FEMALE HEALTH AND EGG QUALITY
 
RELEASE DATE:  June 13, 2002
 
RFA:  HD-02-018
 
National Institute of Child Health and Human Development (NICHD) 
 (http://www.nichd.nih.gov/) 
 
LETTER OF INTENT RECEIPT DATE:  September 16, 2002 

APPLICATION RECEIPT DATE:  October 16, 2002 
 
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 Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations

PURPOSE 

The National Institute of Child Health and Human Development (NICHD) invites 
applications from investigators willing to participate in a multisite 
National Cooperative Program on Female Health and Egg Quality. This Program 
will utilize the cooperative agreement mechanism to try to better understand 
the impact of poor nutrition, extreme exercise, smoking, certain assisted 
reproductive technologies and other adverse health situations upon 
reproductive processes prior to and around the time of fertilization in 
females. The central focus of this Program will be to establish measurable or 
identifiable characteristics of high quality human and nonhuman eggs that 
have full developmental potential. It is thought that a high quality egg is 
an important starting point for the development of a healthy embryo, placenta 
and fetus. It is also thought that low egg quality can lead to certain forms 
of infertility, to abnormal embryonic and fetal development, to low 
birthweight as well as to longterm adult diseases and disorders in the 
offspring. The Barker Hypothesis on fetal origins of adult diseases suggests 
that there can be adverse in utero effects on the fetus that can lead to 
certain adult diseases such as heart attacks, diabetes and chronic high blood 
pressure. This present initiative is based upon the concept that the Barker 
Hypothesis may also pertain to adverse effects on the developing egg before 
and around the time of fertilization. Among the ultimate beneficiaries of 
this Program will be women who have difficulty attaining healthy pregnancies 
and producing healthy offspring owing to low egg quality.

 
RESEARCH OBJECTIVES

Background

This initiative addresses the idea that low egg quality may be responsible 
for difficulties in attaining and maintaining a healthy pregnancy for a 
significant number of females.  It also addresses the possibility that 
certain aspects of egg quality can be affected by adverse health situations 
in females prior to or around the time of fertilization.  These situations 
can include poor nutrition, extreme exercise, smoking and other situations, 
including certain assisted reproductive technologies. Recent studies indicate 
that 10-15 percent of women of reproductive age seek fertility services in 
any given year.  In addition, the incidence of infertility appears to be 
increasing.  There are also data that suggest that numerous adult diseases 
and disorders such as heart attacks, diabetes and chronic high blood pressure 
may have their origins in low quality eggs owing to exposures of females to 
various adverse conditions including poor nutrition, extreme exercise, 
smoking and others.  These exposures may occur long before fertilization and 
may have lasting effects upon egg quality.  This research initiative will 
test various hypotheses as to the mechanisms that may cause low egg quality 
and most importantly, to develop measurable or identifiable characteristics 
that can be used to discriminate between eggs of high quality and eggs of low 
quality.  If the idea is supported by future research, then it is anticipated 
that recommendations for female health could be used to prevent or alleviate 
some of the adverse outcomes of poor egg quality.  Much of this research will 
need to be done in nonhuman organisms in order to be able to obtain 
sufficient numbers of eggs and also in order to conduct certain in vivo and 
in vitro experiments which cannot be done with humans for ethical reasons.

The primary background information for this initiative comes from a 
conference held by NICHD on February 28, 2001 on "Effects of Maternal Health 
on Reproductive Events Leading to Adult Diseases and Disorders in Offspring." 
The distinguished panel of speakers concluded that the biology of human eggs 
is poorly understood and that the quality of these eggs may be affected by 
many risk factors in human females from their childhood through their 
reproductive years.  As a result, the panel suggested that basic and clinical 
studies be done on the preconceptual and periconceptual health of girls and 
women and its potential impact upon egg quality.  In addition, the panel felt 
that the impact upon egg quality should be followed for its effects on embryo 
and fetal development and even into adulthood. The panel also noted that  
decreased fertility, abnormal embryo and fetal development, low birthweight 
as well as diseases covered under the Barker Hypothesis, may also be caused 
by low quality eggs.  There is evidence in support of this concept from 
nutritional studies in livestock and rodents as well as evidence on decreased 
fertility and fecundity in humans that is linked to poor nutrition, extreme 
exercise, smoking or other factors.  The 2001 Surgeon General's Report on 
Women and Smoking notes that women smokers may have certain unique problems 
related to reproductive health.  These include increased risk of delayed 
time-to-pregnancy, and a moderately increased risk for ectopic pregnancies 
and spontaneous abortions.  These risks may be related to egg quality that is 
compromised in women who smoke prior to or around the time of fertilization. 
There are other well-known risks of smoking during pregnancy to women and 
their fetuses. 

