SPECIALIZED COOPERATIVE CENTERS PROGRAM IN REPRODUCTION RESEARCH
 
RELEASE DATE:  October 21, 2003
 
RFA Number:  RFA-HD-04-003
 
Department of Health and Human Services (DHHS)

PARTICIPATING ORGANIZATIONS:  

National Institutes of Health (NIH) 
 (http://www.nih.gov)

COMPONENTS OF PARTICIPATING ORGANIZATIONS:

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

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S):  93.864 

LETTER OF INTENT RECEIPT DATE:  May 14, 2004  
APPLICATION RECEIPT DATE:  June 14, 2004
 
THIS RFA CONTAINS THE FOLLOWING INFORMATION

o Purpose of this RFA
o Research Objectives
o Mechanism of Support 
o Funds Available
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Special Requirements
o Where to Send Inquiries
o Letter of Intent
o Submitting an Application
o Supplementary Instructions
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations

PURPOSE OF THIS RFA

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.  Accordingly, 
the purpose of this RFA is to announce the annual recompetition of the 
Specialized Cooperative Centers Program in Reproduction Research.  
Applications 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.

RESEARCH OBJECTIVES

Background

The ultimate goal of biomedical research supported by the RSB is 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 contraceptive 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., more than three million 
unintended pregnancies--about 60 percent of all pregnancies--occur annually, 
with half resulting in abortion as an outcome.  In half of the abortions 
occurring in the U.S. each year, a contraceptive method being used failed to 
prevent 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 over 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 6.2 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 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 (1.35 million) and are 
estimated to approach two million visits in 2000.  Indeed, approximately 13 
percent of American women will receive infertility services during their 
lifetime.  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 tract disorders affecting fertility are associated with 
significant morbidity and a degree of mortality in some specific instances 
that cannot be ignored.  Accompanying the human costs of morbidities of 
reproductive tract disorders 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 five 
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 that affects one in 100 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 bidirectional transfer of knowledge between the laboratory and 
clinic.  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 that can be used to diagnose, 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 Developmental Biology -- Origins and differentiation of germ 
cells; the endocrine, paracrine, and physiologic mechanisms involved in 
gametogenesis, including germ cell-somatic cell interactions, germ cell 
proliferation and apoptosis, and germ cell transplantation; fertilization, 
including sperm motility and capacitation, zona pellucida binding and 
mechanisms to block polyspermy; pre-implantation embryonic development 
including zygotic gene activation, and mechanisms regulating embryonic stem 
cell differentiation and maintenance of stem cell pluripotency.

o  Reproductive Tract Biology and Physiology -- 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; implantation, including cell-to-cell 
interactions regulating implantation; structure, function, and regulation of 
the oviduct and epididymis.

o  Reproductive Endocrinology and Neuroendocrinology -- 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, and 
treatment of male or female infertility with particular emphasis on defining 
those conditions that 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; use of 
genomics and proteomics to develop novel diagnostics for reproductive 
diseases and disorders.  

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 WHERE TO SEND 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.

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 collaborative research initiatives.  The research focus group will 
consist of an NICHD Staff Research Coordinator from the RSB, CPR, and Key 
Investigators of the relevant subprojects and/or Core Directors.

Further details of the guidance and management structures and processes may 
be found under “Cooperative Agreement Terms and Conditions of Award,” below.
 
MECHANISM OF SUPPORT
 
This RFA will use the NIH Specialized Cooperative Research Center (U54) award 
mechanism.  As an applicant you will be solely responsible for planning, 
directing, and executing the proposed project.  At this time, the NICHD plans 
to reissue this RFA on an annual basis.  The anticipated award date is April 
1, 2005.

The NIH U54 is a cooperative agreement award mechanism in which the Principal 
Investigator retains the primary responsibility and dominant role for 
planning, directing, and executing the proposed project, with NIH staff being 
substantially involved as a partner with the Principal Investigator, as 
described under the section "Cooperative Agreement Terms and Conditions of 
Award"

FUNDS AVAILABLE

The NICHD intends to commit approximately $2.3 million in total costs [Direct 
plus Facilities and Administrative (F & A) costs] in FY 2005 to fund up to 
two 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 for 
recurring costs (i.e., personnel, consultants, supplies, travel and other 
expenses) not to exceed 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 
110 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.

ELIGIBLE INSTITUTIONS
 
You may submit an application if your institution has any of the following 
characteristics:
   
o For-profit or non-profit organizations 
o Public or private institutions, such as universities, colleges, hospitals, 
and laboratories 
o Units of State and local governments
o Eligible agencies of the Federal government
o Domestic institutions/organizations 
o Foreign institutions are not eligible to apply for these grants; however, 
subcontracts from domestic entities to foreign sites are permitted
 
INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS   

Any individual with the skills, knowledge, and resources necessary to carry 
out the proposed research is invited to work with their institution to 
develop an application for support.  Individuals from underrepresented racial 
and ethnic groups as well as individuals with disabilities are always 
encouraged to apply for NIH programs.   
 
