CLINICAL TRIALS NETWORK FOR FEMALE PELVIC FLOOR DISORDERS

Release Date:  July 13, 2000

RFA:  HD-00-013 (This RFA has been reissued, see RFA-HD-05-019)

National Institute of Child Health and Human Development
(http://www.nichd.nih.gov)

Letter of Intent Receipt Date:  October 3, 2000
Application Receipt Date:       November 28, 2000

PURPOSE

The Center for Population Research (CPR) of the National Institute of Child 
Health and Human Development (NICHD) invites applications from investigators 
willing to participate with the NICHD in a multicenter cooperative program 
designed to conduct clinical trials investigating female pelvic floor 
disorders, including pelvic organ prolapse, urinary incontinence, and fecal 
incontinence.  The objective of this program is to facilitate research related 
to these problems by maintaining a network of Clinical Sites and a Data 
Coordinating Center (DCC) that, by rigorous patient evaluation using common 
protocols, can study large numbers of patients and provide answers more 
rapidly than individual sites acting alone.  

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 “Healthy People 2010” at 
http://www.health.gov/healthypeople.  

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic for-profit and non-profit 
organizations, public and private, such as universities, colleges, hospitals, 
laboratories, units of State and local governments, and eligible agencies of 
the Federal government.  The need for continuous and active communication 
among the sites dictates that only institutions in the United States will be 
eligible to apply.  Racial/ethnic minority individuals, women, and persons 
with disabilities are encouraged to apply as Principal Investigators.

An institution may apply for both a Clinical Site and the Data Coordinating 
Center (DCC) grant, however, separate applications are required and the DCC 
application must include a specific plan for maintaining the independent 
operation of each unit (e.g., confidentiality of study-wide data).

MECHANISM OF SUPPORT

This RFA will use the National Institutes of Health (NIH) cooperative research 
project grant (U01) and cooperative clinical research grant (U10) award 
mechanisms, “assistance” mechanisms (rather than “acquisition” mechanisms) in 
which substantial NIH scientific and/or programmatic involvement with the 
awardee is anticipated during performance of the activity.  Under the 
cooperative agreement, the NIH purpose is to support and stimulate the 
recipients’ activity by involvement in the activity and otherwise working 
jointly with the award recipients in a partner role, but it is not to assume 
direction, prime responsibility, or a dominant role in the activity.  Details 
of the responsibilities, relationships, and governance of the study to be 
funded under cooperative agreements are discussed below under “Terms and 
Conditions of Award.”
The Data Coordinating Center will be supported by a U01 award and the Clinical 
Sites (described below) by U10 awards.   The anticipated award date is July 1, 
2001.  

FUNDS AVAILABLE

The NICHD intends to commit approximately $3 million in total costs [direct 
plus Facilities and Administrative (F&A) costs] in FY 2001 to fund six to 
eight new grants for Clinical Sites and one new grant for a Data Coordinating 
Center.  Applicants for the Data Coordinating Center grant may request a 
project period of up to five years and a budget for direct costs of up to 
$600,000 per year.  Applicants for a Clinical Site may request a project 
period of up to five years and a budget for direct costs of up to $200,000 per 
year.  Because the nature and scope of the research proposed may vary, it is 
anticipated that the size of each award also will vary.  Although the 
financial plans of the NICHD 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. 

RESEARCH OBJECTIVES

Background

Within the mission of NICHD, as part of the broad topic of reproductive 
health, priority has been given to research on pelvic floor disorders in 
women.  To this end, the Contraception and Reproductive Health Branch of the 
Center for Population Research (CPR), NICHD, supports research on pelvic floor 
disorders affecting the reproductive system and other pelvic organs.  

The term “pelvic floor disorders” refers to a group of clinical conditions 
that includes pelvic organ prolapse, urinary incontinence, fecal incontinence, 
and other sensory and emptying abnormalities of the lower urinary and 
gastrointestinal tracts.  It is estimated that one or more of these conditions 
affects up to one-third of adult women.  Almost 10 percent of women will 
undergo surgery for urinary incontinence or pelvic organ prolapse during their 
lifetime, and 30 percent of those having surgery will have at least two 
surgical procedures to try to correct the problem.  With the steady increase 
in the population of older women, the national cost burden related to pelvic 
floor disorders is large in terms of direct health care costs, lost 
productivity, and decreased quality of life.

Pelvic floor disorders result in significant morbidity, both in women of 
reproductive age and postmenopausal women.  Many of these conditions lead to 
hysterectomy or other major surgery.  In some cases, alternative management 
strategies might have been effective, but were not understood, accessible or 
affordable.  Outcomes of surgical treatment have not been well documented, for 
some procedures, initial claims of effectiveness have not been supported by 
data from long-term follow-up.

