DEVELOPMENT OF TECHNOLOGIES FOR SALIVA/ORAL FLUID BASED DIAGNOSTICS

Release Date:  January 2, 2002

RFA:  RFA-DE-02-002

National Institute of Dental and Craniofacial Research
 (http://www.nidr.nih.gov/)

Letter of Intent Receipt Dates:  March 11, 2002
Application Receipt Dates:       April 11, 2002
 
PURPOSE
        
The National Institute of Dental and Craniofacial Research (NIDCR) 
invites Cooperative Agreement Applications (U01) for outstanding 
multidisciplinary research aimed at the development of new 
technologies, for which proof-of-principle exists, or for the 
advancement of existing technologies for simultaneous multi-analyte 
detection in saliva and other oral fluids. The focus of such diagnostic 
technologies will primarily be in the areas in which saliva or other 
oral fluid based diagnostics can have a major impact: i) oral 
diagnostics (e.g., periodontal diseases, dental caries and oral 
cancers), ii) systemic disease diagnosis (e.g., autoimmune diseases, 
cardiovascular disease and cancers), iii) drug monitoring, (e.g., drug 
compliance, pharmacokinetics and pharmacogenomics) and iv) 
identification of potentially lethal agents (e.g., anthrax bacillus or 
chemical agents) dispersed by bioterrorists.  

Because of the nature of the research required to stimulate the 
development and transition of current diagnostic technologies (e.g., 
miniaturized analytical systems, microfluidics, microsensors) for the 
detection of saliva/oral fluid derived markers, it is expected that 
potential applicants will include investigators with expertise in 
technology development, chemistry, engineering, physics, biology, 
bioinformatics and clinical sciences. 

The development of saliva/oral fluid based diagnostic technology 
projects 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 design 
goals (a detailed statement of what the development of the 
device/method will accomplish), ii) the design tasks (description of 
the status of the device/method prior to funding and additional design 
aspects that will be completed during the funding period), iii) the 
program plan (includes the overall plan, with a timetable, for 
accomplishing and coordinating design, fabrication, and testing, 
achieving robust operation and high quality data), and iv) the 
anticipated barriers and approaches for overcoming them. 

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 Request for 
Application (RFA), "Development of  Technologies for Saliva/Oral Fluid 
Based Diagnostics" is related to one or more of the NIDCR priority 
areas.  Potential applicants may obtain a copy of "Healthy People 2010" 
at:  http://www.health.gov/healthypeople/.

ELIGIBILITY REQUIREMENTS

Applications may be submitted from domestic institutions, for-profit 
and non-profit organizations, public and private, such as universities, 
colleges, hospitals, laboratories, units of State and local 
governments, and eligible agencies of the Federal government, and 
faith-based organizations. Racial/ethnic minority individuals, women, 
and persons with disabilities are encouraged to apply as Principal 
Investigators. Applications from foreign institutions will not be 
accepted. However, subcontracts to foreign institutions will be 
considered.

All current policies and requirements that govern the research grant 
programs of the National Institutes of Health (NIH) will apply to 
grants awarded under this RFA.  

MECHANISM OF SUPPORT

This RFA will use the NIH cooperative research (U01) award mechanism of 
support, 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 
activity.  Under the cooperative agreement, the NIH purpose is to 
support and stimulate the recipients" activity by involvement in the 
activity and otherwise working jointly with the award recipients in a 
partner role, but it is not to assume direction, prime responsibility, 
or a dominant role in the activity.  Details of the responsibilities, 
relationships and governance of the study to be funded under 
cooperative agreements are discussed below under "TERMS AND CONDITIONS 
OF AWARD."

The total requested project period for an application submitted in 
response to this RFA may not exceed 4 years.  This is a one-time 
solicitation. At this time, the NIDCR has not determined whether or how 
this solicitation will be continued beyond the present RFA. 

The maximum dollar request is limited to $1.00 million in total costs 
for the initial budget period and $4.2 million in total costs for the 
entire project period. The anticipated award date is September 30, 
2002.

