PROTEOMICS IN AGING AND AGE-RELATED DISORDERS 
 
RELEASE DATE:  October 07, 2003
 
RFA Number:  RFA-AG-04-006

Department of Health and Human Services (DHHS)
 
PARTICIPATING ORGANIZATIONS:
National Institutes of Health (NIH)
 (http://www.nih.gov)

COMPONENTS OF PARTICIPATING ORGANIZATIONS:
National Institute on Aging (NIA)
 (http://www.nia.nih.gov)

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S): 93.866 
 
LETTER OF INTENT RECEIPT DATE:  January 23, 2004
APPLICATION RECEIPT DATE:  February 23, 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 Supplementary Instructions
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations

PURPOSE OF THIS RFA 

The National Institute on Aging (NIA) is soliciting applications that 
use proteomic approaches to study age-related changes in protein 
structure and function.  Proteomics research is expected to provide 
significant insights into the cellular and molecular mechanisms of 
aging and age-associated disease processes.  This Request for 
Applications (RFA) encourages projects that advance research to 
identify and quantitate protein expression patterns, post-translational 
modification of proteins, and protein-protein interactions which may 
change in cells or tissues as a direct result of the aging process or 
age-related pathology.  Research projects that take advantage of 
various animal models of aging and of age-related human disease, and 
that focus on cells or tissues of aging physiological systems, such as 
the cardiovascular, musculoskeletal, immune, endocrine and nervous 
systems, are encouraged.
 
RESEARCH OBJECTIVES

Background

The deciphering of whole genomes, both human and other species, allows 
for the identification of the entire complement of genes in a given 
species.  However the genome is only the blueprint for the construction 
of cells and tissues, while the work of a cell is carried out primarily 
by proteins and other macromolecules.  Proteomics is the study of the 
entire complement of proteins expressed in tissues, cells, and 
subcellular organelles, and their functional activities.  Proteomics 
can build upon and extend large, genomic-scale gene expression studies 
by the global analysis of proteins using recently developed high 
throughput technologies.  For example, protein microarrays have been 
used to analyze the activities of thousands of proteins and to examine 
protein interactions on a large scale in yeast.  With the continued 
development of high throughput proteomics technology, dissection of the 
intricate mechanisms of cellular control, including protein stability, 
post-translational modifications such as phosphorylation, and the 
formation/dissociation of multi-protein complexes (subcellular 
machines), which may change with age, disease, and environmental 
conditions becomes a possibility. The purpose of this RFA is to utilize 
these emergent technologies to advance our understanding of the 
molecular mechanisms involved in aging and age-specific disease.

Protein expression is a basic component of any proteomics endeavor 
related to aging. Analysis of the effect of aging on protein expression 
levels in subcellular organelles like mitochondria, in single or groups 
of cells, or in a tissue sample would provide key information about the 
cellular processes that occur during aging. Similar proteomics analysis 
of changes in protein expression in animal models of longevity or age-
related neurodegenerative disorders would be informative about the 
underlying mechanisms contributing to the maintenance or decline of 
cell, tissue and organ function in normal or pathological aging. 
Ongoing advances in protein profiling methods for fixed tissue sections 
and in increasing the sensitivity and quantitation of low abundance 
proteins at the single cell level would be useful in the proteomic 
analysis of aging cells and tissues.  Progress in genomics and 
microarray technologies have led to the concept that, while individual 
molecules might not be adequate markers for complex traits such as 
aging or age-related disease, panels of markers consisting of a defined 
subset of the molecules might serve as valuable predictors of these 
traits. In this context, changes in the proteome of different tissues 
or body fluids promises the possibility of identifying aging and age-
related disease biomarkers.