In September 1998, the NICHD, in collaboration with the Office of Research on 
Women’s Health, the National Institute on Aging, the National Institute of 
Diabetes and Digestive and Kidney Diseases, and the Office of Rare Diseases, 
held a workshop to examine the state of basic, epidemiological, and clinical 
research addressing pelvic floor disorders in women.  A consensus emerged that 
underscored the lack of a substantive knowledge base related to these 
disorders and directions for future research to remedy these deficiencies were 
discussed.  Few data were available on clinical management of pelvic floor 
disorders, and the validity of conclusions was limited by lack of 
standardization in defining conditions and reporting outcomes, small sample 
sizes, mostly retrospective study designs, and high rates of loss to follow-
up.  There is no consensus as to the threshold for intervention and the 
rationale for selection of treatment for particular clinical conditions has 
not been established.  

From the proceedings of the 1998 workshop, NICHD has developed a set of 
initiatives in this field related to basic science, epidemiologic, and 
clinical research on pelvic floor disorders in women.  The overall goal is to 
advance the state of knowledge regarding the pathophysiology of pelvic floor 
disorders and to address the need for rigorous controlled evaluation of 
diagnostic and therapeutic practices for these disorders.

In December 1999, NICHD and other NIH institutes sponsored a Workshop on 
Terminology for Researchers in Female Pelvic Floor Disorders.  During this 
workshop, recommendations were made for standardization of terminology 
regarding definitions of the conditions included under the general term 
“pelvic floor disorders,” for definitions of outcomes after intervention, and 
for minimum data set collection for research studies.  All NIH grant 
applications related to pelvic floor disorders are required to use these 
standard terms.  Interested applicants should request a copy of the 
proceedings of the Terminology Workshop from the program staff listed under 
INQUIRIES, below.

Use of the cooperative agreement mechanism for this initiative has many 
advantages.  The NICHD staff participant will contribute scientifically to 
consensus decision-making and to maintaining balance among the participants.  
Expert statistical consultation in experimental design and analysis is 
provided to assist during protocol development and data analysis.  In this 
way, the research group can identify issues with a high degree of objectivity, 
develop well-designed protocols, and provide a large patient base, so that 
tests and treatments can be evaluated more rapidly and with greater 
statistical validity than would be otherwise possible for individual centers.  
The anticipated efficiency of communication among investigators and 
dissemination of information to practitioners and the public will lead to more 
effective patient care and to more economical use of resources.

Objectives and Research Scope

There are many controversies in the field of pelvic floor disorders that would 
lend themselves to cooperative study.  The scope includes clinical problems in 
pelvic organ prolapse, urinary incontinence, and fecal incontinence.  The 
following should by no means be viewed as exhaustive, and are intended only as 
broad examples of research topics relevant to this RFA:

o Outcomes of different surgical procedures or non-surgical versus surgical 
treatment for pelvic organ prolapse, urinary incontinence, and/or fecal 
incontinence:  Controlled trials to compare outcomes by cure rate and 
functional status (such as quality of life, sexual function, and urinary and 
lower gastrointestinal tract function).

o Diagnostic testing:  Indications and expected versus actual benefit of 
diagnostic testing in patients with pelvic floor disorders, such as use of 
urodynamic testing in patients with urinary dysfunction, use of ancillary 
imaging tests such as video urodynamics, ultrasound (pelvic, perineal, anal), 
magnetic resonance imaging, or defecography.

o Timing of intervention, either surgical or nonsurgical:  Controlled trials 
to compare outcomes of early (anatomic abnormalities that may be asymptomatic) 
versus later (symptom-driven) intervention.

o Postoperative management to maximize recovery and minimize recurrence of 
pelvic floor disorders:  Controlled trials of different postoperative 
management strategies after surgical treatment for pelvic organ prolapse, 
urinary incontinence, and/or fecal incontinence.

Because the prevalence of pelvic floor disorders is substantially greater in 
women than in men and because treatment of pelvic floor disorders is markedly 
different in men and women, participation in the clinical protocols planned 
under this initiative will be restricted to adult women.

Since this list is not meant to be all-inclusive, prospective applicants are 
encouraged to discuss their ideas for applications with the program staff 
listed under INQUIRIES. 

Study Design

While other study designs will be considered as appropriate to the research 
question, randomized trials are the preferred approach.

The Network will include approximately eight Clinical Sites supported by U10 
awards, and a Data Coordinating Center (DCC) supported by a U01 award.  The 
Clinical Sites will recruit, evaluate, and treat the participants in any or 
all of the clinical studies supported by the Network.  The DCC will have 
primary responsibility for data collection and management for each trial.  A 
member of the NICHD program staff, serving as Project Scientist, will 
cooperate with the funded Principal Investigators in designing and executing 
protocols to optimize management in these areas.

