SPECIALIZED COOPERATIVE CENTERS PROGRAM IN REPRODUCTION RESEARCH 

NIH GUIDE, Volume 26, Number 32, September 26, 1997 

RFA: HD-97-008 

P.T. 

National Institute of Child Health and Human Development 

Letter of Intent Receipt Date: January 14, 1998 Application Receipt
Date: April 28, 1998 

PURPOSE 

The National Institute of Child Health and Human Development (NICHD)
through the Reproductive Sciences Branch (RSB) in the Center for
Population Research (CPR) provides funding for a limited number of
research centers in the reproductive sciences. These centers provide an
arena for multidisciplinary interactions among basic and clinical
scientists interested in establishing high quality research programs in
the reproductive sciences. Applications for these centers are sought
from investigators willing to participate with the NICHD under a
cooperative agreement in a multicenter cooperative research program.
Center investigators will be expected to work with NICHD staff in
facilitating research collaborations and interactions within and between
centers. Such a cooperative program will form a national network that
fosters communication, innovation and research excellence with the
ultimate goal of improving human reproductive health through accelerated
transfer of basic science findings into clinical practice. 

HEALTHY PEOPLE 2000 

The Public Health Service (PHS) is committed to achieving the health
promotion and disease prevention objectives of "Healthy People 2000," a
PHS-led national activity for setting priority areas. This Request for
Applications (RFA), Specialized Cooperative Centers Program in
Reproduction Research, is related to the priority area of family
planning. Potential applicants may obtain a copy of "Healthy People
2000" (Full Report: Stock No. 017-001-00474-0 or Summary Report: Stock
No. 017-001-00473-1) through the Superintendent of Documents, Government
Printing Office, Washington, DC 20402-9325 (telephone 202-512-1800). 

ELIGIBILITY REQUIREMENTS 

Applications may be submitted by domestic for-profit and non-profit
organizations, public and private, that meet the requirements stated in
this RFA. Minority individuals, persons with disabilities, and women are
encouraged to apply as Principal Investigators. The need for continuous
and active communications and interactions among the awarded sites
dictates that only domestic institutions in the United States will be
eligible for these Center grant awards. 

MECHANISM OF SUPPORT 

The funding mechanism to be used to assist the scientific community in
participating in this Centers Program will be the National Institutes of
Health (NIH) cooperative specialized center (U54) mechanism. Funding
will be provided by means of cooperative agreements established between
the participating Centers and the NICHD. A cooperative agreement is not
an "acquisition" mechanism. It is an "assistance" mechanism in which
substantial NIH scientific and/or programmatic involvement with the
awardee is anticipated during the performance of the activities
conducted by the awardee. Under a cooperative agreement, the NIH purpose
is to support, stimulate, and expedite the recipient's activities by
jointly being involved with them. NIH staff work cooperatively with the
award recipients in a partner role and do not assume direction, prime
responsibility, or a dominant role in the activity. Details of the
responsibilities, relationships, and governance of the activities to be
funded under the cooperative agreements awarded for this Program are
discussed later in this document under the section "Terms and
Conditions." 

The total project period for an application submitted in response to
this RFA is five years. The anticipated award date is April 1, 1999.
Because the nature and scope of the research proposed in response to
this RFA may vary, it is anticipated that the size of the awards will
also vary within the funding limits available (see Description of a
Center). It is expected that NICHD will solicit additional new or
continuation center applications through annual issuance of an RFA. It
is anticipated that at least three Centers will be funded in each
subsequent annual competition contingent upon the availability of funds.

FUNDS AVAILABLE 

Although this solicitation is included in the fiscal plans for FY 1999,
support for these center grants is contingent upon the availability of
funds for this purpose. The number of grants to be awarded is also
contingent upon a sufficient number of applications deemed meritorious
enough to be considered for an award. It is anticipated that an
estimated total of $2,800,000 (including indirect and direct costs) will
be available for the first year of the Program, which will support up to
three Centers in FY 1999. 

RESEARCH OBJECTIVES 

Background 

The ultimate goals of biomedical research supported by the RSB are to
develop new knowledge leading to clinical applications that will enable
men and women to control their own fertility choices with methods that
are safe, effective, inexpensive, reversible and acceptable to various
population groups. Such research aims to develop new leads for
contraception, procedures for alleviating infertility, and fertility
preserving treatments for reproductive disorders that threaten
fertility. 

The present day need for the availability of contraception options
acceptable to diverse populations remains globally unmet. Among the 600
million women of reproductive age in today's world, as many as 228
million women are at risk of unintended pregnancy from the 39 trillion
acts of intercourse that occur annually. Up to 64 percent of all
worldwide pregnancies are unintended (mistimed or completely unwanted).
Over 50 million abortions occur worldwide each year with minimal
estimates of at least 100,000 abortion-related deaths annually. In the
U.S., 3 million unintended pregnancies--57 percent of all
pregnancies--occur annually with half resulting in abortion as an
outcome. In half of the 1.3 million abortions occurring in the U.S. each
year, a contraception method being used failed to prevent a pregnancy. 