In this special program, major emphasis will be placed upon the determination 
of a number of measurable or identifiable characteristics that could be used 
to evaluate the quality of individual human oocytes or eggs.  These 
characteristics will be used as baseline information in the study of the 
impact of a variety of preconceptual and periconceptual female health 
situations upon egg and preimplantation embryo quality and possible longterm 
effects of these situations.  It is anticipated that this initiative will 
result in an increase in our knowledge of the genetics, cell and molecular 
biology of human and other mammalian oocytes and eggs.  Substantial 
improvements in the culture conditions for the growth and development of 
immature oocytes into mature eggs are also expected.  One important but 
largely unexplored feature of egg quality is the power of the egg cytoplasm 
to reprogram gamete or somatic cell nuclei.  Using nonhuman species, there 
are significant opportunities within this program to study this impressive 
ability. 

Objectives of this Research Program

o To establish measurable or identifiable characteristics of high quality 
human and nonhuman oocytes and eggs 

o To better understand how adverse female health situations can result in the 
formation of low quality oocytes, eggs and preimplantation embryos

o To understand how low quality oocytes, eggs or preimplantation embryos can 
result in longterm adverse outcomes in offspring derived from those oocytes, 
eggs or preimplantation embryos

o To determine whether nutritional or other behavioral approaches could be 
used to prevent or alleviate some of the causes of low quality eggs and 
preimplantation embryos

Research Scope

Examples of research and experimental approaches that are being sought to 
achieve the objectives include, but are not limited to, the following: 

o To develop baseline criteria that can be used to determine the quality of 
individual human oocytes or eggs

o To reveal the elements or mechanisms in oocyte or egg cytoplasm that 
control nuclear reprogramming of gametes or somatic cells including nonhuman 
embryonic stem cells

o To understand the roles of egg polarity and cytoplasmic localizations in 
the formation of high quality mammalian eggs and early embryos, or possible 
longterm effects of abnormal egg polarity

o In vivo and in vitro experiments designed to test the hypothesis that poor 
nutrition or other adverse female health situations can lead to low quality 
oocytes and eggs that can have a longterm impact even into the adulthood of 
the offspring (nutrition, smoking, extreme exercise, certain assisted 
reproduction protocols, etc.)

o Adverse preconceptual and periconceptual female health situations that may 
cause abnormal genomic imprinting with longterm effects, or gender specific 
effects

o To study the impact of maternal diabetes upon egg quality

o The study of oocytes raised or matured in vitro compared with naturally 
ovulated eggs 

o The improvement of oocyte and fertilization culture conditions

o To obtain characteristic gene expression profiles of high and low quality 
oocytes and eggs

o Investigation of adverse health situations that can lead to defects in the 
meiotic process in oocytes

o The establishment of a panel of proteins or other measurable factors 
secreted by high quality and low quality oocytes, eggs or preimplantation 
embryos

o Determine the role of companion somatic cells in the formation of healthy, 
developmentally competent oocytes

o What are the egg properties that are essential for normal fertilization and 
egg activation?

MECHANISM OF SUPPORT
 
This RFA will use the NIH Cooperative Research Project (U01) award mechanism. 
As an applicant you will be solely responsible for planning, directing and 
executing the proposed project.  The anticipated award date is September 1, 
2003.  This RFA uses just-in-time concepts.  

The NIH U01 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 scientific/programmatic partner with the 
Principal Investigator during the performance of the activity. Details of the 
responsibilities, relationships and governance of the studies to be funded 
under this cooperative agreement program are discussed below under 
"Cooperative Agreement Terms and Conditions of Award." 

It is not known at this time whether this RFA will be reissued in the future. 

FUNDS AVAILABLE 
 
The NICHD intends to commit approximately $2 million in total costs [Direct 
plus Facilities and Administrative (F & A) costs] in FY 2003 to fund four to 
five new and/or competitive continuation grants in response to this RFA.  An 
applicant may request a project period of up to five years and a budget for 
direct costs of up to $300,000 per year.  Because the nature and scope of the 
proposed research will vary from application to application, it is 
anticipated that the size of each award will also 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.
 
