COOPERATIVE GRANTS FOR NUTRITIONAL MODULATION OF GENETIC PATHWAYS LEADING 
TO CANCER

RELEASE DATE:  January 22, 2002

RFA:  RFA-CA-03-001

PARTICIPATING INSTITUTES AND CENTERS (ICs):

National Cancer Institute (NCI)
 (http://cancer.gov/)

LETTER OF INTENT RECEIPT DATE:  June 14, 2002
APPLICATION RECEIPT DATE:       July 12, 2002

THIS RFA CONTAINS THE FOLLOWING INFORMATION

o Purpose of this RFA
o Research Objectives
o Mechanism(s) 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 Cancer Institute (NCI) invites applications (U54) to develop 
Cooperative Specialized Centers for both basic and clinical research in areas 
related to dietary nutrients as modifiers of genetic pathways leading to 
cancer.  The overall goal of this initiative is to advance the science of 
nutrition by capitalizing on recent advances in molecular biology and genetics 
and by addressing three extraordinary opportunities identified in The National 
Cancer Institute's 2002 Bypass Budget, i.e. Genes and the Environment, 
Defining the Signatures of Cancer Cells, and Molecular Targets. 
(http://www.cancer.gov/initiatives/).

This Request For Applications (RFA) invites investigators to form 
Interdisciplinary Research Teams to resolve complex gene-nutrient 
interrelationships that relate to cancer prevention.  All research approaches 
are encouraged, as long as they address the following essential features: a 
cancer focus, institutional commitment, organizational capabilities, 
facilities, and interdisciplinary coordination and collaboration.  Receipt of 
a Planning Grant award (P20) is not a prerequisite to apply for this RFA.  A 
team must include investigators from one or more institutions with expertise 
in nutrition and molecular biology/ genetics and may contain others as 
required to address the role(s) of nutrient(s) on genetic pathways leading to 
cancer.  Regardless of the genetic pathway selected the Team must indicate how 
the proposed studies will advance knowledge of the pertinent biology, define 
what events are likely informative in meeting this initiative's goals, focus 
on the development of relevant and practical assays, probes, and other tools 
to assess the effects of the nutrient(s) on that genetic pathway in vivo and 
foster the translation of their research findings into a patient or population 
setting.  Examples of areas of interest include, but are not limited to 
carcinogen bioactivation, cell-cycle control, signal transduction; 
intercellular communication, apoptosis; immune effectors, and angiogenesis.

Public Briefing Date:  February 19, 2002 

An initial informational session for those investigators planning to submit 
applications in response to this RFA will be held Tuesday, February 19, 2002 
from 1:00 PM to 3:00 PM at the Bethesda Marriott, 5151 Pooks Hill Road, 
Bethesda, MD  20814.  Representatives from the NCI's extramural research 
programs, Grants Administration Branch, and Division of Extramural Activities 
will be available to provide information and to answer questions relevant to 
applications responding to this RFA.  Investigators who are unable to attend 
should request transcripts.  Investigators are encouraged to contact 
Nutritional Science Research Group Office at the address listed under 
INQUIRIES to obtain further information about the meeting, confirm their 
attendance or to request a transcript of the meeting. 

RESEARCH OBJECTIVES  

Background

The impetus for this overall program comes from increasing observations that 
link diet with cancer risk.  Data from a multitude of sources, including 
epidemiological and controlled preclinical experiments, indicate that several 
dietary components may have a role in the cancer process.  While the risks of 
breast, prostate, colon, lung and liver cancers have been associated with 
dietary patterns, frequent inconsistencies are noted.  These inconsistencies 
may reflect the multi-factorial and complex nature of cancer and/or the 
specificity that individual dietary constituents have in modifying genetic 
pathways.  Since variation occurs in cancer incidence among and within 
populations with similar dietary patterns, the absolute response may reflect 
complex interactions occurring among nutrients and with other extrinsic 
environmental factors, or with intrinsic gender, ethnic and genetic factors.  
Traditional reduction approaches used by some to examine gene-chemical 
interactions may be inadequate for the study of nutrition and cancer because 
of the likelihood that multiple nutrients interact with multiple genes to 
create a phenotypic effect.  Thus, applications that include components to 
examine nutrient-nutrient interactions and response to whole foods are 
encouraged. 

The National Cancer Institute's 2001 Bypass Budget 
(http://2001.cancer.gov/opps.htm) identified six extraordinary research 
opportunities that offer exciting possibilities for accelerating progress 
against cancer.  Opportunities for moving nutrition research into a new era in 
cancer prevention are identifiable in several of these extraordinary 
opportunities including: Genes and the Environment, Defining the Signatures of 
Cancer Cells, and Molecular Targets.  The diet consumed is an environmental 
exposure that may either enhance or suppress cancer risk and tumor behavior 
depending on its composition.  By addressing the role that diet and dietary 
components have in each of these areas, better insights will emerge about who 
might benefit from selected dietary intervention strategies.  

Astonishing strides have been made in understanding how molecules and pathways 
in pre- and malignant cells differ from their normal counterparts.  The 
discovery and exploitation of molecular targets for cancer prevention have 
arisen from the convergence of scientific advances in several areas but have 
not been totally embraced by the nutrition research community.  Preclinical 
evidence demonstrating that several dietary components can influence Phase I 
and II enzymes involved with carcinogen metabolism, as well as alter pathways 
involved with cell proliferation and differentiation, serve as justification 
for expanding this area of investigation while simultaneously satisfying NCI's 
goal to identify Molecular Targets of Prevention and Treatment.  

