EPIDEMIOLOGY OF CHRONIC PELVIC PAIN OF THE BLADDER AND INTERSTITIAL CYSTITIS
Release Date: July 13, 2000
RFA: DK-00-018 (Request for competing applications from current awardee, see NOT-DK-00-018)
National Institute of Diabetes and Digestive and Kidney Diseases
Letter of Intent Receipt Date: October 13, 2000
Application Receipt Date: November 13, 2000
PURPOSE
The Division of Kidney, Urologic, and Hematologic Diseases (DKUHD) of
the National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK) has a longstanding interest in supporting basic and clinical
research studies of interstitial cystitis. During the past decade it
has become evident that interstitial cystitis represents one of a
number of symptom complexes of chronic pelvic pain of bladder origin.
Currently the magnitude of the burden of the chronic pelvic pain of the
bladder symptom complex on the health of the U.S. population is not
known. In addition, risk factors for these complexes and their impact
on quality of life are also largely unknown. Previous studies of
interstitial cystitis have focused almost entirely on highly selected
populations and do not provide adequate population estimates of its
burden or the impact of the more inclusive complex of chronic pelvic
pain of the bladder. The NIDDK invites cooperative agreement
applications for investigators to utilize ongoing prospective cohort
studies, clinical trials, and large patient databases to design
epidemiological, quality of life, and health resource utilization
studies for chronic pelvic pain of bladder origin and interstitial
cystitis. The overall intent of this solicitation is to obtain
accurate epidemiological information on chronic pelvic pain of bladder
origin in the U.S. population over a wide age range, in women and men,
and in representative racial and ethnic groups. Because the number of
cases of chronic pelvic pain of bladder origin and interstitial
cystitis identified from a single prospective cohort study, clinical
trial, or patient database may be too small and/or may represent a
select population which will not permit generalization of the findings,
this Request for Applications (RFA) requires that investigators
participating as an Epidemiology Study Center combine their data for
further analysis. This RFA also seeks a Data Analysis/Administrative
Core to analyze combined data and to perform certain administrative
functions to facilitate collaboration between the Epidemiology Study
Centers.
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,
Epidemiology of Chronic Pelvic Pain of the Bladder and Interstitial
Cystitis , 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/.
ELIGIBILITY REQUIREMENTS
Applications may be submitted by domestic, for-profit and non-profit,
institutions, public and private organizations, such as universities,
colleges, hospitals, units of State and local government, and eligible
agencies of the Federal government. Foreign institutions are not
eligible to apply. Racial/ethnic minorities, women, and persons with
disabilities are encouraged to apply as Principal Investigators.
Eligible applicants may include Principal Investigators of ongoing
prospective cohort studies or individuals who obtain permission from
the Principal Investigator of a cohort study, to access their
populations for studies as described in this RFA. If the applicant is
not the Principal Investigator of the ongoing cohort study proposed to
be accessed to conduct an ancillary study of the epidemiology of
chronic pelvic of the bladder and interstitial cystitis in response to
this RFA, then the applicant must provide written assurance from the
Principal Investigator of the parent study that the proposed study is
technically and administratively feasible. In the case when the
applicant proposes to access participants of a multi-center clinical
trial assurance must be provided by the trial’s Publications,
Presentations, and Ancillary Studies Subcommittee (or equivalent review
group) and included in the application. Individuals with access to
large patient databases, for example from a health maintenance
organization, are also encouraged to apply. Similarly, applicants
proposing to access large databases must also provide written assurance
of their ability to directly access patients and/or their medical
records or data files to obtain the required information for the
studies described in this RFA. Cohort studies and clinical trials
acceptable for access to achieve the goals of this Request for
Applications may be supported by either a governmental and/or non-
governmental source. An institution or organization may apply for both
an Epidemiology Study Center and the Data Analysis/Administrative Core.
The same person may serve as the Principal Investigator of an
Epidemiology Study Center and the Data Analysis/Administrative Core.
However, separate applications are required for an Epidemiology Study
Center and a Data Analysis/Administrative Core.
MECHANISM OF SUPPORT
The administrative and funding instrument to be used for these awards
will be the cooperative agreement (U01). The cooperative agreement is
an assistance mechanism in which substantial NIDDK scientific and
programmatic involvement is anticipated during the performance of the
activity. Under the cooperative agreement, the NIDDK’s purpose is to
support and encourage the recipient’s activities by working jointly
with the awardees in a partnership role, but not to assume direction,
prime responsibility, or dominance. Details of the responsibilities,
relationships, and governance of a study funded under a cooperative
agreement are described under the section entitled, Terms and
Conditions of Award. The total project period for applications
submitted in response to this RFA must not exceed five years. The
anticipated award date is July 3, 2001. At this time, the NIDDK has
not determined whether or how this solicitation will be continued
beyond the present RFA.