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 or foreign
 
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 encouraged to 
apply.   

SPECIAL REQUIREMENTS 

Minimum Application Requirements

o A competent, experienced Principal Investigator who is committed to 
investigation of these problems and who is willing to cooperate with the 
other Principal Investigators and the NICHD Research Coordinator

o Agreement to participate in Steering Committee meetings that will be held 
three times a year

o Experience with analyzing, characterizing, localizing, and/or measuring 
biological molecules and investigating oocytes, eggs and/or preimplantation 
embryos

o Access to properly managed animal colonies with breeding capabilities 
and/or access to human specimens or tissues

o For those with access to human specimens or tissues appropriate for this 
project, the applicant must be experienced with prospective and retrospective 
analyses of adverse health situations, having demonstrated knowledge of 
appropriate methodologies for clinical design and analyses

Meetings

Principal Investigators are expected to attend three Steering Committee 
meetings of two days each per year. Funds for attending these meetings should 
be included in the budget requests. The first meeting will be a planning 
meeting that will be held in Bethesda, Maryland in September, 2003.

Cooperative Agreement Terms and Conditions of Award

The following terms and conditions of the cooperative agreement award and 
details of the arbitration procedures pertaining to the scope and nature of 
the interaction between the NICHD and the participating awardees will be 
incorporated into the Notice of Grant Award and provided to the Principal 
Investigator and the institutional official at the time of award. The special 
Terms and Conditions of Award are in addition to, not in lieu of, otherwise 
applicable OMB administrative guidelines, HHS grant administration 
regulations at 42 CFR Parts 74 and 92, and other HHS, PHS and NIH grant 
administration policies. 

The administrative funding instrument used for this program will be the U01, 
an "assistance" mechanism (rather than an "acquisition" mechanism), in which 
substantial NIH scientific and/or programmatic involvement with the PI is 
anticipated during performance of the activities. Under the cooperative 
agreement, the NIH purpose is to support and/or stimulate the PI's activities 
by involvement in and otherwise working jointly with the PI in a partnership 
role; it is not to assume direction, prime responsibility, or a dominant role 
in the activities. Consistent with this concept, the dominant role and prime 
responsibility resides with the PI for the project as a whole, although 
specific tasks and activities may be shared between the awardee and the NICHD  
Research Coordinator.  Facilities and Administrative cost (indirect cost) 
award procedures apply to cooperative ageements in the same manner as for 
grants. Business management aspects of these awards will be administered by 
the NICHD Grants Management Branch in accord with HHS, PHS and NIH grant 
administrative requirements.
 
1.	The Primary Rights and Responsibilities of the Awardees

The PI will coordinate project activities scientifically and administratively 
at the awardee institution and at other sites that may be supported by 
subcontracts to this award. The PI will have primary responsibility for 
defining the details of the project within the guidelines of RFA HD-02-018, 
and for performing the scientific activities. The PI will agree to accept 
close coordination, cooperation and participation of the NICHD Research 
Coordinator and the Steering Committee in the scientific and technical 
management of the project.

Specifically, the awardee will:

o Determine experimental approaches, design protocols and direct experiments 
in consultation with the NICHD Research Coordinator and the Steering 
Committee and the awardee will constitute one vote in the group process;

o Analyze and interpret the results

o Present results and plans at Steering Committee meetings

o Accept and implement the common guidelines and procedures approved by the 
Steering Committee

o Publish results

o Modify, delete or add protocols within the scientific scope of the project

o Accept and participate in the cooperative nature of the group process

Awardees will retain custody of, and primary rights to, their data developed 
under these awards, subject to Government rights of access consistent with 
current HHS, PHS and NIH policies.

2. NICHD Responsibilities

NICHD Research Coordinator:

The NICHD Research Coordinator will be a staff member of the Reproductive 
Sciences Branch. The Research Coordinator will have a substantial 
scientific/programmatic involvement that includes facilitating the 
partnership between NIH and the proposed research projects, helping to 
integrate the project's activities with new and emerging research 
opportunities, and ensuring that the project's activities are consistent with 
the mission of NICHD. The Research Coordinator will help to maintain 
scientific balance between accomplishing goals and addressing emerging 
research opportunities.  The role of the NICHD Research Coordinator will be 
to facilitate, but not to direct activities.  It is anticipated that 
decisions will be reached through consensus with the PI through the Steering 
Committee.

