SPECIALIZED COOPERATIVE CENTERS PROGRAM IN REPRODUCTION RESEARCH

Release Date:  September 10, 2001

RFA:  RFA-HD-01-023

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

Letter of Intent Receipt Date:  May 1, 2002
Application Receipt Date:       June 18, 2002

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 2010

The Public Health Service (PHS) is committed to achieving the health 
promotion and disease prevention objectives of “Healthy People 2010,” a PHS-
led national activity for setting priority areas.  This Request for 
Applications (RFA) is related to one or more priority areas.  Potential 
applicants may obtain “Healthy People 2010” at 
http://www.health.gov/healthypeople/. 

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic for-profit and non- profit 
organizations, public and private, such as universities, colleges, hospitals, 
laboratories, units of State and local governments, and eligible agencies of 
the Federal government.  Foreign institutions are not eligible to apply as an 
applicant institution, however, subcontracts from domestic entities to 
foreign sites are permitted.  Racial/ethnic minority individuals, women, and 
persons with disabilities are encouraged to apply as Principal Investigators.

The NICHD will not support more than one Specialized Cooperative Centers 
Program in Reproduction Research (SCCPRR) center award involving departments 
or specialty units of a single grantee institution.

MECHANISM OF SUPPORT

This RFA will use the National Institutes of Health (NIH) specialized 
cooperative research center (U54) award mechanism, an “assistance” mechanism 
(rather than an “acquisition” mechanism) in which substantial NIH scientific 
and/or programmatic involvement with the awardee is anticipated during 
performance of the activity.  Under the cooperative agreement, the NIH 
purpose is to support and stimulate the recipient’s activity by involvement 
in the activity and otherwise working jointly with the award recipients in a 
partner role, but it is not to assume direction, prime responsibility, or a 
dominant role in the activity.  Details of the responsibilities, 
relationships and governance of the studies to be funded under cooperative 
agreements are discussed below under “Terms and Conditions of Award.”  
Potential applicants may obtain the NICHD U54 Specialized Cooperative 
Research Center Grant Guidelines at http://www.nichd.nih.gov/funding/mechanism/u54_guide.cfm.

The total project period for an application submitted in response to this RFA 
may not exceed five years.  The anticipated award date is April 1, 2003. 

FUNDS AVAILABLE

The NICHD intends to commit approximately $4.3 million in total costs [Direct 
plus Facilities and Administrative (F & A) costs] in FY 2003 to fund up to 
four new and/or competing continuation grants in response to this RFA.  An 
applicant for a new center may request a project period of up to five years 
and a budget for direct costs of up to $900,000 for the first year, excluding 
F & A costs on consortium arrangements, with incremental increases not 
exceeding three percent in each subsequent year.  An applicant for a 
competing continuation grant may request a project period of up to five years 
and a budget for direct costs of up to $900,000 in the first year 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.  Applications exceeding the budgetary limits specified above will be 
returned to the applicant without peer review.  Because the nature and scope 
of the research proposed may vary, it is anticipated that the size of awards 
also will vary.  Although the financial plans of NICHD provide support for 
this program, awards pursuant to this RFA are contingent upon the 
availability of funds and the receipt of a sufficient number of meritorious 
applications.

In the event that an application submitted in response to this RFA is not 
funded, one revision of the application may be submitted in response to a 
subsequent RFA.  Requested budgets for revised applications must follow 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 in response to a subsequent RFA that will 
be subject to the direct cost limit of $900,000.

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 nine 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 widespread use of assisted reproductive 
technologies such as intracytoplasmic sperm injection (ICSI) and its variants 
has 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 are 
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 
increasing particularly 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 to 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 as 
well as 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 in 
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, as 
well as 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 that between 5 
and 10 percent of the reproductive age population of U.S. women suffers the 
full blown syndrome of hyperandrogenism, chronic anovulation, and polycystic 
ovaries.  Also poorly understood is the pathogenesis of premature ovarian 
failure which affects one in one-hundred women by age 40.  Interestingly, 16 
percent of women carrying the fragile X pre-mutation present with premature 
ovarian failure.

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 currently not 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 continue and maintain organized, multi-component reproductive 
extramural research programs of high quality that focus on topics 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 that 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 that 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 Genetics--genetics of sex determination including 
clarification of the functional interactions between the known sex 
determination genes,  role of inheritance and expression of parental alleles 
in reproduction including genes and mechanisms important in imprinting and 
methylation during gametogenesis and embryogenesis, and elucidation of the 
genes and genetic mechanisms responsible for normal and skewed X chromosome 
inactivation.

o  Reproductive Medicine -- etiology, pathophysiology, prevention, 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.  