FUNDS AVAILABLE
The NIDDK plans to make four awards for Epidemiology Study Centers and
one award for a Data Analysis/Administrative Core. Approximately
$1,500,000 total cost (direct plus Facilities and Administrative (F&A)
costs)is expected to be available per year of support under this RFA.
It is anticipated that the award for each Epidemiology Study Center
will be about $285,000 total cost per year and the award for the Data
Analysis/Administrative Core will be about $350,000 total cost per
year.
The number of awards to be made is dependent on the receipt of a
sufficient number of applications of high scientific merit and
availability of funds. Although this program is provided for in the
financial plans of the NIDDK, awards pursuant to this RFA are
contingent upon the availability of funds and the receipt of a
sufficient number of applications of outstanding scientific and
technical merit.
RESEARCH OBJECTIVES
Background
Interstitial cystitis is one of a constellation of diseases and
disorders that are characterized by chronic pelvic pain associated with
bladder symptoms of urinary frequency and urgency. Although there have
been several published studies of the epidemiology of interstitial
cystitis, they have focused almost totally on women and on non-minority
populations. There is very little information on the broader, more
inclusive disorder of chronic pelvic pain and associated bladder
symptoms in any population. Estimates of the prevalence of
interstitial cystitis in the U.S. vary ten-fold from 67 per 100,000
women participating in the Nurses Health Study I and Nurses Health
Study II to 870 per 100,000 persons in the National Health Interview
Survey. The disparity in prevalence rates appears to be related
primarily to the definitions utilized to ascertain cases. The few
epidemiological studies of interstitial cystitis reported to date have
many shortcomings. Major limitations of these studies include the
absence of racial and ethnic diversity, the small number of men
studied, and the limited age range of the populations examined. This
has resulted in inadequate information among children and young adults,
men, and minority populations. Another significant limitation is the
use of select populations, including physician-based and urology
clinic-based sources of participants. Perhaps the greatest limitation
is that studies performed to date have restricted their focus to
interstitial cystitis. This approach undoubtedly underestimates the
burden of chronic pelvic pain of bladder origin. Recently, a telephone
survey of over 5,000 women aged 18 to 50 years conducted in the U.S.
found a prevalence of 14.7% for chronic pelvic pain of all causes.
Importantly, over one-half of the cases of chronic pelvic pain had no
diagnosis based on participant self-report.
Chronic pelvic pain of bladder origin is a symptom complex found in
children and adults of all ages, in males and females, and in different
racial and ethnic groups. However, since it is not a clinical
diagnostic category or a clinical designation, the symptom complex is
frequently incorrectly designated by the primary care physician and is
given various clinical labels by the diagnosing physician who is
usually a urologist. For example, the symptom complex is frequently
called interstitial cystitis if it is present in women, and in men the
diagnostic label of prostadynia and/or chronic abacterial prostatitis
is used much more often. Other diagnostic categories for women include
urethral syndrome, non-infectious cystitis and frequency-urgency pain
syndrome while in men it has been called testalgia, orchalgia, and non-
specific urethritis. Children are usually given the diagnosis of
dysfunctional voiding, Hinman syndrome, or tethered cord syndrome.
These disorders are primarily identified via patient report of
symptoms, have vague diagnostic criteria and usually no objective
markers to establish a diagnosis or to adequately assess their
severity. Moreover, these disorders do not have disease
classification codes in the International Classification of Diseases,
and the time from symptom appearance to clinical diagnosis may be many
years, making the identification of precipitating or risk factors
difficult. Studies of interstitial cystitis are also plagued by many
of these same difficulties. Despite similar obstacles, investigators
have made substantial advances in understanding the epidemiology of
other symptom-based complexes/syndromes, such as chronic fatigue
syndrome.
Importantly, few epidemiological studies have focused on risk factors
for chronic pain of bladder origin and interstitial cystitis and the
few studies that have been performed have focused only on factors
exacerbating symptoms in patients with interstitial cystitis.
Epidemiological studies, including case-control studies, are necessary
to further define possible risk factors for both chronic pelvic pain of
bladder origin and interstitial cystitis. In cross-sectional studies
of predominantly white women with interstitial cystitis, quality of
life was substantially reduced. In addition, a recent study has shown
that many prescription and non-prescription therapies are utilized in
the treatment of patients with interstitial cystitis, suggesting that
the economic burden of this symptom complex and chronic pelvic of the
bladder may be substantial. Additional studies are necessary to
further study both quality of life and health resource utilization
among persons with chronic pelvic pain of the bladder and interstitial
cystitis.