Families, family values, and family planning form the cultural essence
and cohesiveness of our existence as human societies. One of the most
basic of human rights--the right to procreate--is frustrated or denied
by the occurrence of infertility in a couple desiring children. It has
been estimated that infertility affects between 37 and 70 million
married couples around the world. In U.S. studies described nearly 50
years ago, it was stated that up to 10 percent of married couples were
'sterile' with the remaining 90 percent having varying degrees of
fertility. More recent and technically rigorous U.S. survey studies have
conservatively identified that there are about 2.3 million infertile
couples, which is about 9 percent of the domestic married couple
population base with wives aged 15-44. In addition, such studies found
that about 4.9 million U.S. women in this age range had an impaired
ability to have children. At least 30-50 percent of infertility is
attributable to male factor infertility for which the pathophysiology is
either not understood at all or, at best, poorly understood. The
prognosis for male infertility treatment outcomes is extremely poor at
present. 

While analyses of the U.S. population base has not found alarming annual
increases in the overall number of infertile couples or the overall
prevalence of infertility, significant age-related increases in
infertility coupled with delayed childbearing in the contemporary couple
population base have been found in such studies. Physician office visits
reflecting current societal life style requirements for infertility
services have markedly increased from 1968 (600,000) to 1988 (1,350,000)
with a projected U.S. peak estimated for 1995 approaching 1,800,000. Of
the infertile couples seeking treatment for infertility, it has been
estimated that up to one-half will be unsuccessful in achieving their
desired outcome. In concert with the increased medical assistance
sought, U.S. infertility service costs have risen to exceed a billion
dollar annual medico-economic impact in the U.S. 

Reproductive disorders affecting fertility are associated with
significant morbidity and a degree of mortality in some specific
instances that cannot be ignored. During the past two decades, the
incidence of ectopic pregnancy has increased from 4.5 to 16.1 per 10,000
pregnancies. The rate appears to be particularly increasing in young
women aged 15-19, perhaps in relationship to the U.S. factors of earlier
age of menarche and initiating sexual activity leading to encountering
tubal disease factors earlier. In 1989, it was reported that 88,400
women experienced an ectopic pregnancy and 34 of them died as a direct
consequence. While improved diagnostic procedures and early intervention
protocols have resulted in markedly reducing mortality, surviving women
are left with an 8-fold risk of reoccurrence and a 20 percent lowered
chance of ever conceiving again. 

Accompanying the human costs of morbidities of reproductive tract
disorders, as noted above, are the attendant substantial costs of the
U.S. health care system involving the diagnosis, treatment, and
follow-up services provided the patients, as well as the added costs to
the patient and the U.S. economy of lost employment and family service
hours. In reproductive aged couples, the obstructive sequelae of male
accessory gland infections account for 8-12 percent of male partner
diagnostic costs for fertility impairment. In reproductive aged females,
it has been estimated that the general incidence of endometriosis is 5
to 15 percent. The incidence of endometriosis in females being
surgically treated for infertility is known to be 30 to 50 percent.
Among infertile females with no other known cause of their infertility,
the incidence of endometriosis has been reported at 40 to 70 percent. A
diagnosis of severe endometriosis often leads to hysterectomy-associated
treatment. While the causative role of endometriosis in infertility
remains poorly understood and its optimal diagnosis and treatment remain
a goal--not an accomplishment--of contemporary medicine, the morbid
impact of the associated pelvic pain has significant human cost and
national economic costs. The etiology of polycystic ovary syndrome
(PCOS), while identified more than 60 years ago by Stein and Leventhal,
remains misunderstood despite 60 years of research. This insidious
disease is currently the most common endocrine disorder of women of
reproductive age. Recent prevalence rate estimates suggest at least 10
percent of the reproductive aged population of U.S. women suffer the
full blown syndrome of hyperandrogenism, chronic anovulation and
polycystic ovaries. While PCOS has been recognized to have a familial
tendency consistent with a genetic factor in its etiology, few
compelling studies clarifying this aspect have been forthcoming prior to
this year. PCOS is a major cause of infertility, other reproductive
system, and other tissue and organ system morbidities. Hysterectomy is a
common patient outcome. PCOS is a major medical economic cost component
in U.S. reproductive health care costs. 