As discussed in more detail under Terms and Conditions of Award, below, 
collaborative responsibilities among the investigators at Clinical Sites, the 
DCC, and the NICHD will be facilitated by a Steering Committee, a Clinical 
Trials Advisory Board, and a Data Safety and Monitoring Committee.

Timetable

It is anticipated that the program will conduct its activities according to 
the following general outline:

Phase I (First Six Months of Study):  Protocol Development

Initially, the Advisory Board and Steering Committee (see section on 
Collaborative Responsibilities under “Terms and Conditions of Award”) will 
review and identify issues of importance in pelvic floor disorders.  They will 
consider items proposed for study by the Network from among those listed above 
in “Objectives and Research Scope” and others.  The Advisory Board and 
Steering Committee will rank in priority order a series of issues that are 
substantive, lie within the scope of existing technical capability, lend 
themselves to multicenter evaluation, involve sufficient numbers of patients 
to be of consequence in terms of morbidity, and address significant public 
health needs.  In this and subsequent activities, the Steering Committee will 
attempt to use electronic and telecommunications whenever possible.

From the list of important issues, the Steering Committee will generate 
protocols and agree on lead sites for the protocols.  Each protocol is to be 
acceptable to the participants, adequate for appraisal of the research issues 
defined, and amenable to data collection in a single format acceptable to all 
sites.  Satisfactory controls will be incorporated, and attention will be 
given to maximize the number of studies possible with minimal data collection.  
Protocol subcommittees may be appointed to develop protocols more efficiently.

Phase II (Second Six Months of Year 01, Years 02-05):  Protocol Implementation

Participating Clinical Sites will incorporate the protocols into the clinical 
management of those patients selected for study.  The Clinical Sites will 
supervise the collection of data with adequate attention to the fidelity of 
records and transcription, and will provide information in uniform data format 
for analysis.  The mode of data transmission and analysis will be determined 
by the Steering Committee in conjunction with the recommendations of the DCC.  
Data summaries will be provided to the Data Safety and Monitoring Committee 
(see section on Collaborative Responsibilities under “Terms and Conditions of 
Award”) on a semi-annual basis, or as indicated by study development.  Format 
and content of final reports and the dissemination of information to the 
scientific community will be determined by the Steering Committee.

Beginning approximately six months after the start of data collection, the 
Data Safety and Monitoring Committee will examine the aggregated data and make 
recommendations to NICHD on the need to modify or terminate studies, as 
described above.  As studies are terminated, the Advisory Board and Steering 
Committee will be expected to initiate identification of new issues and the 
institution of new protocols.

SPECIAL REQUIREMENTS

Because protocols for investigation will not be written until after awards are 
made, it is not possible for applicants to propose the exact work that they 
would actually carry out if funded.  Therefore, to provide peer reviewers and 
NICHD staff with sufficient information regarding the capabilities of the 
investigators, each applicant must submit a “concept” protocol for a new 
study.  The applicant should note carefully that the “concept” study proposed 
may or may not actually be adopted by the Network as one of its protocols.  
The proposal is requested to serve as an indicator of the applicant’s ability 
to participate in the development and design of protocols for cooperative 
clinical investigations.  It is anticipated that the Steering Committee and 
Advisory Board will include the “concept” protocols submitted by the funded 
Clinical Sites and DCC in their consideration of topics for actual protocols.

For the purposes of this RFA only, it is suggested that the “concept” protocol 
address one of the following topics:

o Controlled trials for comparison of outcomes after surgical treatment of 
pelvic floor disorders (pelvic organ prolapse, urinary incontinence or fecal 
incontinence).

o Indications and benefits of diagnostic testing in pelvic floor disorders.

o Timing of intervention for pelvic floor disorders.

o Postoperative management strategies to maximize recovery and minimize 
recurrence of pelvic floor disorders.

The protocol should be written specifically for this Network and will be a key 
factor in evaluation of the application.  Applicants should outline the 
rationale and background of the proposed study, study design and protocol, 
eligibility criteria, and initial sample size and power analyses.

Minimum Requirements for Clinical Site Applicants:

1. Participants must be based in departments providing both inpatient and 
outpatient health care for women.

2. The Principal Investigator and research team at each Clinical Site must 
have a history of previous successful clinical research. 

3. The Principal Investigator should be able to make a substantive, long-term 
commitment of effort to Network responsibilities.  The clinical investigators 
at each Clinical Site must include a urogynecologist and a urologist with 
demonstrated training and experience in the diagnosis and treatment of pelvic 
floor disorders in women.  It is expected that either a urologist or a 
urogynecologist will serve as the Principal Investigator for a Clinical Site.  

4. The Clinical Site must demonstrate willingness and ability to participate 
in a cooperative manner with other Clinical Sites and with the DCC in the 
delineation of research protocols, statistical methods, uniform data 
collection, and data transfer.

