THE SALIVARY PROTEOME: CATALOGUE OF SALIVARY SECRETORY COMPONENTS

RELEASE DATE:  August 1, 2003
 
RFA Number:  RFA-DE-04-007
 
National Institute of Dental and Craniofacial Research (NIDCR)
 (http://www.nidcr.nih.gov)

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER:  93.121  
 
LETTER OF INTENT RECEIPT DATE: December 20, 2003

APPLICATION RECEIPT DATE: January 20, 2004 
 
THIS RFA CONTAINS THE FOLLOWING INFORMATION

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

PURPOSE OF THIS RFA

The National Institute of Dental and Craniofacial Research (NIDCR) 
invites Cooperative Agreement Applications (U01) for outstanding 
multidisciplinary research, aimed at generation of a complete catalogue 
of all salivary secretory components using state of the art, sensitive 
and high-throughput proteomics technologies. These methodologies should 
include two-dimensional gel electrophoresis for profiling complex 
mixtures; protein arrays; yeast two-hybrid systems; phage display; 
antibodies, DNA, RNA, or other molecules as bait for analysis of 
salivary secretory protein complexes for analysis by TOF MS/MS, MALDI-
TOF, ESI-MS/MS. In addition, computational and novel biocomputing 
methods should be utilized for maintenance and provision of a stable, 
comprehensive, fully classified, and accurately annotated protein 
sequence knowledgebase. 

The identification and cataloging of the salivary secretory components 
and their complexes is likely to be design-directed rather than 
hypothesis-driven research.  Therefore, rather than presenting a 
hypothesis and an experimental plan to test it, applicants should 
address: i) the technologies that will allow the identification and 
cataloguing of the parotid, submandibular and sublingual secretory 
components; ii) the program plan that includes the overall plan, with a 
timetable, for accomplishing and coordinating robust operation and high 
quality data; and iii) the anticipated barriers and approaches for 
overcoming them.

RESEARCH OBJECTIVES

Secretions from the major salivary glands (parotid, submandibular and 
sublingual) contain a number of glycoproteins, peptides and non-
glycosylated proteins that contribute to the important roles that 
saliva plays in maintaining the health of the oral cavity and of the 
whole body. To date, through traditional biochemical approaches 
studying individual genes and proteins, salivary researchers have made 
impressive progress on the elucidation of the structure and functions 
of some of the major salivary secretory components. For example, the 
structure and function of the genes and proteins of high molecular 
weight glycoproteins such as mucins, low molecular weight proline rich 
proteins, histatins, amylase and antimicrobial secretory proteins, have 
been determined. Mucins act as lubricates and as protectors of the oral 
mucosa. Proline rich proteins are stabilizers of the calcium phosphate 
equilibrium in saliva and have been shown to help in the re-
mineralization of tooth enamel. Histatins are responsible for 
preventing the sporulation of Candida albicans while lysozyme, 
lactoferrin, saliva peroxidase and secretory immunoglobulins confer the 
immune and non-immune functions of saliva.  However, there is a need 
for the systematic study of all salivary secretory components and their 
complexes, with the aims of identifying and cataloguing them, and 
providing detailed descriptions of their structure and function.  
Proteomics is essential for a comprehensive approach for cataloging all 
salivary secretory components and, if possible, creating the "periodic 
table" of the salivary proteome that will help elucidate disease 
pathogenesis and evaluate the influence of medications on the 
structure, composition and secretion of all salivary secretory 
constituents.    