Similarly, the role of dysfunctional uterine bleeding, either in the
presence or the absence of uterine leiomyomata (fibroids), is not well
understood despite its common occurrence and decades of research. It is
a significant factor in noncompliant contraceptive use or discontinuance
and, therefore, in the unintended pregnancy problem. Uterine myomata
occur in nearly 20 percent of all reproductive aged women, are the
single most common diagnosis from gynecological hospital admissions, may
be the only abnormality observed in an infertile couple, and represent
the most common medical indication for an unintended and often unwanted
hysterectomy that prematurely ends a female's reproductive options.
Hysterectomy to treat the morbidity of certain reproductive disorders is
the second most common major surgery performed in the U.S., with greater
than 500,000 hysterectomies reported each year prior to 1995, the year
signifying the peak of 'baby boom' women in the population. If current
hysterectomy rates had remained at the same pre-1995 prevalence level in
the U.S., it is estimated that up to one- third of all women in the U.S.
will have had a hysterectomy before the age of 60. The annual
performance rate is not constant, however, with a projected level
estimated at more than 800,000 annually beyond the 1995 marker year. 

Recognizing that the interactive needs of basic and clinical research
necessary to address the above and related problems may be so complex
that they cannot be solved by individual investigators working alone
without the intellectual and fiscal resources of a cooperative
specialized center program, it is the intention of the RSB, contingent
upon the availability of funds, to initiate and maintain organized,
multi-component reproductive extramural research programs of high
quality that focus on topics deemed to be of high priority and
significance because of their critically important relationship to the
mission of the RSB. 

Objectives 

The objectives of this Centers Program are to support specialized
reproductive research programs of high quality, and to facilitate and
accelerate the translation of promising new preclinical or clinical
leads into clinical practice. The RSB believes that the partnership
developed between program staff and the award recipients through use of
the cooperative agreement mechanism maximizes the ability of the RSB to
promote, facilitate, and assist the research conducted by the awarded
centers. 

This RFA is specifically designed to stimulate the reproductive sciences
research community to organize and maintain research- based centers of
outstanding quality that, serving as national research resources, form a
cooperative network with NICHD that fosters communication, innovation
and high quality reproductive research. Such networking as afforded by
the cooperative nature of this Centers Program will ensure that the
reproductive research community remains in the forefront of the
development and utilization of new technologies which can be used to
treat and ameliorate reproductive disorders, as well as to identify
novel leads for fertility regulation. 

Research Scope 

The Specialized Cooperative Centers Program in Reproduction Research
(SCCPRR) is composed of research-based center grants designed to support
interactive groups of research projects and supporting core service
facilities. The research activities included in these center grants must
comprise, by definition, a multidisciplinary approach to biomedical
problems addressing the specific research topic areas announced in this
RFA (see below). These centers may have more than one theme, focus, or
emphasis, but all of the subprojects involved must be responsive to one
or more of the specific research areas of reproduction supported by the
RSB. Furthermore, the translational objective of this Program requires
that one of the subprojects be entirely or predominantly clinical. 

The following is a list of topics that are considered to be responsive
to the research mission areas of the RSB. Additionally, these topics
identify areas where research at the basic/clinical interface is deemed
essential to the potential development of new leads or approaches to
fertility control, as well as of diagnostic tools and procedures for the
detection, treatment and effective management of reproductive disorders
that impact on reproductive competence. 

Reproductive Biology and Physiology - gametogenesis, including nuclear
and cytoplasmic mechanisms that direct germ cell mitosis and meiosis,
and somatic cell-germ cell interactions which support gametogenesis;
folliculogenesis, including studies addressing intraovarian control of
follicle selection and atresia by growth factors, cytokines and their
respective binding proteins and receptor antagonists; luteogenesis and
luteolysis, including intraovarian mechanisms which control luteal
lifespan; fertilization; early embryogenesis during the pre- to
peri-implantation period; implantation, including cell-to-cell
interactions regulating implantation. 

Reproductive Endocrinology - fundamental mechanisms of hormone
synthesis, secretion, regulation and action in the context of
reproduction, including intrapituitary mechanisms governing gonadotropin
secretion, and intraneuronal mechanisms and glial-neuron interactions
controlling pulsatile GnRH secretion; identification of elements and
factors controlling gene transcription, and identification of signaling
molecules and pathways mediating hormone action; interaction of the
immune and neuroendocrine systems in controlling fertility; mechanisms
by which nutritional modification alters the hypothalamo-pituitary-
gonadal endocrine axis. 

Reproductive Medicine - pathophysiology, diagnosis and treatment of male
or female infertility; relation of endometriosis to infertility,
treatment of benign gynecologic diseases; improvement of existing and
development of new approaches for assisted reproduction. 

