RELEASE DATE: July 27, 2004
PA NUMBER:  PAR-04-133

March 2, 2006 (NOT-OD-06-046) – Effective with the June 1, 2006 submission date, 
all R03, R21, R33 and R34 applications must be submitted through using 
the electronic SF424 (R&R) application. Accordingly, this funding opportunity 
expires on the date indicated below. A replacement R21 (PAR-06-213) funding 
opportunity announcement has been issued for the submission date of June 1, 2006 
and submission dates thereafter. 

See NOT-OD-06-048 for information on May 1, 2006 Submission Date for AIDS and 
AIDS-related R03 and R21 Applications.

EXPIRATION DATE:  March 2, 2006

Department of Health and Human Services (DHHS)
National Institutes of Health (NIH)

National Institute of Dental and Craniofacial Research (NIDCR)
National Cancer Institute (NCI) 

and Disorders Research, 93.395 Cancer Treatment Research

o Purpose of this PA
o Research Objectives
o Mechanism(s) of Support 
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Special Requirements 
o Where to Send Inquiries
o Submitting an Application
o Supplementary Instructions
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations


The National Institute of Dental and Craniofacial Research (NIDCR) and 
the National Cancer Institute (NCI) invites applications for clinical 
research directed at reducing the incidence and severity of oral 
complications from cancer therapies. The purpose of this PA for pilot 
data grants would be to collect preliminary data to establish an 
adequate foundation for Phase III clinical trials.

Oral complications from cancer therapies are common and can 
substantially impair the comfort and function of patients during and 
after treatment for cancer. In addition, these complications may impact 
on a patient’s willingness to adhere or complete with the prescribed 
therapies. Moreover, scientific data are incomplete and inconsistent 
regarding the effectiveness of various forms currently used to prevent 
and treat these complications. Therefore, the goal of this PA is to 
stimulate the submission of pilot data grants for clinical trials 
targeted to the prevention and management of lesions and symptoms, which 
occur in the oral cavity as a result of cancer therapies.  


In 2004, approximately 1.3 million Americans will be diagnosed with 
cancer and many will receive one or more types of therapies for this 
disease.  Cancer therapies could include surgery, radiation, 
chemotherapy, immunotherapy and/or cell transplantation.  The type of 
therapy will depend on the specific diagnosis, site and staging of the 

A range of side effects accompanies the different types of cancer 
therapy. These side effects may be mild and transient (e.g. alopecia, 
nausea, neutropenia), chronic (e.g. fatigue, lymphedema) and/or late 
and potentially life threatening (e.g. cardiomyopathy).  Also, a number 
of side effects or complications can be seen in the oral cavity.  The 
frequency of oral complications varies with about 40% of those 
receiving chemotherapy, 80% of those having bone marrow 
transplantation, and 100% of those with high-dose radiation to the head 
and neck. The most common complications of the oral cavity include 
mucositis, infection, salivary gland dysfunction, taste dysfunction and 
pain.  Radiation therapy for cancer in the head and neck area can 
result in xerostomia, rampant dental caries, soft tissue necrosis and 

Ulcerative oral mucositis occurs in about 40% of patients receiving 
cancer chemotherapy and it usually occurs within two weeks after 
beginning therapy. Other oral complications include bacterial and viral 
infections.  Relatively little is known about the risk factors for 
chemotherapy induced mucositis or infection.

Ulcerative and non-ulcerative mucositis also is a common side effect of 
radiation therapy.  Other complications related to head and neck 
radiation include damage to the vasculature, connective tissue, 
salivary glands and bone.  These complications may be divided into 
acute complications that occur during therapy and late complications 
that occur after completion of radiation therapy.  Acute complications 
include oropharyngeal mucositis, sialdenitis and xerostomia, infections 
(primary candidiasis) and taste dysfunction.  Occasionally tissue 
necrosis can be seen late during therapy.  Chronic complications 
include mucosal atrophy; mucosal, cutaneous and muscular fibrosis; 
xerostomia and associated caries; osseous and mucosal necrosis, 
secondary infection; and alterations in taste.

A number of studies have used protective mucosal coatings such as 
sucralfate, alone or in combination with antibiotics and analgesics, to 
reduce mucositis and its associated pain and discomfort. Anti-
inflammatory drugs, such as triclosan and indometacin have been found 
to reduce the duration and severity of mucositis in some cases and 
topical applications of vitamin A and E also have been used in attempts 
to reduce mucositis.  The use of low-energy laser therapy has been 
reported to reduce the incidence of mucositis and to enhance  
epithelial healing.  

Saliva is a lubricant in the oral cavity and provides a barrier against 
bacteria and viral infections.  It also helps to moisten food and aids 
in swallowing. The use of amifostine prior to radiation therapy to the 
head and neck region has been shown to help in preserving salivary 
output.  Similarly, pilocarpine can be used to stimulate saliva 
production, provided that functional glands remain after cancer 
therapy. In addition, salivary substitutes can be given to lubricate 
and facilitate oral function.