Applications from institutions that have a General Clinical Research Center 
(GCRC) funded by the National Center for Research Resources may wish to 
identify the GCRC as a resource for conducting the proposed research.  If so, 
a letter of agreement from either the GCRC program director or Principal 
Investigator should be included with the application.

Applicants may wish to propose a consortium of institutions as a multicenter 
Clinical Site.  If so, a single application, with one Principal Investigator, 
should be submitted by an applicant institution on behalf of all institutions 
that compose that Clinical Site.  It is not necessary for each institution 
constituting a multicenter Clinical Site to have a urogynecologist and a 
urologist as clinical investigators, the Clinical Site as a whole must have a 
urogynecologist and a urologist as clinical investigators and it is expected 
that one will serve as the Principal Investigator.

Minimum Requirements for Data Coordinating Center (DCC) Applicants:

1. The applicant must have demonstrated prior experience as a Coordinating 
Center in multicenter studies.

2. The Principal Investigator, with other staff, must have appropriate 
biostatistical, data management, and coordination expertise.

3. The applicant must have the ability to assist in designing protocols and 
the data collection system, including transmission via the Internet. 

4. The applicant must demonstrate the willingness and ability to cooperate 
with the Clinical Sites and NICHD staff in all design, data collection, and 
analysis functions.

Budget Requirements

The budget must reflect the phases of the project as described under 
Application Instructions, below.

Terms and Conditions of Award

The following Terms and Conditions of Award are in addition to, and not in 
lieu of, otherwise applicable OMB administrative guidelines, HHS grant 
administration regulations in 45 CFR Parts 74 and 92 and other HHS, PHS and 
NIH grant administration policies.

The administrative and funding instrument used for this program is a 
cooperative agreement (U01, U10), an “assistance” mechanism, (rather than an 
“acquisition” mechanism) in which substantial NIH scientific and/or 
programmatic involvement with the awardee is anticipated during performance of 
the activity.  Under the cooperative agreement, the NIH’s purpose is to 
support and 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 awardee(s) and the NICHD Project Scientist.  

Cooperative agreements are subject to the same administrative requirements as 
grants.  A Program Officer from the Contraception and Reproductive Health 
Branch, Center for Population Research, NICHD, separate from the Project 
Scientist, will exercise normal program stewardship.  Business management 
aspects of these awards will be administered by the NICHD Grants Management 
Branch in accordance with HHS, PHS, and NIH grant administration requirements.

Awardee Rights and Responsibilities

In collaboration with the other awardees and with assistance from the NICHD 
Project Scientist, awardees will have primary and lead responsibilities to:

1. Define research objectives and approaches.

2. Plan the design and implementation of the clinical protocols.

3. Conduct the studies including participant recruitment and follow-up.

4. Collect and analyze the data.

5. Publish the results, conclusions, and interpretations of studies.

6. Modify or delete protocols, and add new protocols, subject to NICHD 
approval.

Awardees will retain custody of and primary rights to data from their Clinical 
Site developed under the award, subject to current Government policies 
regarding rights of access.

The awardees agree to accept the advisory role of the Clinical Trials Advisory 
Board, the coordinating role of the Steering Committee, and the cooperative 
nature of the group process.

NICHD Staff Responsibilities

The NICHD Project Scientist will have substantial scientific-programmatic 
involvement during conduct of this activity, through technical assistance, 
advice, and coordination above and beyond normal program stewardship for 
grants, as described below.

1. Assist in and facilitate the development of study protocols.

2. As a voting member of the Steering Committee, review and comment on each 
stage of the program before subsequent stages are started, including options 
of modification or termination by mutual consent between the Network and 
NICHD.

3. Assist in maximizing cooperation among the units and help redirect efforts, 
if necessary.  The NICHD Project Scientist may determine jointly with the 
awardees the need to add clinical sites for the purpose of increasing patient 
accrual.

4. Assist, through review, comment, analysis, and, where appropriate, co-
authorship, in reporting results to the community of investigators and health 
care recipients.

The NICHD Program Officer will exercise normal program stewardship, as 
described below.

1. Retain the option to withhold support of a participating unit, if technical 
performance requirements such as compliance with the protocol, meeting patient 
enrollment targets, and adherence to uniform data format are not met.  
Continued support will be contingent upon meeting these requirements.

2. Continuous review of all activities to ensure objectives are being met.

3. Redirecting activities or improving the cooperation and performance of 
participating institutions.

4. Ensuring that the scientific progress of the cooperative agreement is 
commensurate with the funds provided to each of the sites.  If recruitment or 
cost containment becomes an issue, funding on a cost per patient may be 
implemented if necessary.