Research Goals and Scope of the Activity
The intent of this RFA is to solicit applications from investigators
proposing to serve as Epidemiology Study Centers or a Data
Analysis/Administrative Core to develop and conduct a multi-
institution, collaborative research program of the epidemiology, risk
factors, quality of life and functional status, and health resource
utilization of chronic pelvic pain of the bladder and interstitial
cystitis. Investigators will cooperate in a collaborative manner to
develop a protocol to assess the incidence, prevalence, and gender,
racial/ethnic distribution, quality of life, and health resource
utilization of chronic pelvic pain of bladder origin and interstitial
cystitis in their respective cohort studies, and/or clinical trials,
and/or patient databases. An important part of this protocol will be
the development of common definitions of chronic pelvic pain of bladder
origin and interstitial cystitis so that data can be pooled, thereby
improving the statistical precision of estimates of incidence and
prevalence, to permit subgroup analyses, and to identify candidate risk
factors. The level and patterns of health resource utilization will
also be investigated. Investigators will focus on identifying risk
factors for chronic pelvic pain of bladder origin and interstitial
cystitis through a variety of epidemiological approaches, including
nested case-control studies. Quality of life and functional status will
be measured using generic instruments. Development of disease/complex-
specific instruments to measure quality of life, however, will be
considered by the collaborative study group. Health resource
utilization will be assessed uniformly in a representative number of
cases and non-cases by the participating investigators. The overall
intent of this solicitation is to obtain accurate data on chronic
pelvic pain of bladder origin and interstitial cystitis in all ages, in
males and in females, and in a wide range of racial and ethnic groups.
The specific goals of this solicitation are as follows:
1. to develop uniform clinical definitions for chronic pelvic pain of
bladder origin and interstitial cystitis for use by the Epidemiology
Study Centers in the individual cohort studies, clinical trials, and/or
large databases in order to permit combination and analysis of data
across study sites.
2. to document the overall prevalence of the chronic pelvic pain of
bladder origin symptom complex and interstitial cystitis and to
determine prevalence by age, gender, and race/ethnicity.
3. to determine the incidence of chronic pelvic pain of bladder origin
and interstitial cystitis based on race/ethnicity, gender, and other
relevant clinical and demographic factors.
4. to identify possible risk factors for the chronic pelvic pain
associated with the bladder symptom complexes.
5. to assess quality of life, functional status, and co-morbid medical
conditions for these symptom complexes.
6. to estimate health resource utilization related to chronic pelvic
pain of bladder origin and interstitial cystitis compared to a control
population.
Study Phases
The timetable for the study may be subdivided into three phases over a
five-year period.
Phase I (Months 1-6): Protocol Development. This phase includes the
development of common and accepted definitions of chronic pelvic pain
of bladder origin symptom complex and interstitial cystitis.
Standardized questionnaires to be administered to study participants
will be developed based on these accepted definitions. Protocols will
also be established for carrying out the prevalence, incidence, and
risk factor studies. Instruments to assess quality of life and
functional status will be selected from among those currently available
or complex-specific instruments will be developed and validated by the
collaborative study group. Data collection instruments and forms to
assess health resource utilization will also be developed and evaluated
prior to implementation.
Phase II (Months 6-54): Epidemiological Studies Implementation. It is
anticipated that the first study to be conducted will determine
prevalence (first 12 months of Phase II). Upon the establishment of
the prevalence of chronic pelvic pain of bladder origin and
interstitial cystitis the incidence will be assessed over a 36-month
period (months 18-54 of Phase II). During the same period of time
during which the incidence study is conducted, studies of risk factors,
quality of life and functional status, and health resource utilization
will be performed. Concurrent with studies in Phase II will be
analysis of the prevalence data and preparation and publication of
manuscripts in peer-reviewed scientific journals. Interim analyses of
findings from the incidence, risk factor, quality of life and
functional status, and health resource utilization studies will also be
performed.
Phase III (Months 55-60): Final Data Analysis and Close-out of the
Epidemiology Study Centers and the Data Analysis/Administrative Core.
Final analysis of results from the incidence, risk factor, quality of
life and functional status, and health resource utilization studies
will be performed during a six-month period in Phase III. In addition,
manuscripts will be prepared during this phase for publication in peer-
reviewed scientific journals. The Epidemiology Study Centers and the
Data Analysis/Administrative Core will also be closed-out during months
59 and 60.
STUDY COMPONENTS
Epidemiology Study Center
The Epidemiology Study Center investigators will have direct
responsibility for accessing their cohort study participants, clinical
trial subjects, and/or database subjects (or their medical
records/patient data files) to assess, in a uniform manner, the
prevalence, incidence, and risk factors for chronic pelvic pain of
bladder origin and interstitial cystitis. Studies on quality of life
and functional status and health resource utilization will also be
performed in a comparable manner across study sites. The Epidemiology
Study Center will be responsible for assuring high rates of response to
questionnaires, high level of data quality, and timely, accurate
transmission of data to the Data Analysis/Administrative Core. They
will also be responsible for suggesting analyses to the Data
Analysis/Administrative Core.