The field of proteomics has garnered renewed interest, with advances in 
mass spectrometry allowing the analysis of ever-diminishing quantities 
of proteins, and the refinement of identification software is providing 
the means to match these data with translations predicted from 
nucleotide sequence data (originating from the genome projects).  To 
date much of the effort in contemporary proteomics is directed toward 
the development of suitable platforms (chips) in order to interrogate 
each component in a complex mixture prior to its being resolved by mass 
spectrometry. The complex chemical nature of high molecular weight 
glycoproteins, hydrophobic peptides and proteins, the diversity of 
binding interactions, and the variety of conditions for optimum 
binding, make the development of protein-based arrays more challenging 
than that of gene chips. Each element of a chip for protein profiling 
should be functionalized with a capture agent to interrogate its 
interacting partner(s) in a complex protein mixture. Capture agents can 
be specific, such as natural or phage display antibodies, protein–
protein interaction partners or protein binding ligands. The arrays 
must be robust, and linkage to the chip surface should neither mask the 
recognition site(s) nor significantly alter binding parameters, such as 
the dissociation constant (on-rate and off-rate), and specificity of 
the interaction. 

The generation and analysis of proteome data are becoming increasingly 
widespread, as the field of proteomics is moving incrementally toward 
high-throughput approaches. Techniques are also increasing in 
complexity as the relevant technologies evolve. Thus there is a need 
for a systematic approach to modeling, capturing, and disseminating 
proteomics experimental data. The creation, maintenance and provision 
of a stable, comprehensive, fully classified, richly and accurately 
annotated protein sequence knowledgebase, with extensive cross-
references and querying interfaces of structural and functional 
proteomics projects are important in order to understand the genetic 
and biological mechanisms causing human disease.
 
Scope:

This RFA will support the range of activities required to assemble the 
salivary proteome, that is, the first comprehensive list of all 
salivary secretory components and their complexes. It is envisioned 
that these studies will help create the "periodic table" of the 
parotid, submandibular and sublingual secretory components. The 
information will be invaluable in: i) developing an artificial salivary 
gland that secretes the necessary glycoproteins, peptides and proteins; 
ii) launching functional studies of the salivary secretory components; 
and iii) complementing the NIDCR's Program on Salivary-Based Diagnostic 
Technologies; particularly the validation of the developed diagnostic 
technologies.

Applicants should address most if not all of the following topics, 
though additional methods complementing these topics are highly 
encouraged: 

o use of state-of-the-art methods coupled to mass spectrometry to 
analyze salivary secretory protein complexes and to identify and 
catalogue all proteins, peptides and glycoproteins and their complexes 
present in parotid, submandibular and sublingual secretions;

o utilization of specific protein-binding ligands, nucleic acid 
aptamers, polypeptides, oligonucleotides, polysaccharides and 
phospholipids, or even less specific chemistries such as reverse-phase 
media or functional chemical groups to enrich for low abundance 
proteins or to reduce the complexity of the salivary mixture prior to 
mass spectrometry; and

o development of computer programs and algorithms for data entry, 
storage, acquisition and input of data sets as well as development of 
informatics tools and resources to share and analyze the collected 
data.

Accomplishing these activities will require the participation of 
multidisciplinary teams that will include biologists, chemists, 
technology developers, engineers and computer scientists.

MECHANISM OF SUPPORT

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 will use the NIH cooperative agreement (U01) 
award mechanism. The NIH U01 is a cooperative agreement award mechanism 
in which the Principal Investigator retains the primary responsibility 
and dominant role for planning, directing, and executing the proposed 
project, with NIH staff being substantially involved as a partner with 
the Principal Investigator, as described under the section "Cooperative 
Agreement Terms and Conditions of Award".  This RFA uses just-in-time 
concepts and the non-modular budgeting formats.  Follow the 
instructions for non-modular research grant applications. 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 NIDCR intends to commit approximately $3 million in FY 04 to fund 
two new grants in response to this RFA. An applicant may request a 
project period of up to 4 years and a budget for direct costs of up to 
$1 million per year. Although the financial plans of the NIDCR 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
o Faith-based or community-based 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

In order to ensure maximum progress in the identification and 
cataloguing of all parotid, submandibular and sublingual components, 
several special activities will be required of the funded 
investigators. The Principal Investigators (PIs) are expected to 
present a cost-effective plan to recruit and apply the appropriate 
expertise needed to meet the project goals.  The research plan must 
describe how effective communication between the various components 
will be established and maintained, the information flow by which input 
from various perspectives will be gathered and used to implement the 
research plan, and how decisions will be made on resource deployment. 
Principal Investigators will be expected to attend Steering Committee 
meetings (see below) and participate in conference calls on a regular 
basis.  Budget requests should include funds to support travel of the 
PI and one other investigator to attend the scheduled Steering 
Committee meetings.

