Subject: NIH GUIDE - RFA DK-92-04 - V20(44) 11/22/91
From: Dot Baker <[email-masked]>
To: [email-masked]
Date: Thu, 21 Nov 91 13:50 EST

Hi Paul,
   Please post to the NIH Listserver as:
      RFADK-92-04.911122
                        Dottie
 ---------------------------- Text of forwarded message -----------------------
$$XID RFA DK9204 DK-92-04 P1O1 *****************************************
 
COORDINATING CENTER FOR INTERSTITIAL CYSTITIS DATA BASE
 
RFA:  DK-92-04
 
P.T. 34; K.W. 0755018, 0413001, 0785055
 
National Institute of Diabetes and Digestive and Kidney Diseases
 
Letter of Intent Receipt Date:  January 10, 1992
Application Receipt Date:  February 18, 1992
 
PURPOSE
 
The Division of Kidney, Urologic and Hematologic Diseases (DKUHD),
National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK), invites cooperative agreement applications for a central data
coordinating center that will participate with clinical centers in the
development of a data base for interstitial cystitis (IC).  The purpose
of this data base is to determine the natural history of this disorder.
The clinical centers, which have been selected from a previous
solicitation, will prospectively obtain uniform demographic and
diagnostic information as well as clinical samples such as bladder
biopsies from patients with IC.  Data will be transmitted and samples
sent to a central data coordinating center for analysis.  The data
coordinating center will collect, maintain and analyze data and assess
patient samples provided by the clinical centers.  The primary
objectives of this investigation are:  (1) to establish and maintain a
data base of uniformly and accurately collected information, including
results of the analysis of clinical samples, from patients with IC; (2)
to study the natural history of this disorder; and (3) to make
available the data base and patient samples for other interested
investigators to conduct epidemiological and clinical studies.
 
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), Data coordinating Center for the Interstitial
Cystitis Data Base, is related to the priority area of diabetes and
chronic disabling diseases.  Potential applicants may obtain a copy of
"Healthy People 2000" (Full Report: Stock No. 017-001-00473-1) 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).
 
RESEARCH OBJECTIVES
 
Background
 
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, predominantly 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 contained 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, and the
unpredictable and variable remission and recrudescence of symptoms.
 
A first step in better understanding the nature of this disorder is the
establishment of a data base of well- characterized patients with IC
whose disease course will be carefully documented during the period of
follow-up.
 
This RFA is in response to Senate Report 101-516 for the Departments of
Labor, Health and Human Services and Related Agencies Appropriations
Bill, 1991, that provided funds for the NIDDK to establish a national
IC registry.
 
Goals and Scope of the Activity
 
The primary purpose of this activity is to initiate a collaborative
study to develop an IC data base through the collection and analysis of
information and clinical samples from patients with the disorder.  A
protocol and manual of operations will be designed by a Steering
Committee, consisting of investigators of the Clinical Centers,
specialized consultants, representatives of the Data Coordinating
Center, and the NIDDK Project Coordinator.  Patients recruited and
admitted into the study after having met agreed upon diagnostic entry
criteria will have standard demographic information, symptoms related
to IC, and clinical samples collected from them at established
intervals.
 
The primary objectives of this patient data base include the following.
 
1.  To identify the age, sex, race, and other demographic
characteristics of patients with IC.
 
2.  To determine the natural history of this disorder.
 
3.  To collect and analyze patient samples provided by the Clinical
Centers, including bladder biopsies, that may be useful in the
diagnosis of IC.
 
4.  To act as a data and patient sample repository for use by other
investigators wishing to conduct epidemiological and clinical studies.
 
The protocol will be subject to review by an independent expert group,
the External Advisory Committee.  The study will move into its
operational phase following concurrence by awardees and the NIDDK.
 
