Full Text HD-96-008
 
SPECIALIZED COOPERATIVE CENTERS PROGRAM IN REPRODUCTION RESEARCH
 
NIH GUIDE, Volume 25, Number 40, November 22, 1996
 
RFA:  HD-96-008
 
P.T. 04

Keywords: 
  Human Reproduction/Fertility 
  Reproduction 

 
National Institute of Child Health and Human Development
 
Letter of Intent Receipt Date:  January 8, 1997
Application Receipt Date:  May 15, 1997
 
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, 1998.
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
1998, 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 $3,100,000 (including indirect
and direct costs) will be available for the first year of the
Program, which will support up to four Centers in FY 1998.
 
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 10 percent.  The percent utilization of
additional subprojects requiring core services can be less than 10
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 10 percent.  If the
minimum 30 percent utilization by three justifying budgeted center
subprojects and externally- funded RSB projects is chosen, then up to
seven additional 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 50/10
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 new policy results
from the NIH Revitalization Act of 1993 (Section 492B of Public Law
103-43) and supersedes
and strengthens the previous policies (Concerning the Inclusion of
Women in Study Populations, and Concerning the Inclusion of
Minorities in Study Populations), which have been in effect since
1990.  The new policy contains some provisions that are substantially
different from the 1990 policies.
 
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 reprinted
in the NIH Guide for Grants and Contracts, Volume 23, Number 11,
March 18, 1994.
 
Investigators also may obtain copies of the policy from the program
staff listed under INQUIRIES.  Program staff may also provide further
discussion concerning the policy.
 
LETTER OF INTENT
 
Prospective applicants are asked to submit, by January 8, 1997, 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 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@odrockm1.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-96-008,
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
Building 61E, Room 5E03
Bethesda, MD  20892
Bethesda, MD  20817 (for express/courier service)
 
Applications must be received by May 15, 1997.  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 8, 1997
Application Receipt Date:            May 15, 1997
Initial Review Group Peer Review:    October/November 1997
NACHHD Council Review:               January 1998
Earliest Award Date:                 April 1, 1998
 
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 four percent in each subsequent year. However, for
currently existing RSB-supported center sites whose direct costs for
the final year of the preceding project period as stated in the
Notice of Grant Award are in excess of $750,000 in direct costs, the
amount requested cannot exceed 120 percent of the direct costs
awarded in the final competitive segment year of the preceding
project period.  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.
 
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 triage
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 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
 
Evaluation of the applications will be based upon the following:
 
1.  Research Plan
 
o  Scientific merit of the application with respect to its component
subprojects and cores, as well as its overall strength as an
organized center;
 
o  Significance of the application to the objectives of the Program
outlined in this RFA;
 
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)
 
o  Appropriateness of policies to ensure the protection of human
subjects and the humane care and use of laboratory animals; and
 
o  Willingness to work and cooperate with other Centers and the NICHD
in the manner summarized in this RFA.
 
2.  Personnel
 
o  Scientific, clinical, and administrative abilities of the
Principal Investigator and other key participants, particularly, but
not exclusively, in the area of the proposed research;
 
o  Knowledge and experience of the Principal Investigator and other
key investigators in areas relevant to the conduct of the experiments
proposed; and
 
o  Documented commitment time for the proposed studies and the
specifically stated and described willingness of the Principal
Investigator and the key investigators to work and collaborate with
other Centers and with NICHD assistance in the manner summarized in
this RFA.
 
3.  Facilities and Management
 
o  Adequacy of administrative, clinical, and technical capabilities
to conduct the research proposed;
 
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  Institutional assurance to provide support to the Center in such
areas as fiscal administration, personnel management, space
allocation, procurement, planning, and budgeting.
 
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, 1998.  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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