NIDCR CLINICAL TRIAL PLANNING GRANT

RELEASE DATE:  December 4, 2002

PA NUMBER:  PAR-03-042 (This PAR has been reissued, see PAR-06-026)
                       (see clarification NOT-DE-04-002)

EXPIRATION DATE:  This Program Announcement expired on October 19, 2005

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

THIS PA CONTAINS THE FOLLOWING INFORMATION

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 Peer Review Process
o Review Criteria
o Award Criteria
o Required Federal Citations

PURPOSE OF THIS PA

The National Institute of Dental and Craniofacial Research (NIDCR) is 
committed to identifying effective preventive, diagnostic and treatment 
approaches to craniofacial, oral and dental diseases and disorders that 
will improve health by supporting well-executed clinical trials.  The 
NIDCR announces a grant program to support the planning for definitive 
Phase III multicenter clinical trials. 
 
Significant planning is often required before submitting an application 
to conduct a multicenter, randomized clinical trial.  At the time of 
submission, applications requesting support for multicenter clinical 
trials are expected to provide detailed information regarding the 
study's rationale, design, analytic techniques, protocols and 
procedures, facilities and environment, organizational structure, and 
collaborative arrangements.  This information is best conveyed in a 
well-documented Manual of Procedures (MOP), the development of which 
typically represents a costly and time-consuming activity.  The 
Clinical Trial Planning Grant, providing up to $100,000 in annual 
direct costs for up to two years, is an NIDCR support mechanism 
designed to facilitate activities central to the refinement of the 
trial's protocol and procedures and the development of a detailed MOP.  
This Program Announcement replaces PAR-99-157.

RESEARCH OBJECTIVES

Dental and craniofacial diseases and disorders are among the most 
common health problems affecting the people of the United States and 
around the world. The burden imposed by a variety of dental and 
craniofacial diseases and disorders range from birth defects such as 
cleft lip and palate, which occurs in 1 in 525 to 714 live births, to 
injuries to the head and face, resulting in nearly 20 million emergency 
room visits per year, to devastating head and neck cancers, accounting 
for 8000 deaths and over 30,000 new cases per year.  The treatment of 
over 1.2 million cancer patients each year can lead to painful mouth 
ulcers, mucositis, rampant dental caries, fungal infections, impaired 
taste and loss of function of the salivary glands.  Oral infections 
still remain common in our populations.  Dental caries is experienced 
by 45% of school children and 94% of adults have experienced this 
infection at some point in life.  Periodontal infections occur in 90% 
of individuals older than 13 years and may be associated with other 
systemic diseases or conditions such as diabetes, cardiovascular 
disease, respiratory infections, and pre-term/low birth weight babies. 
Orofacial pain which is likely to have been experienced by over 20% of 
adults in the past six months, is a major component of 
temporomandibular joint diseases (TMD) for at least 6% of adults, and 
is a major component of Bell's palsy, trigeminal neuralgia and 
fibromyalgia.  Salivary gland dysfunction in the form of Sjogren's 
syndrome affects between 1 and 4 million Americans while over 30,000 
individuals who have cystic fibrosis are also at higher risk for 
concomitant salivary gland dysfunction. Further, over 500 prescription 
drugs have xerostomic (dry mouth) side effects, increasing the risk for 
both bacterial and fungal oral infections as well as other oral 
conditions.  

The Clinical Trial Planning Grant provides support for the development 
of a comprehensive research protocol for a large-scale, multicenter 
clinical trial.  This grant provides early peer review of the proposed 
clinical trial in terms of its rationale, general design, 
organizational structure and implementation plan.  The planning grant 
is used to support the development of a detailed MOP and can include 
preliminary studies to refine study procedures or to document 
recruitment potential of clinical sites.

Basic elements in the MOP should include identification of the patient 
population; inclusion and exclusion criteria; adequate plans for 
recruitment and retention of participants; experimental design and 
protocols; clear definition of the research hypothesis and outcome 
measures; and quality control/assurance procedures; analytical 
techniques; sample size estimates with justification; administrative 
procedures (including regulatory approvals if necessary); collaborative 
arrangements; duties and responsibilities of study chairperson, 
clinical sites, coordinating center, and other central resource center 
such as a central laboratory or radiographic center; and monitoring 
plans to assure patient protection and data integrity.

Prospective applicants should note that funding of a Clinical Trial 
Planning Grant does not guarantee or imply funding for any subsequent 
competitive application for the support of a full-scale trial.

MECHANISM OF SUPPORT

This PA will use the National Institutes of Health (NIH) R21 
Exploratory/Development Grant award mechanism.  Responsibility for the 
planning, direction, and execution of the proposed project will be 
solely that of the applicant.  The total project period for an 
application submitted in response to this PA may not exceed two years, 
and the annual direct costs may not exceed $100,000 per year.  This 
award may not be renewed.

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

ELIGIBLE INSTITUTIONS 

You may submit an application 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

Before submitting an application for an NIDCR Clinical Trial Planning 
Grant, the investigator should submit a brief description of the 
proposed Phase III clinical trial to the NIDCR for review for 
programmatic relevance.  See http://www.nidcr.nih.gov/ for details or 
contact one of the persons listed in WHERE TO SEND INQUIRIES under 
scientific/research issues.  