Data and patient sample collection will take place in the four Clinical
Centers.  Each Clinical Center is expected to recruit a minimum of 50
patients with the diagnosis of IC per year for four years, or a total
of 200 patients.  Because of the difficulty in the diagnosis of this
disorder, uniform diagnostic criteria have been established and
published (Journal of Urology 142(1): 139, 1989 and American Journal of
Kidney Diseases 8(4):353, 1989).  It is expected that there will be an
initial six to eight month period of collaborative protocol development
prior to patient enrollment, 48 months of patient recruitment, and six
months of final data analysis and reporting of results at the
conclusion of recruitment.
 
The NIDDK will support the function of a separate Data Coordinating
Center (DCC) for the study as outlined in this RFA.  The DCC will have
primary responsibility for collecting, editing, and analyzing data
generated by the Clinical Centers and collection and analysis of
bladder biopsy material and other patient samples.
 
The DCC and Clinical Centers will have primary access and rights to
data and patient samples.  Study investigators will be responsible for
establishing procedures for reviewing requests for use of data and
samples from researchers not directly participating in the study.
 
Study Components
 
1.  Clinical Centers -- A Clinical Center is an institution that is
actively involved in the recruitment, evaluation, and follow-up of
study patients.  The Clinical Center Principal Investigator will also
participate in protocol development for the trial, through the Steering
Committee.  A Clinical Center consists of a small team of researchers,
including part-time effort from a Principal Investigator,
research/nurse coordinator, and clerical staff.  The following
institutions have been awarded grants, from a previous solicitation,
for Interstitial Cystitis Clinical Centers:  University of California
at San Diego, The University of Pennsylvania, Northwestern University,
and the William Beaumont Hospital.
 
2.  Data Coordinating Center -- The DCC will have primary
responsibility for collecting, editing, storing, and analyzing data and
assessing patient samples provided by the Clinical Centers.  The DCC
must be prepared to design a data and patient specimen collection
system, assure quality control and provide appropriate detailed data
reports to the Steering Committee and to the External Advisory
Committee at regular intervals, and would be responsible for the
logistics, planning, and funding of the meetings of these committees.
The DCC would be expected to provide appropriate biostatistics, data
management, handling of patient samples, interpretation and
distribution, and study-wide coordination expertise.  Applicants for
the DCC must provide a detailed description of prior experience in
multicenter studies.  DCC applicants must identify in their
applications a collaborating Central Laboratory (or laboratories) for
testing patient samples, including bladder biopsies.  The Central
Laboratory would be responsible for establishing procedures for
collection of patient samples, including bladder biopsies, serum and
urine samples, testing these samples and reporting results to the DCC
and Clinical Centers, maintaining laboratory quality control
procedures, and providing periodic training in specimen collection and
transport procedures.  For a Central Laboratory supported by a
subcontract from the DCC, all NIH policies and procedures governing
consortium grants must be adhered to.
 
3.  Steering Committee -- A Steering Committee, including Investigators
of the Clinical Centers, specialized consultants, and representatives
of the DCC will be responsible for making the major scientific
decisions governing the conduct of the study, with assistance from the
NIDDK Project Coordinator.  Each member of the Steering Committee will
have one vote.  The Chairman of the Steering Committee will be selected
by members of the Steering Committee.
 
4.  External Advisory Committee -- An External Advisory Committee
composed of experts in relevant medical, statistical, and bioethical
fields will be established to periodically review the progress of the
study and provide advice regarding this progress to the Steering
Committee and NIDDK.  The Chairman of the Steering Committee, the
Principal Investigator of the DCC, and the NIDDK Project Coordinator
may participate as ex-officio non-voting members of this Committee.
External Advisory Committee members will be selected by members of the
Steering Committee.
 
5.  Project Coordinator -- The NIDDK will name the Urology Program
Director within the Division of Kidney, Urologic and Hematologic
Diseases, to be the Project Coordinator, to assist the Steering
Committee and External Advisory Committee in carrying out the study.
The Project Coordinator will provide scientific support to awardees
activities including:  protocol development, quality control, interim
data monitoring, final data analysis and interpretation, preparation of
publications, and performance monitoring.
 