The NICHD Research Coordinator will:

o Ensure that Steering Committee meetings are held on schedule, attend those 
meetings and constitute one vote in the group process 

o Participate in the development of optional approaches and protocol designs 
(and adjustments of protocols and approaches when needed); the Research 
Coordinator will assist and facilitate the process, rather than direct it

o Assist and review all phases of the study to assure consistency of protocol 
compliance, to improve and strengthen cooperation between the sites, and to 
help redirect efforts, or to recommend modification or termination of a site, 
when performance requirements are not met

o Participate in data analyses, interpretations and, when warranted, 
publication of study results

The above responsibilities are in addition to, not in lieu of, the levels of 
involvement normally required for program stewardship of grants.

NICHD Project Officer:

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

o Ensure that all regulatory, fiscal and administrative matters are handled 
according to NIH guidelines

o Will evaluate requests for additional funds or for rebudgeting 

o Carry out continuous review of individual projects to evaluate progress

o Perform other duties required for normal program stewardship of grants

3. Collaborative Responsibilities

Guidance and Management Structure:

The overall guidance and management of the program will be provided by a 
Steering Committee consisting of the Principal Investigators of each of the 
participating sites, one staff member of the Reproductive Sciences Branch, 
NICHD, who will serve as the Research Coordinator, and one of the Principal 
Investigators who will serve as a Chairperson for Steering Committee 
meetings.  Each Principal Investigator will have one vote and the Research 
Coordinator will have one vote.  The Steering Committee will be the main 
governing body of the projects to be funded by RFA HD-02-018.  It will 
oversee and coordinate interactions among the projects, and will mediate 
interactions between the projects and the NIH.  The Steering Committee will 
discuss scientific goals and progress, and recommend further research 
activities based upon research findings of ongoing projects. 

4. Arbitration Process

When agreement between an awardee(s) 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(s), 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 will 
not, in any way, affect the right of an awardee to appeal an adverse action 
in accordance with PHS regulations at 42 CFR Part 50, Subpart D, and HHS 
regulations at 45 CFR Part 16.

WHERE TO SEND INQUIRIES

NICHD encourages inquiries concerning this RFA and welcomes 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:

Richard J. Tasca, Ph.D.
Center for Population Research
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 8B01, MSC 7510
Bethesda, MD  20892-7510
Telephone:  (301) 435-6973
FAX: (301) 580-2389
Email:  rt34g@nih.gov 

o Direct your questions about peer review issues to:

Robert H. 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
Telephone:  (301) 496-1485
FAX:  (301) 402-4104
Email:  rs365f@nih.gov   

o Direct your questions about financial or grants management matters to:

Kathy Hancock
Grants Management Branch
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 8A17, MSC 7510
Bethesda, MD  20892-7510
Telephone:  (301) 496-5482
FAX: (301) 480-4782
Email:  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:

Richard J. Tasca, Ph.D.
Center for Population Research
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 8B01, MSC 7510
Bethesda, MD  20892-7510
Telephone:  (301) 435-6973
FAX: (301) 580-2389
Email:  rt34g@nih.gov 

SUBMITTING AN APPLICATION

Applications must be prepared using the PHS 398 research grant application 
instructions and forms (rev. 5/2001).  The PHS 398 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.

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 as well 
as any appendix material must be sent to:

Robert H. 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
FAX:  (301) 402-4104
Email:  rs365f@nih.gov   
 
APPLICATION PROCESSING:  Applications must be received by 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.
 
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.

PEER REVIEW PROCESS  
 
Upon receipt, applications will be reviewed for completeness by the CSR and 
responsiveness by NICHD. Incomplete and/or non-responsive applications will 
be returned to the applicant without further consideration. 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 NICHD in 
accordance with the review criteria stated below.  As part of the initial 
merit review, all applications will:

o Receive a written critique
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 second level review by the National Advisory Child Health and 
Human Development Council
 
REVIEW CRITERIA

The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health.  In 
the written comments, reviewers will be asked to discuss the following 
aspects of your application in order to judge the likelihood that the 
proposed research will have a substantial impact on the pursuit of these 
goals: 

o Significance 
o Approach 
o Innovation
o Investigator
o Environment
  
The scientific review group will address and consider each of these criteria 
in assigning your application's overall score, weighting them as appropriate 
for each application.  Your application does not need to be strong in all 
categories to be judged likely to have major scientific impact and thus 
deserve a high priority score.  For example, you may propose to carry out 
important work that by its nature is not innovative but is essential to move 
a field forward.

