SPECIALIZED COOPERATIVE CENTERS PROGRAM IN REPRODUCTION RESEARCH

Release Date:  June 22, 1999

RFA:  HD-99-009

National Institute of Child Health and Human Development

Letter of Intent Receipt Date:  January 12, 2000
Application Receipt Date:  April 28, 2000

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" at http://www.crisny.org/health/us/health7.html

ELIGIBILITY REQUIREMENTS

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

MECHANISM OF SUPPORT

This RFA will use the National Institutes of Health (NIH) cooperative
specialized center (U54) award mechanism.  The U54 is a cooperative agreement,
an assistance mechanism (rather than an acquisition mechanism) in which
substantial NIH scientific and/or programmatic involvement with the awardee is
anticipated during the performance of the activities.  Under a cooperative
agreement, the NIH purpose is to support and stimulate the recipient's
activities by involvement in the activity.  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 below
under "Terms and Conditions of Award."

The total project period for an application submitted in response to this RFA
is five years.  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 two Centers will be funded in each subsequent annual
competition contingent upon the availability of funds.  The anticipated award
date is April 1, 2001.

FUNDS AVAILABLE

It is anticipated that an estimated total of $2,200,000 (including direct
costs and costs for facilities and administration) will be available for the
first year of the Program, which will support up to two Centers in FY 2001.
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. 
Although this solicitation is included in the fiscal plans for FY 2001,
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.

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.  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., three 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.  Indeed,
whereas 80 percent of infertile women can be successfully treated, male
infertility can be treated in only 10-20 percent of such men.  However, the
wide-spread use of assisted reproductive technologies such as intracytoplasmic
sperm injection (ICSI) and its variants have enabled otherwise infertile men
to father children, although possible genetic causes of the infertility are
likely transmitted to the progeny.

While analyses of the U.S. population base have 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 in
the U.S. from 1968 (600,000) to 1988 (1,350,000) and is estimated to approach
two million visits in 2000.  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 eight-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 to
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 age couples, the
obstructive sequelae of male accessory gland infections account for eight to
12 percent of male partner diagnostic costs for fertility impairment.  In
reproductive age females, it has been estimated that the general incidence of
endometriosis is five 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 to be 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.

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 age 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.

Polycystic ovary syndrome (PCOS) is a major cause of female infertility, other
reproductive system, and other tissue and organ system morbidities. 
Identified more than 60 years ago by Stein and Leventhal, the etiology of PCOS
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 age population of U.S. women suffer the full blown syndrome of
hyperandrogenism, chronic anovulation and polycystic ovaries.  Also poorly
understood is the pathogenesis of premature ovarian failure which affects two
to four percent of reproductive age women.

It is becoming increasingly apparent that some conditions of male and female
infertility may be genetically based.  In males, there is considerable
evidence from breeding studies and gene knockout experiments in animals that
mutation of over 100 separate genes results in infertility.  More limited
studies in humans show that a number of inherited diseases are associated with
abnormal sperm morphology and function.  These data suggest that a significant
number of men with infertility may have one or more mutations that predispose
to their condition.  However, it is not currently possible to determine which
men have genetic infertility.  Similarly, it is estimated that 15-20 percent
of human pregnancies are chromosomally abnormal as a result of division errors
during oocyte meiosis or early embryonic cleavage.  Such errors not only are
the leading cause of birth defects, but may be the single most important
factor contributing to human infertility.

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.  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 regulation, as 
well as of diagnostic tools and procedures for the detection, treatment and
effective management of reproductive disorders that impact on reproductive
competence.

o  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 life span; fertilization; early embryogenesis
during the pre- to peri-implantation period; implantation, including
cell-to-cell interactions regulating implantation.
o  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 glia-neuron interactions controlling pulsatile GnRH secretion;
identification of elements and factors controlling gene transcription
including co-activators and co-repressors, 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.

o  Reproductive Medicine -- pathophysiology, diagnosis and treatment of male
or female infertility with particular emphasis on defining those conditions
which are genetically based; relation of endometriosis to infertility,
treatment of benign gynecologic diseases; research leading to improved
outcomes across the spectrum of assisted reproductive technologies, as well as
development of new approaches for assisted reproduction.

