of
applications to be reviewed.

The letter of intent is to be sent to Dr. Roy S. Wu at the address
listed under INQUIRIES.

APPLICATION PROCEDURES

The PHS 398 (rev 9/91) research grant application form is to be used
in applying for this RFA.  These forms are available at most
institutional offices of sponsored research; from the Office of
Grants Inquiries, Division of Research Grants, National Institutes of
Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone
(301) 496-7441; and from the NCI Program Director named below.

The RFA label available in the PHS 398 research grant 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 number and title must be typed on line 2a of the
face page of the application form.

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 must be included with
the application.

Submit the signed, typewritten original application, including the
Checklist, and three signed, exact photocopies of each R03.  The
photocopies must be clear and single sided.

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

At the time of submission, send two additional copies of each
application to:

Referral Officer
Division of Extramural Activities
National Cancer Institute
Westwood Building, Room 838
Bethesda, MD  20892

Applications must be received by April 23, 1993.  If an application
is received after that date, it will be returned.  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.  This does not preclude the submission of substantial
revisions of applications already reviewed, but such applications
must include an introduction addressing the previous critique.

REVIEW CONSIDERATIONS

Review Procedure

Upon receipt, applications will be reviewed for completeness by the
DRG and responsiveness by the NCI.  Incomplete applications will be
returned to the applicant without further consideration.
Applications that are judged to be non-responsive will be returned to
the applicant by the NCI.  Applications judged to be non-responsive
to this RFA may be submitted as an investigator initiated regular
research grant (R01) or as a project within a program project grant
(P01) at the next receipt date.  The application would require
modification in accordance with R01 or P01 guidelines.  The revised
application would not be considered an application for a small grant
nor would it be considered a response to another RFA.  Questions
concerning the responsiveness of proposed research to the RFA may be
directed to program staff (see INQUIRIES).

Applications may be triaged by an NCI peer review group on the basis
of relative competitiveness.  The NCI will withdraw from further
competition those applications judged to be non-competitive for award
and notify the applicant Principal Investigator and institutional
official.  Those applications judged to be competitive will undergo
further scientific merit review.  Those applications that are
complete and responsive will be evaluated in accordance with the
criteria stated below for scientific/technical review by an
appropriate peer review group convened by the Division of Extramural
Activities, NCI.  Institutional Review Board (IRB) approval must have
been received and the date of approval provided to NCI prior to peer
review.  If this information is not provided prior to peer review,
the application will be withdrawn from competition by the NCI and
returned to the applicant without review.  The second level of review
will be provided by the National Cancer Advisory Board.

Review Criteria

The factors considered in evaluating the scientific merit of each
application will be:

o  Extent to which the proposed research addresses the goals 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  Research or clinical experience, training, time availability, and
qualifications of the investigators involved;

o  Adequacy of plans for effective collaboration among laboratory,
clinical, and statistical investigators;

o  Adequacy of the available resources and environment (e.g.,
facilities, equipment, statistical resources; patient population);

o  Adequacy of the mechanisms for quality control, study monitoring,
data management and reporting, and data analysis;

o  Adequacy of provisions for the protection of human subjects;

o  Adequacy of the plans for inclusion of females and minorities.

The reviewers will also judge the appropriateness of the proposed
budget and duration in relation to the proposed research.

AWARD CRITERIA

The anticipated date of award is September 30, 1993.  In addition to
the technical merit of the application, the NCI will consider how
well the applicant institution meets the goals and objectives of the
program as described in the RFA, availability of resources, and study
populations.

INQUIRIES

Written and telephone inquiries concerning the objectives and scope
of this RFA and inquiries about whether or not specific proposed
research would be responsive are encouraged and may be directed to
NCI Program Directors at the addresses below.  The NCI Program
Directors welcome the opportunity to clarify any issues or questions
from potential applicants.

For technical information:

Dr. Roy S. Wu
Cancer Therapy Evaluation Program
Division of Cancer Treatment
National Cancer Institute
Executive Plaza North, Room 734
Bethesda, MD  20892
Telephone:  (301) 496-8866
FAX:  (301) 480-4663

For business information:

Ms. Joan Metcalfe
Grants Management Specialist
National Cancer Institute
Executive Plaza South, Room 242
Bethesda, MD  20892
Telephone:  (301) 496-7800, ext. 28
FAX:  (301) 496-8601

Applicants who use express mail or a courier service are
advised to follow the carrier's requirements for showing a street
address.  The addresses for the Executive Plaza North and the
Executive Plaza South are:

Executive Plaza North              Executive Plaza South
6130 Executive Boulevard           6120 Executive Boulevard
Rockville, MD  20852               Rockville, MD  20852

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic
Assistance No 93.395, Cancer Treatment Research.  Awards are made
under the authorization of the Public Health Service Act, Title IV
Sections 301, 410, and 411, Part A (Public Law 78-410, 42 USC 241 as
amended, Public Law 99-158, 42 USC 285a) and administered under PHS
grants policies and Federal Regulations at 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.


$$XID RFA DK9319 DK-93-19 P1O1 *****************************************

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; K.W. 0705075, 0715125

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.