Since this list is not meant to be all-inclusive, prospective applicants
preparing either a competing new or continuation center grant
application are encouraged to discuss program relevancy issues with the
program staff contact cited under INQUIRIES in this RFA. However,
applicants should note that the research scope of this RFA does not
include studies in the area of reproductive oncology or reproductive
epidemiology or studies dealing with post-implantation pregnancy and
parturition. These topic areas are outside the purview of research areas
supported by the RSB, and, therefore, will be deemed nonresponsive to
this RFA. In addition, research proposals for projects or cores directly
involving human in vitro fertilization and/or embryo transfer must be in
compliance with NIH policies for such research and should not,
therefore, include efforts or activities that create human embryos
solely for research purposes. It is also not intended for the Centers to
conduct large clinical trials. 

Guidance and Management Structures 

Overall coordination of the Centers Program consistent with the stated
objectives set forth in the RFA (see Objectives) will be done by a
Steering Committee consisting of all Center Principal Investigators and
an NICHD staff Research Coordinator from the RSB, CPR. The Steering
Committee will employ a consensus decision process to guide the Centers
Program in evaluating the progress of member Center programs, their
proposed new research initiatives within the general scope of the
approved program, the need for collaborations either within or outside
the Center network, and the need to redirect certain efforts of member
Centers due to either sufficient data acquisition to permit conclusion,
the acquisition of data supporting an alternative study initiative or
experience proving that the proposed research is no longer feasible. 

In addition to the Steering Committee, smaller cooperative groups will
be formed that consist of research components of member centers having
common research interests addressing a specific basic and/or clinical
research problem. These research focus groups will perform coordinated
research activities as recommended by the Steering Committee. In turn,
progress of the focus groups will further guide the Steering Committee
in decision-making regarding changes in specific research directions,
translational activities, and new research initiatives. The research
focus group will consist of an NICHD staff Research Coordinator from the
RSB, CPR, and Key Investigators of the relevant subproject and/or Core
Directors. 

Further details of the guidance and management structures and processes
may be found in the 'Terms and Conditions' section below. 

Description of a Center 

The minimal requirements for a Center described in this RFA are as
follows (see sections on Review Criteria and Procedures and Award
Criteria below): 

o Each center will propose a research plan that is responsive to the
objectives of the Centers Program set forth in the RFA (see RESEARCH
OBJECTIVES). 

o Each center will support at least three research subprojects that
thematically address one or more research areas listed under Research
Scope. It is required that one subproject be entirely or predominantly
clinical in nature. For this Centers Program, the definition of clinical
can involve patient studies or use of cultured human cells or tissue.
Although not required, it is strongly encouraged that at least one basic
science subproject be in a similar scientific area as the clinical
subproject in order to facilitate transfer of information from bench to
bedside. Alternatively, a project may be proposed that incorporates both
basic and clinical approaches to a particular problem. 

o An administrative core unit which provides oversight to the Center
that is located at the grantee institution, and is accessed only by
budgeted center subprojects and cores; 

o A competent and experienced principal investigator who is committed to
and directly involved in research dealing with mammalian reproduction; 

o Availability of competent and experienced scientific experts to direct
individual research projects or cores associated with the proposed
Center; 

o Availability of the technical resources and facilities necessary for
the conduct of the experiments; 

o Access to properly managed animal facilities for projects conducting
animal studies; 

o As appropriate, access to inpatient and outpatient reproductive health
care units providing adequate numbers of patients for clinical research
projects that require patient participation [Applications from
institutions which have a General Clinical Research Center (GCRC) funded
by the NIH National Center for Research Resources may wish to identify
the GCRC as a resource for conducting the proposed research. In such a
case, a letter of agreement from either the GCRC Program Director or
Principal Investigator should be included with the application]. 

Optional components of the Center organization include the mix of
subprojects and cores to be included in the Center. 

o The Principal Investigator may choose to organize the Center using
collaborations of projects within the same institution. Alternatively,
Centers may seek to maximize their scientific expertise and research
capabilities by including in the application a subproject and/or a
technical service core to be supported at other institutions through
subcontracted consortium arrangements. No more than one consortium
subproject and one consortium core service facility will be permissible
in each Center. 

o The Principal Investigator may choose one of two center structure
options regarding access to technical service core facilities. 

Closed Access Structure - In this center structure, administrative and
all technical service cores will be utilized by budgeted center
subprojects only. Consistent with NICHD guidelines for establishment of
core facilities, utilization by three subprojects is required to justify
a core technical service facility. Percent utilization by any one of the
three subprojects justifying the core cannot exceed 50 percent or be
less than 5 percent. The percent utilization of additional subprojects
requiring core services can be less than 5 percent. Costs necessary to
use a particular core facility can be incorporated into the budget of
the core unit, and not in the budgets of the research subprojects per
se. No internal chargeback system would be required. 

