NATIONAL TECHNOLOGY CENTERS FOR NETWORKS AND PATHWAYS
 
RELEASE DATE: September 30, 2003
 
RFA Number: RFA-RM-04-005  (formerly RFA-RR-04-003, see NOT-OD-04-008)
                           (see addenda NOT-RM-04-005 and NOT-RM-04-009)
						   
Department of Health and Human Services (DHHS)
 
PARTICIPATING ORGANIZATIONS:
National Institutes of Health (NIH) 
 (http://www.nih.gov)

This RFA is developed as a roadmap initiative.  All NIH Institutes and 
Centers participate in roadmap initiatives.

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBERS:  93.389 
 
LETTER OF INTENT RECEIPT DATE:  February 15, 2004
APPLICATION RECEIPT DATE:  March 16, 2004

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 OF THIS RFA 

Participating Institutes and Centers (ICs) of the National Institutes 
of Health invite applications for NIH National Technology Centers for 
Networks and Pathways (TCNP).  These centers will cooperate in a 
networked national effort to develop highly novel, integrated, and 
broadly applicable proteomics technologies, to include instrumentation, 
biophysical methods, reagents, and infrastructure.  These technologies 
will be specifically directed at the fundamental technological 
challenges inherent in acquiring quantitative information at the high 
anatomic resolution (subcellular) and biologically relevant timescales 
necessary for temporal and spatial characterization of complex 
biochemical pathways and molecular interactions.  Beyond cataloging of 
proteins and their binary interactions, these methods will be directed 
toward quantitatively defining the dynamics of complex systems.

The establishment of the TCNPs was called for in the NIH Roadmapping 
Initiative in 2003.  TCNPs will be supported by U54 awards.  The U54 
awards will principally support technological innovation.  However, in 
addition it is expected that the TCNPs will commit substantial 
resources to collaboration with and education of biomedical 
researchers, as well as the transfer of technologies to other 
laboratories.  It is anticipated that there will be strong, vibrant 
interactions between the centers themselves and related individual 
investigator projects focused on a broad range of significant 
biomedical research questions.   The centers should foster original and 
creative contributions to scientific understanding over and above that 
which would be obtained if each component of the center existed 
independently.
 
RESEARCH OBJECTIVES

Proteomics experiments have consistently been characterized as falling 
into two broad classes, either directed at defining the physical 
interactions of proteins, or concerned with characterizing changes in 
the expression of proteins corresponding to internal or external 
perturbations of cells or systems.  The methodological issue that has 
largely driven this distinction is the inherent difficulty of 
quantitation of individual molecules in complex systems.  The 
distinction is artificial, since in either instance, the goal is to 
define the roles and functions of proteins in inherently dynamic 
systems, whether considered as networks of interactions or steps in a 
biochemical pathway.  

As the results of biophysical experiments are assembled into coherent 
models of these systems, temporal, spatial, and quantitative resolution 
all become increasingly critical factors.  While substantial and rapid 
progress has been made over the past decade in the development of 
analytical technologies for proteomics, the greatest successes have 
overwhelmingly resided in the realm of tightly bound protein complexes.  
In this case, definition of protein identity and interaction are the 
two critical analytical tasks, addressed through the creative 
application of molecular and cellular biological methods, often 
followed by separation and mass spectrometry.  However, despite 
advances, current tools and reagents are still largely inadequate to 
address the larger challenges of quantitative, temporal, and spatial 
resolution of dynamic systems.

Similarly, it will be impossible to fully define dynamic biological 
systems strictly on the basis of proteomic data.  Protein interaction, 
modification, translocation and expression level will need to be 
considered in the context of gene transcription upstream and metabolic 
products downstream.  The same necessity for quantitative, temporal, 
and spatial resolution applies to these analyses.  Acquisition and 
integration of these data are significant challenges, and substantial 
difficulties remain with respect to the fundamental tasks of profiling 
and cataloging biomolecules in complex systems.  While efforts continue 
in development of these fundamental technologies, it is important that 
parallel efforts build technologies directed specifically to the 
dynamics of complex systems.  To facilitate the development of these 
technologies and build infrastructure for support of biomedical 
research, the NIH is embarking on a program to build National 
Technology Centers for Networks and Pathways.

This Request for Applications (RFA) is intended to encourage 
development of highly sensitive tools to measure the dynamics of 
quantity, activity, translocation, or interactions of molecules in 
cells.  Preference will be given to applications that have promise to 
be quantitative, capture information at timescales relevant to the 
study of pathways and networks, and that have promise to be applied at 
subcellular resolution.  It is anticipated that approaches will be 
valuable which can be scaled, facilitating capture of information about 
a comprehensive set of molecules or with the potential for broad, 
flexible application to a range of specific molecules.

These issues are deliberately discussed with respect to fundamental 
analytical challenges, rather than in relation to specific 
technologies, in order to emphasize the overriding importance of 
surmounting these obstacles, irrespective of the analytical strategy 
adopted to pursue those solutions.  This solicitation encourages 
unconventional or alternative approaches as a balanced portion of the 
overall center effort.

Regardless of the system under study or specific experimental 
approaches of proteomics, a common theme in this field is the need for 
synergy among three principal domains: (1) biological issues, including 
study design, sample collection and processing, sample complexity and 
prefractionation; (2) analytical chemistry, including the challenges of 
quantitation, maximization of separation space, and improving dynamic 
range; and (3) informatics, including data handling, statistical 
analyses, validation and curation, integration of results from multiple 
platforms used in the center, and development of improved tools for 
data analysis.  These three domains should each inform the development 
of tools and methods in their counterpart areas.  Accomplishing this 
goal in a climate of specialization demands a fundamentally 
collaborative approach.  It is anticipated that investigators will 
assemble interdisciplinary teams from multiple laboratories.  

