INTERSTITIAL CYSTITIS CLINICAL RESEARCH NETWORK (ICCRN)  
 
RELEASE DATE:  September 17, 2002
 
RFA: DK-03-003
 
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
 (http://www.niddk.nih.gov)

LETTER OF INTENT RECEIPT DATE: October 11, 2002

APPLICATION RECEIPT DATE: November 14, 2002
  
THIS RFA CONTAINS THE FOLLOWING INFORMATION

o Purpose of this RFA
o Research Objectives
o Mechanism of Support 
o Funds Available
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Special Requirements 
o Where to Send Inquiries
o Letter of Intent
o Submitting an Application
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations

PURPOSE OF THIS RFA

The Division of Kidney, Urologic and Hematologic Diseases (DKUHD) of
the National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK) invites cooperative agreement applications for up to 10 Clinical 
Centers to participate in the development and conduct of randomized clinical 
trials to evaluate novel therapies in patients with interstitial cystitis as 
part of the Interstitial Cystitis Clinical Research Network (ICCRN). A Data 
Coordinating Center will be established to provide expertise in protocol 
development including sample size estimation, data analysis, quality control, 
and data management. The Data Coordinating Center will be established through 
a separate cooperative agreement Request for Applications. Ancillary studies 
will be developed by the ICCRN investigators to be conducted in conjunction 
with the clinical trials. The Clinical Centers and the Data Coordinating 
Center will work cooperatively to conduct clinical trials sequentially or 
concurrently.  Because there is substantial commonality in the design and 
conduct of clinical trials for patients with interstitial cystitis and 
chronic prostatitis, or the chronic pelvic pain syndrome, applicants to this 
RFA are invited but not required to apply to a companion RFA also being 
released.  The companion RFA, DK-03-004 titled, Chronic Prostatitis Clinical 
Research Network (CPCRN) is available at: 
http://grants.nih.gov/grants/guide/rfa-files/RFA-DK-03-004.html.  Investigators 
from the ICCRN and the CPCRN will participate in an overarching organization, 
the Urological Chronic Pelvic Pain Syndromes Collaborative Group (UCPPSCG), The 
UCPPSCG will serve to improve the efficiency of protocol development, develop 
common definitions and criteria, and facilitate common data collection, to 
permit comparisons between the clinical trials and the individual disorders.  
This coordination is needed in key areas of protocol development including 
establishment of disease and enrollment criteria, outcome measures, and 
identification of therapies to be evaluated.
 
RESEARCH OBJECTIVES

Background

Interstitial Cystitis is a chronic disorder, diagnosed primarily in women, 
characterized by pelvic pain associated with urinary frequency and urgency. 
Despite considerable effort the etiology of interstitial cystitis has not 
been established.  Moreover, the treatment of interstitial cystitis remains 
sub-optimal. Despite the availability of a large number of purported 
treatments for interstitial cystitis there have been very few rigorously 
conducted randomized clinical trials to justify the use of many of these 
agents. 

The NIDDK has a longstanding interest in clinical and epidemiological 
research for interstitial cystitis and chronic pelvic pain disorders in men. 
In 1991 the Interstitial Cystitis Database (ICDB) study was initiated.  The 
ICDB Study was a 5-year prospective cohort study of over 600 men and women 
with symptoms of urinary urgency, frequency, and pelvic pain.  Reports have 
described the longitudinal changes of urinary symptoms, the impact of 
interstitial cystitis on quality of life, treatment patterns and the 
relationship between findings from bladder biopsies with patient symptoms.  
As a follow-up to the ICDB Study the NIDDK issued an RFA in 1997 to establish 
the Interstitial Cystitis Clinical Trials Group (ICCTG) to plan and conduct 
randomized controlled clinical trials of promising therapies for patients 
with interstitial cystitis.  Two clinical trials have been conducted by the 
ICCTG, one used oral therapy while the other trial administered treatment 
intravesically. Ancillary studies of various biomarkers were developed and 
conducted in conjunction with this trial.  The NIDDK now wishes to build on 
the work begun by the ICCTG and conduct additional clinical trials, either 
sequentially or concurrently, over a second 5-year period.

The NIDDK-supported program, the Chronic Prostatitis Collaborative Research 
Network (CPCRN), was carried out over essentially the same time period as the 
ICCTG.  The CPCRN enrolled nearly 500 men in a prospective cohort study and 
also conducted a randomized clinical trial in nearly 200 men. Over the course 
of the ICCTG and the CPCRN it has become apparent that there were similar 
approaches to conduct clinical trials for these two conditions, including 
development/use of validated symptom indices to measure response to 
treatment, the need for institutions to become referral centers for these 
conditions in order to achieve recruitment goals, and challenges to identify 
novel therapies that allow for rapid accrual of clinical trial participants. 