Collaborative Responsibilities

1. Steering Committee:  The Steering Committee will be the main governing body 
of the study and will have primary responsibility for developing research 
protocols by consensus, supervising the conduct of the studies, and reporting 
results.  The Steering Committee will consist of the Principal Investigators 
(one from each Clinical Site), the Principal Investigator of the DCC, and the 
NICHD staff Project Scientist.  Each member of the Steering Committee will 
have one vote.  The chairperson, who will be someone other than the NICHD 
Project Scientist, will be designated by the Steering Committee.  A member of 
the NICHD grants management staff will serve as advisor to the Committee.  
Subcommittees will be established by the Steering Committee, as it deems 
appropriate.  Awardees will be required to accept and implement the common 
protocols and procedures approved by the Steering Committee.

2. Clinical Trials Advisory Board:  An independent Clinical Trials Advisory 
Board will advise the Steering Committee in identifying and setting priorities 
for research topics on pelvic floor disorders appropriate for study by the 
Network.  Such topics would be of high public health impact, amenable to 
rigorous scientific approaches, and clinically feasible.  The Advisory Board, 
chosen by the NICHD with the advice of the Steering Committee, will include 
members with expertise in clinical trial design, biostatistics, epidemiology, 
gynecology, urology, and urogynecology, as well as the Chair of the Steering 
Committee and the NICHD Project Scientist.  The Advisory Board will evaluate 
the overall hypotheses and scope of planned trial protocols, with additional 
ad hoc scientific and/or clinical experts as needed.

3. Data Safety and Monitoring Committee:  A Data Safety and Monitoring 
Committee (DSMC) convened by the NICHD will have responsibility for reviewing 
the safety of ongoing clinical trials and will advise on their conduct.  
Members of the DSMC will be chosen by the NICHD with the advice of the 
Steering Committee, and will include one member representing the lay 
community.  The DSMC will meet at least every six months, either in person or 
by conference call.  The DSMC will monitor data collection and analysis by the 
DCC, including any reports of adverse events.  When appropriate, the DSMC will 
conduct interim evaluations of the data with respect to the need to terminate 
studies, either because the data suffice to answer the research questions 
posed, data collection provides support for an alternative study initiative, 
or because experience has proven that the research is not feasible.

Arbitration

Any disagreement that may arise on scientific/programmatic matters, within the 
scope of the award, between award recipients and NICHD may be brought to 
arbitration.  An arbitration panel will be composed of three members:  one 
selected by the Steering Committee (with the NICHD Project Scientist not 
voting) or by the individual awardee in the event of an individual 
disagreement, a second member selected by NICHD staff, and a third member 
selected by the first two members.  The decision of the arbitration panel, by 
majority vote, will be binding.  

This special arbitration procedure in no way affects the right of an awardee 
to appeal an adverse action in accordance with PHS regulations at 42 CFR Part 
50, Subpart D, and HHS regulation at 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 subpopulations must be included in all NIH supported biomedical and 
behavioral research projects involving human subjects, unless a clear and 
compelling rationale and justification are 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 103-43).

All investigators proposing research involving human subjects should read the 
“NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical 
Research,” published in the Federal Register of March 28, 1994 (FR 59 14508-
14513) and in the NIH Guide for Grants and Contracts, Vol. 23, No. 11, March 
18, 1994, and available on the Internet at: 
http://grants.nih.gov/grants/guide/notice-files/not94-100.html.

Because the prevalence of pelvic floor disorders in women is substantially 
greater than in men and because treatment of pelvic floor disorders is 
markedly different in men and women, participation in the clinical protocols 
planned under this initiative will be restricted to adult women.

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 subject research, conducted or supported by 
the NIH, unless there are scientific and/or 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," published in the NIH Guide for Grants and 
Contracts, March 6, 1998, and available on the Internet at: 
http://grants.nih.gov/grants/guide/notice-files/not98-024.html. 

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 a letter of intent that includes a 
descriptive title of the proposed research, the name, address, and telephone 
number of the Principal Investigator, the identities of other key personnel 
and participating institutions, and the 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 NICHD staff to estimate the potential review workload and plan 
the review.  

The letter of intent is to be sent to Dr. Anne M. Weber at the address listed 
under INQUIRIES, below, by October 3, 2000.

APPLICATION PROCEDURES

The research grant application form PHS 398 (rev. 4/98) is to be used in 
applying for these grants.  These forms are available at most institutional 
offices of sponsored research, on the Internet at 
http://grants.nih.gov/grants/funding/phs398/phs398.html, and from the Division 
of Extramural Outreach and Information Resources, National Institutes of 
Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone 
301-435-0714, E-mail: Grantsinfo@nih.gov.