It is not required that all participating investigators and 
laboratories be located either at a single institution or in the same 
local geographic area.  However, because of the need for integration of 
technologies at a fundamental level, it is considered critical that 
participating investigators be in a position to work closely together 
in an iterative manner.  This is seen as particularly important for 
example in the effective interfacing of analytical instrumentation.  
These issues should be addressed in detail in the application.  The 
project will be administered through the principal investigator and 
his/her institution.

The TCNPs will focus on technology development, but three features of 
the program will ensure that the technology developed can be applied to 
relevant biological problems.  First, each TCNP is encouraged to select 
a biological focus or model system that will provide a thematic focus 
or context for technology development.   Second, each TCNP will support 
a set of Driving Biological Projects (DBPs), which will provide an 
internal biological context for technology development.  Third, after 
the initial TCNPs have been funded, NIH anticipates releasing a new 
program announcement that will support additional partnerships between 
individual investigators and these centers.  These awards will leverage 
and complement the research activities of the U54 centers in building 
comprehensive technologies for molecular networks and pathways research 
focused around biological processes, cellular organelles, organs, or 
diseases.  It is anticipated that the announcements for partnering 
projects will include both new R01's and R21's as well as competitively 
reviewed supplements to existing projects.  These awards will be made 
by a variety of participating NIH ICs.

All applications in response to this announcement will be evaluated 
primarily for the potential of the proposed activities to address the 
broad challenges discussed above, where it is clear that the technology 
to be developed can be used to obtain the data required to elucidate 
and test models of a molecular network or pathway.  However, it is 
anticipated that these challenges are too broad for a single center to 
address comprehensively.  Investigators will be expected to clearly 
define the scope of their technical and biological activities.  

The funding mechanism for the TCNPs will be a U54 center.  Each TCNP 
will be required to perform or facilitate six different core functions:  
(1) conducting core research in technology development, (2) 
establishing Driving Biological Projects (DBP) to allow biomedical 
researchers to interact with and drive research in the TCNP, (3) 
providing infrastructure to biomedical researchers (hardware, software, 
and personnel as appropriate), (4) enhancing the training for 
biomedical researchers in appropriate proteomics tools and techniques, 
(5) disseminating newly developed tools, reagents, and techniques to 
the broader biomedical research community, and (6) providing formal 
project leadership and management to ensure that these large centers 
achieve their goals within the 5 to 10 year funding lifetime of the 
center.

The technological research in core 1 will be the largest component of a 
TCNP, focused on development of cutting edge technology and methods for 
proteomic characterization of networks and pathways.  

The technological R&D component consists of investigations that are at 
the cutting edge of the technological field with a goal of increasing 
its usefulness in biomedical research. A minimum of three technological 
research projects constitutes this section of the application. An 
element of high risk (high payoff) should be present in one or more of 
these projects and is appropriate for this component. Investigators 
should, however, present alternative approaches to solving 
technological problems in the event that their main conceptual thrust 
should prove unfeasible.

The technological R&D projects to be conducted must be presented in 
detail. For each project describe the background, objectives, 
rationale, methods and procedures, significance, and facilities 
available to conduct the project. If research activities involve 
support at more than one location through a consortium/contractual 
arrangement, the application should provide a separate description, 
detailed budget and budget justification for the consortium/contractual 
component(s). 

In addition to the individual technology development projects, the 
interrelationships of these technologies should be described, as well 
as plans for maximizing connectivity and synergy both in the 
technologies and between participating groups.  These discussions 
should be placed in the context of the overall strategic goals of the 
center's research program.

Development of complex, integrated approaches to formulating networks 
and pathways will require a context within which methods development 
can proceed.  Investigators should consider selection of a model system 
(such as a cellular process, an already characterized network or 
pathway where the connections are mostly known but none of the dynamic 
information), or define a thematic biological research topic that will 
serve as a framework for the technological research and development 
activities of the resource.  Investigators should propose to tackle a 
problem that is both technically challenging and relevant to biomedical 
research.  These projects should be structured to achieve their goal in 
a 5 to 10 year timeframe.

Through collaborations, infrastructure development, training, and 
dissemination, TCNPs will be expected to have a broad-based, 
significant impact on a variety of biological problems.  However, the 
most important deliverables will be the state-of-the-art technology, 
reagents and methods for proteomics research developed in Core 1.

In the context of this solicitation, technology development should be 
interpreted broadly to encompass all aspects from proof of principle of 
an innovative idea through development of practical instruments and 
systems.  It is anticipated that as innovative technology is developed, 
to the extent possible, it will be optimized and brought to bear in 
application to challenging biomedical research problems.  It will be 
considered appropriate to balance evolutionary technology development, 
the refinement and optimization of current technologies, with the more 
challenging development of revolutionary new approaches.

In core 2, an applicant will propose a minimum of 4 projects that 
address cutting edge biological questions within the thematic 
biological research topic of the Center.  The projects will involve 
collaborations with biomedical researchers who would use proteomic 
approaches under development in the TCNP.  It is not essential that the 
biomedical researchers have expertise in analytical chemistry or 
proteomics, but each DBP must have a question that will drive one or 
more specific research projects in core 1.  That linkage must be made 
explicit in the description of each DBP.  