Open Access Structure - In this center structure, budgeted center
subprojects as well as research projects external to the center (e.g.,
R01, R29, R03, P01 subproject) may have access to technical service
cores. However, special consideration must be given to justification of
a technical service core facility and the formal establishment of an
effective chargeback system for all technical service cores. For each
core service facility, at least one of the three projects used to
justify a core must be a budgeted center subproject while the remaining
project(s) used in justifying the core must be externally funded NICHD
projects administered by the RSB. Percent utilization by any internally
budgeted center subproject or externally-funded RSB project used to
justify a particular core facility cannot exceed 50 percent or be less
than 5 percent. An additional seven federally-funded, peer-reviewed
external research projects addressing program-relevant research areas of
the RSB can access the core up to 100 percent of its service capacity.
The 50/5 percent utilization requirement applies to this group of
external projects. Centers must establish an internal management policy
for evaluating the acceptability of proposed RSB program relevant
external projects to access the core facilities. Approval of requests
for core access privileges for external projects which would replace
those described above must be made to RSB Program Staff who then will
evaluate the extent to which the project is relevant to RSB mission
research areas (see Research Scope), and render a decision accordingly. 

If centers choose to operate in an open access format, costs necessary
to utilize a particular core facility by budgeted center subprojects
must be incorporated into the budget of the subproject and not the core
budget in order to accommodate participation in the required chargeback
system. Core budgets will be justified and evaluated based on its access
by budgeted center subprojects and external, program-relevant research
projects as described above. Above and beyond this arrangement,
technology-based core units can offer services to additional external
projects addressing any area of research regardless of funding source
only on a full payback (fee-for-service or in kind) basis. However,
additional funds necessary to provide services to these external
projects (e.g., technical support, supplies, etc.) must come from
sources other than the center funding, such as the supply budgets of the
external projects wishing to access the core facilities. In choosing to
configure a center in an open-access center structure, the Principal
Investigator must have in place and adequately described in the
application management policies which ensure that budgeted center
subprojects are given highest priority in receiving services provided by
the core. 

Centers choosing to configure in an open-access center format may
propose one or more technical service cores that will be utilized
exclusively by budgeted center subprojects. These centers may,
therefore, have a mix of open or restricted access technical service
cores. On the other hand, administrative cores in open center structures
may be accessed only by budgeted center subprojects. 

Once an award is made, centers configured as a closed-access center
structure may, at a later time, choose to convert to an open access
center structure by requesting such conversion in writing to the NICHD. 

Irrespective of the organizational mix selected by the Principal
Investigator, each research subproject or core proposed for inclusion in
the Center must be described independently using the PHS 398 application
format as described in the document "Suggested Format for NICHD U54
Grant Applications," which is available from the program staff listed
under INQUIRIES. For the individual projects or cores, the page limits
stated in the PHS 398 instructions must be followed. 

The overall Center application must also use the PHS 398 format to
provide at the beginning of the application an overall summary of the
Center's organization and cumulative aggregate budgeting for the various
budgetary categories. In both instances, all essential information for
the evaluation of the application must appear in the body of the
application rather than in an appendix. 

SPECIAL REQUIREMENTS 

Terms and Conditions of Award 

Cooperative agreements are assistance mechanisms and are subject to the
same administrative requirements as grants. The following Terms and
Conditions of Award are in addition to, and not in lieu of, otherwise
applicable OMB administrative guidelines, HHS, PHS, and NIH grant
regulations, policies and procedures, with particular emphasis on HHS
regulations at 45 CFR Part 74 and 92. 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. 

1. The purpose of these cooperative agreements is to support a
coordinated research program of specialized centers pursuing high
quality reproductive research with the ultimate goal of facilitating and
accelerating translation of basic science knowledge into clinical
applications which can be used to regulate fertility or diagnose and
treat infertility or reproductive disorders that impact on fertility. 

The primary authorities and responsibilities of the awardees are to
participate cooperatively with the Steering Committee in the following
activities: 

o Pursuit of research objectives consistent with the research scope of
the RFA and research approved during the initial peer review; o Conduct
experiments and collect the resulting data; o Analyze, interpret and
present results and plans to the Steering Committee for approved
activities; o Publish results, conclusions, and interpretation of the
studies. 

The awardees will agree to: 1)accept the coordinating role of the
Steering Committee which includes evaluating objectives and research
goals of the Centers Program, and recommending modification, deletion or
addition of protocols within the Centers Program; 2) follow any common
protocols in which they participate for multicenter projects that are
approved by the Steering Committee; and 3) accept the cooperative nature
of the group process, including the establishment, where appropriate, of
smaller collaborative groups comprised of interacting subprojects and/or
cores focused on a particular reproductive research topic area. 

Awardees will retain custody of and primary rights to their data
developed under the award subject to current government policies
regarding rights of access as consistent with current HHS, PHS, and NIH
policies. 