Study Phases
 
The entire study will consist of three sequential phases as follows:
 
Phase I    Development of Protocol (six to eight months)
Phase II   Recruitment of Study Sample and Interim Data Analysis (48
months)
Phase III  Final Data Analysis and Reporting (six months)
 
Phase I will be completed by the Steering Committee prior to the
involvement of the DCC.
 
Study Responsibilities, Governance, and Funding
 
The primary governing body of the study will be the Steering Committee.
All major scientific decisions concerning protocol development will be
determined by vote of the Steering Committee.  The Committee will have
primary responsibility for the development of the study protocol,
facilitating the conduct of the study, and reporting of study results.
 
It is expected that data and patient samples will be submitted
centrally and that the protocol will define rules regarding access to
data, patient samples and publications.  Study investigators have
primary access to patient data and samples and responsibility for
deciding upon their distribution.  Formal, written requests for use of
study data and samples by non-study investigators will be required.
These requests will be reviewed and acted upon by the Steering
Committee or one of its subcommittees.  Criteria for this review will
be developed as part of study protocol.  An External Advisory Committee
will review progress at least semi- annually and provide advice to the
investigators and the NIDDK regarding progress of the study.
 
Study Phases Budget
 
Each applicant must submit an adequately justified budget for the
entire anticipated project period of five years.  The budget must
include travel funds for DCC members to attend quarterly Steering and
Advisory Committee meetings.  The budgets for each budget period of the
study must be clearly delineated.  The 01 budget period of the grant
will be for a 12-month period July 1, 1992 through June 30, 1993, which
begins in the recruitment phase (Phase II of the trial).  Recruitment
will continue through February 29, 1996.  Phase III, the last six
months of the clinical participation in the study will be from March 1,
1996 through August 31, 1996.  The DCC will continue through June 30,
1997, for data analysis and the writing of publications.
 
The 02, 03, and 04 budget periods for which individual budgets must be
prepared will be for the following 12- month periods:  July 1, 1993 -
June 30, 1994; July 1, 1994 - June 30, 1995; July 1, 1995 - June 30,
1996.  The 05 budget period will be for July 1, 1996 - June 30, 1997.
 
MECHANISM OF SUPPORT
 
The administrative and funding mechanism to be used to undertake this
program will be the cooperative agreement (U01).  The cooperative
agreement is an award instrument establishing an assistance
relationship between NIH and a recipient, in which substantial
programmatic involvement is anticipated between NIH and the recipient,
during performance of the contemplated activity.  NIH assists,
supports, and/or stimulates, and is involved substantially with
recipients in conducting projects similar in program intent to those
for grants, facilitating performance of the effort in a "partner" role.
 
It is anticipated that one award of approximately $250,000 total costs,
during the first year for a Data Coordinating Center, will be made
under this RFA.  Funding is expected to begin in Fiscal Year 1992;
total support for the project will be for approximately five years.
However, based on recommendations from the Steering Committee and the
External Advisory Committee, the NIDDK may wish to extend follow-up of
study participants recruited in the latter half of the study for an
additional one to two years.  This extension in follow-up would also be
supported under the cooperative agreement mechanism.
 
TERMS AND CONDITIONS OF AWARD
 
The tasks or activities in which the awardee will have substantial
responsibilities include data and patient sample collection, quality
control, final data analysis and interpretation, control of
publications, the logistics and funding of Steering Committee meetings,
and collaboration with Clinical Center awardees.  All awardees will
have primary access and rights to data and samples collected in this
study.  The NIDDK Project Coordinator will assist in protocol
development, quality control, interim data monitoring, final data
analysis and interpretation, preparation of publications, and
performance monitoring.
 
The NIDDK reserves the right to terminate or curtail the study (or an
individual award) in the event of a substantial shortfall in (a)
patient recruitment, follow- up, data reporting, quality control, or
other major breach of the protocol; or (b) substantial changes in the
agreed-upon protocol to which the NIDDK does not agree; or (c) human
subject ethical issues that may dictate a premature termination.
 