All cells have unique "signatures" that are characterized by active and 
inactive genes and cellular products.  Evidence already exists that both 
essential and non-essential nutrients can influence cell cycle regulation, 
processes involved with replication/transcription, and factors involved with 
apoptosis.  Part of this protection may relate to their ability to prevent 
oxidative damage.  Compounds suppressing oxidative stress have been reported 
to produce changes in c-fos, c-jun, and c-myc and the tumor suppressor gene 
p53, as well as genes coding for the syntheses of protective molecules such as 
metallothioneins, glutathione, and stress proteins.  Preclinical evidence 
exists that such diverse dietary components as folate, allyl sulfur, genistein 
and resveratrol can alter genes and pathways associated with tumor cell 
proliferation and apoptosis.  This evidence raises the possibility that the 
expanded use of molecular signatures will assist in developing effective 
dietary intervention strategies. 

Defining interactions between genetic pathways and dietary constituents should 
assist in clarifying discrepancies among pre-clinical, epidemiological, and 
intervention studies.  For example, knowledge about genetic pathways that are, 
and are not, influenced by carotenoids may clarify why beta-carotene intake 
emerged in several prospective epidemiological investigations as inversely 
related to lung cancer risk, while it is contraindicated in controlled trials 
with smokers.  By simultaneously examining other extrinsic factors such as 
tobacco exposures and the occurrence of genetic changes accompanying pre-
neoplastic lesions, it may be possible to clarify why a nutrient might be an 
antagonist (antioxidant) in one situation yet an agonist (pro-oxidant) 
in another.

Resolving complex issues about intrinsic and extrinsic determinants of cancer 
are often hampered by the limited scientific breadth of single investigators 
and institutions and/or access to study populations.  The development of 
research teams from multiple units and/or locations offers exciting 
opportunities for addressing several overarching nutrition and cancer issues. 
 Among the benefits are the establishment of meaningful integrated and 
multidisciplinary collaborations among scientists at the interface between the 
biological domain and medical practice.  

Objective and Scope

The explosive increase in the understanding of new genes and pathways for 
regulating cell growth and development, and evaluating the response to 
hormones and other chemicals synthesized by the body offers exciting 
opportunities for understanding how the diet influences cancer prevention.  
Cohort studies that can define key interrelationships between genes and 
dietary exposures, including the content of specific nutrients in target 
tissues, are sometimes beyond the capabilities of individual institutions.  By 
fostering collaborations between investigators and institutions that use new 
genetic approaches, this RFA seeks to improve opportunities to address 
critical research questions that define the mechanism by which nutrients 
modify the cancer process, characterize how gene variation in key molecular 
pathways modulate the response, and how to assess/monitor the biological 
response to foods and their isolated constituents.  

This RFA is meant to foster interdisciplinary teams to resolve issues about 
the physiological significance of dietary components as regulators of genetic 
and epigenetic pathways involved with cancer.  Significant advances will 
require that the approaches taken by these Teams go beyond customary thinking 
and organizations to the creation of new cross-disciplinary and multi-
institutional collaborations.  Thus, in this RFA, the Principal Investigator 
may draw innovative expertise from wherever it may exist; investigators need 
not be limited to a single institution.  Collaborating investigators may be 
from academic, industrial, or government institutions (including NIH 
intramural scientists and non-US sites).  This RFA, however, does not provide 
support/funding for synthesis/production of therapeutic agents.  

Below is a list of some of the areas of research that are viewed as relevant 
for this U54 RFA.  This list is not meant to be all-inclusive and prospective 
applicants are encouraged to discuss program relevance issues with program 
staff cited under INQUIRIES.  These topics also identify areas where research 
at the basic/clinical interface is deemed essential to understanding the role 
of bioactive food components and cancer prevention:

o  Use of natural genetic variations to elucidate how nutritional exposures 
are linked to phenotype;
o  Characterization of molecular events that govern the ability of specific 
nutrients to alter cell cycle checkpoints;
o  Credentialing of target receptors for cancer prevention that are modified 
by dietary constituents;
o  Methylation patterns that are influenced by dietary manipulations that 
influence gene expressions and cellular phenotypes;
o  Antioxidant scavenging and oxygen stress modulation by nutrients;
o  DNA repair mechanisms influenced by dietary constituents; 
o  Intercellular communications that are influenced by bioactive food 
components
o  Signaling pathways that regulate cancer growth, development, 
differentiation and apoptosis as regulated by dietary components; and 
o  Features of DNA damage, DNA repair or cell cycle progression that makes 
them particularly susceptible to dietary intervention strategies 

Specific Objectives 

The central objective of the Teams supported by this initiative is to identify 
and characterize the biological consequences of specific nutrients on key 
genetic pathways involved in cancer processes.  The required components are 
as follows:

o  Selecting one or more cancer-relevant genetic pathways for which evidence 
exists that it may be modified by nutrients.
o  Establishing effective and synergistic collaborations that enhance the 
capabilities of individuals and leverage available resources for the Team.
o  Evaluating and validating assays, probes, and other techniques in 
preclinical models, for assessing genetic effects, changes in biochemical 
processes downstream from the main target; pharmacokinetics or 
pharmacodynamics of bioactive food components and for the establishment of 
quantity-temporal relationships.
o  Identifying how nutrients directed at high-priority genetic 
pathways/targets affect endpoints/biomarkers that may be used as indicators in 
a clinical setting.  A Team may choose to achieve translational goal of their 
research by including (a) acquisition of relevant cells (e.g., from cancers, 
preinvasive neoplastic lesions, or fields at risk for cancer) by biopsy, 
aspiration or plasmapheresis, (b) Techniques for imaging molecular and 
cellular processes such as techniques based on radiotracers or ultrasound or 
optical imaging, or (c) other indicators as appropriate.
o  Exploring new scientific insights into mechanisms and determinants of 
response
o  Exploring new approaches to early clinical trials methodology; for example, 
the use of alternate trial designs and endpoints, or exploring designs based 
on molecular classifications of tumor rather than histology per se.
o  Responsiveness to share information via publications, meetings and support 
of training activities and to disseminate new reagents and techniques 
discovered under this initiative to other investigators.  When appropriate, 
the NCI may facilitate the dissemination of bioactive components and/or 
approaches to other groups funded by this initiate by providing additional 
support to the originating laboratory.  Team investigators are expected to 
participate in NCI-sponsored working groups focused on high-priority genetic 
pathways. Awardees are encouraged to file patent applications in a timely 
manner in order to permit timely presentation and publication of results. 

Organizational Structure

In order to provide the greatest flexibility for organizing research efforts 
in these cooperative agreements, the PI must organize the investigators and 
resources into the following required elements:

1. Overall Research Theme

This RFA is to support any part of the full range of research and development 
from very basic to clinical; involving interdisciplinary teams to resolve 
issues about the physiological significance of dietary components as 
regulators of genetic and epigenetic pathways involved with cancer.

2.  Research Projects

Each application must include at least three meritorious Research Projects, 
which together represent experimental approaches to define and characterize 
the mechanisms by which bioactive food components modulate genetic pathways 
leading to cancer.  The discovery and/or development of assays, probes, and 
other tools suitable for use in preclinical models and clinical research are 
germane to these investigations.  Research Projects may also conduct research 
on the biologic and pharmacodynamic aspects of nutrient interactions to enable 
assessment of how dynamics among nutrient(s) may modify specific genetic 
pathway(s).  

All of the Research Projects must be related to one or more specific genetic 
pathways associated with cancer and the benefits/risks associated with a 
specific nutrient or class of nutrients.  Teams must plan to continually 
select the most promising research approaches that are likely to have impact 
on the development of clinically useful probes. The flexibility of the Team is 
intended to promote the discontinuance of research projects demonstrating 
little or no translational significance and to promote initiation of new 
projects with greater potential.  Translational research is defined as the 
movement of a laboratory discovery into a patient or population setting or the 
movement of an observation in a patient or population setting into a 
laboratory research environment.  

3. Core Services

The Team is encouraged to develop and maintain core resources that are 
essential for the conduct of this research.  Core Services may include 
resources that may already be available at the institution and do not need 
further development/research.  Examples of potential Core Services include 
animal cores, pharmacology, pathology, clinical data monitoring services, and 
statistical support.  An Administrative Core is required and is responsible 
for administrative management and coordination of meetings and other 
activities within the Team and with other potential collaborators such as 
industry and NCI and other funded Teams.  The Principal Investigator of the 
Team must serve as the Principal Investigator of the Administrative Core.  The 
Administrative Core may encompass the other service cores, or, if they are 
separately organized, each service core must provide resources to at least two 
Research Projects and/or Pilot Projects.

4.  Pilot (Developmental) Projects

Every Team must facilitate and support Pilot Projects that take maximum 
advantage of new technological and research opportunities.  These projects may 
be collaborative among scientists within one or more Teams, or with scientists 
outside the Team.  If a clinical trial is not proposed as one of the Research 
Projects, at least one Pilot Project must outline the general plan for a 
(future) clinical trial that incorporates the methodologies, techniques, and 
probes to be developed in the research projects.  Each application must 
propose an institutional review process for selecting Pilot Projects for 
funding that generate feasibility data and have the most promising 
translational research potential.  

While the specific number of pilot projects to be proposed is at the 
discretion of the applicant, requested funding for pilot studies may not 
exceed $125,000 or 10 percent (whichever is larger) of the direct cost budget 
proposed for any 1 year. All proposed pilot projects need not be ongoing at 
any one time, but may be phased in during the life of the award.  It is 
recognized that the relative priority or need for specific pilot projects may 
change during the course of the award. For the first 2 years that funds are 
requested for pilot projects, the application must provide descriptions of the 
projects to be supported.  For years 03-05, the application must provide the 
specific number of pilots planned in each year and a brief description of the 
anticipated direction of these pilots.  Pilot studies should not have 
individual budgets.  The PI can request a single line item in the 
administrative core for pilot studies.  These funds are intended to remain 
flexible and to support studies of a limited duration, e.g., two years or 
less.  Successful feasibility studies may be used to replace full projects 
that are no longer contributing significantly to the objectives of the Team.  
Therefore scientific members of the Team may change during the course of 
the award.

Framing experiments as pilot projects permits maximal flexibility to proceed 
in the directions that seem most scientifically fruitful.  Individual Pilot 
Projects are expected to have small budgets since the majority of the 
personnel and equipment involved will likely be supported by the Research 
Projects and Cores and thus funds would only be needed for supplies, 
animals, etc.  