2. The degree of programmatic involvement of the Research Coordinator is
as follows: 

o Participating in the overall coordination of the Centers Program with
the Steering Committee. This includes efforts to improve and strengthen
inter- and intra-center cooperation amongst the research projects of the
Centers, particularly as it pertains to translational research
activities within and between centers. As a means of improving
inter-center cooperation, the Research Coordinator will directly
participate in the activities of the smaller collaborative groups
established by the Steering Committee comprised of subprojects and/or
cores focused on a particular reproductive research topic area. The
Research Coordinator will also assist the research efforts of the
Centers Program by facilitating access to fiscal and intellectual
resources provided by industry, private foundations and NIH intramural
scientists. The Research Coordinator will, as required, help reprogram
research efforts, including options to modify or terminate them, by
mutual consent between the Centers Program and NICHD. In the event of
disagreements among the Program participants, the Research Coordinator
will assist in forming an arbitration panel as discussed below. 

o Interacting with each individual center awardee evaluating objectives
and research goals of that particular center, deciding optimal research
approaches and protocol designs, and contributing to the adjustment of
research protocols or approaches as warranted. The Research Coordinator
will assist and facilitate this process and not direct it. The Research
Coordinator will also provide assistance in reviewing and commenting on
all major transitional changes of an individual center's activities
prior to implementation to assure consistency with required goals of the
Centers Program. 

o Retaining the option to recommend the withholding of support from a
Center subproject or core materially failing to meet the technical
performance requirements established by the Centers Program. This
includes identifying jointly with participants of the Steering Committee
the need to add additional research subprojects or service cores to
Centers or to phase out a Center subproject or core when performance
standards have not been met; and 

o Participating, where warranted, in data analyses, interpretations, and
the dissemination of study findings to the research community and health
care recipients including co- authorship of the publication of results
of studies conducted by the Centers. 

3. Overall Coordination of the Centers Program consistent with the
stated intent of the RFA will be done by a Steering Committee consisting
of the Principal Investigators from each of the participating Centers
and one NICHD staff member from the RSB, CPR, NICHD, who will be the
Research Coordinator. A member of the NICHD grants management staff will
serve as a nonvoting advisor to the Committee. A chairperson for the
Steering Committee will be chosen by a majority vote of the Principal
Investigators. The Steering Committee meetings will be convened at least
once per year. The purpose of these meetings is to share scientific
information, assess scientific progress, identify new research
opportunities and potential avenues of collaborations such as with
industry, private foundations and/or NIH intramural scientists,
establish priorities that will accelerate the translation of preclinical
findings into clinical applications, reallocate resources and conduct
the business of the cooperative research program. In anticipation that
some centers will have common research interests that address a specific
basic and/or clinical research problem, it is envisioned that research
focus groups will be formed to conduct coordinated research activities
recommended by the Steering Committee. The Steering Committee will
approve multicenter protocols on specific research activities. As
needed, the Steering Committee will develop a publication policy
regarding joint authorship of research reports derived from such
collaborative efforts. 

4. Arbitration 

When agreement between an awardee and NICHD staff cannot be reached on
scientific/ programmatic issues that may arise after the award, an
arbitration panel will be formed. The panel will consist of one person
selected by the Principal Investigator, one person selected by NICHD
staff, and a third person selected by these 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 regulations 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 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 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," 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, Volume 23, Number 11, March 18, 1994. 

LETTER OF INTENT 

Prospective applicants are asked to submit, by January 14, 1998, a
letter of intent that includes: 1) a descriptive title of the proposed
research; 2) the name, address, and telephone number of the Principal
Investigator; 3) the identities of other key personnel and participating
institutions along with the tentative titles of the respective
subprojects; and 4) the number and title of the RFA in response to which
the application may be submitted. Although a letter of intent is not
required, is not binding, and does not enter into the review of
subsequent applications, the information that it contains allows NICHD
staff to estimate the potential review workload and to avoid conflict of
interest in the review. 

The letter of intent is to be sent to Dr. Louis V. DePaolo at the
address listed under INQUIRIES. 

APPLICATION PROCEDURES 

Contents of Applications 

A response to this RFA should consist of an application that includes: 

o A description of a Specialized Center in Reproduction Research
consisting of multiple individual research subprojects, an
Administrative Core and, if applicable, one or more technology- based
core service facilities. For suggested formatting instructions see the
document, "Suggested Format for NICHD U54 Grant Applications," available
from the program staff listed under INQUIRIES. 

o A description of the capabilities of the Center to meet or exceed the
minimal requirements stated below (see Description of a Center). 

o A proposed five-year research plan that presents the applicant's
perception of the Center's organization and component functions. This
plan should demonstrate the applicant's knowledge, ingenuity,
practicality, and commitment in organizing a multiproject research
infrastructure for conducting basic and clinical studies in the
reproductive sciences. The research plan for the Center and all
component subprojects must address the "Research Scope" described
earlier. 

o The stated willingness of the Principal Investigator to cooperate in a
coordinated cooperative program involving multiple Centers with the
objective of developing research project and/or service core
interactions between Centers. 

o Substantive evidence of departmental and institutional support for and
commitment to the proposed Center. 