Thus, investigators responding to this research solicitation are encouraged 
to submit grant applications to the RFA for the Chronic Prostatitis Clinical 
Research Network (RFA DK-03-004).  Successful applicants for these RFAs will 
work together as the Urological Chronic Pelvic Pain Syndromes Collaborative 
Group with the goals to shorten the period of protocol development for the 
two clinical trials groups, to collect common information to permit 
comparisons of the clinical characteristics of these two conditions, to 
develop clinically relevant definitions of the urologic chronic pelvic pain 
syndromes, to facilitate decisions on treatments to be evaluated, and to 
increase the rate of accrual of study participants.  
Organization of the Interstitial Cystitis Clinical Research Network

The Interstitial Cystitis Clinical Research Network will be a cooperative 
network of up to 10 Clinical Centers, one Data Coordinating Center, and the 
Division of Kidney, Urologic and Hematologic Diseases.  Clinical Centers are 
responsible for proposing and prioritizing protocols, participating in 
protocol development, conducting the trials, developing and participating in 
ancillary studies related to the trials, and disseminating research findings.  
All individual Clinical Centers are required to participate in a cooperative 
and interactive manner with one another and with the Data Coordinating Center 
in all aspects of the network.  The Data Coordinating Center will support 
protocol development and provide sample size calculations, statistical 
advice, data analysis, data management and quality control, and coordinate 
the activities of the Steering Committee, and overall study coordination and 
quality assurance.  Because the protocols to be implemented by the ICCRN will 
be developed cooperatively specific clinical trial and ancillary study 
designs are not called for in this RFA.

A Steering Committee composed of the principal investigators of the Clinical 
Centers and the Data Coordinating Center and the NIDDK Project Scientist will 
be the main governing body of the ICCRN.  Each Clinical Center, the Data 
Coordinating Center, and the NIDDK will have one vote.  All major scientific 
decisions will be determined by majority vote of the Steering Committee.  The 
Steering Committee will have primary responsibility for the general 
organization of the network, finalizing common clinical protocols, 
facilitating the conduct and monitoring of the studies, and reporting study 
results.

Subcommittees of the Steering Committee will be established as necessary, for 
example it is envisioned that committees will be established for study 
design, forms development, ancillary studies, recruitment, publications and 
presentations, and others as necessary.

An independent Data and Safety Monitoring Board (DSMB) will be established by 
the NIDDK from among experts in urology, urogynecology, biostatistics, 
behavioral medicine, nursing, and ethics.  The DSMB will review the protocols 
prior to implementation and monitor patient safety and review protocol 
performance at least annually.  As part of its monitoring responsibility the 
DSMB will submit recommendations to NIDDK regarding the continuation of each 
study and prepare a report for principal investigators to provide to their 
institutional review boards (IRBs). 

An overarching administrative structure for the ICCRN and the Chronic 
Prostatitis Clinical Research Network (to be funded under RFA DK-03-004), 
known as the Urological Chronic Pelvic Pain Syndromes Collaborative Group, 
will be created to coordinate the development of protocols for each of these 
networks and to facilitate comparative analyses of the clinical and 
demographic characteristics of the trial participants as well as outcomes.  
It is envisioned that at a portion of the Steering Committee meetings for the 
ICCRN and CPCRN will be held jointly.

Objectives of research program:

The objectives of the research program described in this RFA are to:

1) establish a collaborative group of clinical trial centers with clinical 
expertise in  chronic pelvic pain, clinical pain management, and interstitial 
cystitis

2) design randomized controlled clinical trials  to  treat the symptoms 
associated with interstitial cystitis

3) develop and conduct ancillary studies, which will provide further 
understanding of interstitial cystitis

4) determine if there is a different response to therapy between newly 
diagnosed and chronic, long-term patients with the disorder

5) recruit sufficient numbers of patients with interstitial cystitis, 
including an adequate number of newly diagnosed cases, into these clinical 
trials

6) jointly work with other Interstitial Cystitis Clinical Research Network 
investigators, including the Data Coordinating Center, to analyze and 
interpret the results of the trials

7) participate in the Urological Chronic Pelvic Pain Syndromes Collaborative 
Group to facilitate the efficient conduct of clinical trials in both 
interstitial cystitis and chronic prostatitis

8) develop a clinically relevant definition of the urologic chronic pelvic 
pain syndromes, based on the clinical findings from these and other related 
clinical studies.
 