Data Analysis/Administrative Core
The Data Analysis/Administrative Core will be responsible for
establishing a database to accommodate data sent by the Epidemiology
Study Centers, including relevant demographic and clinical information
to be transferred from the primary databases established for the
primary focus of the cohort studies, clinical trials, and patient
databases. They will also conduct analyses as suggested by the
Epidemiology Study Centers as well as propose original analyses to the
collaborative group for their consideration. The Data
Analysis/Administrative Core will also prepare reports on the progress
of the various studies, including data quality control, and interim and
final results. The Data Analysis/Administrative Core will also be
responsible for arranging meeting and conference calls of the Steering
and Planning Committee, arranging for meeting of the group of external
advisors, and other administrative functions necessary to coordinate
the efficient operation of the collaborative study group.
Steering and Planning Committee
The primary governing body of the study will be the Steering and
Planning Committee comprised of each of the Principal Investigators of
the Epidemiology Study Centers and the Principal Investigator of the
Data Analysis/Administrative Core, the Chairperson of the Steering and
Planning Committee, and the NIDDK Project Scientists (described in
detail under Terms and Conditions). The Steering and Planning
Committee will develop the epidemiological definitions for chronic
pelvic pain of bladder origin and interstitial cystitis, participant
questionnaires and data collection forms, and design epidemiological
studies to elucidate risk factors. They will evaluate currently
available quality of life and functional status assessment instruments
for their utility in this study as well as design data collection
instruments for the study of health resource utilization. The Steering
and Planning Committee will review analyzed data and write manuscript
describing the findings.
Group of External Advisors
An independent group of experts in areas such as urology,
urogynecology, pain epidemiology, and biostatistics who are not
otherwise involved in the study will be recruited by the NIDDK to
evaluate the proposed protocol and review periodically the progress of
the study (described in detail under Terms and Conditions).
Project Scientists
The NIDDK will identify two Project Scientists for the study. The
Project Scientists will assist the Steering and Planning Committee and
group of external advisors in carrying out the study (described in
detail under Terms and Conditions).
SPECIAL REQUIREMENTS
Terms and Conditions of Award
The following terms and conditions will be incorporated into the award
statement and provided to each Principal Investigator as well as to the
institutional officials at the time of the award. These terms are in
addition to, not in lieu of, otherwise applicable Office of Management
and Budget (OMB) administrative guidelines, HHS Grant Administration
Regulations at 45 CFR Part 74 and 92, and other HHS and NIH Grants
Administration policy statements.
1. Collaborative Responsibilities. The administrative and funding
instrument used for this program is the cooperative agreement (U01), an
assistance mechanism (rather than an acquisition mechanism), in
which substantial NIH scientific and/or programmatic involvement with
awardees 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 the cooperative agreement concept, the
dominant role and prime responsibility for the planned activity reside
with the awardees for the project as a whole, although specific tasks
and activities in carrying out the activity will be shared among the
awardees and NIDDK Project Scientists.
2. Awardees Rights and Responsibilities. Awardees will have
substantial and lead responsibilities in all tasks and activities.
These include protocol development, accessing study participants or
their data, data collection, data quality control, final data analysis
and interpretation, and preparation of publications. The awardees
agree to work cooperatively with the other Epidemiology Study Centers
and agree to follow the common protocol developed by the Steering and
Planning Committee. The awardees agree also to transmit the agreed
upon study data in a timely manner to the Data Analysis/Administrative
Core for combination and analysis. Awardees will retain custody of and
have primary rights to their data developed under these awards, subject
to Government (e.g., NIDDK, NIH, or PHS) rights or access consistent
with current HHS and NIH policies.
3. NIDDK Staff Responsibilities. The NIDDK will name two Project
Scientists from within the Division of Kidney, Urologic and Hematologic
Diseases whose function will be to assist the Steering and Planning
Committee in carrying out the study. One Project Scientist will have
clinical expertise in urology and the other will have experience in the
development and conduct of multi-center clinical studies. The Project
Scientists will have substantial scientific-programmatic involvement in
protocol development, quality control, interim data analysis, and final
data analysis and interpretation, preparation of publications, and
coordination and performance monitoring. The NIDDK Project Scientists
will have voting membership on the Steering and Planning Committee and
will have one vote between them. One of the NIDDK Project Scientists
will also serve as Executive Secretary of the group of external
advisors. The NIDDK reserves the right to terminate or curtail the
study (or an individual award) in the event of difficulties in
accessing the cohort studies, clinical trials, or patient databases or
poor response rates to the questionnaires, in timely data reporting,
achieving high levels of data quality, or other major breaches of the
protocol, or human subject ethical issues that may dictate a premature
termination.
4. Governance.
The Steering and Planning Committee, composed of each of the Principal
Investigators of the Epidemiology Study Centers, the Principal
Investigator of the Data Analysis/Administrative Core, the NIDDK
Project Scientists, and the Chairman of the Steering and Planning
Committee, will be the main governing board of the study. This
committee will have the primary responsibility for developing the
common protocol, facilitating the conduct and monitoring of the
epidemiological, quality of life and functional status, and health
resource utilization studies, and reporting the study results. Each
member of the Steering and Planning Committee will have one vote (NIDDK
Project Scientists will have one vote between them), and all major
scientific decisions will be determined by a majority vote of the
Steering and Planning Committee. A Chairperson will be chosen from
among the Steering and Planning Committee members (but not one of the
NIDDK Project Scientists) or alternatively, from among experts in the
field of urology or epidemiology who are not participating directly in
the study.