FUNDS AVAILABLE

For Fiscal Year 2002, $3.00 million in total costs will be committed to 
fund applications submitted in response to this RFA. It is anticipated 
that 2-3 awards will be made.  Proposed funding levels are subject to 
change due to budgetary, administrative and/or scientific 
considerations, and are dependent upon the receipt of a sufficient 
number of applications of high scientific merit. Although this program 
is provided for in the financial plans of the NIDCR, the award of 
grants pursuant to this RFA is also contingent upon the availability of 
funds for this purpose.
RESEARCH OBJECTIVES

Background

The composition of saliva and of other oral fluids reflects tissue 
fluid levels of therapeutic, hormonal, immunological or toxicological 
molecules, as well as the presence of markers for infectious and 
neoplastic diseases. These fluids provide sources for assessment and 
monitoring of systemic health and disease states and exposure to 
environmental, occupational, or abusive substances as well as to agents 
dispersed by bioterrorists. 

Proof-of-principle has been established regarding the use of saliva and 
other oral fluids to monitor a number of systemic diseases and 
conditions as well as substance abuse. The analysis of these fluids, 
therefore, has great diagnostic potential in a variety of clinical 
situations.  Oral fluid based diagnostics may, in many instances, prove 
more accurate and less expensive, than current methodologies. Moreover, 
they are non-invasive.

Although oral fluids, particularly saliva, have been used for the 
diagnosis of some diseases, progress has not met expectations. In 1993 
a conference supported by the NIDCR was held to explore the 
possibilities for maximizing the utility of saliva as a diagnostic 
medium. The conference report stated that the development of new 
technologies with increased sensitivity and accuracy would undoubtedly 
increase the use of saliva in diagnostics. To date, remarkable 
technological advances are promising to revolutionize the field of 
diagnostics as we now know it.  Techniques that are emerging from a 
combination of miniaturization technologies and discoveries in many 
different fields of biology, chemistry, physics and engineering are 
expected to lead to high throughput, automated, portable, low cost, 
more efficient, and rapid biochemical analyses.  Miniaturization of 
diagnostic technologies will be able, with minute amounts of body 
fluids, to yield critical patient information reflecting health and 
disease status. Scientists predict that pocket-sized analyzers ("lab-
on-a-chip") that can perform multiple operations in parallel in non-
laboratory settings such as battlefields, airports, factories, 
hospitals, clinics or homes will be developed. Current technologies 
provide a basis for these kinds of tests/devices that will allow the 
simultaneous assessment of multiple analytes in health and disease and 
will provide clinicians with new prevention and therapeutic strategies. 

The NIDCR, realizing the potential of new technologies and advanced 
instrumentation in the development of saliva and other oral fluid-based 
diagnostics sponsored a workshop on "Development of New Technologies 
for Saliva and Other Oral Fluid Based Diagnostics" on September 12-14, 
1999. The purpose of this workshop was to capitalize on recent and 
future developments in this field.  More than 100 individuals from 
university and industry with expertise in salivary and oral biology, 
instrumentation, engineering and clinical sciences participated. Their 
charge was to develop a set of recommendations to help the NIDCR create 
a research program in the area of oral fluid based diagnostics. 
Briefly, these experts recommended a need to: 

1. Establish new interdisciplinary/collaborative programs combining 
dental, medical, biological, chemical and engineering sciences to 
create innovative technologies such as microfluidics, recognition 
chemistry, and computer engineering for oral fluid based 
diagnostics,  
2. Foster academic-industry partnerships and broaden interactions with 
government laboratories,  
3. Increase emphasis on training of a new cadre of individuals with 
expertise that can facilitate collaborations among disciplines 
(single or multi-institution based) to train graduate students, 
postdoctoral fellows, and clinical fellows. 

The summary of the recommendations of the workshop participants has 
been published on the NIDCR"s home page 
http://www.nidr.nih.gov/about/strat-plan/Biomat_Biomet_Tiss_Eng.PDF.