MECHANISM OF SUPPORT
 
This RFA will use the NIH U01 award mechanism.  As an applicant you will be 
solely responsible for planning, directing, and executing the proposed 
project.  This RFA is a one-time solicitation.  The anticipated award date is 
July 1, 2003.
The NIH U01 is a cooperative agreement award mechanism in which the Principal 
Investigator retains the primary responsibility and dominant role for 
planning, directing, and executing the proposed project, with NIH staff being 
substantially involved as a partner with the Principal Investigator, as 
described under the section "Cooperative Agreement Terms and Conditions of 
Award"  

FUNDS AVAILABLE 
 
The NIDDK intends to commit approximately $3,200,000 in FY 2003 to fund up to 
10 Clinical Centers in response to this RFA. This amount includes $700,000 
for the trial-wide conduct of concurrent ancillary studies.   An applicant 
should request a project period of up to 5 years and a budget for total costs 
of up to $320,000 per year. The costs should be divided as follows: $250,000 
total costs per year to conduct the clinical trials and $70,000 total costs 
each year to be set aside for ancillary studies.  The protocols for the 
ancillary studies to be conducted by the ICCRN will be developed 
collaboratively by the Steering Committee. Although the financial plans of 
the NIDDK provide support for this program, awards pursuant to this RFA are 
contingent upon the availability of funds and the receipt of a sufficient 
number of meritorious applications.  At this time it is not known if this RFA 
will be reissued.  The NIDDK is committed to providing support to the 
Clinical Centers in relation to the number of participants randomized and 
followed-up.  To that end, in Year 2 of the program support will be provided, 
in part, on a per-successfully-enrolled participant basis.
 
ELIGIBLE INSTITUTIONS
 
You may submit an application if your institution has any of the following 
characteristics: 
	
o For-profit or non-profit organizations 
o Public or private institutions, such as universities, colleges, hospitals, 
and laboratories 
o Units of State and local governments
o Eligible agencies of the Federal government  
o Domestic or foreign

INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS   

Any individual with the skills, knowledge, and resources necessary to carry 
out the proposed research is invited to work with their institution to 
develop an application for support.  Individuals from underrepresented racial 
and ethnic groups as well as individuals with disabilities are always 
encouraged to apply for NIH programs. 

Principal investigators must be physicians with clinical expertise related to 
interstitial cystitis and/or chronic prostatitis and the urologic chronic 
pelvic pain syndrome of. Experience in recruiting interstitial cystitis 
patients into randomized clinical trials and successfully following them is 
essential.  Principal investigators are encouraged to establish a multi-
disciplinary team including expertise in such clinical areas as chronic pain 
management, behavioral medicine, and other chronic pelvic pain disorders.  

SPECIAL REQUIREMENTS

The ability to recruit (and retain a high proportion) a sufficient number of 
patients into the clinical trials to be performed by the ICCRN is the most 
important requirement for a successful Clinical Center.  It is projected that 
each Clinical Center will need to have the capacity to randomize 4-6 study 
participants each month beginning in year 2 of the program and continuing 
through year 4.  It is likely that at least one of the clinical trial 
protocols will require newly diagnosed cases of interstitial cystitis, 
representing at least one-third of the overall participants to be recruited 
over the life of this program.  A center must also participate in a 
collaborative and interactive manner to develop the study protocols (both 
clinical trial and ancillary studies) and carry out the trials/ancillary 
study protocols of the Interstitial Cystitis Clinical Research Network and 
must be willing to participate as a member of the Urological Chronic Pelvic 
Pain Syndromes Collaborative Group.

Cooperative Agreement Terms and Conditions of Award

The following terms and conditions will be incorporated into the award 
statement and provided to the Principal Investigator(s) as well as the 
institutional official at the time of the award.  These special Terms of 
Award are in addition to and not in lieu of otherwise applicable OMB 
administrative guidelines, HHS Grant Administration Regulations at 45 CFR 
Parts 74 and 92, the NIH Grant Policy statement.

The administrative and funding instrument used for this program is a 
cooperative agreement (U01), an "assistance" mechanism (rather than an 
"acquisition" mechanism) in which substantial NIH scientific and/or 
programmatic involvement with the awardee is anticipated during the 
performance of the activity.  Under the cooperative agreement, the NIH 
purpose is to support and/or stimulate the recipient"s activity by 
involvement in and otherwise working jointly with the award recipient in a 
partner role, but it is not to assume direction, prime responsibility, or a 
dominant role in the activity.  Consistent with this concept, the dominant 
role and prime responsibility for the activity resides with the awardee(s) 
for the project as a whole, although specific tasks and activities in 
carrying out the studies will be shared among the awardees and the NIDDK 
Project Scientist.

1) Awardees Rights and Responsibilities

The awardee(s) will have lead responsibilities in all aspects of development 
and implementation of the clinical trial protocols, including any 
modification of study design, conduct of the trials and ancillary studies, 
quality control, data analysis and interpretation, preparation of 
publications, and collaboration with other investigators, unless otherwise 
provided for in these terms or by action of the Steering Committee.  
Modification of protocols will be approved by the Steering Committee.  
Awardees will follow a common protocol and manual of procedures for all 
clinical trials and ancillary studies conducted under this RFA.