The purpose of this core is twofold.  The selected biomedical research 
problems should provide both a driver and a test-bed for the 
technological research and development carried out in core 1.  In 
addition, interactions with these projects should serve to ensure that 
the research carried out in core 1 has direct relevance to biomedical 
research.  These collaborations will last for at most three years 
without separate funding.  It is anticipated that some DBPs will begin 
during the first year, while others may be phased in over the lifetime 
of the award.  If appropriate, the PI and collaborating researchers 
must present plans to use these DBPs as a foundation for the 
collaborators to compete for independent funding for continuation of 
the work.  Plans must also be presented to select additional DBPs in an 
ongoing manner as these are completed.  It is anticipated that 
independently funded biological projects, either pre-existing or 
matured DBPs, will form strong continuing interactions with the TCNPs  
It is expected that many of the biomedical researchers in core 2 will 
not be at the same institution as the parent TCNP.

It is anticipated that technologies proposed in applications will be at 
different stages of maturity, both among and between centers. It 
therefore may be appropriate that the proposed function of a DBP 
collaboration may be limited at least initially to helping the center 
appropriately define a specific problem.

The new tools, reagents, and methods that are being developed are 
likely to require substantial infrastructure to implement them.  Core 3 
will provide that infrastructure.  This infrastructure will be used to 
develop appropriate components and to provide the biomedical community 
with access to these components.  It is appropriate to request 
hardware, software, and associated personnel in this core.  

It is expected that demand may outstrip available resources.  Specific 
plans should be presented for the following:  ongoing selection and 
prioritization of new DBPs, other biological collaborative projects, 
and routine service work.  

The NIH's long-term goals in proteomics recognize the need to develop a 
new generation of multi-disciplinary scientists.  In core 4, each 
center should develop mechanisms for ensuring that graduate students 
and postdoctoral fellows receive broad, relevant training beyond the 
specific contributions they make to the infrastructure and research 
projects of the center.  In addition, there should be plans for 
workshops, training courses, or other mechanisms to train the larger 
biomedical research community about the new tools and techniques that 
the TCNP is developing.

The focus of core 5 is to disseminate new discoveries, reagents, 
methods and technology to the biomedical community and to participate 
in an effort to develop standards for data sharing and integration.  
Publications and a genuinely useful web site are excellent ways to 
broadcast some of the discoveries of the TCNP, but those routes may not 
be sufficient to inform biomedical investigators who require guidance 
in pursuing solutions to their questions.  Innovative plans to 
disseminate discoveries to the biomedical community should be presented 
in core 5.  It is also appropriate to discuss how hardware, analytical 
methods, or software will be made available to the community in this 
core and to justify possible restrictions.  Finally, where appropriate, 
plans to make data sets and databases available on a continuing basis 
should be presented.  The development of data standards and ontologies 
is extremely important for sharing and communicating data and 
information.  It is expected that multiple TCNPs will participate 
actively in an effort to develop standards for data sharing and 
integration.

It is essential to provide appropriate project leadership and 
management for these large centers.  In core 6 the investigator should 
describe management plans.  Investigators are strongly encouraged to 
consider proposing a project manager for the TCNP.  The investigators 
should undertake a planning process and document an action plan.  
Elements of an action plan include determining which cores will be 
established; establishing overall policies and procedures for 
management of cores and Center resources.  In addition, outcome 
measurements should be determined and include how progress on action 
plans will be measured.  In addition to a project manager, it is 
expected that the TCNP will interact with an advisory panel to the 
program, selected by investigators and program staff after awards are 
made.  This committee will meet on an at least an annual basis to 
review progress and offer advice.  Program directors will attend these 
meetings. 

Multiple institutes and centers at NIH continue to support programs to 
develop centers in proteomics.  Recipients of those awards or contracts 
are welcome to apply for the U54 centers in this announcement.  It is 
anticipated that in those cases, the U54 application may be tailored to 
complement the center's existing mission while addressing the 
additional unique features of this program.  No preference will be 
given either to recipients or non-recipients of previous proteomics 
center awards or contracts.

MECHANISM OF SUPPORT

This RFA will use the 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 September, 2004.  

This RFA uses just-in-time concepts.  It also uses the non-modular 
budgeting formats.  This program does not require cost sharing as 
defined in the current NIH Grants Policy Statement at 
http://grants.nih.gov/grants/policy/nihgps_2001/part_i_1.htm.  

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 initial period of support for a 
U54 center will be five years.  NIH may reissue this RFA and allow 
competitive renewals for a second period of up to five years.  If 
competing segments of a U54 award are shorter than five years, grantees 
may apply for more than one renewal, but no center will receive more 
than ten years total of NIH funding.  

FUNDS AVAILABLE
 
The participating ICs intend to commit approximately $7.4 million in FY 
2004 to fund 2 to 4 new centers in response to this RFA. An applicant 
should request a project period of 5 years.  The budget (direct costs) 
may not exceed $2 million 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 the ICs 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(s) if your institution has any of the 
following characteristics:

o Public or private institutions, such as universities, colleges, 
hospitals, and laboratories 
o Eligible agencies of the Federal government
o Domestic institutions/organizations
o Foreign institutions are not eligible to apply
 
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 

Applicants are encouraged to contact program staff well in advance of 
the letter of intent submission date, in order to discuss the proposed 
research program, budget, organization of the center, and its potential 
biomedical impact.  These contacts help to assure that applicants have 
a clear understanding of program policies and priorities, especially 
with respect to any special situations, such as the inclusion of 
consortia, subcontracts, etc.  It will also allow staff to assess 
responsiveness to this RFA and provide appropriate guidance as needed.

Principal investigators and key personnel as appropriate are expected 
to participate in an annual meeting in the Washington, DC area.  Funds 
for travel to the meeting should be requested in the budget.

The annual progress report for the U54 award will use the standard 2590 
form.  In addition, to the basic information in that form, the annual 
progress report for the U54 centers will be more involved.  Additional 
information in the progress report will include both the progress made 
in the center as well as the relationship between the center and the 
individual investigator awards.  Details of the U54 progress report are 
spelled out in the notice of grant award and in the Terms and 
Conditions section of this RFA.  Applications for U54 centers should 
contain appropriate personnel to collect the needed information and to 
prepare this progress report.