Of particular relevance to aging are protein modifications.  Commonly 
observed changes in proteins with aging include: 1) Undesirable post-
translational modifications, such as oxidation, glycation, aggregation, 
and changes in protein folding and degradation rates; and 2) Decreased 
ability to induce desirable modifications in response to external 
stimuli, as exemplified by decreased phosphorylation rate of signal 
transduction molecules. Proteomics presents a powerful way to identify 
the constellation of protein modifications leading to studies on the 
cellular mechanisms responsible for the changes.  For example, protein 
oxidation in aging is an active area of research, and a global profile 
of oxidized proteins in cells or tissues should provide greater insight 
into the relevance of oxidative modification of proteins to aging or 
disease (e.g., Alzheimer's disease) processes, and into the action of 
"age-retarding" (e.g., dietary restriction) manipulations.  Subsequent 
studies might then explore the extent of oxidative modification of 
specific proteins and its effect on protein activity.   Research on 
other kinds of protein modifications and the biological significance of 
such modifications in aging and age-related disease is needed.

Proteins typically are not present in isolation in cells, but rather 
interact with other proteins in a signaling pathway or as part of 
multi-protein complexes.  Cellular receptors are often multi-protein 
complexes, the function of which requires the stable or transient 
interaction of membrane and intracellular proteins alike to form 
signaling complexes.  Age-dependent subtle disruption of these 
interactions could have dramatic effects on cellular and tissue 
function and responsiveness to the external milieu.  Isolation of 
protein complexes followed by mass spectrometry analysis has been and 
will continue to be a powerful method for describing networks of 
protein interactions and for unraveling the mechanisms of protein-
protein interactions in response to stimuli and as a function of age 
and disease.  Protein microarrays could be used for a proteome-wide 
analysis of protein activities and interactions as has been done in 
yeast.  The challenge is to move the protein chip technology from the 
proteome of a simple organism to that of a more complex one.

Protein structural or conformational changes brought about by oxidative 
or other modifications may also lead to abnormal (and often 
pathological) protein aggregation, which contributes to several well-
known age-related pathologies, such as Alzheimer's disease or inclusion 
body myositis.  Damaged, mutated or misfolded proteins are targeted for 
degradation by the ubiquitin-proteasome system or by lysosomes.  Little 
is known about the composition and activity of the proteasome or 
molecular chaperones in aging or diseased cells and tissues.  
Proteomics research could provide further insights into the molecular 
mechanisms regulating protein aggregation and degradation in aging and 
how changes in these processes contribute to age-related disease.  For 
example, proteomics approaches could be used to identify protein co-
factors that modulate protein misfolding, to characterize the 
composition and dynamics of protein aggregates, and to characterize 
protein ubiquitination and other modifications involved in protein 
degradation which may change in cells or tissues as a result of the 
aging process.

The Neuroscience and Neuropsychology of Aging Program and the Biology 
of Aging Program at the NIA encourage applications that use proteomics 
approaches to identify physiologically relevant changes in the proteome 
during aging or in the development of age-related disorders.  Such an 
effort should help in furthering our understanding of both the 
molecular mechanisms behind these changes, and the physiological 
repercussions on the health of the individual. Such a global proteomic 
analysis is expected to provide significant insights into the cellular 
and molecular mechanisms of normal and pathological aging.  The Biology 
of Aging Program supports research on tissue culture models, on lower 
organisms that serve as models of aging, and on most tissues and organs 
of the body outside of the nervous system, including the 
cardiovascular, musculoskeletal, endocrine, and immune systems.  The 
Neuroscience and Neuropsychology of Aging Program supports research on 
the nervous system, including basic neurobiology, motor and sensory 
systems, integrative neurobiology, cognition and the dementias of 
aging, particularly Alzheimer's disease.