Awardees will retain custody and have primary rights to their data developed 
under these awards, subject to Government rights of access consistent with 
current HHS, PHS, and NIH policies, for a period of one year after completion 
of the trial.  After that time the NIDDK expects that data will be made 
available to the broader scientific community via a Central Repository to be 
established by the NIDDK under a separate solicitation.  The collaborative 
protocol and governance policies will call for the continued submission of 
data centrally to the DCC for a collaborative database, procedures for data 
analysis, reporting and publication, and procedures to protect and ensure the 
privacy of medical data and records of individuals.  The NIDDK Project 
Scientist, on behalf of the NIDDK, will have the same access, privileges and 
responsibilities regarding the collaborative data as the other members of the 
Steering Committee.

2) NIH Staff Responsibilities

The NIDDK will name a Project Scientist from within the Division of Kidney, 
Urologic and Hematologic Diseases whose function will be to assist the 
Steering Committee in carrying out the study.  The Project Scientist will 
have substantial scientific-programmatic involvement in quality control, 
interim data analysis, safety monitoring, and final data analysis and 
interpretation, preparation of publications, and coordinating and performance 
monitoring.  The dominant role and prime responsibility for these activities 
resides with the awardees for the project as a whole, although specific tasks 
and activities in carrying out the studies will be shared among the awardees 
and the Project Scientist.  The NIDDK will have final approval of all 
protocols.  The NIDDK will assign a separate program official to be 
responsible for stewardship of the awarded grants.

The NIDDK reserves the right to terminate or curtail the trial (or an 
individual award) in the event of (a) failure to develop or implement a 
mutually agreeable collaborative protocol, (b) substantial shortfall in 
participant recruitment, follow-up, data reporting, quality control, or other 
major breach of the protocol, (c) substantive changes in the agreed-upon 
protocol with which the NIDDK cannot concur, (d) reaching a major study 
endpoint substantially before schedule with persuasive statistical 
significance or, (e) human subject ethical issues that may dictate a 
premature termination.

3) Collaborative Responsibilities

The Steering Committee, composed of each of the Principal Investigators of 
the DCC and the Clinical Centers, the NIDDK Project Scientist, and the 
Chairman of the Steering Committee, will be the main governing board of the 
trials.  This committee will have the primary responsibility for approval of 
the common clinical trial and ancillary study protocols, recruitment of 
participants, facilitating participant follow-up, adherence to specimen 
collection and shipping, monitoring of completeness of data collection and 
timely transmission of data to the DCC, and reporting of study results.  It 
will also be responsible for establishing study policies in such areas as 
ancillary studies, publications and presentation, and performance standards.  
Each member of the Steering Committee will have one vote and all major 
scientific decisions will be determined by a majority vote of the Steering 
Committee.  A Chairperson will be chosen either from among the Steering 
Committee members (but not the NIDDK Project Scientist), or alternatively, 
from among experts in the field of urologic chronic pelvic pain syndromes who 
are not participating directly in the study.  Subcommittees will be 
established for specific purposes as needed, such as for ancillary studies, 
publications and presentations, quality control, recruitment, protocol 
adherence, among others.

Each Clinical Center awardee and the Data Coordinating Center awardee agree 
to the governance of the study through the Steering Committee.  The Steering 
Committee voting membership shall consist of the Principal Investigators of 
the Clinical Centers and the Data Coordinating Center and the NIDDK Project 
Scientist. 

An organizational structure, the Urological Chronic Pelvic Pain Syndromes 
Collaborative Group, consisting of awardees for the Interstitial Cystitis 
Clinical Research Network and the Chronic Prostatitis Clinical Research 
Network (to be funded under RFA DK-03-004), will be established.  The 
awardees agree to participate in this group to facilitate the efficient 
design and conduct of clinical trials for both interstitial cystitis and 
chronic prostatitis.  Members of the Collaborative Group will include 
Clinical Center Principal Investigators of the ICCRN and the CPCRN, the 
Principal Investigator(s) of the Data Coordinating Center(s) for both of the 
networks, and the NIDDK Project Scientist.  As members of the Urological 
Chronic Pelvic Pain Syndromes Collaborative Group investigators will hold 
joint Steering Committee meetings to facilitate use of common outcome 
measures and other data collection and to share data from their studies.  
They will also share a common Data and Safety Monitoring Board.
  