Because of the complexity of the TCNP, program staff from NIH will 
likely want to visit periodically to conduct an administrative site 
visit.  U54 centers should be prepared for annual visits and should 
budget appropriately (including travel for collaborators and other 
necessary costs).

The complexity of these centers necessitates a project manager(s).  U54 
centers should budget appropriately for these manager(s).  One of the 
review criteria for these centers will be the qualifications of these 
project managers as well as whether the institution has an appropriate 
career pathway for these individuals.  Because of their important role, 
it is recommended that the project manager be listed as one of the key 
personnel.

A principle underlying this program is that substantial benefits in 
technology development and biological problem solving will accrue 
through successful integration of the biological, analytical, and 
informatics domains of the center.  The application should articulate a 
specific organizational plan.  This plan should describe anticipated 
interactions between key personnel in support of the overarching goals 
of the resource.  It should also maximize synergy between the component 
technologies.  Ultimately, a successful center will function as a 
coherent whole, rather than a collection of individual technological 
capabilities.  In cases where geographically distributed collaboration 
is essential, the management plan should include provisions for 
teleconferencing or videoconferencing as appropriate.  The applicant 
may include these provisions in the budget if appropriate.

To address the joint interests of the government in the availability 
of, and access to, the results of publicly funded research, NIH 
requires applicants who respond to this RFA to propose detailed plans 
for sharing the research resources generated through the grant. It is 
expected that the resources to be shared include all materials 
developed in projects funded under the RFA. A reasonable time frame for 
release of materials should be specified in the application and will be 
considered during the review of the plan for sharing.
 
It is expected that the investigator's data and biomaterials sharing 
plan will include the access to biomaterials and methods not currently 
available to the wider scientific community.   In other words, plans 
for the development of resources for use by the biomedical community 
should have the appropriate timeliness and mileposts. For example 
software development should include plans and timeliness for alpha 
testing, beta testing, production release, interface development, bug 
reporting, integration with other codes, extension to multiple 
platforms, etc.
 
Data sharing will be as important as software sharing for many National 
Programs.  All awards made under this RFA are subject to the Final NIH 
Statement on Sharing Research Data 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html).  

The scientific review group will evaluate the adequacy of the proposed 
plan for sharing and data access. Comments on the plan and any concerns 
will be presented in an administrative note in the Summary Statement. 
The adequacy of the plan will be considered by NIH program staff and 
will be important in determining whether the grant shall be awarded. 
The sharing plan approved by program staff, after negotiation with the 
applicant when necessary, will become part of the terms and conditions 
of the award. NIH program staff will evaluate the compliance with the 
sharing plan and scientific progress in the non-competing continuation 
of the grant award application.

INTELLECTUAL PROPERTY RIGHTS 
 
NIH is interested in ensuring that the research resources developed 
through this PA become readily available to the research community.
 
With regard to patentable research results, such as genetically encoded 
reporters, cell lines, and vectors, the NIH requires applicants who 
respond to this RFA to develop a plan addressing if, or how, they will 
exercise their intellectual property rights while making available to 
the broader scientific community research resources produced in 
projects funded under this RFA. This is expected to include an 
elaboration of the applicant's anticipated plans to generate, or not 
generate, patents and/or exclusive or non-exclusive licensing of 
biomaterials and other patentable subject matter created in projects 
funded under this RFA. This plan should be consistent with the 
applicant's institution's policies on intellectual property rights. 
 
This plan is also expected to include disclosure of any pre-existing 
agreements involving intellectual property rights, including options to 
for-profit research sponsors that are associated with biomaterials and 
data that may be generated. The requirement for this plan is in 
addition to the requirement for the plan for sharing and disseminating 
research resources described in the previous section. 
 
The majority of transfers to not-for-profit entities should be 
implemented under terms no more restrictive than the Uniform Biological 
Materials Transfer Agreement (UBMTA). In particular, recipients are 
expected to use the Simple Letter Agreement provided at 
http://www.nih.gov/od/ott/RTguide_final.htm, or another document with 
no more restrictive terms, to readily transfer unpatented tools 
developed with NIH funds to other recipients for use in NIH-funded 
projects. If the materials are patented or licensed to an exclusive 
provider, other arrangements may be used, but commercialization option 
rights, royalty reach-through, or product reach-through rights back to 
the provider are inappropriate. 
 
Similarly, when for-profit entities are seeking access to NIH-funded 
tools for internal use purposes, recipients should ensure that the 
tools are transferred with the fewest encumbrances possible. The Simple 
Letter Agreement may be expanded for use in transferring tools to for-
profit entities, or simple internal use license agreements with 
execution or annual use fees may be appropriate.
 
The scientific review group will evaluate the adequacy of the proposed 
plan for handling intellectual property rights. Comments on the plan 
and any concerns will be presented in an administrative note in the 
Summary Statement. NIH program staff in determining whether the grant 
shall be awarded will consider the adequacy of the proposed plan. The 
plan as approved, after negotiation with the applicant when necessary, 
will be a condition of the award. Evaluation of non-competing 
continuation applications will include assessment of the awardee's 
adherence to the proposed plan.  
 
Applicants also are reminded that the grantee institution is required 
to disclose each subject invention to NIH within two months after the 
inventor discloses it in writing to grantee institutional personnel 
responsible for patent matters. The awarding institute reserves the 
right to monitor awardee activity in this area to ascertain if patents 
or patent applications on mutagenesis protocols, cell lines, vectors, 
or other patentable subject matter are adversely affecting the goals of 
this RFA.
 