Open Information Forum for Prospective Applicants

A one-day open information forum will be held for prospective applicants, 
approximately four to six weeks after issuance of this RFA.  For prospective 
applicants who cannot attend the forum in person, conference call capability 
will be provided.  At this forum, NICHD program staff will address any 
questions that prospective applicants might have regarding the clinical or 
scientific concepts of the RFA.  Attendance is not required and is not a pre-
condition for submission of an application.  Prospective applicants may obtain 
additional information regarding the time, date, and location of this forum at 
http://www.nichd.nih.gov/RFA/HD-00-013/HD-00-013.htm or may contact the NICHD 
program staff listed under INQUIRIES.  Applicants planning to attend the 
meeting or to participate in the conference call are asked to submit their 
questions in writing to the NICHD program staff listed under INQUIRIES at 
least one week in advance of the forum.  A list of questions asked during the 
forum and a written summary of the responses from NICHD program staff will be 
posted following the meeting at 
http://www.nichd.nih.gov/RFA/HD-00-013/HD-00-013.htm or will be provided to 
persons who request it.

Application Instructions

For Clinical Site and DCC applications, the concept protocol should be 
presented in the Research Plan section of the PHS 398 within the standard 25-
page limit.  The concept protocol should reflect the requirements stated in 
the "SPECIAL REQUIREMENTS" section above.

The following should be addressed or included in Clinical Site applications:

1. The application should include a summary of prior research experience.  
Specifically, contributions in key areas such as protocol design, patient 
recruitment and retention, data analysis and interpretation, and publication 
are important.  Research on pelvic floor disorders in women is especially 
relevant.

2. Ability to enroll and retain sufficient numbers of patients with pelvic 
floor disorders for meaningful studies should be documented, including plans 
for recruitment of minority/ethnic women and plans to minimize loss to follow-
up.  Applications should state the numbers of patients seen annually for the 
different types of pelvic floor disorders (including, but not necessarily 
limited to, patients with pelvic organ prolapse, urinary incontinence, and 
fecal incontinence).

3. Key personnel should include physician staff representing several areas of 
expertise, either based in the participating department or available as 
collaborators.  These areas could include obstetrics, gastroenterology, 
colorectal surgery, radiology, and physical therapy.  In addition, an 
experienced full-time research nurse (study coordinator) must be among the key 
personnel.  Additional research nursing staff and clerical staff (e.g., data 
entry clerk) should be available as appropriate for the proposed study.  
Established research teams should describe their current program with any 
plans for change related to this application, newly formed teams should 
describe their plans for development and implementation of the team"s program 
for interaction and collaboration.  Description of the team should include 
sufficient commitment of staff time for satisfactory conduct of the study.

4. The application should describe available laboratory and radiology 
facilities for appropriate testing of study participants, in such areas as 
urodynamics, ultrasound, contrast studies such as defecography, and other 
radiological and related techniques that may be required to diagnose and 
follow the conditions under study.

5. Institutional and departmental commitment to this program must be 
demonstrated, including adequate space in which to conduct clinical and 
research activities.

6. The application must demonstrate willingness and ability to cooperate with 
other Clinical Sites, the DCC, and NICHD staff in all design, data collection, 
and analysis functions. For those applicants with previous experience in 
multicenter studies (especially randomized trials) using common protocols, 
this experience should be documented.  For applicants without previous 
experience, the capability and willingness to work with other centers on 
common protocols should be described.

7. As noted above, all grant applications related to pelvic floor disorders 
are required to use the standard terminology as recommended at the NIH 
Terminology Workshop for Researchers in Female Pelvic Floor Disorders held in 
December 1999.  

The following should be addressed or included in Data Coordinating Center 
applications:

1. The application should include documentation of adequate and appropriate 
resources (in addition to personnel) to fulfill all DCC responsibilities.

2. The application must demonstrate experience in developing and monitoring 
quality control.

3. The DCC will report to the Data Safety and Monitoring Committee at least 
every six months regarding accumulating data and the Clinical Sites’ 
performance.  The application should document the ability to meet such 
reporting deadlines as well as the overall timetable.

4. The application must include a plan detailing methods of data receipt, 
analysis, quality control, and reporting, including communications with 
administrative and clinical personnel.

5. There should be evidence of strong institutional support for the study, 
including adequate space for data analysis and management activities.  An 
organizational structure for the study should be developed in the application, 
delineating lines of authority and responsibility for dealing with problems in 
all general areas.

6. The application must demonstrate willingness and ability to cooperate with 
the Clinical Sites and NICHD staff in all design, data collection, and 
analysis functions.

7. If an institution applies for both a Clinical Site and the DCC, the DCC 
application must address the issue of how the DCC would maintain operational 
independence if both were funded (for example, maintenance of blinding for 
investigators involved at the Clinical Site and the DCC).

8. As noted above, all grant applications related to pelvic floor disorders 
are required to use the standard terminology as recommended at the NIH 
Terminology Workshop for Researchers in Female Pelvic Floor Disorders held in 
December 1999. 