4) Establishment of a Data and Safety Monitoring Board

The NIDDK will establish an independent Data and Safety Monitoring Board with 
expertise from a variety of disciplines, for example, urology, urogynecology, 
chronic pelvic pain, biostatistics, behavioral medicine, nursing and ethics.  
The DSMB will be advisory to the NIDDK and will have the responsibility for 
reviewing and approving protocols prior to implementation.  The NIDDK 
Guidelines on DSMB can be found at the following URL: 
http://www.niddk.nih.gov/patient/patient.htm#policy. Once a trial has been 
initiated they will have responsibility for review of patient safety, 
adherence to the study protocol, and evaluation of interim and final results.  
A joint DSMB for the Interstitial Cystitis Clinical Research Network and the 
Chronic Prostatitis Clinical Research Network will be established. All 
protocols developed by the Steering Committee will be reviewed by the DSMB 
and the NIDDK Project Scientist for adequacy of plans for subgroup analyses 
based on gender and minority group.

5) Arbitration

Any disagreement that may arise in scientific/programmatic matters (within 
the scope of the award), between award recipient and the NIDDK may be brought 
to arbitration.  An arbitration panel will be composed of three members, one 
selected by the Steering Committee (with the 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 awardee"s 
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 regulation at 
45 CFR part 16, or the rights of NIDDK under applicable statutes, regulations 
and terms of the award.

WHERE TO SEND INQUIRIES

We encourage inquiries concerning this RFA and welcome the opportunity to 
answer questions from potential applicants.  Inquiries may fall into three 
areas:  scientific/research, peer review, and financial or grants management 
issues:

o Direct your questions about scientific/research issues to:

John W. Kusek, Ph.D. 
Clinical Trials Program Director
Division of Kidney, Urologic and Hematologic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
Two Democracy Plaza, Room 617
6707 Democracy Boulevard
Bethesda, MD  20892-5458
Telephone:  (301) 594-7735
Fax:  (301) 480-3510
Email:  [email protected] 

Leroy M. Nyberg, Ph.D., M.D.
Urology Program Director
Division of Kidney, Urologic and Hematologic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
Two Democracy Plaza, Room 617
6707 Democracy Boulevard
Bethesda, MD  20892-5458
Telephone:  (301) 594-7717
Fax:  (301) 480-3510
Email:  [email protected]

o Direct your questions about peer review issues to:

Francisco O. Calvo, Ph.D.
Chief, Review Branch
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard
Room 752, MSC 5452
Bethesda, MD 20892-5452
Telephone:  (301) 594-8885
FAX:  (301) 480-3505
Email:  [email protected]

o Direct your questions about financial or grants management matters to:

Teresa Farris Marquette
Senior Grants Management Specialist
Grants Management Branch
National Institute of Diabetes and Digestive and Kidney Diseases
Room 758, MSC 5452
Two Democracy Plaza
6707 Democracy Boulevard
Bethesda, Maryland 20892-5452
Telephone: (301) 594-7682
FAX: (301) 480-3504
Email: [email protected]
 
LETTER OF INTENT
 
Prospective applicants are asked to submit a letter of intent that includes 
the following information:

o Descriptive title of the proposed research
o Name, address, and telephone number of the Principal Investigator
o Names of other key personnel 
o Participating institutions
o Number and title of this RFA 

Although a letter of intent is not required, is not binding, and does not 
enter into the review of a subsequent application, the information that it 
contains allows IC staff to estimate the potential review workload and plan 
the review.
 
The letter of intent is to be sent by the date listed at the beginning of 
this document.  The letter of intent should be sent to:

Chief, Review Branch 
Division of Extramural Activities, NIDDK
6707 Democracy Boulevard, Rm. 752 MSC 5452
Bethesda, MD  20892-5452
(For express/courier service: Bethesda, MD  20817)
Telephone:  (301) 594-8897
FAX:  (301) 480-3505

SUBMITTING AN APPLICATION

Applications must be prepared using the PHS 398 research grant application 
instructions and forms (rev. 5/2001).  The PHS 398 is available at 
http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive 
format.  For further assistance contact GrantsInfo, Telephone (301) 710-0267, 
Email: [email protected].
 
SUPPLEMENTAL INSTRUCTIONS: 1) Recruitment and Retention Capabilities: The 
application should discuss the number of participants the Clinical Center 
anticipates will be recruited for protocols for the Interstitial Cystitis 
Clinical Research Network. For the purposes of this application and these 
studies the definition of interstitial cystitis will not be the NIDDK 
research definition but will be a clinical definition based on the clinical 
experience of the applicant. Each applicant should describe his/her clinical 
definition of interstitial cystitis. This definition should only include 
criteria that have been published in peer-reviewed journals.  The application 
should provide evidence that the investigators are capable of randomizing 4-6 
participants per month in years 2 through 4 of the program, one-third of 
these participants must be newly diagnosed cases.  Applicants should describe 
the target population from which they expect to recruit the required number 
of subjects as study participants, and plans for recruitment of minorities, 
as required.  The applicant should include a brief discussion of previous 
relevant research efforts.  The applicant should also discuss in detail the 
recruitment strategies to procure the expected number of study participants.  
Specific plans for recruitment of minority participants must also be 
discussed.  Projections on recruitment should be based on prior experience in 
clinical trials.  Specific plans and previous experience in retaining 
randomized study participants for the duration of the clinical trial should 
also be documented.