All applicants must document their ability to meet or exceed the minimum
requirements as set forth in the 'Description of a Center.' This
specifically includes understanding of and commitment to the cooperative
nature of this Program. 

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

The research grant application form PHS 398 (rev. 5/95) is to be used in
applying for these awards. Applications kits are available at most
institutional offices of sponsored research and may be obtained from the
Grants Information Office, Office of Extramural Outreach and Information
Resources, National Institutes of Health, 6701 Rockledge Drive, MSC
7910, Bethesda, MD 20892-7910, telephone 301/710-0267, email:
ASKNIH@od.nih.gov. 

Additional suggestions for formatting the application into a Center
grant application are provided in the document "Suggested Format for
NICHD U54 Grant Applications," which is available from the program staff
listed under INQUIRIES. 

The RFA label available in the PHS 398 (rev. 5/95) application form must
be affixed to the bottom of the face page of the application. 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, SPECIALIZED COOPERATIVE CENTERS PROGRAM IN
REPRODUCTION RESEARCH, and number, RFA HD-97-008, must be typed on line
2 of the face page of the application form and the YES box must be
checked. Submit a signed, typewritten original of the application,
including the Checklist, and three signed, photocopies, in one package
to: Division of Research Grants National Institutes of Health 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: 

Susan Streufert, Ph.D. Division of Scientific Review National Institute
of Child Health and Human Development 6100 Executive Boulevard, Room
5E03 Bethesda, MD 20892-7510 Rockville, MD 20852 (for express/courier
service) 

Applications must be received by April 28, 1998. The Division of
Research Grants (DRG) will not accept any application in response to
this RFA 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. The NICHD will not accept for review
competing new or continuation applications that have been revised more
than one time. If a revised competing continuation application is not
selected for funding, the applicant institution may then only submit a
new, substantially different application. 

Schedule 

Letter of Intent Receipt Date: January 14, 1998 Application Receipt
Date: April 28, 1998 Initial Review Group Peer Review: October/November
1998 NACHHD Council Review: January 1999 Earliest Award Date: April 1,
1999 

Budgets 

Applications from new center sites may not request more than $750,000 in
direct costs for the first year, with incremental increases not
exceeding three percent in each subsequent year. For currently existing
RSB-supported center sites, direct costs requested for the first year
can be either $750,000 or 120 percent of the direct costs awarded for
the final competitive segment year of the preceding project period as
stated in the Notice of Grant Award whichever is higher. A submitted
application exceeding the budgetary limits specified above will be
returned to the applicant unreviewed. 

In the event that an application submitted in response to this RFA is
not funded, one revision of the application will be accepted in response
to a subsequent RFA. Budgets for revised applications must be submitted
in accord with the recommendations of the peer review group who
evaluated the initial submission unless a different budget has been
approved in advance by the NICHD. If a revised competing continuation
application is not selected for funding, the applicant institution may
then submit only a new, substantially different application that will be
subject to the direct cost limit of $750,000. 

Principal Investigators should request travel funds to support their
participation in the annual Steering Committee Meeting, and Key
Investigators of budgeted center subprojects should request travel funds
to support participation in either the Steering Committee Meeting or a
research focus group meeting. 

REVIEW CONSIDERATIONS 

Upon receipt, applications will be reviewed for completeness by DRG and
responsiveness to the RFA by NICHD staff. Incomplete applications will
be returned to the applicant without further consideration. Any
application that does not meet the minimum requirements as set forth in
the 'Description of a Center' section of this RFA will be considered
unresponsive to the RFA and returned to the applicant. This includes,
but is not limited to, an evaluation by NICHD staff of the program
relevancy of the proposed research subprojects and external projects
being proposed to access core facilities. 

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, a process
may be used in which applications will be determined to be competitive
or noncompetitive based on their scientific merit relative to other
applications received in response to this RFA. Applications determined
to be noncompetitive by the review committee will be withdrawn from
further consideration, and the principal investigator will receive a
summary statement reflecting the reviewers' evaluation. Applications
judged to be competitive will be further discussed and assigned a
priority score. They will then receive a second level review by the
National Advisory Child Health and Human Development Council (NACHHD). 

Applications submitted in response to this RFA and judged to be
competitive may also receive a site visit as part of the review process.
However, applicants should assure that their applications are complete
and can stand on their own. 

Review Criteria 

The scientific and technical merit peer review focuses on three areas:
(1) review of the component research subprojects; (2) review of the core
units, and (3) review of the overall center as an integrated effort. 