Any disagreement that may arise in scientific-programmatic matters
between award recipients and NIDDK may be brought to arbitration.  An
arbitration panel will be composed of three members---one selected by
the Steering Committee (with NIDDK member not voting) or by the
individual awardee in the event of an individual disagreement, a second
member selected by NIDDK, and the third member selected by the two
prior members.  This special arbitration procedure in no way affects
the awardees' right to appeal an adverse action that is otherwise
appealable in accordance with the 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 administration guidelines, HHS Grant
Administration Regulations at 45 CFR part 74, and other HHS, PHS, and
NIH grants administration policy statements.
 
DISCIPLINE AND EXPERTISE
 
Skills in data base management; biostatistics; collection and
assessment of patient samples, such as bladder biopsies; and the
development of collaborative studies are appropriate for the DCC.
Sub-contracting of various aspects of the tasks of the DCC to other
institutions with special expertise, e.g., experts in pathological
diagnosis, tissue preparation and storage, may be included in the
application.
 
ELIGIBILITY REQUIREMENTS
 
Domestic universities, medical colleges, hospitals, and other public
and private research institutions, including State and local government
units, are eligible. Applications from foreign institutions will not be
considered since only a small number of centers will participate in
this program.  Applications from minority investigators and women are
encouraged.
 
REVIEW PROCEDURES
 
Upon receipt, applications will be reviewed by NIDDK staff for their
responsiveness to the objectives of this RFA.  If an application is
judged unresponsive, the applicant will be contacted and given the
opportunity to withdraw the application, or have it considered for the
investigator-initiated research grant program.
 
In cases where the number of applications is large, the NIDDK may
conduct a preliminary scientific peer review to eliminate those
applications that are clearly not competitive.  The NIDDK will withdraw
from further competition those applications judged to be noncompetitive
and notify the applicant and institutional official.
 
Those applications judged to be both responsive and competitive will be
further evaluated according to the review criteria stated below for
scientific and technical merit by an appropriate peer review group,
convened by the Division of Extramural Activities, NIDDK.  Subsequent
review will be by the National Diabetes and Digestive and Kidney
Diseases Advisory Council.
 
If the application submitted in response to this RFA is substantially
similar to a grant application already submitted to the NIH for review,
but has not yet been reviewed, the applicant will be asked to withdraw
either the pending application or the new one.  Simultaneous submission
of identical applications will not be allowed, nor will essentially
identical applications be reviewed by different review committees.
Therefore, an application cannot be submitted in response to this RFA
that is essentially identical to one that has already been reviewed.
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 CRITERIA
 
The evaluation of applications for the DCC will be based primarily on
the scientific merit of the proposed study.  Specific criteria for
review of applications will be as follows:
 
1.  Documentation of the specific competence and previous experience of
professional, technical, and administrative staff pertinent to the
operation of a DCC for a collaborative study, and available on-site
medical consultation, and the time these professionals will devote to
the project.  Prior experience with similar studies in the collection
of data from multiple clinical sites, and experience in monitoring the
quality and timeliness of such data, must be demonstrated.  Experience
in collection and testing of patient samples from multiple clinic sites
must also be documented.
 
2.  The approach to soliciting cooperation from the participating
Clinical Centers and exercising appropriate leadership in data
acquisition, management, and analysis.
 
3.  Ability to identify and enlist the cooperation of a central
laboratory  or laboratories for processing patient samples and bladder
biopsy material.
 
4.  Suitability of the proposed data management and data analysis
plans.
 
5.  Suitability of proposed plans for collection and testing of patient
samples.
 
6.  Appropriateness of the budget for the proposed work.
 
7.  The adequacy of the proposed facility, technical hardware, and
space.
 
8.  The organizational and administrative structure of the proposed
program.
 
9.  Evidence of the degree of commitment and support of the
organization/institution for the proposed program, including the
relative position of the proposed project staff within the applicant
organizational structure.
 