An independent group of external advisors, selected by the Director,
NIDDK, will review periodically the progress of the study. This group
will include experts in the relevant medical, epidemiological,
statistical, and ethics fields who are not otherwise involved in the
study. The external advisors will review the study protocol and
evaluate results, monitor data quality, and provide operational and
policy advice to the Steering and Planning Committee and to the NIDDK
regarding the status of the study. One of the NIDDK Project Scientists
will serve as Executive Secretary of the group. The members of the
group will review progress and report to the NIDDK at least once each
year, or more often if necessary.
5. Arbitration
Any disagreement that may arise on scientific/programmatic matters
(within the scope of the award) between recipients and the NIDDK may be
brought to arbitration. An arbitration panel will be composed of three
members, one selected by the Steering and Planning 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 selected 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 45 CFR
Part 16.
INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS
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
biomedical and behavioral research projects involving human subjects,
unless a clear and compelling rationale and justification is provided
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 1003-43).
All investigators proposing research involving human subjects should
read the NIH Guidelines for Inclusion of Women and Minorities as
Subjects in Clinical Research which have been published in the Federal
Register of March 28, 1994 (FR 59 14508-14513) and in the NIH GUIDE FOR
GRANTS AND CONTRACTS of March 18, 1994, Volume 23, Number 11, available
on the web at:
http://grants.nih.gov/grants/guide/notice-files/not94-100.html.
It is recognized that in cases where recruitment of all of the participants
of an established cohort study or clinical trial has been completed, the
gender and racial/ethnic characteristics of the population intended to be
accessed in response to this RFA is fixed. However, if the applicant
proposes to utilize a subset of the cohort study or clinical trial population,
a sampling scheme must be proposed that ensures adequate representation of
women and minority subjects.
INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN
SUBJECTS
It is the policy of the NIH 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. 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 was published in the NIH Guide for Grants and Contracts,
March 6, 1998, and is available at the following URL address:
http://grants.nih.gov/grants/guide/notice-files/not98-025.html. It is
also recognized that in cases where the participants of a cohort study
or clinical trial have already been recruited, the age distribution of
the population intended for use in response to this RFA cannot be
modified. However, if the applicant proposes to utilize a subset of
the cohort study or clinical trial population, and children are
included in the whole study population, a sampling scheme must be
proposed that ensures adequate representation of children.
Investigators also may obtain copies of these policies from the program
staff listed under INQUIRIES. Program staff may also provide
additional relevant information concerning the policy.
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. Reviewers are cautioned that
their anonymity may be compromised when they directly access an
Internet site.
LETTER OF INTENT
Prospective applicants are asked to submit, by October 13, 2000, a
letter of intent that includes a descriptive title of the proposed
research, name, address, and telephone number of the Principal
Investigator, identities of other key personnel and participating
institutions, and 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 a
subsequent application, the information it contains allows the NIDDK
staff to estimate the potential review workload and plan the review.
The letter of intent is to be sent to:
Chief, Review Branch
Division of Extramural Activities
National Institute of Diabetes, Digestive, and Kidney Diseases
Room 653, MSC 5452
6707 Democracy Boulevard
Bethesda, Maryland 20892-5452 (for courier service use 20817)
Telephone: (301) 594-8885
Fax: (301) 480-3505
Email: hagana@extra.niddk.nih.gov
APPLICATION PROCEDURES
Applications must be submitted on the standard research grant
application form PHS 398 (rev. 4/98). Application kits are available
at most institutional offices of sponsored research and may be obtained
from the Division of Extramural Outreach and Information Resources,
National Institutes of Health, 6701 Rockledge Drive, MSC 7910,
Bethesda, Maryland 20892-7910, telephone (301) 710-0267, E-mail:
GrantsInfo@nih.gov.
The RFA label available in the form 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. For purposes of identification
and processing, item 2 of the face page of the application must be
marked YES and the RFA number and the words Epidemiology of Chronic
Pelvic Pain of the Bladder and Interstitial Cystitis must be typed in.
The RFA label and line 2 of the application should both indicate the
RFA number. The RFA label 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.
The sample RFA label available at:
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf has been
modified to allow for this change. Please note this is in pdf format.
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
must be sent to:
Chief, Review Branch
Division of Extramural Activities
National Institute of Diabetes, Digestive, and Kidney Diseases
Room 653 MSC 5452
6707 Democracy Boulevard
Bethesda, Maryland 20892-5452 (For express/courier service, use 20817)
Applications must be received by November 13, 2000. If an application
is received after this 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 a substantial revision of an application
already reviewed, but such an application must follow the guidance in
the PHS 398 applications instructions for the preparation of revised
applications, including an introduction addressing the previous
critique.