2) Proposed Clinical Trial Concept:  The general concept draft for a single 
randomized controlled clinical trial to be considered by the ICCRN should be 
included in the application.  The general concept draft, which should not 
exceed two pages, must be consistent with the scientific focus of the RFA.  
Concept issues to be considered include identification of the intervention(s) 
and rationale, primary and secondary outcome measures, sample size estimate, 
and proposed subgroup analyses based on sex/gender and minority status.

3) Evidence of Institutional Support:  There should be evidence of strong 
institutional support for the Clinical Center (CC), including adequate space 
in which to conduct clinical activities and office space for staff.  An 
organizational structure for the CC should be set forth in the application, 
delineating lines of authority and responsibility for dealing with problems 
in all general areas as well as stated willingness to follow commonly agreed 
upon protocols.  The Principal Investigator should also indicate his/her 
willingness to and that of their institution to participate in a funding plan 
that reimburses for recruitment and follow-up on a per participant basis.

4) Ancillary Studies: It is not expected that the applicants propose specific 
ancillary studies to be conducted by the ICCRN.  These studies will be 
developed and designed by the ICCRN Steering Committee. Any ancillary studies 
proposed in the application will not be reviewed or considered in the overall 
priority score.

5) Willingness to Collaborate in the Network and the Urological Chronic 
Pelvic Pain Syndromes Collaborative Group: The applicant should indicate 
willingness to participate in the Network as outlined in this solicitation, 
fully participate in the Steering Committee meetings and abide by its 
decisions, and indicate prior experience in collaborative, multi-center 
research.  Investigators must also indicate willingness to participate in the 
Urological Chronic Pelvic Pain Syndromes Collaborative Group.

6) Use of a General Clinical Research Center:  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. In such a case, a letter of 
agreement from either the GCRC Program Director or Principal Investigator 
should be included with the application.

7) Per capita reimbursement: Applicants should indicate their willingness, 
and that of the institution involved, to discuss a financial arrangement for 
reimbursement on a per-participant basis (capitation) of operational costs 
for each trial.

BUDGET

Clinical centers should prepare a budget for each year of the five years of 
the program not to exceed $320,000 total costs (direct and facilities and 
administrative costs) per year, funds for operation of the Clinical Center 
must not exceed $250,000 total costs for each year.  Applicants must set 
aside a total of $70,000 (total costs) each year for five years for ancillary 
studies.  The funds for the ancillary studies should be included in the 
"other" budget category. The first 8 months of year 1 will be a period of 
intensive protocol development with monthly meetings of the Steering 
Committee to be held in the Washington, D.C. area.  The total percent effort 
for the Principal Investigator and co-investigator during this period should 
be 40%.  It is anticipated that recruitment for the first trial will begin in 
year 2.  Applicants should budget for key personnel for study coordination 
and data entry. In budget year 2, restricted by the budget cap of $250,000 
total costs for Clinical Centers, the NIDDK intends to fund the Clinical 
Centers under a plan to reimburse on a per randomized patient basis with 
infrastructure costs provided for key personnel to coordinate the trial and 
transmit data.  Beginning in year 2 and for the duration of the program, 
applicants should budget for three meetings each year of the Steering 
Committee to be generally held in the Washington, D.C. area.

USING THE RFA LABEL: The RFA label available in the PHS 398 (rev. 5/2001) 
application form must be affixed to the bottom of the face page of the 
application.  Type the RFA number on the label.  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 2 of the face page of the application form 
and the YES box must be marked. The RFA label is also available at: 
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf.
 
SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten original of 
the application, including the Checklist, and three signed, photocopies, in 
one package to:
 
Center For Scientific Review
National Institutes Of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD  20892-7710
Bethesda, MD  20817 (for express/courier service)
 
At the time of submission, two additional copies of the application and 5 
copies of appendix material, if warranted, must be sent to Chief, Review 
Branch at the address listed in the Where to Send Inquiries section.
 
APPLICATION PROCESSING: Applications must be received by the application 
receipt date listed in the heading of this RFA.  If an application is 
received after that date, it will be returned to the applicant without 
review.
 
The Center for Scientific Review (CSR) will not accept any application in 
response to this RFA that is essentially the same as one currently pending 
initial review, unless the applicant withdraws the pending application.  The 
CSR 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 already reviewed, but such applications must 
include an Introduction addressing the previous critique.

PEER REVIEW PROCESS  
 
Upon receipt, applications will be reviewed for completeness by the Center 
for Scientific Review and responsiveness by the National Institute of 
Diabetes and Digestive and Kidney Diseases.  

Incomplete and/or non-responsive applications will be returned to the 
applicant without further consideration.