SEMINAR FOR PROSPECTIVE APPLICANTS
 
A one-day seminar for prospective applicants will be held approximately
one month after the publication of this announcement.  The purpose of
this seminar is to give background information on the clinical aspects
of IC, an update on the activities of the Clinical Centers, and respond
to any questions about the preparation of an application in response to
this RFA.  Interested persons may contact the Urology Program Director,
Dr. Leroy M. Nyberg, for further information (see below).
 
METHOD OF APPLYING
 
Letter of Intent
 
Prospective applicants are asked but not required to submit a letter of
intent to apply to the RFA.  This letter is to include the name,
telephone number, and mailing address of the Principal Investigator,
the names of other key personnel, the name of the applicant
institution, and the number and title of this RFA.  Such a letter of
intent is not binding, 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 to apply to this RFA, are to be received by January
10, 1992, and are to be addressed to:
 
Dr. Robert D. Hammond
Chief, Review Branch
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
Westwood Building, Room 603
Bethesda, MD  20892
FAX:  (301) 402-1277
 
Format for Applications
 
Submit applications on form PHS 398 (rev. 10/88, reprinted 9/89), the
application form for the traditional NIH research project grant.
Copies of this form are available in the applicant institution's office
of sponsored research and may be obtained from the Office of Grants
Inquiries, Division of Research Grants, Westwood Building, Room 449,
National Institutes of Health, Bethesda, MD  20892, telephone:
301/496-7447.
 
Use the conventional format for research project grant applications and
ensure that the points identified in the section above on "Review
Procedures and Criteria" are fulfilled.  To identify the application as
a response to the RFA, CHECK "YES" on item 2 of page 1 of the
application and enter "DK-92-04, DCC for IC Data Base."
 
THE RFA LABEL FOUND IN THE FORM PHS 398 (REVISED 10/88, REPRINTED 9/89)
APPLICATION KIT MUST BE AFFIXED TO THE BOTTOM OF THE FACE PAGE OF THE
ORIGINAL COMPLETED APPLICATION FORM.  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.
 
Application Procedure
 
Send or deliver the completed, signed application and four complete
photocopies to the following, making sure that the original application
with the RFA label attached is on top:
 
Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
Bethesda, MD  20892
 
SEND TWO ADDITIONAL COPIES OF THE APPLICATION TO DR. HAMMOND AT THE
ADDRESS LISTED UNDER "LETTER OF INTENT." IT IS IMPORTANT TO SEND THESE
TWO COPIES AT THE SAME TIME AS THE ORIGINAL AND FOUR COPIES ARE SENT TO
THE DIVISION OF RESEARCH GRANTS, OTHERWISE THE NIDDK CANNOT GUARANTEE
THAT THE APPLICATION WILL BE REVIEWED IN COMPETITION FOR THE RFA.
 
Applications must be received by February 18, 1992.  An application not
received by this date will be returned to the applicant.
 
SCHEDULE
 
Letter of Intent:                           January 10, 1992
Application receipt date:                   February 18, 1992
Initial Review:                             April 1992
National Diabetes and Digestive and
 Kidney Diseases Advisory Council Review:   May/June 1992
Anticipated Award Date:                     July 1992
 
INQUIRIES
 
Inquiries regarding the clinical and scientific aspects of this
announcement may be directed to:
 
Leroy M. Nyberg, Jr., Ph.D., M.D.
Urology Program Director
Division of Kidney, Urologic and Hematologic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
Westwood Building, Room 3A-05
5333 Westbard Avenue
Bethesda, MD  20892
Telephone:  (301) 496-7133
FAX:  (301) 402-0223
 
Inquiries regarding fiscal and grants administration matters may be
directed to:
 
Mrs. Nancy Dixon
Grants Management Specialist
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
Westwood Building, Room 639
Bethesda, MD  20892
Telephone:  (301) 496-7467
 
AUTHORITY AND REGULATIONS
 
This program is 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 Grants 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.