Since this list is not meant to be all-inclusive, prospective applicants
preparing either a new or competing continuation center grant application are
encouraged to discuss program relevance issues with the program staff contact
cited under INQUIRIES.  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 this 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 of Award" section below.

Description of a Center

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

o A research plan that is responsive to the objectives of the Centers Program
set forth in the RFA (see RESEARCH OBJECTIVES).

o At least three research subprojects that thematically address one or more
research areas listed under Research Scope.  It is required that at least 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 research.

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 may not exceed 50 percent or be less than five percent. 
The percent utilization of additional subprojects requiring core services may
be less than five percent.  Costs necessary to use a particular core facility
may be incorporated into the budget of the core unit, and not in the budgets
of the research subprojects per se.  No internal charge-back 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 charge-back 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 may
not exceed 50 percent or be less than five percent.  An additional seven
federally-funded, peer-reviewed external research projects addressing
program-relevant research areas of the RSB may 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 charge-back system.  Core
budgets will be justified and evaluated based on  access by budgeted center
subprojects and external, program-relevant research projects as described
above.  Above and beyond this arrangement, technology-based core units may
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 describe 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 should
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 and on the Internet at
http://www.nichd.nih.gov/RFA/HD-99-009/HD-99-009.htm.  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 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 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  Pursue research objectives consistent with the research scope of the RFA
and research favorably recommended by 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 and NIH policies.

2.  The degree of programmatic involvement of the NICHD 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 comprising
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.

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.

Budgets

Applications from new center sites may not request more than $750,000 in
direct costs for the first year (including subcontract total costs), with
incremental increases not exceeding three percent in each subsequent year. 
For existing RSB-supported center sites, direct costs requested for the first
year may be either $750,000 or 120 percent of the direct costs awarded for the
final competitive segment 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 without
peer review.

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 the submission of a different budget request has been
authorized 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.

Travel to Meetings

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

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of the NIH that women and members of minority groups and
their subpopulations must be included in all NIH-supported biomedical and
behavioral research projects involving human subjects, unless a clear and
compelling rationale and justification are provided that inclusion is
inappropriate with respect to the health of the subjects or the purpose of the
research.  This policy results from the NIH Revitalization Act of 1993
(Section 492B of Public Law 103-43).

All investigators proposing research involving human subjects should read the
"NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical
Research," which have been published in the Federal Register of March 28, 1994
(FR 59 14508-14513) and the NIH Guide for Grants and Contracts, Volume 23,
Number 11, March 18, 1994, available on the web at:
http://grants.nih.gov/grants/guide/notice-files/not94-100.html.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of NIH that children (i.e., individuals under the age of 21)
must be included in all human subjects research, conducted or supported by the
NIH, unless there are scientific and ethical reasons not to include them.  All
investigators proposing research involving human subjects should read the "NIH
Policy and Guidelines on the Inclusion of Children as Participants in Research
Involving Human Subjects" that was published in the NIH Guide for Grants and
Contracts, March 6, 1998, and is available on the Web at: 
http://grants.nih.gov/grants/guide/notice-files/not98-024.html.

Investigators also may obtain copies of these policies from the program staff
listed under INQUIRIES.  Program staff may also provide additional relevant
information concerning policy.

LETTER OF INTENT

Prospective applicants are asked to submit a letter of intent that includes: a
descriptive title of the proposed research and the respective subprojects; the
name, address, and telephone number of the Principal Investigator; the
identities of other key personnel and participating institutions; and the
number and title of this RFA.  Although a letter of intent is not required, is
not binding, and does not enter into the review of 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 the program staff listed under INQUIRIES
by January 12, 2000.

APPLICATION PROCEDURES

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

For suggested formatting instructions, see the document, "Suggested Format for
NICHD U54 Grant Applications," available from the program staff listed under
INQUIRIES and on the Internet at:
http://www.nichd.nih.gov/RFA/HD-99-009/HD-99-009.htm.

Minimum Application Requirements

An application in response to this RFA should include:

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.

o  A description of the capabilities of the Center to meet or exceed the
minimal requirements for a Center stated in this RFA (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 above.

o  A statement describing the 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.

o  For competing renewal applications, evidence of having met the Terms and
Conditions of the award.

