EXPLORATOR/DEVOPMENTAL (R21) AWARDS FOR RESEARCH ON AIDS/HIV INFECTION 
AND THE ORAL CAVITY
 
RELEASE DATE:  April 1, 2002
 
RFA:  DE-02-007
 
National Institute of Dental and Craniofacial Research (NIDCR)
 (http://www.nidcr.nih.gov)

LETTER OF INTENT RECEIPT DATE: April 24, 2002

APPLICATION RECEIPT DATE:  May 24, 2002 

THIS RFA CONTAINS THE FOLLOWING INFORMATION

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

PURPOSE OF THIS RFA

The National Institute of Dental and Craniofacial Research (NIDCR) 
invites investigator-initiated grant applications for support of 
research on HIV infection and the oral complications of AIDS/HIV 
infection in the oral cavity.  The intent of this RFA is to stimulate 
novel, innovative, or high impact AIDS research within the framework of 
the exploratory/developmental (R21) grant mechanism.

RESEARCH OBJECTIVES

Background

HIV has infected more than 50 million people and AIDS has killed more 
than 21 million people worldwide.  Approximately 40,000 new cases of 
HIV infection are reported in the United States each year, and the 
rates of infection are climbing in certain subpopulations of 
individuals such as women, racial and ethnic minorities, young 
homosexual men, individuals with addictive disorders, and people over 
50 years of age.   

In response to this pandemic, the NIH is committed to a comprehensive 
biomedical and behavioral research program to better understand the 
basic biology of HIV infection, develop effective therapies to treat it 
and the associated health complications, and design interventions to 
prevent new infections from occurring.  For more information on the NIH 
Plan for HIV-Related Research, please see 
http://www.nih.gov/od/oar/public/public.htm.  In particular, the NIDCR 
plans to support research that will 1) increase our understanding of 
HIV infection in the oral cavity with regards to transmission, 
including breast feeding, and the potential application of these 
findings to other routes of transmission, such as the rectum or vagina, 
2) develop improved therapy for the opportunistic infections associated 
with HIV immunosuppression, 3) reduce and eliminate benign as well as 
malignant oral tumors related to AIDS, 4) address international 
differences, particularly those seen in developing countries, in HIV 
infection and lesions in the oral cavity, and 4) reduce the 
disproportionate impact of AIDS on minority populations in the United 
States.  

As a result of rapid changes and advances in research on AIDS/HIV 
infection, investigators are exploring new ideas and approaches for the 
diagnosis, treatment, and prevention of HIV infection and complications 
of AIDS/HIV infection in the oral cavity.  Collaborative research, new 
investigators, investigators using unique cohorts of patients and high 
risk/high impact projects may require support prior to submission of a 
fully developed R01 grant application.   

The objective of this initiative is to encourage applications for 
innovative, high risk/high impact research requiring preliminary 
testing or development, exploration of the use of approaches and 
concepts new to AIDS/HIV infection, research and development of new 
technologies, techniques or methods, or initial research and 
development of data upon which significant future research may be 
built.  Applications will be considered as high impact if they 
demonstrate the potential for ground-breaking, precedent-setting 
significance, and high risk because they either lack sufficient 
preliminary data to ensure their feasibility, or involve using a new 
model system or technique. While this program announcement is intended 
to encourage innovation and high impact research, and while minimal 
preliminary data are expected to be described in the application, 
applications should clearly indicate that the proposed research and/or  
development is scientifically sound, that the qualifications of the 
investigators are appropriate, and that resources available to the 
investigators are adequate.  Applications from both individuals and 
groups interested in this oral AIDS research are encouraged.  However, 
team approaches to these efforts are especially encouraged in the 
belief that a synergistic blend of expertise and resources could 
advance the science more quickly.  

Scope

Research in any area related to AIDS/HIV infection and the oral cavity 
would be responsive to this RFA.   This includes studies on: 

o The cells infected by HIV in the oral cavity, 

o Novel ways to use the oral cavity to vaccinate against HIV and 
opportunistic infections, 

o The potential utilization of oral lesions in assessing 
seroconversion, disease severity or response to therapy, 

o The role of innate as well as adaptive immunity on oral HIV infection 
or oral complications of AIDS, 

o The influence of protease inhibitors and highly active antiretroviral 
therapy (HAART) on oral lesions and the shedding of HIV into the 
saliva, 

o HIV-induced salivary dysfunction, 

o Oral neurological problems associated with AIDS, 

o The diagnosis, prevention or treatment of oral tumors, including 
Kaposi"s sarcoma, lymphoma, warts or oral hairy leukoplakia, 

o Development of novel methods to use oral fluids or tissues to assess 
HIV infections.   

o Mechanisms of persistence of HIV in the oral tissues, 

o Comparisons of HIV infection and complications in the oral cavity 
with other mucosal sites, or, 

o Age, gender, health status, race, or cultural differences in HIV 
infection, the associated complications, and responses to therapies and 
vaccines. 