While the framework for management of pilot funds and the mechanism for 
operating the program are left to the discretion of the PI, the application 
must provide specific information to enable adequate scientific evaluation by 
a peer review committee.  The application should include: 

o A full description of the management of the pilot project component, 
including a description of the process to be followed in selecting new pilot 
projects and replacing projects proposed in the application, should it 
become necessary.

o A full description of each pilot study proposed in the first 2 years, 
including its rationale, objectives, approach, investigators, and significance 
to the overall undertaking.  A description of the number and anticipated 
direction of pilot projects in the 03-05 years, including their significance 
to the Program.  The research description of any individual pilot project may 
not exceed five pages; the entire narrative for this Pilot Project Component 
may not exceed 25 pages regardless of the number of pilot projects proposed. 

o For competing renewal applications, information should be provided in the 
pilot project component description on the past experience in utilizing pilot 
funds to further the goals.  The narrative should include an assessment of the 
overall benefits derived from the availability of pilot resources. 

o A budget should be submitted for the pilot project component as a whole for 
each year in which pilots are proposed as a line item within the 
Administrative Core.  For years 01 and 02, this budget will reflect costs of 
pilots proposed in the application.  For years 03-05, the budget will estimate 
cost based on the number and kind of studies to be pursued.  

5.  Planning Committee.  
A Planning Committee with representation from the Principal Investigator from 
each Team and from NCI Program Staff (NSRG Project Scientist see below) will 
be established to help coordinate the activities and exchange information and 
techniques among the Teams (see below).  The expectation is that successful 
feasibility studies will be developed by the Planning Committee that will 
allow new technologies and approaches to become a core function and/or be 
distributed more widely to other investigators funded by this RFA.  

The research activities included in these cooperative agreements are 
explicitly translational and are, of necessity, highly interdisciplinary.  
Each Team must be able to deal expertly with nutritional biochemistry and 
cancer biology, and with such matters as chemistry, pharmacokinetics, cellular 
and molecular imaging, in vivo animal models, and early clinical trials as 
needed.  

MECHANISM OF SUPPORT
 
This RFA will use NIH U54 award mechanism.  As an applicant you will be solely 
responsible for planning, directing, and executing the proposed project.  This 
RFA is a one-time solicitation.  Future unsolicited, competing-continuation 
applications based on this project will compete with all investigator-
initiated applications and will be reviewed according to the customary peer 
review procedures.  The anticipated award date is April, 2003.
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".

The U54 mechanism may support any part of a full range of research development 
from very basic to clinical.  The U54 is a cooperative agreement, an 
assistance mechanism (rather than an acquisition mechanism) in which 
substantial NIH scientific and/or programmatic involvement with the awardee is 
anticipated during the performance of the activities. Under a cooperative 
agreement, the NIH's purpose is to support and stimulate the recipient's 
activities by involvement in and otherwise working jointly with the award 
recipient in a partner role. 

NIH staff work cooperatively with the award recipients in a partner role and 
do not assume direction, prime responsibility, or a dominant role in the 
activity. Details of the responsibilities, relationships, and governance of 
the activities to be funded under the cooperative agreements awarded for this 
Program are discussed below under "Terms and Conditions of Award."

At this time the NCI has not determined whether or how this solicitation will 
be continued beyond the present RFA.  If it is determined that there is a 
continuing program need, the NCI will either invite recipients of awards under 
this RFA to submit competitive continuation cooperative agreement applications 
for review or re-issue the RFA for re-competition.  If the NCI does not 
continue the program, awardees will be able to submit grant applications 
through existing investigator-initiated grant programs that will be reviewed 
according to the customary peer review procedures.
 
FUNDS AVAILABLE

The NCI intends to commit approximately $5.3 million in FY 2003 to fund 3 to 4 
Teams in response to this RFA.  An applicant may request a project period of 
up to five years. Because the nature and scope of the proposed research will 
vary from application to application, it is anticipated that the size and 
duration of each award will also vary. Although the financial plans of the NCI 
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. At this time, it is not known if this RFA will 
be reissued.

ELIGIBLE INSTITUTIONS
 
You may submit (an) application(s) 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 
o Faith-based organizations 

Foreign organizations are not eligible to serve as grantees but may be part 
of domestic applications.  PIs must be United States citizens, non-citizen 
alien nationals, or permanent residents of the United States.  An application 
must contain three or more related and interactive research projects that 
provide an interdisciplinary, yet thematic, approach to a nutrient-genetic 
pathway issue involved with cancer prevention.  Applications will not be 
accepted that include research activities focused exclusively on clinical 
research or exclusively on basic research, or that are limited to 
epidemiological or large scale clinical trials.

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

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 grant administration regulations in 45 CFR Part 
74 and 92 and administered under the NIH Grants Policy Statement. 

The administrative and funding instrument used for this program is a 
cooperative centers agreement (U54), an "assistance" mechanism (rather than an 
"acquisition" mechanism) in which substantial NIH scientific and programmatic 
involvement with the awardee is anticipated during the grant award.  The NIH 
purpose is to support and stimulate the activity by working jointly with the 
recipient in a partner role, but it is not to assume direction, prime 
responsibility or a dominant role in the activity.  The prime responsibility 
for the research resides with the awardees, although some activities may be 
carried out as a collaboration among the awardees with coordination and 
facilitation by the NCI-NSRG Project Scientist as described below.