Restricted availability of unique research resources, upon which 
further studies are dependent, can impede the advancement of research 
and delivery of health care.  Thus, the NIH is interested in ensuring 
that the information about new methods, technologies, and computer 
software that is developed through this program becomes readily 
available to the research community for further research and 
development, with the expectation that this will eventually lead to 
information and products that improve the health of the public. For 
this reason, applicants should develop and propose specific plans for 
sharing the data, materials, and software generated through the grant.  
These plans should be consistent with the policies of their 
institutional offices of technology transfer.  NIH has developed 
guidance on developing such policies; information is available at:  
(http://www.ott.nih.gov/policy/rt_guide_final.html).

The scientific review group will evaluate the adequacy of the proposed 
plans for sharing data. 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 NIDCR program staff and will 
be important in determining whether a grant shall be awarded. The 
sharing 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 
effectiveness and timeliness of research resource release.

Applicants are reminded that the grantee institution is required to 
disclose each invention to NIH within two months after the inventor 
discloses it in writing to grantee institutional personnel responsible 
for patent matters. 

COOPERATIVE AGREEMENT TERMS AND CONDITIONS OF AWARD 

These special Terms of Award are in addition to and not in lieu of 
otherwise applicable OMB administrative guidelines, PHS regulations at 
42 CFR Part 52 and DHHS grant administration regulations at 45 CFR 
Parts 74 and 92, as applicable, and other DHHS, PHS, and NIH Grant 
Administration policy statements. 

As stated above, the administrative and funding instrument used for 
this program is a cooperative agreement (U01), an "assistance" 
mechanism (rather than an "acquisition" mechanism) in which substantial 
NIH scientific and/or programmatic involvement with the awardee is 
anticipated during performance of the activities. Under the cooperative 
agreement, NIDCR's purpose is to work with the PI as a partner to 
assist and stimulate planning and implementation.  NIDCR will not 
assume primary direction, responsibility, or a dominant operating role 
in the research.   The primary role and total responsibility for this 
program resides with each Principal Investigator. The NIDCR, as noted 
below, will share specific tasks and activities in completing the 
agreement. 

1. Awardee Rights and Responsibilities

o The PI will have primary authority and responsibility to define 
objectives and approaches and to plan, conduct, analyze, and publish 
results, interpretations, and conclusions of studies conducted under 
the terms and conditions of the cooperative agreement award.  In 
addition, the PI agrees to follow the common protocols developed by the 
Steering Committee.

o The PI will assume responsibility and accountability to the awardee 
organization officials and to the NIDCR for the performance and proper 
conduct of the research supported by the project in accordance with the 
terms and conditions of the award.

o The PI will serve as a voting member of the Steering Committee, will 
attend the Planning Meeting and two Steering Committee meetings in the 
first year, and one Steering Committee meeting a year in subsequent 
years.

o The PI will be responsible for sharing standardized information on 
new developments and/or methods for solving obstacles with the 
investigators funded through this initiative and with the NIDCR staff.  

o The PI will be responsible for implementing the plan for sharing 
data, materials and software resulting from this grant.  
 
o The PI will establish an Internal Advisory Committee to provide 
scientific and administrative oversight.  The Internal Advisory 
Committee will be composed of the lead institute personnel and other 
technical or research personnel.  The committee is expected to meet at 
least twice a year. Minutes of these meetings will be made available to 
NIDCR staff upon request. 

o Awardees will retain custody of, and have primary rights to, the data 
developed under these awards, subject to Government rights of access 
consistent with current DHHS and NIH policies. 

o Upon completion of the project, the PI is expected to put all study 
design materials and procedure manuals into the public domain and/or 
make them available to other investigators, according to the approved 
plan for making data and materials available to the scientific 
community and the NIDCR, for the conduct of research at no charge other 
than the costs of reproduction and distribution.