Because 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, below.  However, applicants should note that the 
research scope of this RFA does not include studies in the area of 
reproductive oncology, reproductive toxicology or reproductive epidemiology 
or studies dealing with post-implantation pregnancy and parturition.  These 
topic areas are outside the scope of research supported by the RSB and, 
therefore, will be deemed non-responsive to this RFA. Further, applications 
proposing research activities focused exclusively on clinical research or 
exclusively on basic research, or applications or components thereof 
proposing epidemiological or large scale clinical trial research, will not be 
considered responsive 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 to provide the 
entire Center network with access to new technologies, 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 under “Terms and Conditions of Award,” below.

SPECIAL REQUIREMENTS

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 this 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 the purpose 
of this Centers Program, the definition of ‘clinical’ includes studies that 
involve patients 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 that provides oversight to the Center, located 
at the applicant institution and 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 
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.  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 Funds may be requested to provide support for one or more pilot projects 
relevant to the center’s goals.  Support for a pilot project is limited to a 
two-year period.  Funding may not exceed 10 percent of the center grant’s 
first-year direct cost budget, inclusive of the portion budgeted for pilot 
projects, or $90,000 per year, whichever amount is smaller.  With NICHD staff 
approval, the period of support may be extended one additional year.  Funds 
for pilot projects may be requested in new or competing continuation 
applications only.  As such, the proposed research plan must be described in 
sufficient detail, comparable to the other subprojects submitted in the 
application, to permit evaluation of the project using the review criteria 
listed under REVIEW CONSIDERATIONS.  If a pilot project is favorably 
recommended for an initial two-year period, funds will be included each year 
for the full five years.  Funds in Years 03-05 will be contingent upon review 
and approval of additional pilot projects by NICHD staff.  Funding levels in 
these out-years will be based on the level of funding for this purpose in 
Years 01 and 02.

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, 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 and 
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.

Travel to Meetings

Principal Investigators should request travel funds to support their 
participation in the annual Steering Committee Meeting as well as one 
research focus group meeting.  Key Investigators of budgeted center 
subprojects and Directors of technical service cores should request travel 
funds to support participation in two research focus group meetings.

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.

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.

1.  Awardee Rights and Responsibilities

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 DHHS and NIH policies.

2.  NICHD Responsibilities

NICHD Research Coordinator:

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, 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.

NICHD Project Officer:

NICHD will appoint a Project Officer, apart from the Research Coordinator, 
who will:

o  Have the option to withhold support to a participating institution if 
technical performance requirements are not met,

o  Carry out continuous review of all activities to ensure objectives are 
being met, and

o  Exercise the normal stewardship responsibilities of an NIH Program 
Officer.

3. Collaborative Responsibilities
  
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 DHHS 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 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 
UPDATED "NIH Guidelines for Inclusion of Women and Minorities as Subjects in 
Clinical Research," published in the NIH Guide for Grants and Contracts on 
August 2, 2000 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-048.html), 
a complete copy of the updated Guidelines are available at  
http://grants.nih.gov/grants/funding/women_min/guidelines_update.htm.  The 
revisions relate to NIH-defined Phase III clinical trials and require:  a) 
all applications or proposals and/or protocols to provide a description of 
plans to conduct analyses, as appropriate, to address differences by 
sex/gender and/or racial/ethnic groups, including subgroups if applicable, 
and b) all investigators to report accrual, and to conduct and report 
analyses, as appropriate, by sex/gender and/or racial/ethnic group 
differences.

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.  
This policy applies to all initial (Type 1) applications submitted for 
receipt dates after October 1, 1998.

All investigators proposing research involving human subjects should read the 
“NIH Policy and Guidelines on the Inclusion of Children as Participants in 
Research Involving Human Subjects,” published in the NIH Guide for Grants and 
Contracts, March 6, 1998, and available at:   
http://grants.nih.gov/grants/guide/notice-files/not98-024.html.

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

URLS IN NIH GRANT APPLICATIONS OR APPENDICES

All applications and proposals for NIH funding must be self-contained within 
specified page limitations.  Unless otherwise specified in an NIH 
solicitation, Internet addresses (URLs) should not be used to provide 
information necessary to the review because reviewers are under no obligation 
to view the Internet sites.  Reviewers are cautioned that their anonymity may 
be compromised when they directly access an Internet site.

PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT

The Office of Management and Budget (OMB) Circular A-110 has been revised to 
provide public access to research data through the Freedom of Information Act 
(FOIA) under some circumstances.  Data that are (1) first produced in a 
project that is supported in whole or in part with Federal funds and (2) 
cited publicly and officially by a Federal agency in support of an action 
that has the force and effect of law (i.e., a regulation) may be accessed 
through FOIA.  It is important for applicants to understand the basic scope 
of this amendment.  NIH has provided guidance at: 
http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. 

Applicants may wish to place data collected under this RFA in a public 
archive, which can provide protections for the data and manage the 
distribution for an indefinite period of time.  If so, the application should 
include a description of the archiving plan in the study design and include 
information about this in the budget justification section of the 
application. In addition, applicants should think about how to structure 
informed consent statements and other human subjects procedures given the 
potential for wider use of data collected under this award.

LETTER OF INTENT

Prospective applicants are asked to submit a letter of intent that includes a 
descriptive title of the proposed research, the name, address, and telephone 
number of the Principal Investigator, the identities of other key personnel 
and participating institutions, and the number and title of this RFA.  
Although a letter of intent is not required, is not binding, and does not 
enter into the review of a subsequent application, the information that it 
contains allows NICHD staff to estimate the potential review workload and 
plan the review.

The letter of intent is to be sent to Dr. Louis De Paolo by May 1, 2002.

APPLICATION PROCEDURES

The research grant application form PHS 398 (rev. 5/01) is to be used in 
applying for these grants.  These forms are available at most institutional 
offices of sponsored research, on the Internet at 
http://grants.nih.gov/grants/funding/phs398/phs398.html, and from the 
Division of Extramural Outreach and Information Resources, National 
Institutes of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-
7910, telephone 301-435-0714, E-mail:  Grantsinfo@nih.gov. 
 
Application Instructions

Applications for the U54 grant are to be prepared in a manner consistent with 
the information presented in the NICHD U54 Cooperative Specialized Research 
Center Grant Guidelines, available from the contacts listed under INQUIRIES, 
below, and at http://www.nichd.nih.gov/funding/mechanism/u54_guide.cfm.

At minimum, 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 multi-project 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 during the previous funding period.

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

Submission Procedures

The RFA label available in the PHS 398 (rev. 5/01) application form must be 
stapled to the bottom of the face page of the application and must display 
the RFA number HD-01-023.  A sample RFA label is available at 
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf.   Please note this 
is in the pdf format.  Failure to use this label could result in delayed 
processing of the application such that it may not reach the review committee 
in time for review.  In addition, the RFA title and number must be typed on 
line 2 of the face page of the application form and the YES box must be 
marked.

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

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

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

Director
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 June 18, 2002.  If an application is 
received after that date, it will be returned to the applicant without 
review.

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

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed for completeness by CSR and for 
responsiveness to the RFA by NICHD staff.  Incomplete and/or non-responsive 
applications will be returned to the applicant without further consideration.  
Any application that does not meet the minimum application requirements as 
set forth under SPECIAL REQUIREMENTS 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, all applications will receive a written 
critique and may undergo a process in which only those applications deemed to 
have the highest scientific merit will be discussed, assigned a priority 
score, and receive a second level review by the National Advisory Child 
Health and Human Development (NACHHD) Council.

A site visit will not be part of the review process.  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.  Applications 
submitted in response to this RFA will be evaluated according to the review 
criteria described in the NICHD U54 Cooperative Specialized Research Center 
Grant Guidelines, available from the contacts listed under INQUIRIES, below, 
and at http://www.nichd.nih.gov/funding/mechanism/u54_guide.cfm.

SCHEDULE

Letter of Intent Receipt Date:    May 1, 2002
Application Receipt Date:         June 18, 2002
Peer Review:                      October/November 2002
Council Review:                   January 2003
Earliest Anticipated Award Date:  April 1, 2003

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.    

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.
Reproductive Sciences Branch
National Institute of Child Health and Human Development
6100 Executive Boulevard, 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. Kathy Hancock
Grants Management Branch
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 8A17M, MSC 7510
Bethesda, MD  20892-7510
Telephone:  (301) 496-5482
FAX:  (301) 402-0915
E-mail:  kh47d@nih.gov 

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance No. 
93.864, Population Research.  Awards are made under authorization of Sections 
301 and 405 of the Public Health Service Act, as amended (42 USC 241 and 284) 
and administered under NIH grants policies and Federal Regulations 42 CFR 52 
and 45 CFR Parts 74 and 92.  This program is not subject to the 
intergovernmental review requirements of Executive Order 12372 or Health 
Systems Agency review.

The PHS strongly encourages all grant 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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