1. Awardee Rights and Responsibilities:

a.  Awardees will have primary responsibility for the project as a whole, 
including research design and conduct, data collection, data quality control, 
data analysis and interpretation and preparation of publications, as well as 
collaborations with other awardees.  Awardees will retain primary custody of 
and have primary rights to the data developed under these awards, subject to 
government rights of access consistent with current HHS, PHS, and NIH 
policies.  However, awardees must be committed to making the assays and probes 
and other research tools and research materials they develop available to the 
cancer research community.  

b.  The Principal Investigator must plan to participate in regular meetings of 
a Planning Committee to discuss progress and directions of research and to 
insure that the necessary interdisciplinary interactions are taking place.  

c.  Awardees agree to participate on common projects identified by the 
Planning Committee on common research interests that address a specific basic 
and/or clinical research problem.

d.  The Principal Investigator must plan to participate in regular meetings 
with the Team to discuss progress and directions of research and to insure 
that the necessary interdisciplinary interactions are taking place.  Plans to 
extend meetings via teleconferencing, videoconferencing or web conferencing, 
as well as fact to face meetings, are appropriate.  

e.  The Principal Investigator and/or another designated investigators will 
attend an Annual Meeting to be organized by NCI staff in Washington D.C.  In 
addition, the PI will be a voting member of the Planning Committee which meets 
twice a year (one meeting will be coordinated with the Annual Meeting).

f.  Each Team will submit biannual progress reports to the NCI that describe 
activities and accomplishments during the previous funding period.

g.  An NIH intramural scientist (IMS) may not serve as the Principal 
Investigator but may participate as part of the Awardee Team.  The 
participation of an IMS is independent of and unrelated to the role of the 
NSRG Project Scientist as described below.  An IMS who is part of the award's 
project team will have the same programmatic rights and responsibilities as 
other investigators.  

h.  Intellectual Property Plan.  In order to encourage timely presentation and 
publication of results, the Awardees are encouraged to file patent 
applications in a timely manner, according to approved implementation plan.   

i.  All Awardees must adhere to the Principles and Guidelines for Recipients 
of NIH Research Grants and Contracts on Obtaining and Disseminating Biomedical 
Research Resources (64 Federal Register 72090).  The Principles and Guidelines 
can be accessed electronically at:  (http://ott.od.nih.gov/).

j.  Awardees shall include the following terms concerning intellectual 
property rights, or provide an alternative plan.  In no event will an award be 
made absent incorporation of either the terms below, or Institution's own plan. 

"Institution agrees to grant to commercial collaborator: (i) a paid-up 
nonexclusive, nontransferable, royalty-free, world-wide license to all 
Institution Inventions for research purposes only; and (ii) a time-limited 
first option to negotiate an exclusive, world-wide royalty-bearing license for 
all commercial purposes, including the right to sub-license, to all 
Institution Inventions on terms to be negotiated in good faith by the 
collaborator and Institution. The collaborator shall notify Institution, in 
writing, of its interest in obtaining such an exclusive license to any 
Institution Invention within six (6) months of the collaborator's receipt of 
notice of such Institution Invention(s). In the event that a collaborator 
fails to so notify Institution, or elects not to obtain an exclusive license, 
then the collaborator's option shall expire with respect to that Institution 
Invention, and Institution will be free to dispose of its interests in such 
Institution Invention in accordance with Institution's policies. If 
Institution and collaborator fail to reach agreement within ninety (90) days, 
(or such additional period as collaborator and Institution may agree) on the 
terms for an exclusive license for a particular Institution Invention, then 
for a period of six (6) months thereafter Institution shall not offer to 
license the Institution Invention to any third party on materially better 
terms than those last offered to collaborator without first offering such 
terms to collaborator, in which case collaborator shall have a period of 
thirty (30) days in which to accept or reject the offer.

Institution agrees that notwithstanding anything contained herein to the 
contrary, any inventions, discoveries or innovations, whether patentable or 
not, which are not Subject Inventions as defined in 35 USC 201(e), arising out 
of any unauthorized use of the collaborator's agent and/or any modifications 
to the agent, shall be the property of the collaborator (hereinafter 
"Collaborator Inventions").  Institution will promptly notify the collaborator 
in writing of any such Collaborator Inventions and, at collaborator's request 
and expense, Institution will cause to be assigned to collaborator all right, 
title and interest in and to any such collaborator inventions and provide 
collaborator with assignment or other documents).  Institution may also be 
conducting other research using the agent under the authority of a separate 
Material transfer Agreement (MTA) with the collaborator.  Inventions arising 
there under shall be subject to the terms of the MTA, and not to this clause." 
35 USC.

k.  Protection of Proprietary Data
Raw and primary data may be provided exclusively to the NCI, industrial 
collaborators, and the FDA, as appropriate.  This provision shall not affect 
the investigators' right to disseminate their research findings through 
publications or presentations.

2. NCI Staff responsibilities:

a.  The NCI Program Director from the Division of Cancer Prevention, 
Nutritional Science Research Group (NSRG) and other staff members within the 
NSRG will work closely with individual investigators (including NIH intramural 
scientists) to facilitate collaborations with other NCI-funded research groups 
and to leverage the resources available for this effort.  An assigned NCI 
program official will be responsible for normal program stewardship and 
monitoring of the award.  

b.  A NSRG Project Scientist will assist in the coordination of activities 
that involve all the awardees, such as annual meetings and Planning Committee 
meetings.  This individual will also assist the research efforts of the Team 
by facilitating access to fiscal and intellectual resources provided by 
industry, private foundations and NIH intramural scientists.  The NSRG Project 
Scientist will serve as a voting member of the Planning Committee.  As 
required, when projects are not making headway, the NSRG Project Scientist, 
will help reprogram research efforts within the peer-reviewed scope of work, 
including options to modify or terminate projects, by mutual consent between a 
Team and NCI.