Principles and guidelines for recipients of NIH research awards on 
obtaining and disseminating biomedical research resources can be found 
at http://www.nih.gov/od/ott/RTguide_final.htm. A reasonable time frame 
for release of materials should be specified in the application and 
will be considered during the review of the plan for sharing.
  
COOPERATIVE AGREEMENT TERMS AND CONDITIONS OF AWARD

The following Terms and Conditions will be incorporated into the award 
statement.  The following special terms of award are in addition to, 
and not in lieu of, otherwise applicable OMB administrative guidelines, 
HHS grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 
is applicable when State and local Governments are eligible to apply), 
and other HHS, PHS, and NIH grant administration policies:

1. The administrative and funding instrument used for this program will 
be the U54, an "assistance" mechanism (rather than an "acquisition" 
mechanism), in which substantial NIH scientific and/or programmatic 
involvement with the awardees is anticipated during performance of the 
activities.  Under the cooperative agreement, the NIH purpose is to 
support and/or stimulate the recipients' activities by involvement in 
and otherwise working jointly with the award recipients in a 
partnership role.  The NIH purpose 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 awardees for the project as a whole, although specific tasks and 
activities may be shared among the awardees and designated NIH Science 
Officers.

2. PI Rights and Responsibilities

The PI will coordinate project activities scientifically and 
administratively at the awardee institution.  The PI will have primary 
responsibility for defining the details for the projects within the 
guidelines of this RFA, and for performing all scientific activities.  
The PI will agree to accept the close coordination, cooperation, and 
participation of the NIH Science Officer(s), Molecular Pathways and 
Network Steering Committee (MPANSC) and Molecular Pathways and Network 
Scientific Panel (MPANSP) in those aspects of scientific and technical 
management of the project as described below.  Specifically, the PI 
will:

o  Determine experimental approaches, design protocols, direct 
experiments, and work cooperatively to set project milestones, in 
consultation with  the Molecular Pathways and Network Steering 
Committee (MPANSC).

o  Release data according to the approved plans for sharing research 
resources generated through the award, and publish results, as agreed 
upon by  the Molecular Pathways and Network Steering Committee 
(MPANSC).

o  Submit periodic progress reports in a standard format, as agreed 
upon by Molecular Pathways and Network Steering Committee (MPANSC).

o  Accept and implement the common guidelines and procedures approved 
by Molecular Pathways and Network Steering Committee (MPANSC)and 
Molecular Pathways and Network Scientific Panel (MPANSP).

o  Share with other Molecular Pathways and Network facilities research 
resources, tools, and data of interest to those facilities, as directed 
by MPANSC and MPANSP.

o  The PI and other critical staff should participate in MPANSC 
meetings  held in the metropolitan Washington, DC area at least twice 
per year.

3. NIH Program Staff Responsibilities

The NIH Science Officer(s) will have substantial scientific/ 
programmatic involvement during the conduct of this activity through 
technical assistance, advice, and coordination above and beyond normal 
program stewardship for grants.  This includes functioning as a peer 
with the PIs, facilitating the partnership relationship between NIH and 
the facilities funded under this RFA, helping to maintain the overall 
scientific balance in the program commensurate with new research and 
emerging research opportunities, and ensuring that the activities of 
the centers are consistent with the missions of the participating 
Institutes.

The role of NIH will be to facilitate and not to direct activities.  It 
is anticipated that decisions will be reached by consensus of the PIs 
and that NIH staff will be given the opportunity to offer input to this 
process as members of MPANSC. 

Specifically, the NIH Science Officer(s) will:

o  Provide relevant scientific expertise and overall knowledge.

o  Participate with other MPANSC members in the group process of 
setting research priorities and milestones, deciding optimal research 
approaches and protocol designs, and contributing to the adjustment of 
research protocols or approaches as warranted.  
  
o  Provide information about ongoing NIH-supported research and 
resource collections.
  
o  Attend MPANSC meetings as one voting member, and assist to develop 
operating guidelines, quality control procedures, and consistent 
policies for dealing with recurrent situations that require coordinated 
action.  The Science Officer(s) must be informed of all major 
interactions of members of MPANSC.  The MPANSC will be responsible for 
preparing within 30 days a concise summary of each MPANSC meeting.

o Serve as scientific liaison between the awardees and other NIH 
program staff.

o Assist in promoting the centers to the scientific community at
large.

o Assist in developing timetables for the wide distribution of 
biomaterials and data to the scientific community.

o Coordinate the activities of facilities to ensure the efficient long-
term storage and timely release of biomaterials and data to the wider 
scientific community.

o Help determine the most appropriate mechanisms for storage and 
distribution of biomaterials and data to the scientific community, 
i.e., storage and distribution by one of the facilities funded under 
this RFA and/or by another NIH-funded facility.

o Retain the option to recommend re-allocating NIH support among 
awardees, as scientific goals evolve.

o Participate in data analyses and, where warranted, co-authorship of 
papers resulting from projects funded under this RFA.

NIH Program Director

NIH will appoint a Program Director who will have responsibility for 
normal program oversight and stewardship of the award.  The Program 
Director may also serve as the designated Science Officer.  The Program 
Director will:

o Have the option to recommend withholding support to a participating 
institution if technical performance requirements are not met.

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

o Appoint the MPANSC Chair based on a recommendation from MPANSC 
committee members.

o Serve as a non-voting member of MPANSC if not also participating as a 
Science Officer.

Serve as administrative liaison to MPANSP, attending MPANSP meetings as 
a non-voting member, to help coordinate activities of facilities funded 
under this RFA other NIH molecular pathways and network initiatives.  
The Program Director(s) will also coordinate the activities of 
facilities funded under this RFA with other US and international 
efforts.