Budget Requirements

All applications must include an adequately justified year-by-year budget, 
reflecting the changes in proposed activities as the studies progress through 
their various phases.  Since the project proposed in the grant application may 
not be adopted by the Network, development of the budget should be viewed as 
estimated.

During the first six months, the budget will be for development of the 
protocols, manuals of procedures, and data collection forms for the studies.  
The database will be created by the DCC during this time.

During the second phase of the study (the second six months of Year 01, and 
Years 02-05), the budget should reflect recruitment of a full complement of 
participants for the clinical trials plus follow-up of these participants over 
the time course of study.  Interim data analysis, preparation of reports to 
the Steering Committee and Advisory Board, and writing of papers for 
publication will be performed during this phase.  

Budget Requirements for Clinical Site Applications

For a Clinical Site, the budget should request support for the minimum number 
of full-time and/or part-time staff needed to successfully carry out the 
proposed trial.  The personnel list should include a Principal Investigator, 
co-investigator(s), study coordinator, and data entry clerk.  The budget 
should request a minimum of 10 percent effort for the Principal Investigator.

For the first six months, the travel budget should be estimated based on 
travel for two key investigators from each Clinical Site (the Principal 
Investigator and one co-investigator) to attend two-day, monthly meetings of 
the Steering Committee in the Washington, DC area.

The second phase of the study (the second six months of Year 01, and Years 02-
05) will require meetings of the Steering Committee approximately every four 
months for one to two days in the Washington, DC area.  The travel budget 
should be estimated based on travel for the Principal Investigator plus, if 
desired, one additional co-investigator, from each Clinical Site.  In 
addition, travel for centralized training of the study coordinator and data 
entry clerk must also be budgeted (assume central training for one to two days 
to be held in the Washington, DC area annually during Years 01-05).  
Therefore, the travel budget for the first year should include eight Steering 
Committee meetings for up to two people from each site (six in the first six 
months, and two in the second six months of Year 01), and one meeting for 
centralized training for two people.  The travel budget for the second, third, 
fourth, and fifth years should include three Steering Committee meetings per 
year for up to two people from each site, and one meeting per year for 
centralized training for two people.

Budget Requirements for Data Coordinating Center (DCC) Applications

For a DCC, the budget should request support for the minimum number of full-
time and/or part-time staff needed to successfully conduct the proposed trial.  
The Personnel list should include a Principal Investigator, co-
investigator(s), statistician(s), computer programmer(s), and data manager(s). 

Travel by DCC staff (the Principal Investigator and one additional person) for 
the following meetings should be budgeted (all meetings will be held in the 
Washington, DC area except the site visits).  In Year 01, there will be a 
total of 17 trips:  eight Steering Committee meetings (six meetings in the 
first six months and two meetings in the second six months), one Clinical 
Trials Advisory Board meeting, plus site visits to each of eight Clinical 
Sites before initiation of the first protocol.  For each year in Years 02-05, 
there will be a total of 12 trips each year:  three Steering Committee 
meetings, one Clinical Trials Advisory Board meeting, plus site visits to each 
of eight Clinical Sites each year. 

Submission Instructions

The RFA label available in the PHS 398 (rev. 4/98) application form must be 
stapled to the bottom of the face page of the application and must display the 
RFA number HD-00-013.  A sample RFA label is available at 
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf.  Please note this is 
in the pdf format.  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.

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 should be 
sent to:

L.R. Stanford, Ph.D.
Division of Scientific Review
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 5E03, MSC 7510
Bethesda, MD  20892-7510
Bethesda, MD  20852 (for express/courier service)
Telephone:  (301) 496-9254

Applications must be received by November 28, 2000.  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.

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed for completeness by the CSR and 
for responsiveness to the RFA by NICHD staff.  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 NICHD in accordance with the review criteria stated below.  As part of the 
initial merit review, all applications will receive a written critique and may 
undergo a process in which only those applications deemed to have the highest 
scientific merit will be discussed, assigned a priority score, and receive a 
second level review by the National Advisory Child Health and Human 
Development (NACHHD) Council.

Review Criteria for the Evaluation of All Applications

The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health.  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.  For example, an 
investigator may propose to carry out important work that by its nature is not 
innovative but is essential to move a field forward.

(1) 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?

(2) Approach:  Are the conceptual framework, design, methods, and analyses 
adequately developed, well integrated, and appropriate to the aims of the 
project?  Does the applicant acknowledge potential problem areas and consider 
alternative tactics?

(3) Innovation:  Does the project employ novel concepts, approaches, or 
methods?  Are the aims original and innovative?  Does the project challenge 
existing paradigms or develop new methodologies or technologies?

 (4) 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 (if any)?