2. NIDCR Staff Responsibilities 
 
The dominant role and prime responsibility for the project as a whole 
resides with the awardees although specific tasks and activities in 
carrying out the studies will be shared by awardees and the NIDCR. The 
Institute will designate a Program Scientist who will have substantial 
scientific-programmatic involvement above and beyond normal program 
stewardship during contact of this activity. 

o The NIDCR Program Scientist will be a voting member of the Steering 
Committee and its subcommittees. 

o The NIDCR will designate a Program Director and a Grants Management 
Specialist to provide administrative oversight of the cooperative 
agreement.

o The NIDCR Program Scientist will be responsible for using the 
information of the Steering committee to coordinate and facilitate the 
research activities for the creation of the salivary proteome, and 
attend and participate in all meetings of the Steering Committee.   

o The NIDCR Program Scientist will help the Steering Committee develop 
and draft operating policies and policies addressing recurring 
situations that require coordinated action.

o The NIDCR Program Director will review the scientific progress of the 
individual grants for compliance with operating policies developed by 
the Steering Committee, and may recommend to the NIDCR to withhold 
support, suspend, or terminate an award for lack of scientific progress 
or failure to adhere to policies established by the Steering Committee. 

o The NIDCR reserves the right to require the transfer of appropriate 
reagents, tools and pertinent data that are generated as the result of 
participation in research supported under these awards to an eligible 
third party, in order to advance the research. Collaborators supported 
under these awards must be informed of this right.

o Support or other involvement of industry or any other collaborators 
in any study performed by the awardees may be advantageous and 
appropriate.  However, except for licensing of patents or copyrights, 
support or involvement of any third party will occur only following 
notification to, and concurrence by the NIDCR.

3. Collaborative Responsibilities (Steering Committee)

o The NIDCR Program Scientist and PIs of the projects funded under this 
RFA will be responsible for forming a Steering Committee as defined 
below.  The Steering Committee will act as the main governing board 
that will review the progress of the research activities, develop 
collaborative protocols, identify technological impediments to the 
progress, select strategies to surmount them, and identify 
opportunities for sharing techniques and tools developed within each 
individual project.  The Steering Committee will advise NIDCR Program 
Staff of scientific developments and opportunities that may enhance the 
achievement of the program.  

o The Steering Committee will be composed of the PI from each project 
funded through RFA DE-04-007, and the NIDCR Program Scientist. The PI 
from each project will have one vote and the NIDCR Program Scientist 
will have one vote. 

o The Steering Committee may, as it deems necessary, invite additional, 
non-voting scientific advisors to meetings at which research priorities 
and opportunities are discussed. 

o There will be two meetings of the Steering Committee in the first 
year and one meeting per year in the following years. The first meeting 
of the PIs funded under this RFA will be a Planning Meeting in the 
Bethesda, MD area soon after grants are awarded. At the planning 
Meeting the Steering Committee will be formed and select a chairperson.  
At the first Steering Committee meeting the members may: (a) draft a 
charter to detail policies and procedures and develop a process for 
monitoring compliance with the policies and procedures and for 
recommending that the NIDCR Program Director act on evidence of non-
compliance with Steering Committee policies; (b) agree upon the terms 
of the charter; and (c) discuss the approaches that were proposed in 
the project applications and any relevant new information, and set 
initial priorities for the projects to be pursued.