Applications that are complete and responsive to the RFA will be evaluated 
for scientific and technical merit by an appropriate peer review group 
convened by the National Institute of Diabetes and Digestive and Kidney 
Diseases in accordance with the review criteria stated below.  As part of the 
initial merit review, all applications will:

o Receive a written critique
o Undergo a process in which only those applications deemed to have the 
highest scientific merit will be discussed and assigned a priority score
o Receive a second level review by the NIDDK National Advisory Council or 
Board. 
 
REVIEW CRITERIA

Applicants are expected to address issues identified under the following 
sections in this RFA: SPECIAL REQUIREMENTS, SUBMITTING AN 
APPLICATION/SUPPLEMENTAL INSTRUCTIONS as well as the OBJECTIVES OF THE 
RESEARCH PROGRAM. All applications will be reviewed according to the criteria 
listed below.  In the written comments, reviewers will be asked to discuss 
the following aspects of the application in order to judge the likelihood 
that the proposed research will have a substantial impact on the goals of 
this solicitation.  Each of the criteria will be addressed and considered in 
assigning the overall score, weighting them as appropriate for each 
application.  Note that the application does not 
need to be strong in all categories to be judged likely to have major 
scientific impact and thus deserve a high priority score.

o Patient access and study population
o Study design 
o Qualifications and experience
o Willingness to participate in the Network and the Urological Chronic 
Pelvic Pain Syndromes Collaborative Group
o Institutional resources for patient care and follow-up

Patient access and study population:  The ability to recruit a sufficient 
number of patients into the trials is essential.  It is anticipated that 4-6 
study participants will need to be randomized each month for the first 4 
years of the Network. At least one-third of the total must be newly diagnosed 
cases.  Applicants must provide creditable estimates of the number of 
patients with interstitial cystitis that they could screen each month to 
evaluate eligibility, provide realistic estimates for rates of participation 
(randomization), and identify all sources of potential study participants.  
Based on previous experience, applicants must specify their track record in 
recruiting for clinical trials of interstitial cystitis or other urological 
chronic pelvic pain disorders, including their achieved recruitment for each 
trial, the percent of goal, and their rates of follow-up at the end of the 
trial.

Proposed Clinical Trial Concept:  A brief concept draft regarding a proposed 
clinical trial should be included in the grant application.  The draft should 
include the intervention(s) and their rationale, primary and secondary 
outcome measures, sample size estimate, and a  plan for subgroup analysis 
based on sex/gender and minority status.

Qualifications and experience:  The expertise, training, and experience of 
the investigators and staff in interstitial cystitis clinical trials and 
other urological chronic pelvic pain disorders, evidence of understanding of 
randomized multi-center trials, administrative abilities of the Principal 
Investigator, study nurse and/data coordinator and the level of commitment to 
the program for the effective function of the Interstitial Cystitis Clinical 
Research Network.

Willingness and ability to participate in the Network and the Urological 
Chronic Pelvic Pain Syndromes Collaborative Group:  Applicant institution"s 
history of collaborative research, depth of commitment, willingness to 
randomize patients, and ability to work with other Network centers and NIDDK.  
The applicant must also be willing to work collaboratively with the 
Urological Chronic Pelvic Pain Syndromes Collaborative Group.

Institutional resources for patient care and follow-up:  Adequacy of 
institutional resources including personnel and space.

ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, your 
application will also be reviewed with respect to the following:

o PROTECTIONS:  The adequacy of the proposed protection for participants in 
all clinical studies. 

o INCLUSION:  The adequacy of plans to include subjects from both genders, 
all racial and ethnic groups (and subgroups), and children as appropriate for 
the scientific goals of the research.  Plans for the recruitment and 
retention of subjects will also be evaluated. (See Inclusion Criteria 
included in the section on Federal Citations, below)

o BUDGET:  The reasonableness of the proposed budget and the requested period 
of support in relation to the proposed research.

RECEIPT AND REVIEW SCHEDULE

Letter of Intent Receipt Date:    October 11, 2002	
Application Receipt Date:         November 14, 2002
Peer Review Date:                 March/April 2003
Council Review:                   June 11-12, 2003
Earliest Anticipated Start Date:  July 1, 2003

AWARD CRITERIA

Award criteria that will be used to make award decisions include:

o Scientific merit (as determined by peer review)
o Availability of funds
o Programmatic priorities.
 
REQUIRED FEDERAL CITATIONS 

MONITORING PLAN AND DATA SAFETY AND MONITORING BOARD:  Research components 
involving Phase I and II clinical trials must include provisions for 
assessment of patient eligibility and status, rigorous data management, 
quality assurance, and auditing procedures.  In addition, it is NIH policy 
that all clinical trials require data and safety monitoring, with the method 
and degree of monitoring being commensurate with the risks (NIH Policy for 
Data Safety and Monitoring, NIH Guide for Grants and Contracts, June 12, 
1998: http://grants.nih.gov/grants/guide/notice-files/not98-084.html).  

INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH:  It is the policy of 
the NIH that women and members of minority groups and their sub-populations 
must be included in all NIH-supported clinical research projects unless a 
clear and compelling justification is provided indicating that inclusion is 
inappropriate with respect to the health of the subjects or the purpose of 
the research. This policy results from the NIH Revitalization Act of 1993 
(Section 492B of Public Law 103-43).

All investigators proposing clinical research should read the AMENDMENT "NIH 
Guidelines for Inclusion of Women and Minorities as Subjects in Clinical 
Research - Amended, October, 2001," published in the NIH Guide for Grants and 
Contracts on October 9, 2001 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html), a 
complete copy of the updated Guidelines are available at 
http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.
The amended policy incorporates: the use of an NIH definition of clinical 
research, updated racial and ethnic categories in compliance with the new OMB 
standards, clarification of language governing NIH-defined Phase III clinical 
trials consistent with the new PHS Form 398, and updated roles and 
responsibilities of NIH staff and the extramural community.  The policy 
continues to require for all NIH-defined Phase III clinical trials that: a) 
all applications or proposals and/or protocols must provide a description of 
plans to conduct analyses, as appropriate, to address differences by 
sex/gender and/or racial/ethnic groups, including subgroups if applicable, 
and b) investigators must report annual accrual and progress in conducting 
analyses, as appropriate, by sex/gender and/or racial/ethnic group 
differences.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS: 
The NIH maintains a policy that children (i.e., individuals under the age of 
21) must be included in all human subjects research, conducted or supported 
by the NIH, unless there are scientific and ethical reasons not to include 
them. This policy applies to all initial (Type 1) applications submitted for 
receipt dates after October 1, 1998.

All investigators proposing research involving human subjects should read the 
"NIH Policy and Guidelines" on the inclusion of children as participants in 
research involving human subjects that is available at 
http://grants.nih.gov/grants/funding/children/children.htm.    

REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS: NIH 
policy requires education on the protection of human subject participants for 
all investigators submitting NIH proposals for research involving human 
subjects.  You will find this policy announcement in the NIH Guide for Grants 
and Contracts Announcement, dated June 5, 2000, at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT: The 
Office of Management and Budget (OMB) Circular A-110 has been revised to 
provide public access to research data through the Freedom of Information Act 
(FOIA) under some circumstances.  Data that are (1) first produced in a 
project that is supported in whole or in part with Federal funds and (2) 
cited publicly and officially by a Federal agency in support of an action 
that has the force and effect of law (i.e., a regulation) may be accessed 
through FOIA.  It is important for applicants to understand the basic scope 
of this amendment.  NIH has provided guidance at 
http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.

It is expected that the Steering Committee will place data and biological 
specimens collected from the trial participants after a year from their 
completion in a public archive established by the NIDDK, which can provide 
protections for the data/specimens and manage their distribution for an 
indefinite period of time.   To facilitate this transfer of data and 
biological specimens applicants will have to structure informed consent 
statements and other human subjects procedures given the potential for wider 
use of data and specimens collected under this award.

URLs IN NIH GRANT APPLICATIONS OR APPENDICES: All applications and proposals 
for NIH funding must be self-contained within specified page limitations. 
Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) 
should not be used to provide information necessary to the review because 
reviewers are under no obligation to view the Internet sites.   Furthermore, 
we caution reviewers that their anonymity may be compromised when they 
directly access an Internet site.

HEALTHY PEOPLE 2010: The Public Health Service (PHS) is committed to 
achieving the health promotion and disease prevention objectives of "Healthy 
People 2010," a PHS-led national activity for setting priority areas. This 
RFA is related to one or more of the priority areas. Potential applicants may 
obtain a copy of "Healthy People 2010" at 
http://www.health.gov/healthypeople. 

AUTHORITY AND REGULATIONS: This program is described in the Catalog of 
Federal Domestic Assistance No. 93-849 and is not subject to the 
intergovernmental review requirements of Executive Order 12372 or Health 
Systems Agency review.  Awards are made under authorization of Sections 301 
and 405 of the Public Health Service Act as amended (42 USC 241 and 284)) and 
administered under NIH grants policies described at 
http://grants.nih.gov/grants/policy/policy.htm and under Federal Regulations 
42 CFR 52 and 45 CFR Parts 74 and 92.  

The PHS strongly encourages all grant recipients to provide a smoke-free 
workplace and discourage the use of all tobacco products.  In addition, 
Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in 
certain facilities (or in some cases, any portion of a facility) in which 
regular or routine education, library, day care, health care, or early 
childhood development services are provided to children.  This is consistent 
with the PHS mission to protect and advance the physical and mental health of 
the American people.

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