This list is illustrative and not meant to be inclusive.  Investigators 
are encouraged to propose other studies related to AIDS/HIV infection 
and the oral cavity, and to contact the research/science staff listed 
below to determine whether the project would be responsive to this RFA.  
 
MECHANISM OF SUPPORT
 
This RFA will use the NIH Exploratory/Developmental (R21) Research 
Grant award mechanism.  As an applicant you will be solely responsible 
for planning, directing, and executing the proposed project.  The R21 
grant cannot be renewed, if additional research support is necessary, 
investigators could then apply for further funding through the regular 
research grants, e.g., the research project grant (R01), mechanism.  
The anticipated award date is September 2002.

This RFA uses just-in-time concepts.  It also uses the modular 
budgeting format. (see 
http://grants.nih.gov/grants/funding/modular/modular.htm).   

FUNDS AVAILABLE
 
The NIDCR intends to commit approximately $1.8 million in FY2002 to 
fund 8 to 10 new grants in response to this RFA.  Applicants may 
request a project period of up to two years and a budget for direct 
costs of up to $150,000 per year.  This cap may be exceeded by $25,000 
to accommodate the facilities and administrative (indirect) costs 
associated with collaborative research at another institution.  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 NIDCR provides support for this program, awards pursuant to this 
RFA are contingent upon the availability of funds and the receipt of a 
sufficient number of meritorious applications.  At this time, it is 
not known if this RFA will be reissued.

ELIGIBLE INSTITUTIONS
 
You may submit (an) application(s) if your institution has any of the 
following characteristics: 
	
o For-profit or non-profit organizations 
o Public or private institutions, such as universities, colleges, 
hospitals, and laboratories 
o Units of state and local governments
o Eligible agencies of the Federal government  
o Domestic or foreign
 
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 
 
Grantees will meet annually at or near NIH, Bethesda, MD, to share 
results, to ensure that the NIDCR has a coherent view of the advances 
in the field, and to have an opportunity for collective problem solving 
among investigators.  Applicants should budget for travel in their 
requested budget for the principal investigator and one additional 
young investigator to attend this annual meeting. 
 
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:

Dennis F. Mangan, Ph.D. 
Division of Basic and Translational Sciences
National Institute of Dental and Craniofacial Research
Building 45, Suite 4AN-18
Bethesda, MD  20892-6402
Telephone:  (301) 594-2421
Fax:  (301) 480-8318
Email: [email protected] 

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
Building 45, Room 4AN-44F
Bethesda, MD  20892-6402
Telephone:  (301) 594-2904
FAX:  (301) 480-8303
Email:  [email protected]

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

William Powell
Division of Extramural Activities
National Institute of Dental and Craniofacial Research
Building 45, Room 4AN-44K
Bethesda, MD  20892-6402
Telephone:  (301) 594-4800
FAX:  (301) 480-8303
Email: [email protected]
 
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. Hausch at 
the address listed above. 

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) 710-0267, Email: [email protected].
 
SUPPLEMENTAL INSTRUCTIONS: 
 
All application instructions outlined in the PHS 398 application kit 
are to be followed with the following modifications for R21 
applications:

1. FACE PAGE, Item 6:  Up to a total of two years of support may be 
requested.

2. Items a-d of the Research Plan for the R21 application may not 
exceed ten (10) pages, including tables and figures.  The following 
information should be taken into account for items a, b and c:  

o  Item a, SPECIFIC AIMS--The instructions for this section suggest 
that the applicant state "the hypotheses to be tested".  Since some 
applications submitted in response to this RFA may also be design- or 
problem-driven (e.g., development of novel technologies), or need-
driven (initial research to develop a body of data upon which future 
research will build), hypothesis testing per se may not be the driving 
force in developing such a proposal and, therefore, may not be 
applicable.  The application should state the hypotheses, design, 
problem and/or need which will drive the proposed research.

o  Item b, BACKGROUND AND SIGNIFICANCE--In this section, it is 
important to identify clearly how the application addresses the 
specific objectives of this RFA and the purpose of the R21 mechanism.

o  Item c, PRELIMINARY STUDIES/PROGRESS REPORT Minimal preliminary 
data are required for an R21 application.  