4. Arbitration
 
Any disagreement that may arise on scientific and programmatic matters 
within the scope of the cooperative agreement and between award 
recipients and NIDCR may be brought to arbitration.  An arbitration 
panel will be composed of three members: one selected by the Principal 
Investigator; a second member selected by NIDCR; and, the third member 
selected by the two prior selected members.  This special arbitration 
procedure in no way affects the awardee's right to appeal an adverse 
action that is subject to appeal in accordance with PHS regulations at 
42 CFR Part 50, Subpart D, and DHHS regulations at 45 CFR Part 16.
 
WHERE TO SEND INQUIRIES

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

o Direct your questions about scientific/research issues to:

Eleni Kousvelari, DDS, D.Sc.
Chief, Cellular & Molecular Biology, Physiology 
& Biotechnology Branch
Division of Basic and Translational Sciences
National Institute of Dental and Craniofacial Research
Natcher Building, Room 4AN 12K
Bethesda, MD  20892-6402
Telephone:  (301) 594-2427
FAX:  (301) 480-8318
Email:  kousvelari@de45.nidr.nih.gov

o Direct your questions about peer review issues to:

H. George Hausch, Ph.D.
Division of Extramural Activities
National Institute of Dental and Craniofacial Research
National Institutes of Health
Natcher Bldg. 45, Room 4AN-44F 
Bethesda, MD 20892-6402
Telephone: (301) 594-2904 
FAX: (301) 480-8303 
Email: George.Hausch@nih.gov 

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

Mary Daley, Chief
Grants Management Branch, 
Division of Extramural Activities
National Institute of Dental and Craniofacial Research
National Institutes of Health
Natcher Bldg. 45, Room 4AN-44B
Bethesda, MD  20892
Telephone: (301) 594-4808
FAX: (301) 480-3562
Email: daleym@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 
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 NIDCR 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 (December 20, 2003).  The letter of intent should be 
sent to:

Eleni Kousvelari, DDS, D.Sc.
Chief, Cellular & Molecular Biology, Physiology 
& Biotechnology Branch
Division of Basic and Translational Sciences
National Institute of Dental and Craniofacial Research
Natcher Building, Room 4AN 12K
Bethesda, MD  20892-6402
Telephone:  (301) 594-2427
FAX:  (301) 480-8318
Email:  kousvelari@de45.nidr.nih.gov

SUBMITTING AN APPLICATION

Applications must be prepared using the PHS 398 research grant 
application instructions and forms (rev. 5/2001).  The PHS 398 is 
available at http://grants.nih.gov/grants/funding/phs398/phs398.html in 
an interactive format.  For further assistance contact GrantsInfo, 
Telephone (301) 435-0714, Email: GrantsInfo@nih.gov.

SUPPLEMENTAL INSTRUCTIONS 

The form PHS 398 should be modified as follows: Biographical Sketches  
should be included for all personnel. Page limitations for the Research 
Plan have been increased to a maximum of 40 pages from the usual 25 
page limit for the "Research Plan" of an application. This 40 page 
limit is an absolute maximum.  However, applicants are encouraged to be 
concise and use fewer pages.  

Applicants should divide the "Research Plan" into the following 
sections: 

o Description of the proteomics and biocomputational technologies;

o Description of the design aspects/plans that will be completed during 
the period of the award;

o Description of how the technologies will contribute to automated, low 
cost, more efficient, and rapid identification and cataloguing of all 
salivary secretory components; 

In the sections listed above, the roles and expertise of all key 
personnel, collaborators, and consultants who are associated with this 
part of the application should be well documented. Applicants must 
provide methods to maintain records, establish, standardize, and 
distribute protocols and provide for quality control and budgetary 
oversight. Applicants also should include the description of the 
internal advisory board consisting of the Principal Investigator and 
other key personnel that will oversee the daily operation of the 
activities. Applicants should state their willingness to collaborate 
and share data freely with the other investigators supported by this 
RFA and the wider research community. Applicants should discuss their 
willingness to serve on the Steering Committee and should state their 
willingness to follow the common protocols that will be developed by 
the Committee.  Applicants should also describe how they would comply 
with the involvement of NIDCR Program Scientists to work together 
cooperatively.