SCOPE 

To be eligible for support under this program, a technology must have 
been developed to the stage that proof-of-principle has been 
demonstrated. To warrant the investment that will be needed to 
accomplish the requested goals, the technologies involved must be able 
to contribute to automated, low cost, more efficient, and rapid 
analyses for simultaneous multi-analyte detection. This program will 
support the range of activities required to drive the development and 
transition of current diagnostic technologies (e.g., miniaturized 
analytical systems, microfluidics, microsensors) for the detection of 
saliva/oral fluid derived markers. Included are the development of 
technologies and fabrication of devices for simultaneous multi-analyte 
detection in saliva or other oral fluids that will allow assessment of 
multiple conditions regarding diagnosis, prognosis, pharmacokinetics, 
prediction of adverse pharmacological interactions and identification 
of potentially lethal agents dispersed by bioterrorists. This may 
involve: 

1. Design and fabrication of high density sensor technology for 
the collection, detection, and discrimination of closely 
related molecules or conditions, 
2. Studies on the improvement of detection systems, ( e.g., 
development of  more sensitive assays and rare event 
monitoring techniques),  
3. Development of laboratory or home based diagnostic systems to 
evaluate individual patients or populations at risk, 
4. Use of new, highly sensitive technologies to improve the 
sensitivity to proteomic and genomic material in saliva, and
5. development of computer programs and algorithms for 
acquisition and input of dissimilar sets of data, and for data 
entry, storage and analysis. 

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

The NIDCR anticipates that projects supported by this RFA may not 
result directly in a commercial-grade product.  However, a plan for 
technology dissemination would strengthen the application.  NIDCR will 
not provide the substantial amount of funding that will likely be 
required to support the commercialization. Since such additional 
investment is likely to come from the private sector and because of the 
important expertise available in the private sector to accomplish the 
tasks required of such projects, its participation in projects is 
encouraged, although not required.

SPECIAL REQUIREMENTS

In order to ensure maximum progress in the projects funded by this 
initiative and to realize the maximum potential of saliva as a 
diagnostic and monitoring fluid, several special activities will be 
required of the funded investigators. The Principal Investigators are 
expected to present a cost-effective plan to recruit and apply the 
appropriate expertise needed to meet project goals and to shift 
resources as requirements change. For example, substantial engineering 
capacity may be required early in the project, but not later, while 
device testing may be modest initially, but escalate later. 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 the 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. 

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 DHHHS, 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 activity. 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 two Steering Committee meetings a year in subsequent 
years.

o The PI will be responsible for sharing with the investigators funded 
through this initiative and with the NIDCR staff: i) standardized 
saliva and/or oral fluid samples and specific markers, ii) information 
on new developments and/or methods for solving obstacles in 
instrumentation design and development, and iii) knowledge on 
regulatory issues related to the development and review by the Food and 
Drug Administration (FDA) of the new diagnostic technologies.
 
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 monthly. Minutes of these meetings will be made available to 
NIDCR staff upon request. The Internal Advisory Committee is charged 
with both prioritizing projects and periodically reviewing the 
different activities to ensure that the objectives outlined in the 
application are being met.

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 HHS 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 during conduct of this activity. 
Alternatively, the Program Director responsible for normal stewardship 
may function as a Program Scientist.  

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

o The NIDCR Program Scientist will be responsible for making additional 
links among the engineering and instrumentation developers and the oral 
biology scientist, use the information of the Steering committee to 
coordinate and facilitate the research activities for the saliva/oral 
fluid based diagnostic technologies, and attend and participate in all 
meetings of the Steering Committee.   

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

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

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 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 of prototype detection systems to "real-time" diagnostic 
systems using saliva as a diagnostic medium, 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-02-002, 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 annually, both 
in the Bethesda, MD area, at times agreed upon by the Steering 
Committee and the NIDCR.

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 from among the members who represent the awardees. At the 
Planning Meeting the Steering Committee 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 HHS regulations at 45 CFR Part 16.