1. Component Research Subproject Criteria: 

The review criteria for the component research subprojects are: 

o The scientific merit of each individual project which evaluates the
research plan, significance, approach and innovativeness when
appropriate; 

o Accomplishments and progress to date of the component research
subprojects in the case of competing renewal applications; 

o Qualifications, experience and commitment of the Key Investigators and
their ability to devote the required time and effort to the subproject
and the Center; 

o Willingness of the Key Investigators to work and collaborate with
other Center Programs as appropriate and with NICHD assistance in the
manner summarized in this RFA; 

o Appropriateness of the budget for each component research subproject; 

o Adequacy of animal facilities and appropriateness of animal care
management where animal work is proposed; 

o Adequacy of clinical facilities and appropriateness of patient care
management where clinical work is proposed; and 

o Adequacy of plans to include both genders and minorities and their
subgroups as appropriate for the scientific goals of the research. Plans
for the recruitment and retention of subjects will also be evaluated.
(See INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN
SUBJECTS). 

2. Core Unit Criteria: 

The criteria for reviewing the Core Units are: 

o Qualifications, experience and commitment of key personnel in the
services provided by the core unit, as well as their ability to devote
the required time and effort in providing services to the Center; 

o Accomplishments of the Core Unit in the case of competing renewal
applications; 

o Appropriateness of the budget for each core unit that considers cost
effectiveness and quality control for core units; 

o Appropriateness of the use of core services by the budgeted center
subprojects, and, if applicable, by external projects. 

o Adequate plans for chargeback and priority management procedures for
technical core units offering services to external projects. 

3. Overall Center Criteria: 

The criteria for reviewing the Center as an integrated effort are: o
Overall strength of the Center in terms of the combined strength of the
research subprojects and core units, and the significance of the
application to the objectives of the Program outlined in this RFA; 

o Leadership ability and scientific stature of the Principal
Investigator particularly, but not exclusively in the area of the
proposed research, and his/her ability to meet the Center's demands of
time and effort; 

o Specifically stated and described willingness of the Principal
Investigator to work and cooperate with other Center Programs as
appropriate, and with NICHD assistance in the manner summarized in this
RFA; 

o An appropriate organizational and administrative structure for
effective attainment of Center objectives that considers arrangements
for internal quality control of ongoing research, the allocation of
funds, day-to-day management, contractual agreements, and internal
communication among Center investigators; 

o The institutional environment in which the research will be conducted,
including the availability of space, equipment, and subjects, if
proposed; adequacy of administrative, clinical and technical
capabilities to conduct the research proposed; physical proximity of
investigators; and the potential for interaction with scientists from
other areas; 

o Appropriateness of policies to ensure the protection of human
subjects, the humane care and use of laboratory animals, and the
environment; and 

o Demonstrated commitment of the Institution to the Center and its
objectives in terms of providing research facilities and management
support. 

4. Budgeting 

Appropriateness of the proposed budget and duration in relation to the
proposed research. 

AWARD CRITERIA 

The anticipated date of award is April 1, 1999. Applications approved by
the NACHHD Council will be considered for award based on scientific and
technical merit; program balance; and availability of funds. The NICHD
will not support more than one SCCPRR center award involving departments
or specialty units of a single grantee institution. In order to receive
funding, an individual domestic institution's application for a
Specialized Cooperative Center Grant must have three or more related,
interactive, and high quality research subprojects that provide a
multidisciplinary, yet thematic, approach to the problems to be
investigated. At least one of the subprojects must be clinically
oriented. Awards will not be made for applications with research
activities focused exclusively on clinical research or exclusively on
basic research or for applications or components thereof proposing
epidemiological or large scale clinical trial research. 

INQUIRIES 

Written and telephone inquiries concerning this RFA are encouraged. The
opportunity to clarify any issues or questions from potential applicants
is welcome. 

Direct inquiries regarding programmatic issues and address the letter of
intent to: 

Louis V. DePaolo, Ph.D. Center for Population Research National
Institute of Child Health and Human Development Building 61E, Room 8B01
Bethesda, MD 20892-7510 Telephone: (301) 496-6515 FAX: (301) 496-0962
Email: depaolol@hd01.nichd.nih.gov 

Direct inquiries regarding fiscal matters to: 

Ms. Melinda Nelson Office of Grants and Contracts National Institute of
Child Health and Human Development Building 61E, Room 8A17 Bethesda, MD
20892-7510 Telephone: (301) 496-5481 FAX: (301) 402-0915 Email:
nelsonm@hd01.nichd.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
the PHS Act, Title IV, Part A (Public Law 78-410, as amended by Public
Law 99-158, 42 USC 241 and 285). These special Terms of Award are in
addition to, and not in lieu of, otherwise applicable OMB administrative
guidelines administered under PHS grants policies and Federal
Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to
the intergovernmental review requirements of Executive Order 12372 or
Health Systems Agency review. 

The PHS strongly encourages all grant and contract 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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