Information to be Included in Applications
Details of the Proposed Study Protocol: Applicants for the
Epidemiology Study Center should describe a research plan involving
multi-center participation to address the objectives of the study and
to reach the study goals. Applicants should outline the rationale and
background of the proposed epidemiological, quality of life and
functional status, risk factor and health resource utilization studies.
An application for the Epidemiology Study Center should provide
evidence of the size (by ten-year age intervals) of the prospective
cohort study, clinical trial, and/or patient database to be accessed
and its racial, ethnic, and gender composition. Applicants must also
describe the feasibility of contacting study participants initially and
obtaining follow-up information and their experience in such an
undertaking. The means by which information is to be obtained from
participants (i.e., telephone contact, mail, in-person, access to
medical records, etc.) should also be specified. Recommendations
should also be made regarding which generic measure(s) of quality of
life should be implemented by the study group and if necessary, a
rationale for developing complex-specific quality of life and
functional status instruments. Plans for acquiring information on
health resource utilization should be included in the application.
Applications for the Data Analysis/Administrative Core should include
plans for data collection, and overall quality control of the study.
Information on proposed plans for study-wide data analysis should also
be included for each of the major areas of study. A plan for the
acquisition of data from the primary database of the ongoing cohort
studies, clinical trials, and patient databases to be included in the
database established under this RFA should be proposed. A description
of anticipated problems in carrying out this study and their proposed
solutions should be included in the application.
Institutional Support: There should be evidence of strong
institutional support for the study, including adequate space in which
to conduct data analysis/management (for the Data
Analysis/Administrative Core) activities. An organizational structure
for the study should be set forth in the application, delineating lines
of authority and responsibility for dealing with anticipated problems
in all general areas as well as stated willingness to follow the
commonly agreed upon protocol.
Previous Experience: The applicant should include a succinct
discussion of previous relevant research efforts in epidemiological
studies and any relevant experience/success in working collaboratively
with investigators outside their own research institution.
Suggested Personnel Requirements: The application must describe the
expertise of key scientific, technical and administrative personnel and
include a mechanism for replacing key professional or technical
personnel should the need arise. For the Epidemiology Study Center,
expertise in epidemiology is necessary. Medical expertise in urology
is also important. Members may be full-time or part-time and may serve
in more than one capacity, as appropriate. The expertise required for
the Data Analysis/Administrative Core must also include expertise in
epidemiology, biostatistics, data management, computer programming and
database development. Consultants in urology and quality of life are
also advisable.
Budget Preparation by Year
Applicants for the Epidemiology Study Centers and the Data
Analysis/Administrative Core must include an adequately justified year-
by-year budget, reflecting the major changes in proposed activities as
the studies progress through their various phases.
During Phase I (First 6 months of Year 1), the budget will be for
development of the protocol by the Epidemiology Study Centers in
collaboration with the Data Analysis/Administrative Core. The Data
Analysis/Administrative Core will begin to create the database
necessary to accommodate pooled data for the prevalence, incidence,
quality of life and functional status, and health resource utilization
studies. A database for relevant clinical and demographic information
obtained from the parent (primary) database for the ongoing
studies/patient databases will also be established. The travel budget
for Phase I should be estimated based on travel for two key
investigators to attend two-day, bimonthly meetings of the Steering and
Planning Committee in the Washington, D. C. area.
During Phase II (Second six months of Year 1, Years 2, 3, 4, and the
first 6 months of Year 5). The budget should reflect the initiation of
the prevalence, incidence, quality of life and functional status, risk
factor, and health resource utilization studies. Demographic and
clinical information from the parent database of the ongoing cohort
studies/clinical trials and large databases will also be obtained.
Interim data analysis and preparation of reports to the Steering and
Planning Committee and the group of external advisors will also occur.
Manuscripts describing the findings of the studies will also be
prepared. It is anticipated that the final results of the prevalence
study will become available in Phase II. Interim reports will be
prepared for studies of incidence, risk factors, quality of life and
functional status, and health resource utilization. This phase of the
program will require meeting approximately every six months in the
Washington, D.C. area. The travel budget for Phase II should be
estimated based on travel for the Principal Investigator and the
Project Coordinator for both the Epidemiology Study Center and the Data
Analysis/Administrative Core. Budgets for the Data
Analysis/Administrative Core should include travel for any consultants.
During Phase III (Final 6 months of Year 5). The major activities
include final data analysis of the incidence, risk factor, quality of
life and functional status, and health resource utilization studies.
Manuscripts suitable for submission to peer-reviewed scientific
journals will also be prepared during this phase. Three meetings of
the investigators should be budgeted for the final six-month period of
the grant.