Objectives and Scope

The main objective of this RFA is to identify patterns of protein 
change in critical systems that dictate the loss of function of cells 
and tissues as a function of age and in age-related diseases.  Use of, 
or modest enhancements to, existing techniques and validation of 
alternative available methods are encouraged.  Age-related studies that 
use animal models or human tissue are of interest.  However, clinical 
studies in humans, beyond collection of body fluids, tissues, or cells 
for in vitro analysis, are outside the scope of this RFA.  Research 
proposals that focus on individual proteins (as opposed to full or 
partial proteome studies) also will not be considered responsive to 
this RFA. The examples below illustrate the types of research and 
experimental approaches that are of special interest, but these are 
only examples, and should not be considered as an exclusive list.

o Analysis of global patterns of protein abundances and their changes 
during normal and pathological aging in various tissues, cells, or 
subcellular compartments.

o Proteomic analysis of age-related changes in critical cellular 
pathways that form the basis for age-related changes in cell or tissue 
function. 

o Detection and quantification of patterns of post-translational 
protein modifications as a function of aging.

o Proteomic approaches for analyzing protein aggregation and 
degradation during aging and their association with age-related 
disorders.

o Proteomics-based analysis of age-related changes in protein-protein 
interactions and in the structure and function of multi-protein 
complexes.

o Molecular imaging techniques to study age-related protein 
modification, localization, and interactions in cells or tissues.

o Studies on the biological relevance and function of changes in 
protein quantity, modification and interactions in aging and age-
specific disease, e.g., studies that directly link changes in the 
proteome with changes in organ function or animal behavior during 
aging.

MECHANISM OF SUPPORT

This RFA will use NIH research project grant (R01) and 
exploratory/developmental research grant (R21) award mechanisms.  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 30, 2004.  Applications that 
are not funded in the competition described in this RFA may be 
resubmitted as NEW investigator-initiated applications using the 
standard receipt dates for NEW applications described in the 
instructions to the PHS 398 application.

The R21 mechanism (see 
http://grants.nih.gov/grants/guide/pa-files/PA-03-107.html) is intended 
to encourage exploratory and developmental research projects by providing 
support for the early and conceptual stages of these projects. For example, 
such projects could assess the feasibility of a novel area of investigation 
or a new experimental system that has the potential to enhance health-related 
research.  Another example could include the unique and innovative use of an 
existing methodology to explore a new scientific area.  Applications 
for R21 awards should describe projects distinct from those supported 
through the traditional R01 mechanism.  For example, long-term 
projects, or projects designed to increase knowledge in a well-
established area will not be considered for R21 awards.  Applications 
submitted under this mechanism should be exploratory and novel.  These 
studies should break new ground or extend previous discoveries toward 
new directions or applications.

This RFA uses just-in-time concepts.  It also uses the modular 
budgeting format. (see 
http://grants.nih.gov/grants/funding/modular/modular.htm).   
Specifically, if you are submitting an application with direct costs in 
each year of $250,000 or less, use the modular budget format.  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.  

FUNDS AVAILABLE
 
The NIA intends to commit approximately $1.5 million in FY 2004 to fund 
5 to 7 new grants in response to this RFA. An applicant may request a 
project period of up to 5 years and a budget for direct costs of up to 
$250,000 per year under the R01 mechanism.  For an R21 grant 
application, an applicant may request a project period of up to two 
years and a combined budget for direct costs of up to $275,000 for the 
two year period, with no more than $200,000 being requested in any 
single year.  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 NIA 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 For-profit or non-profit organizations 
o Public or private institutions, such as universities, colleges,             
hospitals, and laboratories 
o Units of State and local governments
o Eligible agencies of the Federal government  
o Domestic or foreign institutions/organizations

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

Sharing of Unique Research Resources and Data: Restricted availability 
of unique research resources, upon which further studies are dependent, 
can impede the advancement of research. The NIH is interested in 
ensuring that particular research resources developed through grants 
become readily available to the broader research community in a timely 
manner for further research, development, and application, in the 
expectation that this will lead to products and knowledge of benefit to 
the public health.