4. Collaborative Responsibilities - MPANSC Functions

MOLECULAR PATHWAYS AND NETWORK STEERING COMMITTEE (MPANSC): A committee 
that is the main governing board of all of the molecular pathways and 
network facilities funded under this RFA, and the committee through 
which the NIH interacts and collaborates with the facilities.  Voting 
membership includes the NIH Science Officers(s) (one vote total), the 
PI of each awarded cooperative agreement, and three scientists with 
relevant expertise who are not affiliated with any of the funded 
projects.

NIH will interact and collaborate with the facilities principally 
through the MPANSC.  After appointment by NIH, the Science Officer(s) 
will schedule the first meeting and set the agenda, following which the 
Chair of MPANSC will rotate among the PIs and will be responsible for 
developing meeting agendas and chairing meetings. MPANSC will meet at 
least twice per year, but may use video or teleconferencing rather than 
face-to-face meetings, at the discretion of the committee members.  
Additional MPANSC members may be added by action of MPANSC. Other NIH 
staff may attend MPANSC meetings, when their expertise is required for 
specific discussions.  

MPANSC will coordinate the activities of the centers and the exchange 
of information and biomaterials with the wider scientific community.  

MPANSC will discuss scientific progress, make recommendations regarding 
how the centers achieve their scientific goals.  MPANSP recommendations 
will be addressed by MPANSC.

5. Molecular Pathways and Networks Scientific Panel (MPANSP)

MOLECULAR PATHWAYS AND NETWORK SCIENTIFIC PANEL (MPANSP): A committee 
that is advisory to NIH. MPANSP ensures coordination among TCNP 
projects funded under this RFA and evaluates their progress in relation 
to the evolving goals for trans-NIH initiatives on proteomics, 
molecular pathways and networks.

MPANSP will use its knowledge of the activities of all of the 
participating facilities to ensure adequate investigation, 
communication and sharing, and to avoid redundant activities.  It will 
advise NIH with respect to the coordination of all activities that 
involve molecular networks and pathways.  MPANSP will evaluate and make 
recommendations regarding the coordination of the activities of the 
facilities that are funded by the molecular pathways and networks 
initiative, and other related activities such as computation and data 
management that may be developed in the future.

It will be the responsibility of MPANSP to make recommendations that 
will lead to exchanging research tools, research resources, adopting 
common policies on data sharing, creating compatible databases, and 
other activities that will make these facilities of maximal utility to 
the scientific community.  MPANSP will also recommend standards for 
data format and nomenclature, as well as develop common guidelines and 
procedures for deposition of the primary data.

The committee will consist of about 10 scientists (advisors) who are 
not affiliated with any of the molecular pathways and network centers.  
They will be appointed by NIH.  These advisors will be selected for 
their broad expertise in relevant topics.  MPANSP will meet at least 
once each year.  A schedule for subsequent meetings will be prepared at 
the first meeting.
 
NIH will select one member to be the committee chair, after considering 
MPANSP's recommendations.  The chair will schedule the first meeting, 
will be responsible for developing meeting agendas and chairing the 
meetings. Additional MPANSP members may be added by an action of the 
original MPANSP members.  The MPANSC Chair and Science Officer(s) will 
attend MPANSP as non-voting members and will act as representatives of 
MPANSC.  Other NIH staff and MPANSC members may attend MPANSP meetings, 
when their expertise is required for specific discussions.

6.  Milestones and Evaluations

The progress of the TNCPs will be reviewed annually by the NIH Program 
Director(s) and MPANSP to assure that satisfactory progress is being 
made in achieving the project objectives.  During the first year of 
funding, and during subsequent years if deemed necessary by the Program 
Director, reviews may be more frequent.  Should problems arise in the 
conduct of the study, the NIH Program Director may require that the 
awardee submit quarterly reports on progress and fiscal matters.  

The progress report will have two components.  The first will be the 
standard NIH progress report (Form 2590).  The second will be a more 
specialized report that will go to the NIH Science Officer(s) and the 
NIH Program Director. This specialized report should be included as an 
attachment to the standard progress report. The contents or the report 
may be changed according to programmatic needs, based on discussion 
between NIH program officials, the PI and MPANSC.

The awardees' yearly milestones will be provided to MPANSC and MPANSP.  
It is expected that the milestones should be adjusted annually at the 
award anniversary dates, both to incorporate a group's scientific 
accomplishments and progress in the field in general, as well as to 
reflect MPANSC and MPANSP recommendations.  Following the evaluation of 
milestones, NIH program staff may recommend augmenting any project or 
reducing or withholding funds for any project that substantially fails 
to meet its milestones or to remain state-of-the-art.

7. Arbitration Process

Any disagreements that may arise in scientific or programmatic matters 
within the scope of the award between recipients and the NIH may be 
brought to arbitration.  This special arbitration procedure in no way 
affects the awardee's right to appeal an adverse action that is 
otherwise appealable in accordance with PHS regulations 42 CFR Part 50, 
Subpart D and HHS regulation at 45 CFR Part 16.  An Arbitration Panel 
will help resolve both scientific and programmatic issues that develop 
during the course of work that restrict progress.  The Arbitration 
Panel will be composed of three members: a designee of MPANSC chosen 
without the NIH staff voting, one NIH designee, and a third designee 
with expertise in the relevant area who is chosen by the other two (in 
the case of an individual disagreement, the first member is chosen by 
the individual awardee rather than by MPANSC).