Although several interventions are available and they have shown some 
benefit at preventing or reducing the severity of oral complications 
related to cancer therapy, well-designed clinical trials are needed to 
determine which interventions are most efficacious for different 
categories of patients and cancer therapies. These interventions should 
be tailored to the specific therapy protocols, as well as the health 
and immune status of the patient.  

Objectives and Scope

The goal of this PA is to stimulate research on the prevention and/or 
management of symptoms and lesions in the oral cavity and pharynx 
resulting from cancer therapies.  Applications responsive to this PA 
are for pilot data grants leading to Phase III clinical trials.  
Applications for small clinical trials will not be responsive to this 

The pilot data grant applications to be supported under this award may 
involve limited pilot testing of novel experimental hypotheses, design-
driven development of new or novel techniques or technologies, and/or 
the acquisition of a body of data that has potentially high-impact on 
the reduction of mucositis and other oral complications related to 
chemotherapy, radiation or other cancer therapies. Also, data collected 
under this PA may include but is not limited to:  collection of 
preliminary data for establishing measures of effectiveness and/or 
safety; testing and documenting recruitment mechanisms and their 
effectiveness; short-term studies to address questions to optimize the 
design of the Phase III clinical trial; small studies to refine an 
intervention strategy (e.g., dosage, duration, delivery system, etc.); 
and, the development and testing of participant inclusion criteria and 
data collection and outcome instruments.  

This PA will use the NIH Exploratory/Developmental (R21) award mechanism 
for clinical pilot data grants. As an applicant you will be solely 
responsible for planning, directing, and executing the proposed project.   
The pilot data grant from the NIDCR Clinical Program is described in the 
following website (see

Applicants may request a project period of up to two years with a 
combined budget for direct costs of up to $275,000 for the two-year 
period.  For example, the applicant may request $100,000 in the first 
year and $175,000 in the second year.  The request should be tailored to 
the needs of the project.  Normally, no more than $200,000 may be 
requested in any single year.  

This PA uses just-in-time concepts.  It also uses the modular budgeting 
formats (see  
Specifically, if you are submitting an application with direct costs in 
each year of $250,000 or less, use the modular budget format.  This 
program does not require cost sharing as defined in the current NIH 
Grants Policy Statement at  

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 institutions/organizations
o Foreign institutions are not eligible to apply. 


Any individual with the skills, knowledge, and resources necessary to 
conduct the proposed research is invited to work with their institution 
to develop an application in response to this PA. Individuals from 
underrepresented racial and ethnic groups as well as individuals with 
disabilities are always encouraged to apply for NIH programs.   


Before submitting an application for an NIDCR Clinical Pilot Data 
Grant responsive to this PA, the investigator may wish to submit a brief 
description of the proposed Phase III clinical trial to the NIDCR for 
review for programmatic relevance.  See for 
details or contact Dr. Canto listed in WHERE TO SEND INQUIRIES under 
scientific/research issues. The brief description is optional for 
submissions to NCI. 


Inquiries are encouraged early in the development of a NIDCR Clinical 
Pilot Data Grant responsive to this PA.  The opportunity to clarify any 
issues or questions from potential applicants is welcome and highly 
encouraged.  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:

Dr. Maria Teresa Canto
Division of Clinical research and Health Promotion
National Institute of Dental and Craniofacial Research
45 Center Drive, Room 4As43B, MSC 6401
Bethesda, MD 20892-6401
Telephone:  (301) 594-5497
FAX:  (301) 480-8322

Dr. Roy S. Wu
Clinical Grants & Contracts Branch
Cancer Therapy Evaluation Program
Division of Cancer Treatment & Diagnosis
National Cancer Institute
Executive Plaza North, Room 7009
6130 Executive Boulevard
Bethesda, MD 20892-7432
Phone: 301-496-8866
Fax: 301-480-4663

o Direct your questions about peer review issues to:

Dr. H. George Hausch
Division of Extramural Activities
National Institute of Dental and Craniofacial Research
45 Center Drive, Room 4An-44F, MSC 6401
Bethesda, MD 20892-6401
Telephone:  (301) 594-2904

o Direct your questions about financial or grants management matters 

Chris Myers
Grants Management Specialist
Grants Management Branch
Division of Extramural Activities
National Institute of Dental and Craniofacial Research
Building 45, Room 4AS51
45 Center Drive
Bethesda, Maryland 20892-6402
Phone: 301-594-4799
Fax: 301-480-3562

Applications must be prepared using the PHS 398 research grant 
application instructions and forms (rev. 5/2001). Appendices will be 
accepted in applications responsive to this PA. Applications must have a 
DUN and Bradstreet (D&B) Data Universal Numbering System (DUNS) number 
as the Universal Identifier when applying for Federal grants or 
cooperative agreements. The D&B number can be obtained by calling (866) 
705-5711 or through the web site at 
The D&B number should be entered on line 11 of the face page of the PHS 
398 form. The PHS 398 document is available at in an 
interactive format.  For further assistance contact GrantsInfo, 
Telephone (301) 710-0267, Email: 
The title and number of this program announcement must be types on line 
2 of the face page of the application form and YES box must be marked.