Data sharing promotes many goals of the NIH research endeavor. It is 
particularly important for unique data that cannot be readily 
replicated. Data sharing allows scientists to expedite the translation 
of research results into knowledge, products, and procedures to improve 
human health.  The NIH endorses the sharing of final research data to 
serve these and other important scientific goals, and expects and 
supports the timely release and sharing of final research data from 
NIH–supported studies for use by other researchers. Data should be made 
as widely and freely available as possible while safeguarding the 
privacy of participants, and protecting confidential and proprietary 
data. 

To address this interest in assuring that research data and resources 
are accessible NIH normally requires that applicants seeking $500,000 
or more in direct costs in any single year submit a plan for data 
sharing.  However, this RFA requires a data sharing plan for all 
applications for both the R01 and R21 mechanisms.  NIA requires 
applicants who respond to this RFA to submit a plan (1) for sharing 
final research data generated through the grant or state why data 
sharing is not possible, (2) for sharing research resources generated 
through the grant, and (3) for exercising intellectual property rights, 
should any be generated through this grant, while making such research 
resources available to the broader scientific community.
 
The data sharing plan should conform to NIH Data Sharing Policy in 
accordance with the Final NIH Statement on Sharing Research Data 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html).  
Guidance on NIH data sharing policy and implementation, including FAQs, 
is available at: http://grants.nih.gov/grants/policy/data_sharing/.

The sharing of research resources plan and intellectual property plan 
must make unique research resources readily available for research 
purposes to qualified individuals within the scientific community in 
accordance with the NIH Grants Policy Statement 
(http://grants.nih.gov/grants/policy/nihgps_2001/) and the Principles 
and Guidelines for Recipients of NIH Research Grants and Contracts on 
Obtaining and Disseminating Biomedical Research Resources 
(http://www.ott.nih.gov/policy/rt_guide_final.html or
http://ott.od.nih.gov/NewPages/64FR72090.pdf).
  
Applicants are encouraged to discuss the plans with their Institutional 
Official and office of technology transfer prior to submission of the 
application.  The applicant organization signature on the application 
indicates the agreement of the organization with the plan in the 
application.

Annual Meeting of Investigators: It is the intent of the NIA to provide 
support for proteomics research by promoting collaboration and sharing 
of information among investigators on projects of interest to the NIA.  
Principal Investigators (PI) on grants resulting from this RFA must 
participate in annual meetings convened by the NIA to facilitate 
scientific interactions and information exchange among investigators 
and NIA program staff.  Travel to this annual meeting, expected to be 
in Bethesda, MD, should be included in the budget request in the 
application. 

WHERE TO SEND INQUIRIES

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

o Direct your questions about scientific/research issues regarding 
projects focused on the nervous system to:

Bradley C. Wise, Ph.D
Neuroscience and Neuropsychology of Aging Program
National Institute on Aging
7201 Wisconsin Avenue, Suite 350 MSC 9205
Bethesda, MD  20892-9205
Telephone:  (301) 496-9350
FAX: (301) 496-1494
Email:  wiseb@nia.nih.gov

o Direct your questions about scientific/research issues regarding 
projects focused on non-neural tissues to:

Felipe Sierra, Ph.D.
Biology of Aging Program
National Institute on Aging
7201 Wisconsin Avenue, Suite 2C231 MSC 9205
Bethesda, MD  20892-9205
Telephone:  (301) 496-6402
FAX: (301) 402-0010
Email:  sierraf@nia.nih.gov

o Direct your questions about peer review issues to:

Mary Nekola, Ph.D.
Chief, Scientific Review Office
National Institute on Aging
7201 Wisconsin Avenue, Suite 2C212 MSC 9205
Bethesda, MD  20892-9205
Telephone:  (301) 496-9666
FAX: (301) 402-0066
Email: nekolam@nia.nih.gov

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

Jeff Ball
Grants and Contracts Management Office
National Institute on Aging
7201 Wisconsin Avenue, Suite 2N212 MSC 9205
Bethesda, MD  20892
Telephone:  (301) 496-1472
FAX:  (301) 402-3672
Email:  ballj@nia.nih.gov
 