c.  The NSRG Project Scientist will interact with each Team, evaluating the 
progress of that particular Team, help coordinate research approaches between 
Teams, and contribute to the adjustment of research projects or approaches as 
warranted. The NSRG Project Scientist will assist and facilitate this process 
and not direct it. This individual will also provide assistance in reviewing 
and commenting on all major transitional changes of an individual Team's 
activities prior to implementation to assure consistency with the goals of 
this RFA-CA-03-001.

d.  The NSRG Project Scientist will coordinate this activity with other 
ongoing studies supported by NCI to avoid duplication of effort and to 
encourage sharing and collaboration in the development of new clinically 
useful reagents and methodologies for assessing nutrient-gene interactions.  
The NSRG Project Scientist will coordinate access to other resources from NCI 
including NCI sponsored agents for preclinical and clinical testing, drug 
screening, preclinical toxicology testing, assistance in IND filing, etc.

e.  The NSRG Project Scientist will organize an annual meeting of all funded 
PIs or their designees to share progress and research insights that may 
benefit all of the projects.  In addition, he/she will be responsible for 
organizing biannual meetings of the Planning Committee.

f.  The NSRG Project Scientist will assist, where warranted, in data analyses, 
interpretations, and the dissemination of study findings to the research 
community and health care recipients including co-authorship of the 
publication of results of studies conducted by the Teams, subject to NIH 
publication policies.

3. Collaborative responsibilities:

The Planning Committee will provide overall coordination of the Teams; voting 
members will consist of the Team Principal Investigators, and 1 NCI Program 
Staff (NSRG Project Scientist).  Additional Program Staff and scientists other 
than PIs may attend as non-voting members of the Planning Committee where 
additional expertise may be required.  A non-NIH chairperson for the Planning 
Committee will be chosen by a majority vote of the Principal Investigators.  
The Planning Committee will identify the need for collaborations either within 
or outside the Teams and the need to redirect certain efforts as mandated by 
establishment of sufficient data to reach conclusions, data supporting 
alternative approaches, or experience proving that the proposed research is no 
longer feasible.  Some Teams will have common research interests that address 
a specific basic and/or clinical research problem; research focus groups may 
be formed to conduct coordinated research activities identified by the 
Planning Committee.  The Planning Committee will make recommendations 
regarding genetic targets and possible research tools.  It will also seek 
input from the scientific research communities and consider how to have an 
impact on nutritional recommendations to the larger community.  The Team 
investigators must be willing to consider addressing future scientific needs 
discussed by the Planning Committee. 

The Planning Committee will meet twice yearly. 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.

4.  Arbitration: 

When agreement between an awardee and NCI 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 
awardee, one person selected by NCI staff, and a third person selected by 
these two members.  The decision of the arbitration panel, by majority vote, 
will be binding. This special arbitration procedure in no way affects the 
right of an awardee to appeal an adverse action in accordance with PHS 
regulations at 42 CFR Part 50, Subpart D, and HHS regulations at 45 CFR Part 16.

WHERE TO SEND INQUIRIES 

Written and telephone inquiries concerning this RFA are encouraged.  The 
opportunity to clarify any issues or questions from potential applicants is 
welcome. Direct inquiries regarding programmatic issues and address the letter 
of intent to: 

John A. Milner
Chief, Nutritional Science Research Group, DCP,
National Cancer Institute
Executive Plaza North
6130 Executive Blvd, EPN Suite 3164
Rockville, MD  20852
Email:  milnerj@mail.nih.gov
Telephone:  (301) 496-0108
FAX:  (301) 480-3925

Direct inquiries regarding review issues to:

NCI Referral Officer 
Division of Extramural Activities 
National Cancer Institute 
6116 Executive Boulevard, Room 8041, MSC 8329 
Rockville, MD 20852 (express service) 
Bethesda, MD  20892-8329
Telephone  (301) 496-3428
Fax:  (301) 402-0275
Email:  ncidearefof-r@mail.nih.gov

Direct inquiries regarding fiscal matters to: 
 
Ms. Priscilla Grant
Grants Administration Branch
National Cancer Institute
6120 Executive Boulevard, EPX Suite 243 
Bethesda, MD  20892-7150
Rockville, MD  20852 (for express/courier service)
Telephone:  (301)496-3160
Fax:  (301) 496-8601
Email:  cm113g@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 subsequent applications, the information that it 
contains allows NCI 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:

John A. Milner
Chief, Nutritional Science Research Group, DCP,
National Cancer Institute
Executive Plaza North
6130 Executive Blvd, EPN Suite 3164
Rockville, MD  20852

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.

USE P01/U54 Grant Guidelines and Descriptions located at 
(http://deainfo.nci.nih.gov/flash/awards.htm).

SUPPLEMENTAL INSTRUCTIONS:  A collaborating NIH Intramural Scientist (IMS) may 
not receive salary, equipment, supplies, or other remuneration from this RFA. 
The IMS must obtain approval of his/her NIH Institute Scientific Director to 
allocate resources to the project.  This letter must specify that no more than 
$300,000 direct costs of intramural resources will be allocated to the project 
and provide assurance that the conduct of the project will comply with the 
DHHS regulations for research involving human subjects (if applicable) and 
with the PHS policy of vertebrate animal research.).

Each applicant Team must provide in the application a detailed description of 
the approach to be used for obtaining patent coverage and for licensing where 
appropriate, in particular where the invention may involve investigators from 
more than one institution.  Procedures must be described for resolution of 
legal problems should they arise. Your attention is drawn to P.L. 96-517 as 
amended by P.L. 98-620 and 37 CFR Part 401.  Instructions were also published 
in the NIH Guide for Grants and Contracts (NIH Guide, Vol. 19, No. 23, June 
22, 1990).)