APPLICATION RECEIPT DATES: Applications submitted in response to this 
program announcement will be accepted at the standard application 
deadlines, which are available at  Application deadlines also are 
indicated in the PHS 398 application kit.

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

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)

In order to facilitate the review of applications assigned to the 
NIDCR, the applicant must, at the same time, mail or deliver two copies 
of the application to:

Dr. H. George Hausch
Division of Extramural Activities
National Institute of Dental and Craniofacial Research
45 Center Drive, Room 4AN-44F - MSC 6402
Bethesda, MD  20892-6402

RESEARCH WILL NO LONGER BE ACCEPTED.  This policy does not apply to 
courier deliveries (i.e., FED EX, UPS, DHL, etc.).  This policy for 
applications addressed to the Center for Scientific Review was 
published in the NIH Guide to Grants and Contracts at  

APPLICATION PROCESSING: Applications must be mailed on or before the 
receipt dates described at  The CSR 
will not accept any application in response to this PA 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 a substantial revision of an 
unfunded version of an application already reviewed, but such 
application must include an Introduction addressing the previous 

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.


Applications submitted for this PA will be assigned on the basis of 
established PHS referral guidelines.  An appropriate scientific review 
group convened by NIDCR in accordance with the standard NIH peer review 
procedures ( will evaluate 
applications for scientific and technical merit.  

As part of the initial merit review, all applications will:

o Undergo a selection process in which only those applications deemed 
to have the highest scientific merit, generally the top half of 
applications under review, will be discussed and assigned a priority 
o Receive a written critique
o Receive a second level review by an appropriate national advisory 
council or board

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. 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.

o Significance 
o Approach 
o Innovation
o Investigator
o Environment

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 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 the proposed pilot activities 
on the concepts or methods that drive this field?  Will a successful 
outcome from this pilot work lead directly to the development of a 
definitive Phase III clinical trial that would likely advance the field 
of craniofacial, oral, or dental research?

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

(3) Innovation:  In general, pilot data grants leading to a Phase III 
clinical trial are not expected to be innovative.  For pilot data grants 
leading to a Phase III clinical trial, innovation will be evaluated on 
the basis of whether the pilot data grant tests new paradigms of public 
health policy or standards of clinical practice.

(4) 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?  Is the principal investigator an independent researcher?

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

ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, the 
following items will be 

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).
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).


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


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.

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

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 
(; a 
complete copy of the updated Guidelines are available at  
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 

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. 

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

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

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

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.

The Department of Health and Human Services (DHHS) issued final 
modification to the “Standards for Privacy of Individually Identifiable 
Health Information”, the “Privacy Rule,” on August 14, 2002.  The 
Privacy Rule is a federal regulation under the Health Insurance 
Portability and Accountability Act (HIPAA) of 1996 that governs the 
protection of individually identifiable health information, and is 
administered and enforced by the DHHS Office for Civil Rights (OCR).  

Decisions about applicability and implementation of the Privacy Rule 
reside with the researcher and his/her institution. The OCR website 
( provides information on the Privacy Rule, 
including a complete Regulation Text and a set of decision tools on “Am 
I a covered entity?”  Information on the impact of the HIPAA Privacy 
Rule on NIH processes involving the review, funding, and progress 
monitoring of grants, cooperative agreements, and research contracts 
can be found at

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 PA is related to one or more of the priority areas. 
Potential applicants may obtain a copy of "Healthy People 2010" at

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

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.


Clarkson JE, Worthington HV, Eden OB. Interventions for preventing oral 
mucositis for patients receiving treatment (Cochrane Review). In: The 
Cochrane Library, Issue 1, 2004. Chicheste, UK: John Wiley & Sons, Ltd.

Clarkson JE, Worthington HV, Eden OB. Interventions for treating oral 
candidiasis for patients with cancer receiving treatment (Cochrane 
Review). In: The Cochrane Library, Issue, 2004. Chichester, UK: John 
Wiley & Sons, Ltd.
Duncan M, Grant G. Review article: oral and intestinal mucositis – 
causes and possible treatments. Aliment Pharmacol Ther 2003;18:853-74.

Jenal, A, Tiwari RC et. al. CA A Cancer Journal for Clinicians, 

Oral complications of chemotherapy and head/neck radiation (PDQ), (date last modified 8/19/2003).

Peterson DE, Sonis ST. Executive Summary, Journal of the National 
Cancer Institute Monographs 2001;29 3—5.

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Office of Extramural Research (OER) - Home Page Office of Extramural
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