3.  Appendix material is restricted to photos, and color, glossy 
figures, if any.  

SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS: 
Applications 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 may 
request direct costs in $25,000 modules up to a total of six modules 
($150,000).  This cap may be exceeded by one module ($25,000) to 
accommodate the facilities and administrative (indirect) costs 
associated with collaborative research at another institution.

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/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
Building 45, Room 4AN-44F
Bethesda, MD  20892-6402
 
APPLICATION PROCESSING: Applications must be received by 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.
 
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.

PEER REVIEW PROCESS  
 
Upon receipt, applications will be reviewed for completeness by the CSR 
and responsiveness by the NIDCR.  Incomplete and/or non-responsive 
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:

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 NIDCR National Advisory 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 your application in order to judge the likelihood 
that the proposed research will have a substantial impact on the 
pursuit of these goals: 

o Significance 
o Approach 
o Innovation
o Investigator
o Environment
  
The scientific review group will address and consider each of these 
criteria in assigning your application"s overall score, weighting them 
as appropriate for each application.  Your application does not need to 
be strong in all categories to be judged likely to have major 
scientific impact and thus deserve a high priority score.  For example, 
you may propose to carry out important work that by its nature is not 
innovative but is essential to move a field forward.

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

(2) APPROACH:  Are the conceptual framework, design, methods, and 
analyses adequately developed, well integrated, and appropriate to the 
aims of the project?  Do you acknowledge potential problem areas and 
consider alternative tactics?

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

(5) ENVIRONMENT:  Does the scientific environment in which your 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, your 
application will also be reviewed with respect to the following:

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

o INCLUSION:  The adequacy of plans to include subjects from both 
genders, all racial and ethnic groups (and subgroups), and children as 
appropriate for the scientific goals of the research.  Plans for the 
recruitment and retention of subjects will also be evaluated. (See 
Inclusion Criteria included in the section on Federal Citations, below)

o DATA SHARING:  The adequacy of the proposed plan to share data. 

o BUDGET:  The reasonableness of the proposed budget and the requested 
period of support in relation to the proposed research.

o OTHER REVIEW CRITERIA:  Reviewers will be instructed to consider the 
application in the context of the R21 mechanism.  The applicant must 
establish both the novelty and the potential impact of the project.  In 
keeping with the exploratory/developmental nature of the R21, 
preliminary data are not required, however, the application must be 
well-reasoned and scientifically sound.  Where appropriate, specific 
criteria by which to judge the success of novel approaches (including 
milestones that will mark progress) should be explicitly described.  

Both applicants and reviewers are urged to remember that an R21 
Exploratory/Developmental research project need not be hypothesis 
driven.  It may, instead, be problem-driven (e.g., investigation of 
novel phenomenon), design-driven (e.g., development of a new instrument 
or technology), or need-driven (e.g., development of a new experimental 
system or model).  The application must, however, clearly articulate 
the problem, hypothesis or need which will drive the proposed research.  

RECEIPT AND REVIEW SCHEDULE

Letter of Intent Receipt Date: April 24, 2002
Application Receipt Date: May 24, 2002
Peer Review Date: June/July 2002
Council Review:  August 2002
Earliest Anticipated Start Date:  September 2002

AWARD CRITERIA

Award criteria that will be used to make award decisions include:

o Scientific merit (as determined by peer review)
o Availability of funds
o Programmatic priorities.
 
REQUIRED FEDERAL CITATIONS 

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

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

All investigators proposing clinical research should read the AMENDMENT 
"NIH Guidelines for Inclusion of Women and Minorities as Subjects in 
Clinical Research - Amended, October, 2001," published in the NIH Guide 
for Grants and Contracts on October 9, 2001 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html), a 
complete copy of the updated Guidelines are available at 
http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_20
01.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.

HUMAN EMBRYONIC STEM CELLS (hESC):  Criteria for federal funding of 
research on hESCs can be found at 
http://grants.nih.gov/grants/stem_cells.htm and at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html.  
Only research using hESC lines that are registered in the NIH Human 
Embryonic Stem Cell Registry will be eligible for Federal funding (see 
http://escr.nih.gov).   It is the responsibility of the applicant to 
provide the official NIH identifier(s) for the hESC line(s)to be used in 
the proposed research.  Applications that do not provide this 
information will be returned without review. 

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

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

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

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

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

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

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