NCI acknowledges that some commercial collaborators that are members of 
applicant Teams, or who provide agents to applicant Teams, may require that 
Institution agree to grant to them certain intellectual property rights, as 
described by the terms above.  If Institution voluntarily agrees to the 
described terms, then they should appear in the Institution's Team 
application.  NCI recognizes that Institutions' ability to access agents from 
commercial collaborators for this effort may be limited absent such a 
voluntary agreement, or a substantially similar independent agreement between 
Institution and commercial collaborators providing agents.  However, in no 
event will the award of cooperative agreement be dependent upon the described 
terms' being part of an Institution's Team application.  Rather, Institution's 
Team application may provide Institution's own plan for accessing agents from 
commercial collaborators. 

USING THE RFA LABEL:  The RFA label available in the PHS 398 (rev. 5/01) 
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
(20817 FOR EXPRESS SERVICE)
 
At the time of submission, two additional copies and all appendix material of 
the application must also be sent to:

NCI Referral Officer 
Division of Extramural Activities 
National Cancer Institute 
6116 Executive Boulevard, Room 8041, MSC 8239 
Rockville, MD 20852 (express service) 
Bethesda, MD  20892-8329

APPLICATION PROCESSING:  Applications must be received by July 12, 2002.  If 
an application is received after that date, it will be returned to the 
applicant without review.   

The Center for Scientific Review (CSR) will not accept any application in 
response to this RFA that is essentially the same as one currently pending 
initial review, unless the applicant withdraws the pending application. The 
CSR will not accept any application that is essentially the same as one 
already reviewed. This does not preclude the submission of substantial 
revisions of applications already reviewed, but such applications must include 
an Introduction addressing the previous critique.  Applications must meet all 
eligibility requirements as described above and must address all programmatic 
requirements (see SPECIAL REQUIREMENTS above) in the RFA. 

APPLICATIONS HAND-DELIVERED BY INDIVIDUALS TO THE NATIONAL CANCER INSTITUTE 
WILL NO LONGER BE ACCEPTED.  This policy does not apply to courier deliveries 
(i.e. FEDEX, UPS, DHL, etc.) 
(http://grants.nih.gov/grants/guide/notice-files/NOT-CA-02-002.html)  
This change in practice is effective immediately.  
This policy is similar to and consistent with the policy for applications 
addressed to Centers for Scientific Review as published in the NIH Guide 
Notice http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-012.html.

PEER REVIEW PROCESS  
 
Upon receipt, applications will be reviewed for completeness by the CSR and 
responsiveness by the NCI.  

Incomplete applications will be returned to the applicant without further 
consideration.  And, if the application is not responsive to the RFA, CSR 
staff may contact the applicant to determine whether to return the application 
to the applicant or submit it for review in competition with unsolicited 
applications at the next appropriate NIH review cycle.

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 Division of Extramural Affairs (DEA) at NCI 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 Cancer Advisory Board.

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.

The factors to be considered in the evaluation of all applications are 
given below. 

A. INDIVIDUAL RESEARCH PROJECTS:

1. SIGNIFICANCE: How important are the selected 
target(s)/pathway(s)/mechanism(s)?
Are the selected targets considered high priority for the development of 
intervention strategies? Will development of the proposed assays, probes, and 
other tools improve the identification of individuals who might benefit from 
dietary intervention strategies?  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?  If there is a foreign component within the application has it been 
adequately justified.  How effective is the strategy for selecting assessment 
tools?  Have preclinical models been proposed in which the nutrients or 
classes of nutrients been shown to have activity? Have the investigators 
considered the appropriate negative and positive controls?  

Will the design of preclinical experiments permit conclusions that will be 
ultimately applicable to dietary intervention strategies?  Does the 
investigator identify potential limitations in currently available models and 
possible approaches to rectifying them?

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

4. INVESTIGATOR:  Does the training, experience, qualifications, 
accomplishments and availability of the proposed Investigators and evidence of 
ability, organizational structure and availability to function as a team meet 
requirements to carryout the proposed project? 

5. ENVIRONMENT: Is there evidence of prior experience with preclinical and 
clinical evaluation of nutrients and genetic pathways?  Is there an 
explanation of how the organization will provide support and expertise to this 
project and the proposed PI?  Is there prior experience of the PI/Organization 
with multi-institutional research projects, or is there a clear plan to 
organize multi-institutional research projects if they are proposed?  Does the 
preparation of the projects indicate that experts from different backgrounds 
communicated with each other in writing the grant application?

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 subjects from both genders, 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 DATA SHARING:  The adequacy of the proposed plan to share data. 

o BUDGET: The initial review group will also examine the reasonableness of the 
proposed budget and the requested period of support in relation to the 
proposed research.  The support for attendance at Planning Committee meetings 
can be provided through the Team's award as part of the travel budget.

B. CORES

1.  Qualifications, experience and commitment of key personnel in the services 
provided by the core unit, as well as their ability to devote the required 
time and effort in providing services to the Team.
2.  Appropriateness of the use of the core services by the proposed projects
3.  Adequate plans for charge back and priority management procedures for 
service/technical core units

C. DEVELOPMENTAL/PILOT PROJECTS

1.  Are the specific plans for use of developmental funds consistent with the 
Team's overall goals and priorities?  Do the Pilot Projects interact with the 
Research Projects and Cores?
2.  Does the quality of the pilot projects proposed by the Team demonstrate 
the effectiveness of the selection process?3.  Are proposed studies adequately 
considering women and minorities in the design?  
4.  Is the budget appropriate for what has been proposed for investigation?