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS

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

All investigators proposing clinical research should read the AMENDMENT 
"NIH Guidelines for Inclusion of Women and Minorities as Subjects in 
Clinical Research - Amended, October, 2001," published in the NIH Guide 
for Grants and Contracts on October 9, 2001 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html), 
a complete copy of the updated Guidelines are available at 
http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.  
The amended policy incorporates: the use of an NIH 
definition of clinical research, updated racial and ethnic categories 
in compliance with the new OMB standards, clarification of language 
governing NIH-defined Phase III clinical trials consistent with the new 
PHS Form 398, and updated roles and responsibilities of NIH staff and 
the extramural community.  The policy continues to require for all NIH-
defined Phase III clinical trials that: a) all applications or 
proposals and/or protocols must provide a description of plans to 
conduct analyses, as appropriate, to address differences by sex/gender 
and/or racial/ethnic groups, including subgroups if applicable, and b) 
investigators must report annual accrual and progress in conducting 
analyses, as appropriate, by sex/gender and/or racial/ethnic 
group differences.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of NIH 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 was published in 
the NIH Guide for Grants and Contracts, March 6, 1998, and is available 
at the following URL address:  
http://grants.nih.gov/grants/guide/notice-files/not98-024.html.

Investigators also may obtain copies of these policies from the program 
staff listed under INQUIRIES.  Program staff may also provide 
additional relevant information concerning the policy.

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.  This policy announcement is found 
in the NIH Guide for Grants and Contracts Announcement dated June 5, 
2000, at the following website: 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.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.  Reviewers are cautioned that 
their anonymity may be compromised when they directly access an 
Internet site. 

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.

LETTER OF INTENT

Prospective applicants are asked to submit a letter of intent that 
includes a descriptive title of the proposed research, the name, 
address, and telephone number of the Principal Investigator, names of 
other key personnel and, if applicable, participating institutions, as 
well as the number and title of this RFA. Although a letter of intent 
is not required, is not binding, and does not enter into the review of 
subsequent applications, the information that it contains allows NIDCR 
staff to estimate the potential review workload and plan the review.

The letter of intent is to 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 18A
Bethesda, MD  20892-6402
Telephone:  (301) 594-2427
FAX:  (301) 480-8318
Email:  kousvelari@de45.nidr.nih.gov

APPLICATION PROCEDURES/SPECIAL INSTRUCTIONS

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.

However, the form PHS 398 should be modified as follows. Biosketches 
and "Other Support" pages should be included for all personnel. Page 
limitations 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.  Budget pages, budget justifications, 
material transfer agreements, and letters from collaborators and 
consultants and their biosketches are not included in this page limit.

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

o Description of the diagnostic area (autoimmune disease, periodontal 
disease, identification of lethal agents, oral cancers etc.), for which 
such a prototype will be developed,

o Description of the existing technology of which proof-of-principle 
exists (status of the device/method prior to funding),

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

o Description of how the technologies to be developed will contribute 
to automated, low cost, more efficient, and rapid simultaneous 
biochemical analysis for multi-analyte detection. 

In the last three 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.

BUDGET INSTRUCTIONS  

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. Subcontract budgets should be a separate page, and the 
subcontract indirect costs should be calculated and listed in the usual 
place as part of the total costs of the budget. 

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

The RFA label should be affixed to the bottom of the face page of the 
application with the RFA number typed on the label. The RFA label is 
available in the PHS 398 (rev. 5/2001) application form.  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.

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 to CSR, two additional copies of the 
application must be sent to:

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

Applications must be received no later than April 11, 2002.  If an 
application is received after that date, it will be returned to the 
applicant without review.

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

REVIEW CONSIDERATIONS

General Considerations

Applicants are encouraged to submit and describe their specific 
concepts concerning the most appropriate means of accomplishing the 
goals of the cooperative study.  Applications are expected to address 
issues identified under "SPECIAL REQUIREMENTS", "TERMS AND CONDITIONS 
OF AWARD" and "SPECIAL INSTRUCTIONS". All applications will be judged 
on the basis of the scientific merit of the proposed project and the 
documented ability of the investigators to meet the RESEARCH OBJECTIVES 
of the RFA. Although the technical merit of the proposed protocol is 
important, it will not be the sole criterion for evaluation of a study. 
Other factors considered to be important for review include 
demonstrated expertise in technology development, a multi-disciplinary 
team of collaborators, substantial interactions among collaborating 
researchers, demonstration of appropriate facilities and resources, 
willingness to share data and reagents freely. 

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. 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 
receive a written critique and 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, assigned 
a priority score, and receive a second level review by the National 
Dental and Craniofacial Research Advisory Council.