All applicants must document their ability to meet or exceed the minimum
requirements as set forth here.  This specifically includes understanding of
and commitment to the cooperative nature of this Program, and willingness to
meet the Terms and Conditions of Award.

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 should be included with the application.

Submission Procedures

The RFA label and line 2 of the application should both indicate the RFA
number.  The RFA label must be affixed to the bottom of the face page 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-99-009, must be typed on line 2
of the face page of the application form and the YES box must be checked.

The sample RFA label available at:
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf has been modified to
allow for this change.  Please note this is in pdf format.

Submit a signed, typewritten original of the application, including the
Checklist, and three signed photocopies in one package to:

CENTER FOR SCIENTIFIC REVIEW
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710
BETHESDA, MD 20892-7710
BETHESDA MD 20817 (for express/courier service).

At the time of submission, two additional copies of the application must be
sent to:

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

Applications must be received by April 28, 2000.  The Center for Scientific
Review (CSR) will not accept any application in response to this RFA that is
essentially the same as one currently pending initial review, unless the
applicant withdraws the pending application.  The CSR will not accept any
application that is essentially the same as one already reviewed.  This does
not preclude the submission of substantial revisions of applications already
reviewed, but such applications must include an introduction addressing the
previous critique.  The NICHD will not accept for review new or competing
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.

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed for completeness by CSR and
responsiveness to the RFA by NICHD staff.  Incomplete and/or non-responsive
applications will be returned to the applicant without further consideration. 
Any application that does not meet the minimum application requirements as set
forth under APPLICATION PROCEDURES will be considered unresponsive to the RFA. 
Responsiveness includes, but is not limited to,  the program relevance of the
proposed research subprojects and external projects being proposed to access
core facilities, as determined by NICHD.

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 by the scientific review group in
which all applications receive a written critique and only those applications
deemed to have the highest scientific merit will be discussed, assigned a
priority score, and receive a second level review by the National Advisory
Child Health and Human Development Council (NACHHD).

Applications submitted in response to this RFA may receive a site visit as
part of the review process.  However, applicants should ensure that their
applications are complete as written 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:

o  Significance: Does this study address an important problem?  If the aims of
the application are achieved, how will scientific knowledge be advanced?  What
will be the effect of these studies on the concepts or methods that drive this
field?

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

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

o Investigators: Is the Key Investigator and collaborators, if any,
appropriately trained and well suited to carry out this work?  Is the work
proposed appropriate to the experience level of the key investigator and other
researchers (if any)?  Is the Key Investigator committed to devote the
required time and effort to the subproject and the Center?  Please comment on
the willingness of the Key Investigator to work and collaborate with other
Center Programs as appropriate and with NICHD assistance in the manner
summarized in this RFA.

o Environment: Does the scientific environment in which the work will be done
contribute to the probability of success?  Do the proposed experiments take
advantage of unique features of the scientific environment or employ useful
collaborative arrangements?  Is there evidence of institutional support?

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

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;

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

o Adequacy of plans for including children as appropriate for the scientific
goals of the research, or justification for exclusion.

2.  Core Unit Criteria:

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 the core unit, including 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 charge back 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 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, if applicable, 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  Demonstrated institutional commitment to the Center and its objectives in
terms of providing research facilities and management support.
Schedule

Letter of Intent Receipt Date:  January 12, 2000
Application Receipt Date:  April 28, 2000
Peer Review:  October/November 2000
NACHHD Council Review:  January 2001
Earliest Award Date:  April 1, 2001

AWARD CRITERIA

Applications recommended by the NACHHD Council will be considered for award
based on scientific and technical merit as determined by peer review; 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 be considered for 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, MSC 7510
Bethesda, MD  20892-7510
Telephone:  (301) 435-6970
FAX:  (301) 496-0962
E-mail:  ld38p@nih.gov

Direct inquiries regarding fiscal matters to:

Ms. Melinda Nelson
Grants Management Branch
National Institute of Child Health and Human Development
Building 61E, Room 8A17, MSC 7510
Bethesda, MD  20892-7510
Telephone:  (301) 496-5482
FAX:  (301) 402-0915
E-mail: mn23z@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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