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.]

o  Plans for data sharing.  These should be addressed in the significance and 
budget sections of 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, R21, 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 that 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 that 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.

Cooperative Agreement 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 administrative and funding instrument used for this program is NIH 
Specialized Cooperative Research Center (U54), in which substantial NIH 
scientific and/or programmatic involvement with the awardee is anticipated 
during the performance of the activity.  Under the cooperative agreement, the 
NIH purpose is to support and/or stimulate the recipient's activity by 
involvement in and otherwise working jointly with the award recipient in a 
partnership role, but it is not to assume direction, prime responsibility, or 
a dominant role in the activity.  Consistent with this concept, the dominant 
role and prime responsibility for the activity resides with the awardees for 
the project as a whole, although specific tasks and activities in carrying 
out the research will be shared among the awardees and the NICHD Research 
Coordinator.  

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 that 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 comprising 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:

The NICHD Research Coordinator will have substantial programmatic involvement 
above and beyond normal program stewardship, by:

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 to evaluate 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, when appropriate, 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.

WHERE TO SEND INQUIRIES

We encourage inquiries concerning this RFA and welcome the opportunity to 
answer questions from potential applicants.  Inquiries may fall into three 
areas:  scientific/research, peer review, and financial or grants management 
issues:

o Direct your questions about scientific/research issues 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
Email:  ld38p@nih.gov 

o Direct your questions about peer review issues to:

Robert Stretch, Ph.D.
Director, Division of Scientific Review
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 5B01, MSC 7510
Bethesda, MD  20892-7510
Rockville, MD  20852 (for express/courier service)
Telephone:  (301) 496-1485
Email:  stretch@nih.gov

o Direct your questions about financial or grants management 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) 480-4782
E-mail:  kh47d@nih.gov 
 
LETTER OF INTENT
 
Prospective applicants are asked to submit a letter of intent that includes 
the following information:

o Descriptive title of the proposed research
o Name, address, and telephone number of the Principal Investigator
o Names of other key personnel 
o Participating institutions
o 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 by the date listed at the beginning of 
this document.  The letter of intent should be sent 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 

SUBMITTING AN APPLICATION

Applications must be prepared using the PHS 398 research grant application 
instructions and forms (rev. 5/2001).  Applications must have a Dun and 
Bradstreet (D&B) Data Universal Numbering System (DUNS) number as the 
Universal Identifier when applying for Federal grants or cooperative 
agreements.  The DUNS number can be obtained by calling (866) 705-5711 or 
through the web site at http://www.dunandbradstreet.com/.  The DUNS number 
should be entered on line 11 of the face page of the PHS 398 form.  The PHS 
398 document is available at 
http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive 
format.  For further assistance contact GrantsInfo, Telephone (301) 435-0714, 
Email: GrantsInfo@nih.gov.
 
SUPPLEMENTARY 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 WHERE TO SEND INQUIRIES, above, 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 Cooperative Agreement Terms and Conditions of 
Award.
 
USING THE RFA LABEL:  The RFA label available in the PHS 398 (rev. 5/2001) 
application form must be affixed to the bottom of the face page of the 
application.  Type the RFA number on the label.  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. The RFA label is also available at: 
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf.
 
SENDING AN APPLICATION TO THE NIH:  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:

Robert Stretch, Ph.D.
Director, Division of Scientific Review
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 5B01, MSC 7510
Bethesda, MD 20892-7510
Rockville, MD 20852 (for express/courier service)
 
APPLICATION PROCESSING:  Applications must be received on or before the 
application receipt date listed in the heading of this RFA.  If an 
application is received after that date, it will be returned to the applicant 
without review.

Although there is no immediate acknowledgement of the receipt of an 
application, applicants are generally notified of the review and funding 
assignment within eight weeks.
 
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.  
However, when a previously unfunded application, originally submitted as an 
investigator-initiated application, is to be submitted in response to an RFA, 
it is to be prepared as a NEW application.  That is, the application for the 
RFA must not include an Introduction describing the changes and improvements 
made, and the text must not be marked to indicate the changes from the 
previous unfunded version of the application.  

Only one revision of a new or competing continuation application submitted in 
response to this RFA may be submitted in response to a subsequent RFA.

PEER REVIEW PROCESS  

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 not be reviewed.  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:

o Undergo a process in which only those applications deemed to have the 
highest scientific merit, generally the top half of the applications under 
review, will be discussed and assigned a priority score
o Receive a written critique
o Receive a second level review by the National Advisory Child Health and 
Human Development 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.