Review Criteria

To ensure that the applications for this Program are evaluated 
appropriately, the standard NIH review criteria have been adapted to be 
more appropriate for proposals that are design- rather than hypothesis-
driven.  The score should reflect the overall impact that the award 
would have on the accomplishment of NIDCR"s goals, based on 
consideration of the following five criteria.  Each of these criteria 
will be addressed and considered in assigning the overall score, 
weighting them as appropriate for each application.  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 the goals of 
this research program.

(1)  Significance:  Does this proposal address an important problem?  
If the aims of the application are achieved, will the new technology 
result in efficient and cost-effective accomplishment of diagnostic 
technologies based on saliva and/or other oral fluids?

(2)  Approach:   Is the proposed approach likely to yield the desired 
results? Has proof-of-principle of the underlying technology been 
achieved? Are the advantages of the proposed technology over competing 
technologies clearly articulated?  Are the design principles clearly 
articulated and likely to be achieved?  Does the applicant acknowledge 
potential problem areas and consider alternative tactics? Are plans in 
place to monitor and document the quality of the products?  Are plans 
clearly in evidence and appropriate for establishing and maintaining 
effective partnership between technology developers and experienced 
users?  Is the project timely and likely to remain at the state-of-the-
art level throughout the period of requested support?  Are plans for 
information dissemination and technology transfer adequate?

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

(4)  Investigator:  Are the experiences of the PI and team members 
appropriate to the tasks and well balanced, and is there evidence of 
firm commitment to the project from each of the key parties of the 
collaboration?  Is the PI capable of coordinating and managing the 
proposed project?  Is there evidence of interdisciplinary/ 
multidisciplinary collaborations? Is there evidence that the team 
members can work together effectively?  Do the PI and team members have 
a track record of developing useful technology?

(5)  Environment:  Does the scientific and technological 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?

In addition to the above criteria, in accordance with NIH policy, all 
applications will also be reviewed with respect to the following, to 
the extent that these issues pertain to a particular application:

o The adequacy of plans to include genders, minorities and their 
subgroups, and children for the scientific goals of the research.  
Plans for the recruitment and retention of subjects will also be 
evaluated,

o The reasonableness of the proposed budget and duration in relation to 
the proposed research,

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

o Provisions for the safety of the research environment.

Schedule

Letter of Intent Receipt Date:    March 11, 2002
Application Receipt Date:         April 11, 2002
Peer Review Date:                 May 2002
Council Review:                   August 2002
Earliest Anticipated Start Date:  September 2002

AWARD CRITERIA

The following award criteria will be considered in making award 
decisions: 

o Quality of the proposed project as determined by peer review,
o Availability of funds, and 
o Contribution to program goals. 

INQUIRIES

Inquiries are encouraged.  The opportunity to clarify any issues or 
questions from potential applicants is welcome.

Direct inquiries regarding programmatic issues to:

Eleni Kousvelari, DDS, D.Sc.
Chief, Cellular & Molecular Biology, Physiology 
& Biotechnology Branch
Division of Basic & Translational Sciences
National Institute of Dental & Craniofacial Research
National Institutes of Health
Building 45, Room 4AN-18A
Bethesda, MD  20892-6402
Telephone:  301-594-2427
Fax:  301-480- 8318
Email:  Kousvelari@de45.nidr.nih.gov

Direct inquiries regarding fiscal matters to:

Martin R. Rubinstein
Grants Management Officer
Division of Extramural Activities
National Institute of Dental and Craniofacial Research
National Institutes of Health
Building 45, Room 4AN-38
Bethesda, MD  20892-6402
Telephone:  (301) 594-4800 
Fax: (301) 480-8301 
email:  Martin.Rubinstein@ nih.gov

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance 
No. 93.121, Oral Diseases and Disorders Research Awards.  Awards are 
made under authorization of Sections 301 and 405 of the Public Health 
Service Act as amended (42 USC 241 and 284) and administered under NIH 
grants policies and Federal Regulations 42 CFR 52 and 45 CFR Parts 74 
and 92.  This program is not subject to the intergovernmental review 
requirements of Executive Order 12372 or Health Systems Agency review.

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



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