WHERE TO SEND INQUIRIES

We encourage your inquiries concerning this PA 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:

Dr. Richard Mowery
Division of Population and Health Promotion Sciences
National Institute of Dental and Craniofacial Research
45 Center Drive, Room 4As43F, MSC 6401
Bethesda, MD 20892-6401
Telephone:  (301) 594-4848
FAX:  (301) 480-8322
Email: rm33a@nih.gov

Or 

Dr. Bruce Pihlstrom
Division of Population and Health Promotion Sciences
National Institute of Dental and Craniofacial Research
45 Center Drive, Room 4As43H, MSC 6401
Bethesda, MD 20892-6401
Telephone:  (301) 594-4830
FAX:  (301) 480-8322
Email:  pihlstrb@mail.nih.gov

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 
to:

Ms. Anne Welkener
Division of Extramural Activities
National Institute of Dental and Craniofacial Research
45 Center Drive, Room 4AS-55, MSC 6402
Bethesda, MD  20892-6402
Telephone:  (301) 594-4806
Email:  Anne.Welkener@nih.gov

SUBMITTING AN APPLICATION

Applications must be prepared using the PHS 398 research grant 
application instructions and forms (rev. 5/2001).  The PHS 398 is 
available at http://grants.nih.gov/grants/funding/phs398/phs398.html in 
an interactive format.  For further assistance contact GrantsInfo, 
Telephone (301) 710-0267, Email: GrantsInfo@nih.gov.  The title and 
number of the program announcement must be typed in Section 2 on the 
face page of the application. As with most applications to NIH, the 
research plan is limited to 25 pages. All information for review of the 
NIDCR Clinical Trial Planning Grant application must be included in the 
body of the application; appendices are considered supplementary 
material.

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

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

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

APPLICATIONS HAND-DELIVERED BY INDIVIDUALS TO THE NATIONAL INSTITUTES 
OF HEALTH AND THE NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL 
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 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-012.html.  

APPLICATION PROCESSING: Applications must be received by or mailed on 
or before the receipt dates described at 
http://grants.nih.gov/grants/funding/submissionschedule.htm.  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 
application already reviewed, but such application must include an 
Introduction addressing the previous critique.

PEER REVIEW PROCESS

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 (http://www.csr.nih.gov/refrev.htm) will evaluate 
applications for scientific and technical merit.  

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

o Receive a written critique
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 
score
o Receive a second level review by the National Advisory Dental and 
Craniofacial Research Council.

REVIEW CRITERIA

The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health.  
In the written comments, reviewers will be asked to discuss the 
following aspects of 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.

Even though this initiative supports development of an MOP, the 
development of plans for the RCT must be sufficiently far enough along 
that the following information will be available and must be included 
in the application as it will be assessed during the review:

(1) SIGNIFICANCE:  The background and significance of the application 
must address the rationale for a future, full-scale, multi-center 
randomized clinical trial (RCT) including:
o detailed information adequate to determine the significance and need 
for a RCT including the public health importance of the study 
hypothesis;
o reason for selection of intervention and mode of delivery including 
details such as dose or a particular procedure;
o the biological mechanisms and/or clinical data that support 
conducting a RCT. 

(2) APPROACH:  Study Design.  The application must include a 
description of the proposed experimental design of the planned RCT 
including, but not limited to: 
o  translation of the clinical question into a statistical hypothesis; 
o sample size estimate and justification; 
o the selection of primary and secondary endpoint(s); 
o randomization, masking (if appropriate), and inclusion/exclusion 
criteria; 
o potential weaknesses of the proposed  study methods and plans for 
dealing with them;  
o plans to standardize and track adherence to the clinical protocol in 
each center; 
o methods for standardization of procedures for data management and 
quality control;
o discussion of statistical issues; and, 
o detailed description of and timeline for planning grant activities. 

Plans to Address Patient Recruitment/Retention. The application must
address the following items:
o availability of the requisite eligible patient pool;
o availability of children, women and minority individuals as trial 
participants and specific recruitment and retention plans for their 
inclusion; and
o plans for recruitment outreach and, as appropriate, follow-up 
procedures to ensure collection of data at stated intervals and 
retention of patients to ensure full and adequate follow-up. 

(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) Investigators. The application must include a clear statement of
the leadership and proposed organization of the RCT including:
o identification of a principal investigator (study chair) and director
for a coordinating center;
o professional training and/or experience of the study chair and 
coordinating center director in such areas as the clinical problem 
under study, administration of complex projects, development of study 
design;
o inclusion of statisticians, data managers and study coordinators;
o procedures and plans for adding or dropping centers; and,
o essential committee structure appropriate to the complexity of the 
trial (e.g., Planning, Steering, Executive committees).

5) ENVIRONMENT:  Does the scientific environment in which your work 
will be done contribute to the probability of success?  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:

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.

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)

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

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

AWARD CRITERIA

Applications submitted in response to a PA will compete for available 
funds with all other recommended applications.  The following will be 
considered in making funding decisions:  

o Scientific merit of the proposed project as determined by peer review
o Availability of funds 
o Relevance to program 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_2001.htm.
The amended policy incorporates: the use of an NIH definition 
of clinical research; updated racial and ethnic categories in 
compliance with the new OMB standards; clarification of language 
governing NIH-defined Phase III clinical trials consistent with the new 
PHS Form 398; and updated roles and responsibilities of NIH staff and 
the extramural community.  The policy continues to require for all NIH-
defined Phase III clinical trials that: a) all applications or 
proposals and/or protocols must provide a description of plans to 
conduct analyses, as appropriate, to address differences by sex/gender 
and/or racial/ethnic groups, including subgroups if applicable; and b) 
investigators must report annual accrual and progress in conducting 
analyses, as appropriate, by sex/gender and/or racial/ethnic group 
differences.

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

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

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

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

Applicants may wish to place data collected under this 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 PA 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, 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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