(1) SIGNIFICANCE:  Does your study address an important problem? If the aims 
of your application are achieved, how do they advance scientific knowledge?  
What will be the effect of these studies on the concepts or methods that 
drive this field?

(2) APPROACH:  Are the conceptual framework, design, methods, and analyses 
adequately developed, well integrated, and appropriate to the aims of the 
project?  Do you acknowledge potential problem areas and consider alternative 
tactics?

(3) INNOVATION:  Does your project employ novel concepts, approaches or 
methods? Are the aims original and innovative?  Does your project challenge 
existing paradigms or develop new methodologies or technologies?

(4) INVESTIGATOR:  Are you appropriately trained and well suited to carry out 
this work?  Is the work proposed appropriate to your experience level as the 
principal investigator and to that of other researchers (if any)?

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

ADDITIONAL REVIEW CRITERIA:  In addition to the above criteria, your 
application will also be reviewed with respect to the following:

o PROTECTIONS:  The adequacy of the proposed protection for humans, animals, 
or the environment, to the extent they may be adversely affected by the 
project proposed in the application

o INCLUSION:  The adequacy of plans to include appropriate subjects, all 
racial and ethnic groups (and subgroups), and children, as appropriate for 
the scientific goals of the research.  Plans for the recruitment and 
retention of subjects will also be evaluated. (See Inclusion Criteria 
included in the section on Federal Citations, below)

o BUDGET:  The reasonableness of the proposed budget and the requested period 
of support in relation to the proposed research

RECEIPT AND REVIEW SCHEDULE

Letter of Intent Receipt Date:  September 16, 2002 
Application Receipt Date:  October 16, 2002 
Peer Review Date:  February/March 2003
Council Review:  June 2003
Earliest Anticipated Start Date:  September 1, 2003

AWARD CRITERIA

Award 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
o Sufficient compatibility of features to enhance the likelihood of a 
successful collaborative program 
 
REQUIRED FEDERAL CITATIONS 

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 AMENDMENT "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.

BAN ON FUNDING OF HUMAN EMBRYO RESEARCH:  In accord with directives derived 
from H.R. 2264 and S. 1061 and (Section 510) and included in the Labor, HHS 
and Education Fiscal Year 2002 Omnibus Appropriations Bill enacted into law 
(Public Law 107-116) on January 10,2002, funds provided for awards must only 
be used in compliance with the following directive:

This section (510) continues the current ban that prohibits NIH from using 
appropriated funds to support human embryo research.  Grant, cooperative 
agreement and contract funds may not be used for 1) the creation of a human 
embryo or embryos for research purposes; or (2) research in which a human 
embryo or embryos are destroyed, discarded, or knowingly subjected to risk of 
injury or death greater than that allowed for research on fetuses in utero 
under 45 CFR 46.208(a)(2) and section 498(b) of the Public Health Service Act 
(42 U.S.C. 289g(b)).  For purposes of this section, the term "human embryo" 
or "embryos" includes any organism not protected as a human subject under 45 
CFR 46 as of the date of the enactment of this Act, that is derived by 
fertilization, parthenogenesis, cloning, or any other means from one or more 
human gametes or human diploid cells. You will find this policy announcement 
in the NIH Guide for Grants and Contracts Announcement, dated January 25, 
2002, at http://grants2.nih.gov/grants/guide/notice-files/NOT-OD-02-029.html

HUMAN EMBRYONIC STEM CELLS (hESC):  Criteria for federal funding of research 
on hESCs can be found at http://grants.nih.gov/grants/stem_cells.htm 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.

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 No. 93.864, Population Research and is not 
subject to the intergovernmental review requirements of Executive Order 12372 
or Health Systems Agency review.  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 described at 
http://grants.nih.gov/grants/policy/policy.htm and under Federal Regulations 
42 CFR 52 and 45 CFR Parts 74 and 92. 

The PHS strongly encourages all grant 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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