For an Epidemiology Study Center, the budget should request support for
the minimum number of full and/or part-time staff to successfully carry
out the proposed studies. An Epidemiology Study Center personnel list
could include a principal investigator, co-investigator, study
coordinator, and data entry clerk.
For applications for the Data Analysis/Administrative Core, the budget
should include the time and effort of key personnel for database
management, programming, data analysis, and administrative functions to
support the collaborative group. Travel by Data
Analysis/Administrative Core staff to Washington, D.C. for the
following meetings should be budgeted: group of external advisors (one
meeting per year for each of five years) and the Steering and Planning
Committee (four in Year 1-Phase I and two meetings annually during
Years 2-4, and three meetings in Year 5).
The following is a list of yearly major activities to assist in the
preparation of budgets for each of the five years of the program.
Year 1 (months 1-6): Develop the study protocol for the collaborative
studies. The database will be established by the Data
Analysis/Administrative Core for the prevalence study and initial work
will begin for the remaining studies. The database for relevant
demographic and clinical information to be obtained from the parent
database of the accessed studies will also be established.
Year 1 (months 7-12): Initiate the prevalence study. Refine the
protocol for incidence, risk factor, quality of life and functional
status, and health resource utilization studies. Database development
will continue by the Data Analysis/Administrative Core. Obtain relevant
demographic and clinical information from parent databases.
Year 2 (12 months): Begin the incidence and risk factor studies. At
the end of Year 2, begin writing papers on the design of the study and
prevalence study findings. Continue database development (Data
Analysis/Administrative Core). Obtain relevant demographic and
clinical information from parent databases.
Year 3 (12 months): Continue incidence and risk factor studies.
Implement quality of life, functional status and health resource
utilization studies. Manuscripts describing the prevalence will be
completed in Year 3. Obtain relevant demographic and clinical
information from parent databases.
Year 4 (12 months): Continue incidence study and complete risk factor
studies. Continue quality of life and health resource utilization
studies. Interim analyses continue for these studies. Obtain relevant
demographic and clinical information from parent databases.
Year 5 (months 1-6): Complete incidence, quality of life, functional
status, and health resource utilization studies. Interim analysis
continues for these studies. Obtain final demographic and clinical
information from parent databases.
Year 5 (months 7-12): Complete final data analysis for the incidence,
risk factor, quality of life, functional status, and health resource
utilization studies. Prepare manuscripts and report results at
scientific meetings and in peer-reviewed scientific journal articles.
Close-out of both the Epidemiology Study Centers and the Data
Analysis/Administrative Core will take place during the final two
months of the program.
REVIEW CONSIDERATIONS
Upon receipt, applications will be reviewed for completeness by the CSR
and for responsiveness by the NIDDK. 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 NIDDK in accordance with the review
criteria stated below. As part of the initial merit review, a process
will be used by the initial review group in which all applications
deemed to have the highest scientific merit, generally the top half of
the applications under review, will be discussed, assigned a priority
score, and receive a second level of review by the National Diabetes
and Digestive and Kidney Disease Advisory Council.
Review Criteria
Applicants are encouraged to submit and describe their own ideas about
how best to meet the goals of the cooperative study as outlined in this
RFA, and are expected to address issues identified under INFORMATION TO
BE INCLUDED IN APPLICATIONS. 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 pursuit of these goals. Each of these
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.
Review Criteria for Epidemiology Study Centers
Significance: Does this study address an important problem? If the
aims of the application are achieved, how will scientific knowledge be
advanced? What will be the effect of these studies on the concepts or
methods that drive this field?
Approach: Are the conceptual framework, design, and methods adequately
developed, well integrated, and appropriate to the aims of the project?
Does the applicant acknowledge potential problem areas and consider
alternative tactics? What is the total sample size of the cohort,
clinical trial, and/or database? What is the racial/ethnic, gender,
and age composition of the population to be accessed? How stable
(number of study subjects lost to follow-up, out migration, etc.) is
the target population and what has been the response rate of the
population for previous ancillary studies? The applicant must provide
plans to ensure the complete, reliable, and timely transmission of
study data to the Data Analysis/Administrative Core. Knowledge of the
possible problems associated with the conduct of epidemiological
studies at disparate institutions using different epidemiological
studies and anticipating possible solutions is necessary.
Investigator: Is the investigator appropriately trained and well
suited to carry out this work? Is the work proposed appropriate to the
experience level of the Principal Investigator and other researchers?
Is the investigator experienced in collaborating with other
investigators in a multi-center study?
Necessary Expertise: Documented experience in epidemiology is
required. Demonstrated knowledge of clinical aspects of chronic pelvic
pain of bladder origin and/or interstitial cystitis from either a
consultant or co-investigator is recommended. Consultants in the
fields of quality of life and health resource utilization are also
necessary.
Staff Qualifications: Documented specific competence and relevant
experience of professional, technical, and administrative staff
pertinent to the operation of an Epidemiology Study Center.