D. OVERALL PROGRAM ORGANIZATION AND CAPABILITY:

a.  SIGNIFICANCE: Does the proposed work address an important genetic pathway 
in the cancer process?  If the aims of the application are accomplished, how 
will scientific knowledge be advanced?  What will be the effect of these 
studies on the concepts or methods that drive these types of investigations? 

b.  APPROACH: Are the conceptual framework, design, methods, and analyses 
adequately developed, well-integrated, and appropriate to the aims of the 
project?  Does the applicant acknowledge potential problem areas and consider 
alternative tactics?

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

d.  INVESTIGATORS: Are the Principal Investigator and collaborators 
appropriately trained and well suited to carry out this work?  Does the 
research experience of the PI demonstrate expertise in nutrition or cancer 
prevention?  Is the work proposed appropriate to the experience level of the 
key investigator and other researchers?  Is the Principal Investigator 
committed to devote the required time and effort to the Team?  Does the PI 
demonstrate willingness to work and collaborate with other Team Programs as 
appropriate and with NCI assistance in the manner summarized in this RFA.

e.  ENVIRONMENT: Does the scientific environment in which the work will be 
performed contribute to the probability of success?  Are resources such as 
space, equipment, preclinical models, technical and clinical capabilities 
described that are needed for the success of the research?  Do the proposed 
experiments take advantage of unique features of the scientific environment or 
employ useful collaborative arrangements? Is there evidence of institutional 
support? 

f.  In addition, the criteria for reviewing the integrated effort are:

   o  Overall strength of the Investigators in terms of the combined strength 
of the research projects, pilot projects and core units, and the significance 
of the application to the objectives of the Program outlined in this RFA;
   o  Leadership ability and scientific stature of the Principal Investigator, 
particularly, but not exclusively in the area of the proposed research, and 
his/her ability to meet the demands of time and effort;
   o  An appropriate organizational and administrative structure for effective 
attainment of the objectives that considers arrangements for internal quality 
control of ongoing research, the allocation of funds, day-to-day management, 
contractual agreements, if applicable, and internal communication among 
investigators;
   o  Demonstrated institutional commitment to the investigators and their 
objectives in terms of providing research facilities and management support. 

OVERALL EVALUATION AND SCORING OF APPLICATIONS  

The individual Research Projects will be assigned numerical priority scores 
while the Cores will be rated superior, satisfactory, or NRFC, without numeric 
scores.  The Pilot Projects will be rates as a group reflective the ability of 
investigators to select quality preliminary studies.  The Pilot studies as a 
unit will be rated superior, satisfactory or not recommended for further 
consideration (NRFC).  A single numerical priority score will then be assigned 
to the Team application as a whole after discussing all of the review elements 
listed above.  The score will be based on the overall quality of the Research 
Projects, the Developmental/ Pilot Projects, the overall effectiveness and 
adequacy of shared resources, the overall program organization and capability, 
the plans for interactions with the Team, and the potential for adding 
critical knowledge about the role of bioactive food components in modulating 
the cancer process. 

RECEIPT AND REVIEW SCHEDULE

Letter of Intent Receipt Date:    June 14, 2002
Application Receipt Date:         July 12, 2002
Peer Review:                      November, 2002
Review by NCAB:                   February, 2003
Earliest Anticipated Award Date:  April, 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

REQUIRED FEDERAL CITATIONS 

MONITORING PLAN AND DATA SAFETY AND MONITORING BOARD: Research components 
involving Phase I and II clinical trials must include provisions for 
assessment of patient eligibility and status, rigorous data management, 
quality assurance, and auditing procedures.  In addition, it is NIH policy 
that all clinical trials require data and safety monitoring, with the method 
and degree of monitoring being commensurate with the risks (NIH Policy for 
Data Safety and Monitoring, NIH Guide for Grants and Contracts, June 12, 1998: 
http://grants.nih.gov/grants/guide/notice-files/not98-084.html).

Clinical trials supported or performed by NCI require special considerations.. 
 The method and degree of monitoring should be commensurate with the degree of 
risk involved in participation and the size and complexity of the clinical 
trial.  Monitoring exists on a continuum from monitoring by the principal 
investigator/project manager or NCI program staff or a Data and Safety 
Monitoring Board (DSMB).  These monitoring activities are distinct from the 
requirement for study review and approval by an Institutional review Board 
(IRB).  For details about the Policy for the NCI for Data and Safety 
Monitoring of Clinical trials see: 
http://deainfo.nci.nih.gov/grantspolicies/datasafety.htm.  For Phase I and II 
clinical trials, investigators must submit a general description of the data 
and safety monitoring plan as part of the research application.  See NIH Guide 
Notice on "Further Guidance on a Data and Safety Monitoring for Phase I and II 
Trials" for additional information:  
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-038.html.  
Information concerning essential elements of data 
safety monitoring plans for clinical trials funded by the NCI is available:  
http://nci.nih.gov/clinicaltrials/conducting/dsm-guidelines.

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 are 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.  A 
continuing education program in the protection of human participants in 
research in now available online at:  http://cme.nci.nih.gov/.

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 PA 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. 93.3393 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 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.


Weekly TOC for this Announcement
NIH Funding Opportunities and Notices


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