RECEIPT AND REVIEW SCHEDULE

Letter of Intent Receipt Date:  May 14, 2004    
Application Receipt Date:  June 14, 2004
Peer Review Date:  October/November 2004
Council Review:  January 2005
Earliest Anticipated Start Date:  April 1, 2005

AWARD CRITERIA

Criteria that will be used to make award decisions include:

o Scientific merit (as determined by peer review)
o Availability of funds
o Programmatic priorities.
 
REQUIRED FEDERAL CITATIONS 

HUMAN SUBJECTS PROTECTION:  Federal regulations (45CFR46) require that 
applications and proposals involving human subjects must be evaluated with 
reference to the risks to the subjects, the adequacy of protection against 
these risks, the potential benefits of the research to the subjects and 
others, and the importance of the knowledge gained or to be gained.
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm 

SHARING RESEARCH DATA:  Starting with the October 1, 2003 receipt date, 
investigators submitting an NIH application seeking $500,000 or more in 
direct costs in any single year are expected to include a plan for data 
sharing or state why this is not possible  
(http://grants.nih.gov/grants/policy/data_sharing).  Investigators should 
seek guidance from their institutions on issues related to institutional 
policies, local IRB rules, as well as local, state and Federal laws and 
regulations, including the Privacy Rule.  Reviewers will consider the data-
sharing plan, but will not factor the plan into the determination of the 
scientific merit or the priority score.

INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH:  It is the policy of 
the NIH that women and members of minority groups and their sub-populations 
must be included in all NIH-supported clinical research projects unless a 
clear and compelling justification is provided indicating 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 clinical research should read the "NIH Guidelines 
for Inclusion of Women and Minorities as Subjects in Clinical Research - 
Amended, October, 2001," published in the NIH Guide for Grants and Contracts 
on October 9, 2001 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); 
a complete copy of the updated Guidelines is available at 
http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. 
The amended policy incorporates: the use of an NIH definition of clinical 
research; updated racial and ethnic categories in compliance with the new OMB 
standards; clarification of language governing NIH-defined Phase III clinical 
trials consistent with the new PHS Form 398; and updated roles and 
responsibilities of NIH staff and the extramural community.  The policy 
continues to require for all NIH-defined Phase III clinical trials that: a) 
all applications or proposals and/or protocols must 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) investigators must report annual accrual and progress in conducting 
analyses, as appropriate, by sex/gender and/or racial/ethnic group 
differences.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS:   
The NIH maintains a policy 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 that is available at 
http://grants.nih.gov/grants/funding/children/children.htm.  

REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS:  NIH 
policy requires education on the protection of human subject participants for 
all investigators submitting NIH proposals for research involving human 
subjects.  You will find this policy announcement in the NIH Guide for Grants 
and Contracts Announcement, dated June 5, 2000, at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

HUMAN EMBRYONIC STEM CELLS (hESC):  Criteria for federal funding of research 
on hESCs can be found at http://stemcells.nih.gov/index.asp and at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html.  Only 
research using hESC lines that are registered in the NIH Human Embryonic Stem 
Cell Registry will be eligible for Federal funding (see http://escr.nih.gov).   
It is the responsibility of the applicant to provide the official NIH 
identifier(s) for the hESC line(s) to be used in the proposed research.  
Applications that do not provide this information will be returned without 
review. 

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.

STANDARDS FOR PRIVACY OF INDIVIDUALLY IDENTIFIABLE HEALTH INFORMATION:  The 
Department of Health and Human Services (DHHS) issued final modification to 
the “Standards for Privacy of Individually Identifiable Health Information,” 
the “Privacy Rule,” on August 14, 2002.  The Privacy Rule is a federal 
regulation under the Health Insurance Portability and Accountability Act 
(HIPAA) of 1996 that governs the protection of individually identifiable 
health information, and is administered and enforced by the DHHS Office for 
Civil Rights (OCR).  Those who must comply with the Privacy Rule (classified 
under the Rule as “covered entities”) must do so by April 14, 2003 (with the 
exception of small health plans which have an extra year to comply).  

Decisions about applicability and implementation of the Privacy Rule reside 
with the researcher and his/her institution.  The OCR website 
(http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including 
a complete Regulation Text and a set of decision tools on “Am I a covered 
entity?”  Information on the impact of the HIPAA Privacy Rule on NIH 
processes involving the review, funding, and progress monitoring of grants, 
cooperative agreements, and research contracts can be found at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

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

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

AUTHORITY AND REGULATIONS:  This program is described in the Catalog of 
Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the 
intergovernmental review requirements of Executive Order 12372 or Health 
Systems Agency review.  Awards are made under the authorization of Sections 
301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) 
and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92.  All 
awards are subject to the terms and conditions, cost principles, and other 
considerations described in the NIH Grants Policy Statement.  The NIH Grants 
Policy Statement can be found at 
http://grants.nih.gov/grants/policy/policy.htm. 

The PHS strongly encourages all grant recipients to provide a smoke-free 
workplace and discourage the 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.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.


Weekly TOC for this Announcement
NIH Funding Opportunities and Notices


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