WHERE TO SEND INQUIRIES

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

o Direct your questions about scientific/research issues to:

Douglas M. Sheeley
Division of Biomedical Technology
National Center for Research Resources
6701 Democracy Boulevard, Room 968
Bethesda, MD  20892-4874
Telephone:  (301) 594-9762
FAX:  301-480-3659
Email: sheeleyd@mail.nih.gov

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

Ms. Mary Niemiec
Office of Grants Management
National Center for Research Resources
6701 Democracy Boulevard, Room 1036
Bethesda, MD  20892-4874
Telephone:  (301) 435-0842
FAX:  301-480-3777
Email: niemiecm@mail.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 including those involved with the 
Driving Biological Projects and other collaborations
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 IC staff to estimate the potential review 
workload and plan the review.

The letter of intent (and the subsequent proposal itself) should NOT 
include the names of potential members of the proposed center's 
External Advisory Committee if it chooses to form one.

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:

Douglas M. Sheeley
Division of Biomedical Technology
National Center for Research Resources
6701 Democracy Boulevard, Room 968
Bethesda, MD  20892-4874
Telephone:  (301) 594-9762
FAX:  301-480-3659
Email: sheeleyd@mail.nih.gov

SUBMITTING AN APPLICATION

Applications must be prepared using the PHS 398 research grant 
application instructions and forms (rev. 5/2001). Applications must 
have a DUN and Bradstreet (D&B) Data Universal Numbering System (DUNS) 
number as the Universal Identifier when applying for Federal grants or 
cooperative agreements. The DUNS number can be obtained by calling 
(866) 705-5711 or through the web site at 
http://www.dunandbradstreet.com/. The DUNS number should be entered on 
line 11 of the face page of the PHS 398 form. The PHS 398 document is 
available at http://grants.nih.gov/grants/funding/phs398/phs398.html in 
an interactive format.  For further assistance contact GrantsInfo, 
Telephone (301) 435-0714, Email: GrantsInfo@nih.gov.
 
SUPPLEMENTARY INSTRUCTIONS 

It is recognized that the proposals in response to this RFA will be 
longer and more complex than many other NIH proposals.  In order to 
ensure effective review, the Research plan should be divided into 
sections according to the cores defined below, and separate page limits 
should be observed for each section of up to 25 pages each. If a core 
has research projects, up to 25 pages are allowed for each research 
project in cores 1 and 2. See the RFA sections on RESEARCH OBJECTIVES 
and SPECIAL REQUIREMENTS for additional application instructions for 
the cores. 

The U54 center will be required to have six cores:  (1) conducting core 
research in technology development, (2) establishing Driving Biological 
Projects (DBP) to allow biomedical researchers to interact with and 
drive research in the TCNP, (3) providing infrastructure to biomedical 
researchers (hardware, software, and personnel as appropriate), (4) 
enhancing the training for a field of biomedical researchers in 
appropriate tools and techniques, (5) disseminating newly developed 
tools and techniques to the broader biomedical research community, and 
(6) providing formal project leadership and management to ensure that 
these large National Programs achieve their goals within the 5 to 10 
year funding lifetime of the center.  

Form Pages 4-5: The budget should be completed as described in the 
instruction sheet for Application for a Public Health Service Grant 
(Form PHS 398).  Form page 4 (the detailed budget) should be provided 
for each of cores 1,2,4,5,6,and 7.  Form page 4 should be provided for 
each of the DBPs (core 3).  A separate total budget for the entire 
center should also be prepared using form page 4.

The budget justification beginning on PHS Form Page 5 should include a 
detailed justification for key personnel. As part of the justification, 
the percent effort that all staff are spending on each core should be 
specified.  For example, a particular postdoctoral fellow might spend 
75% effort on core 1 and 25% effort on one of the DBP in core 2.

A detailed justification should also be supplied for equipment over 
$25,000 requested for the TCNP.  Details of the physical location for 
this equipment should be provided.  Existing equipment should also be 
described.

Form page 4 (the detailed budget) should be provided for any sub-
contractual or consortium arrangements.  A detailed budget 
justification should also be provided for such arrangements.  Use 
continuation pages as needed. 

Section 9, Research Plan D:  Each of the six cores should be described.  
It will be best if the applicant uses separate headings for each of 
these cores.  Cores 1 and 2 should be broken into appropriate 
subheadings.
 
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/labels.pdf.
 
SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten 
original of the application, including the Checklist, and five 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)
 
APPLICATION PROCESSING: Applications must be received on or before the 
application receipt date listed in the heading of this RFA.  If an 
application is received after that date, it will be returned to the 
applicant without review. 

Although there is no immediate acknowledgement of the receipt of an 
application, applicants are generally notified of the review and 
funding assignment within 8 weeks.
 
The Center for Scientific Review (CSR) will not accept any application 
in response to this RFA that is essentially the same as one currently 
pending initial review, unless the applicant withdraws the pending 
application.  However, when a previously unfunded application, 
originally submitted as an investigator-initiated application, is to be 
submitted in response to an RFA, it is to be prepared as a NEW 
application.  That is, the application for the RFA must not include an 
Introduction describing the changes and improvements made, and the text 
must not be marked to indicate the changes from the previous unfunded 
version of the application.  

PEER REVIEW PROCESS  
 
Upon receipt, applications will be reviewed for completeness by the CSR 
and responsiveness by the ICs. Incomplete and/or unresponsive 
applications will not be reviewed.  

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 NIH in accordance with the review criteria 
stated below.  As part of the initial merit review, all applications 
will:

o Undergo a process in which only those applications deemed to have the 
highest scientific merit, generally the top half of the applications 
under review, will be discussed and assigned a priority score
o Receive a written critique
o Receive a second level review by an appropriate National Advisory 
Council or 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 evaluate the 
application in order to judge the likelihood that the proposed research 
will have a substantial impact on the pursuit of these goals. The 
scientific review group will address and consider each of the following 
criteria in assigning the application's overall score, weighting them 
as appropriate for each application. 

o Significance 
o Approach 
o Innovation
o Investigator
o Environment

The 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, an investigator may propose to carry out 
important work that by its nature is not innovative but is essential to 
move a field forward.