Environment: Does the scientific environment in which the work will be
done contribute to the probability of success? Documented adequacy of
the proposed facility and space is necessary. Is there evidence of
institutional support and commitment for the proposed program?
Access to an Established Prospective Cohort Study, Clinical Trial
Population, and/or Large Patient Database: Evidence of the ability to
conduct the epidemiological, quality of life and functional status,
risk factor, and health resource utilization studies as described in
this RFA is necessary. Examples of ancillary studies utilizing the
cohort, clinical trial, and/or database should be provided. Assurance
that an ancillary study focused on the goals of the RFA can recruit a
sufficient number of participants must be clearly described.
Documentation must be provided on the ability to re-contact study
subjects or ongoing access to patient data/medical records or patient
data files, in order to carry out incidence surveys and other studies
requiring follow-up data. Applicants other than the Principal
Investigator of the prospective cohort study must provide written
documentation that the cohort study is available for the purposes
specified in the RFA. Investigators proposing the use of a clinical
trial population must provide written assurance from their Steering and
Planning Committee that the participants can be accessed as an
ancillary study to the ongoing trial. Similarly, written documentation
indicating access is required from applicants proposing to use large
patient databases.
Review Criteria for a Data Analysis/Administrative Core:
Significance: Does the study address an important problem? If the
aims of the applications are achieved, how will scientific knowledge be
advanced? What will be the effect of these studies on the concepts or
methods that drive this field?
Approach: Are the conceptual framework, design, and methods adequately
developed, well integrated, and appropriate to the aims of the project?
Does the applicant acknowledge potential problem areas and consider
alternative tactics? Experience in developing databases for combining
data from the Epidemiology Study Centers, plans for analysis of the
pooled data, and efforts to ensure high quality data collection should
be described. Plans are also necessary for the timely and secure
transmission of data from the Epidemiology Study Centers to the Data
Analysis/Administrative Core.
Investigator: Is the investigator appropriately trained and well
suited to carry out this work? Is the work proposed appropriate to the
experience level of the Principal Investigator and other researchers?
Is the investigator experienced in collaborating with other
investigators in a multi-center study? Documented experience in
epidemiology and biostatistics is required. Demonstrated knowledge of
clinical aspects of chronic pelvic pain of bladder origin and/or
interstitial cystitis from either a co-investigator or consultant will
be judged. The level of expertise of consultants in quality of life
and health resource utilization will be considered. Experience in
database development, database management, and statistical analysis is
required. The ability of the investigators from the Data
Analysis/Administrative Core to take the lead in developing a
cooperative relationship among the participating Epidemiology Study
Centers and exercise appropriate leadership in matters of study design,
data acquisition, data management, data quality, and data analysis,
will be evaluated.
Environment: Does the scientific environment in which the work will be
done contribute to the probability of success? Documented adequacy of
the proposed facility and space is necessary. Is there evidence of
institutional support and commitment for the proposed program?
In addition to the above criteria, in accordance with NIH policy, all
applications will be reviewed with respect to the following.
The reasonableness of the proposed budget.
The adequacy of the proposed protection for humans and the environment,
to the extent they may be adversely affected by the studies described
in this RFA. The scientific review group will also examine the safety
of the research environment.
Schedule
Letter of Intent Receipt Date: October 13, 2000
Application Receipt Date: November 13, 2000
Special Review Committee: March/April 2001
NDDK Advisory Council: May 30-31, 2001
Anticipated Award Date: July 3, 2001
AWARD CRITERIA
Award criteria that will be used to make award decisions include:
Scientific merit as determined by peer review
Availability of funds
Cost
The size, age, racial and ethnic composition of the population proposed
to be accessed
INQUIRIES
Written and telephone inquiries concerning this RFA are strongly
encouraged. The opportunity to clarify any issues or questions form
potential applicants is welcome.
For information relating to the NIDDK, programmatic inquiries may be
made to:
John W. Kusek, Ph.D.
Clinical Trials Program Director or
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
Room 617 MSC 5458
6707 Democracy Boulevard
Bethesda, Maryland 20892-5458 (for express or courier service use
20817)
Telephone: (301) 594-7735
FAX: (301) 480-3510
Email: kusekj@ep.niddk.nih.gov
nybergl@ep.niddk.nih.gov
Fiscal and administrative inquiries may be directed to:
Trude Hilliard
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
Room 642 MSC 5456
6707 Democracy Boulevard
Bethesda, Maryland 20892-5456 (for express/courier service use 20817)
Telephone: (301) 594-8859
FAX: (301) 480-3504
Email: hilliardt@extra.niddk.nih.gov
AUTHORITY AND REGULATIONS
This program is described in the Catalog of Federal Domestic Assistance
Nos. 93.849 and 93.864. 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 Public Health Service 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.
The Public Health Service strongly encourages all grant and contract
recipients to provide a smoke-free work place and promote the non-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 Public Health Service mission to protect and advance the physical
and mental health of the American people.
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