(5) Environment:  Does the scientific environment in which the work will be 
done contribute to the probability of success?  Do the proposed experiments 
take advantage of unique features of the scientific environment or employ 
useful collaborative arrangements?  Is there evidence of institutional support 
in such areas as fiscal administration, personnel management, space 
allocation, procurement, planning, equipment, and budgeting?

o Demonstrated willingness to work and cooperate with other units in the 
Network (Clinical Sites and Data Coordinating Center) and the NICHD as 
summarized in this RFA. 

o Adequacy of administrative, clinical, and data organizational management 
facilities as described in the minimum requirements.

In addition to the above criteria, in accordance with NIH policy, all 
applications also will be reviewed with respect to the following:

o The adequacy of plans to include minorities and their subgroups as 
appropriate for the scientific goals of the research.  Plans for the 
recruitment and retention of subjects also will be evaluated.

o The reasonableness of the proposed budget and duration in relation to the 
proposed research.

o The adequacy of the proposed protection for humans, animals or the 
environment, to the extent they may be adversely affected by the project 
proposed in the application.  

Review Criteria for the Evaluation of Clinical Site Applications

In addition to the review criteria for all applications, Clinical Site 
applications will be evaluated according to the following:

o Innovation

The final study protocols will be developed collaboratively by the Steering 
Committee.  Thus, in reviewing the concept protocol, the peer review group 
will focus on evidence that:

1. The applicant possesses the knowledge necessary to contribute meaningfully 
to the final designs, including understanding of the scientific, ethical, and 
practical issues underlying the proposed study.

2. The applicant demonstrates knowledge of the potential problems associated 
with the conduct of the proposed study, and identifies solutions or 
alternatives.

3. Justification of the proposed sample size is provided.

o Investigator

1. The application provides evidence of the investigator’s training, 
experience, scientific, clinical, and administrative abilities, academic 
productivity, and specific competence relevant to the operation of a Clinical 
Site. 

2. Clinical Site applications provide evidence of a successful clinical 
research team. 

Review Criteria for the Evaluation of Data Coordinating Center (DCC) 
Applications

In addition to the review criteria for all applications, DCC applications will 
be evaluated according to the following:

o Innovation

The final study protocols will be developed collaboratively by the Steering 
Committee.  Thus, in reviewing the concept protocol, the peer review group 
will focus on evidence that:

1. The applicant possesses the knowledge necessary to contribute meaningfully 
to the final designs, including understanding of the scientific, ethical, and 
practical issues underlying the proposed study.

2. The applicant demonstrates knowledge of the potential problems associated 
with the conduct of the proposed study, and identifies solutions or 
alternatives.

3. Justification of the proposed sample size is provided, in addition to 
proposed plans for data collection, management, editing, processing, analysis, 
and reporting.

o Investigator

1. The application provides specific evidence of experience and qualifications 
of team members who would be responsible for data quality and management 
activities.

2. The application documents knowledge and experience in areas relevant to the 
conduct of collaborative clinical research, especially randomized clinical 
trials.  This includes the adequacy of the approach to developing a 
cooperative relationship among the Clinical Sites and exercising appropriate 
leadership in matters of study design, data acquisition, data management, data 
quality, and data analysis.

o Environment

1. Experience of DCC personnel in utilizing procedures that ensure the safety 
and confidentiality of all records.

2. Adequacy of the proposed facility, technical hardware, and space, and 
appropriateness of the organizational and administrative structure of the 
proposed DCC.

SCHEDULE

Letter of Intent Receipt Date:    October 3, 2000
Application Receipt Date:         November 28, 2000
Peer Review Date:                 February-March 2001
Council Review:                   June 2001
Earliest Anticipated Start Date:  July 1, 2001

AWARD CRITERIA

Criteria that will be used to make award decisions include scientific merit 
(as determined by peer review), availability of funds, and programmatic 
priorities.

INQUIRIES

Inquiries concerning this RFA are encouraged.  The opportunity to clarify any 
issues or questions from potential applicants is welcome.

Direct inquiries regarding programmatic issues to:

Anne M. Weber, M.D., M.S.
Center for Population Research
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 8B13C, MSC 7510
Bethesda, MD  20892-7510
Telephone:  (301) 435-6972
FAX:  (301) 480-1972
E-mail:  webera@mail.nih.gov 

Direct inquiries regarding fiscal matters to:

Mr. Michael Loewe
Grants Management Branch
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 8A17J, MSC 7510
Bethesda, MD  20892-7510
Telephone:  (301) 435-7008
FAX:  (301) 402-0915
E-mail:  loewem@exchange.nih.gov 

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance No. 
93.864, Population Research.  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 and Federal Regulations 42 CFR 52 
and 45 CFR Parts 74 and 92.  This program is not subject to the 
intergovernmental review requirements of Executive Order 12372 or Health 
Systems Agency review.

The PHS strongly encourages all grant recipients to provide a smoke-free 
workplace 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 
PHS mission to protect and advance the physical and mental health of the 
American people.



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