LETTER OF INTENT
 
Prospective applicants are asked to submit a letter of intent that 
includes the following information:

o Descriptive title of the proposed research
o Name, address, and telephone number of the Principal Investigator
o Names of other key personnel 
o Participating institutions
o Number and title of this RFA

Although a letter of intent is not required, is not binding, and does 
not enter into the review of a subsequent application, the information 
that it contains allows IC 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:

Dr. Mary Nekola
Chief, Scientific Review Office
National Institute on Aging
7201 Wisconsin Avenue, Suite 2C212 MSC 9205
Bethesda, MD  20892
Telephone:  (301) 496-9666 
FAX: (301) 402-0066
Email: nekolam@nia.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: All instructions for the PHS 398 (rev. 
5/2001) must be followed, with these exceptions:

o Research Plan

For R21 applications only, items a - d of the Research Plan (Specific 
Aims, Background and Significance, Preliminary Studies, and Research 
Design and Methods) may not exceed a total of 15 pages.  No preliminary 
data is required for R21 proposals but may be included if it is 
available.  Please note that a Progress Report is not needed for R21 
awards; competing continuation applications for an 
exploratory/developmental grant will not be accepted.

Appendix. Use the instructions for the appendix detailed in the PHS 398 
except that for R21 applications no more than 5 manuscripts, previously 
accepted for publication, may be included.

SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS:  Applications 
requesting up to $250,000 per year in direct costs must be submitted in 
a modular grant format.  The modular grant format simplifies the 
preparation of the budget in these applications by limiting the level 
of budgetary detail.  Applicants request direct costs in $25,000 
modules.  Section C of the research grant application instructions for 
the PHS 398 (rev. 5/2001) at 
http://grants.nih.gov/grants/funding/phs398/phs398.html includes step-
by-step guidance for preparing modular grants.  Additional information 
on modular grants is available at 
http://grants.nih.gov/grants/funding/modular/modular.htm.

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 three signed, 
photocopies, in one package to:
 
Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD  20892-7710
Bethesda, MD  20817 (for express/courier service)
 
At the time of submission, two additional copies of the application and 
all copies of the appendix material must be sent to:

Dr. Mary Nekola
Chief, Scientific Review Office
National Institute on Aging
7201 Wisconsin Avenue, Suite 2C212 MSC 9205
Bethesda, MD  20892-9205
 
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 NIA. Incomplete applications will not be 
reviewed.

If the application is not responsive to the RFA, NIH 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 NIA in accordance with the review criteria 
stated below.  As part of the initial merit review, all applications 
will:

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

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 AND MINORITIES IN RESEARCH: The adequacy of plans to 
include subjects from both genders, and all racial and ethnic groups 
(and subgroups), 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 and Resources: Reviewers will comment, as 
appropriate, on the adequacy and feasibility of the sharing of research 
resources and intellectual property plans.  The reasonableness of the 
data sharing plan or the rationale for not sharing research data also 
will be assessed by the reviewers.  However, reviewers will not factor 
the proposed research resources and data sharing plans into the 
determination of scientific merit or priority score.  Comments on the 
plans and any concerns will be presented in an administrative note in 
the Summary Statement.
 
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: January 23, 2004
Application Receipt Date: February 23, 2004
Peer Review Date: June 2004
Council Review: August 2004
Earliest Anticipated Start Date: September 1, 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 

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

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

All investigators proposing clinical research should read the "NIH 
Guidelines for Inclusion of Women and Minorities as Subjects in 
Clinical Research - Amended, October, 2001," published in the NIH Guide 
for Grants and Contracts on October 9, 2001 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a 
complete copy of the updated Guidelines 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.

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

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

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.


Weekly TOC for this Announcement
NIH Funding Opportunities and Notices


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