Applicants who have additional funds to support ('leverage') the 
proposed project should indicate the source of funds (institutional, 
NIH grant number, etc.) that permit them to accomplish the project 
goals. 

Applicants must budget for travel and per diem expenses for 
participation in the Steering Committee meetings, workshops, and 
symposia. Applicants should budget for at least one meeting in the 
Bethesda, MD area each year.

USING THE RFA LABEL: The RFA label available in the PHS 398 (rev. 
5/2001) application form must be affixed to the bottom of the face page 
of the application.  Type the RFA number on the label.  Failure to use 
this label could result in delayed processing of the application such 
that it may not reach the review committee in time for review.  In 
addition, the RFA title and number must be typed on line 2 of the face 
page of the application form and the YES box must be marked. The RFA 
label is also available at: 
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf.
 
SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten 
original of the application, including the Checklist, and three signed, 
photocopies, in one package to:
 
Center For Scientific Review
National Institutes Of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD  20892-7710
Bethesda, MD  20817 (for express/courier service)
 
At the time of submission, two additional copies of the application 
must be sent to:
H. George Hausch, Ph.D.
Division of Extramural Activities 
National Institute of Dental and Craniofacial Research 
National Institutes of Health 
Natcher Bldg. 45, Room 4AN-44F, 
MSC 6402 
Bethesda, MD 20892-6402 

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.  While the investigator may 
still benefit from the previous review, the RFA application is not to 
state explicitly how.

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

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

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

o Significance 
o Approach 
o Innovation
o Investigator
o Environment

The scientific review group will address and consider each of these 
criteria in assigning the application's overall score, weighting them 
as appropriate for each application.  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?  

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 CONSIDERATIONS 

DATA SHARING: 
The scientific review group will evaluate the adequacy of the proposed 
plans for sharing data. Comments on the plan 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 will be evaluated in relation to the proposed research.  

RECEIPT AND REVIEW SCHEDULE

Letter of Intent Receipt Date:  December 20, 2003
Application Receipt Date:  January 20, 2004
Peer Review Date:  April 2004
Council Review:  August 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 

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.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN 
SUBJECTS:  The NIH maintains a policy that children (i.e., individuals 
under the age of 21) must be included in all human subjects research, 
conducted or supported by the NIH, unless there are scientific and 
ethical reasons not to include them. This policy applies to all initial 
(Type 1) applications submitted for receipt dates after October 1, 
1998.

All investigators proposing research involving human subjects should 
read the "NIH Policy and Guidelines" on the inclusion of children as 
participants in research involving human subjects that is available at 
http://grants.nih.gov/grants/funding/children/children.htm

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

PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT: 
The Office of Management and Budget (OMB) Circular A-110 has been 
revised to provide public access to research data through the Freedom 
of Information Act (FOIA) under some circumstances.  Data that are (1) 
first produced in a project that is supported in whole or in part with 
Federal funds and (2) cited publicly and officially by a Federal agency 
in support of an action that has the force and effect of law (i.e., a 
regulation) may be accessed through FOIA.  It is important for 
applicants to understand the basic scope of this amendment.  NIH has 
provided guidance at 
http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.

Applicants may wish to place data collected under this RFA in a public 
archive, which can provide protections for the data and manage the 
distribution for an indefinite period of time.  If so, the application 
should include a description of the archiving plan in the study design 
and include information about this in the budget justification section 
of the application. In addition, applicants should think about how to 
structure informed consent statements and other human subjects 
procedures given the potential for wider use of data collected under 
this award.

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

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

AUTHORITY AND REGULATIONS: This program is described in the Catalog of 
Federal Domestic Assistance Nos. 93.121 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 administered under NIH grants 
policies described at http://grants.nih.gov/grants/policy/policy.htm 
and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. 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

	Office of Extramural Research (OER)			National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892			Department of Health and Human Services (HHS)
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