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

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?

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?

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

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

ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, the 
following items will be considered in the determination of scientific 
merit and the priority score:

Some of the cores for the TCNPs have specific additional review 
criteria.
 
CORE 1:  This solicitation seeks to build a program in which a 
significant fraction of the effort is aimed at developing highly novel 
technologies that have the potential to provide quantitative 
information at high anatomic resolution (subcellular) and biologically 
relevant timescales needed to elucidate the function of molecular 
pathways and networks. This RFA therefore encourages the inclusion of 
the more challenging development of revolutionary new approaches as a 
component of the application. The degree of novelty of this component 
or components, and its potential impact, will be an important review 
criterion.

CORE 2:  Do the investigators have appropriate plans to obtain support 
for the DBPs after their support from the TCNP has terminated? 

CORES 1-2: Will the work proposed in these cores help establish an 
integrated approach to characterization of pathways and networks?  Is 
the proposed work essential to establishing this approach?

CORE 3:  Are the infrastructure requests adequate to meet the demands 
that are likely to come from biomedical researchers?

CORES 4 and 5:  Will the proposed training and dissemination tools help 
create a new group of multi-disciplinary or interdisciplinary 
investigators?

CORE 6:  The reviewers will be asked to address the proposed management 
of the project.  Will the proposed management structure allow the TCNP 
to achieve its goals?  Does the institution have an appropriate career 
path for the project manager?  Is the mechanism to terminate old DBPs 
and choose new ones adequate?  Will the plans to incorporate individual 
investigator awards work?

Reviewers will be instructed to consider all six components of the 
project as important, even if a particular component is only a 
relatively small part of the budget.  For example outreach and 
training, while not as costly as the core development of the 
technologies, is considered to be critically important for the TCNP to 
have the appropriate impact on biomedical research.    

SOFTWARE AVAILABILITY:  Does the plan for distributing the software 
reasonable allow wide and easy access?  Are any fee structures 
appropriate?  

PROTECTION OF HUMAN SUBJECTS FROM RESEARCH RISK: The involvement of 
human subjects and protections from research risk relating to their 
participation in the proposed research will be assessed. (See criteria 
included in the section on Federal Citations, below).
 
INCLUSION OF WOMEN, MINORITIES AND CHILDREN IN RESEARCH: 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 in the 
sections on Federal Citations, below).

CARE AND USE OF VERTEBRATE ANIMALS IN RESEARCH: If vertebrate animals 
are to be used in the project, the five items described under Section f 
of the PHS 398 research grant application instructions (rev. 5/2001) 
will be assessed.  

ADDITIONAL REVIEW CONSIDERATIONS

Sharing Research Data

Applicants requesting more than $500,000 in direct costs in any year of 
the proposed research must include a data-sharing plan in their 
application. The reasonableness of the data sharing plan or the 
rationale for not sharing research data will be assessed by the 
reviewers. However, reviewers will not factor the proposed data-sharing 
plan into the determination of scientific merit or priority score.

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:  February 15, 2004
Application Receipt Date:  March 16, 2004
Peer Review Date:  June 2004
Council Review:  September 2004
Earliest Anticipated Start Date:  September 2004

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 

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

DATA AND SAFETY MONITORING PLAN:  Data and safety monitoring is 
required for all types of clinical trials, including physiologic, 
toxicity, and dose-finding studies (phase I); efficacy studies (phase 
II); efficacy, effectiveness and comparative trials (phase III).  The 
establishment of data and safety monitoring boards (DSMBs) is required 
for multi-site clinical trials involving interventions that entail 
potential risk to the participants.   (NIH Policy for Data and Safety 
Monitoring, NIH Guide for Grants and Contracts, June 12, 1998: 
http://grants.nih.gov/grants/guide/notice-files/not98-084.html).  

INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH: It is the 
policy of the NIH that women and members of minority groups and their 
sub-populations must be included in all NIH-supported clinical research 
projects unless a clear and compelling justification is provided 
indicating that inclusion is inappropriate with respect to the health 
of the subjects or the purpose of the research. This policy results 
from the NIH Revitalization Act of 1993 (Section 492B of Public Law 
103-43).

All investigators proposing clinical research should read the "NIH 
Guidelines for Inclusion of Women and Minorities as Subjects in 
Clinical Research - Amended, October, 2001," published in the NIH Guide 
for Grants and Contracts on October 9, 2001 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a 
complete copy of the updated Guidelines 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 
applications 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 applications for 
research involving human subjects.  You will find this policy 
announcement in the NIH Guide for Grants and Contracts Announcement, 
dated June 5, 2000, at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

HUMAN EMBRYONIC STEM CELLS (hESC):  Criteria for federal funding of 
research on hESCs can be found at http://stemcells.nih.gov/index.asp 
and at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html.
Only research using hESC lines that are registered in the 
NIH Human Embryonic Stem Cell Registry will be eligible for Federal 
funding (see http://escr.nih.gov).   It is the responsibility of the 
applicant to provide, in the project description and elsewhere in the 
application as appropriate 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.

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

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

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

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

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

The PHS strongly encourages all grant recipients to provide a smoke-
free workplace and discourage the use of all tobacco products.  In 
addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits 
smoking in certain facilities (or in some cases, any portion of a 
facility) in which regular or routine education, library, day care, 
health care, or early childhood development services are provided to 
children.  This is consistent with the PHS mission to protect and 
advance the physical and mental health of the American people.


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