GENERAL DENTAL PRACTICE-BASED RESEARCH NETWORK
 
RELEASE DATE:  November 18, 2003
 
RFA Number:  RFA-DE-05-006 (see NOT-DE-04-001 and NOT-DE-04-003)

Department of Health and Human Services (DHHS)
  
PARTICIPATING ORGANIZATION:
National Institutes of Health (NIH)
 (http://www.nih.gov)

COMPONENT OF PARTICIPATING ORGANIZATION:
National Institute of Dental and Craniofacial Research (NIDCR)
 (http://www.NIDCR.nih.gov) 

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER 
93.121 Oral Diseases and Disorders Research
 
LETTER OF INTENT RECEIPT DATE: June 18, 2004
APPLICATION RECEIPT DATE: July 16, 2004  
 
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 Network Chairs
o Special Requirements
o Where to Send Inquiries
o Letter of Intent
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

PURPOSE OF THIS RFA 

The National Institute of Dental and Craniofacial Research (NIDCR) 
invites cooperative agreement applications to establish and support a 
dental Practice-Based Research Network (PBRN). For each PBRN supported 
under this RFA, the NIDCR will support one Network Chair and one 
Coordinating Center to plan, implement and maintain a general dental 
PBRN. The primary purpose of grants funded under this RFA is to provide 
an infrastructure to conduct multiple clinical trials and prospective 
observational studies that will answer questions facing general dental 
practitioners in the routine care of their patients. The PBRN 
infrastructure must provide a flexible and adaptable electronic 
communications network/platform that will provide a common means for 
connectivity, data sharing, and communication within the PBRN and with 
other medical and dental PBRNs currently in existence or that may be 
created in the future. At least 100 dental practices will be recruited 
to participate in the network during the first year of operation.  

Applicants for the Network Chair and Coordinating Center must prepare 
separate applications for peer review and must submit them jointly as a 
package. Peer review of the paired applications will primarily focus on 
the capability and capacity of the Network Chair and Coordinating 
Center to conduct the required activities (see REVIEW CRITERIA AND 
ADDITIONAL REVIEW CRITERIA).

Substantial involvement between the funded investigators and NIDCR 
staff is anticipated in the selection of hypotheses, trial and protocol 
design, monitoring of progress, and analysis and publication of data.  
 
RESEARCH OBJECTIVES
 
Background

Practice-based research networks can generate important and timely 
information to guide the delivery of health care and improve patient 
outcomes. Many of the unique questions faced by dental health 
practitioners on a daily basis are most appropriately addressed in 
dental practice settings in the context of the oral health care 
delivery system. Indeed, the recent American Dental Association Future 
of Dentistry Report specifically recommended that national clinical 
research networks be established that link treatment approaches and 
outcomes in private practice settings.  By connecting practitioners 
with experienced clinical investigators, PBRNs can enhance the clinical 
research agenda of the NIDCR and produce findings that are immediately 
relevant to practitioners and their patients.  PBRNs can support a 
variety of clinical studies with clear and easily defined outcome 
measures, and they typically draw on the experience and insight of 
practicing clinicians to help identify and frame research questions.  
Because research is conducted in the real-world environment of dental 
practice, results are more likely to be readily accepted and adopted by 
practitioners and translated into daily practice.  Moreover, because 
PBRNs use the existing personnel and infrastructure of established 
dental practices, certain types of clinical studies can be conducted in 
a cost-effective manner.
 
Scientific Aims  

The overall objective of the RFA is to develop a PBRN to accelerate the 
development and conduct of clinical trials and clinical studies on 
important issues concerning oral health care related to general dental 
practice.  The PBRN will perform relatively short-term, clinical 
studies, with emphasis on comparing the effectiveness of various oral 
health treatments, preventive regimens, and dental materials.  The 
primary objective of each study carried out by the PBRN will be to 
strengthen the knowledge base for clinical decision-making by testing 
particular clinical approaches and evaluating the effectiveness of 
strategies for the prevention, management and treatment of oral 
diseases and conditions.  

Secondary objectives of the PBRN will be to conduct anonymous chart 
reviews as allowed by HIPPA, to provide data on disease and treatment 
trends, and to obtain estimates of the prevalence of less common 
conditions.
 
Research Scope

The proposed network would perform approximately 16 to 22 short-term, 
clinical trials and clinical studies during the 7-year project period 
focusing on general dental practice.  The specific protocols to be 
carried out by the PBRN will be determined according to procedures 
detailed below, after the network is established.

Some examples of research topics that could be addressed in well-
designed clinical studies and would be appropriate for the PBRN 
include, but are not limited to, the following:

o Effectiveness of various methods for restoring fractured teeth

o Short-term pulpal consequences of restorative and pulp capping 
procedures
 
o Comparative studies of implant vs. fixed or removable prosthetic 
replacement of lost teeth
 
o Utility and short-term effectiveness of various temporary 
restorations 

o Utility of various forms of periodontal instrumentation

o Short-term failure rates of various restorative materials for 
specific types of restorations

o Trends in composite and amalgam use for posterior class I and II 
restorations
  
o Estimates of the prevalence of xerostomia

Applications submitted in response to this RFA should not propose 
specific clinical studies to be conducted by the PBRN. 

Project Organization  

The PBRN will be composed of a Network Chair, a Coordinating Center 
(CC), an Executive Committee (EC), a Protocol Review Committee (PRC), a 
Data and Safety Monitoring Board (DSMB), 100 or more participating 
practices, and designated NIDCR staff.  The responsibilities of each 
component of the PBRN are described below.  

The NIDCR will be responsible for organizing and providing support for 
the PBRN and will be involved substantially with the awardees as a 
partner in providing overall scientific guidance, consistent with the 
Cooperative Agreement mechanism. A designated NIDCR staff person will 
monitor subject recruitment and study progress, ensure disclosure of 
conflicts of interest and adherence to NIDCR policies, and serve on the 
Executive and Protocol Review Committees.  The NIDCR staff person, 
together with the NIDCR Grants Management Specialist, will provide 
fiscal oversight of the network, including calculation of capitation 
budget rates and awards.  The NIDCR, in collaboration with the Network 
Chair and Coordinating Center Principal Investigator, will appoint the 
DSMB.

Network Chair

The Network Chair, in collaboration with NIDCR, will provide overall 
scientific leadership for the network. The Chair will be responsible 
for the following activities: stimulating and soliciting ideas for new 
studies from practitioner-investigators; providing oversight of 
development of protocols; operational and fiscal management of the 
network; and arranging meetings and conference calls of the Executive 
Committee and the Protocol Review Committee.

With the assistance from the Coordinating Center and in consultation 
with the NIDCR, the Network Chair will also: 1) develop requirements 
for participation of practitioner-investigators, 2) recruit and select 
practitioner-investigators, 3) develop clinical research training 
procedures and materials for practitioner-investigators, 4) conduct 
clinical research training and certification of practitioner-
investigators and their staff, 4) monitor the performance of 
practitioner-investigators, 5) develop systems to assist practitioner-
investigators in maintaining high rates of patient recruitment and 
retention, 6) host an annual research meeting for participating 
practitioner-investigators, 7) inform network participants of progress 
in protocol development and study-related issues, and 8) assume a 
leadership role in manuscript preparation and administrative issues 
related to the network.

The Network Chair will serve as Chair of the Executive Committee and as 
the non-voting Executive Secretary of the Protocol Review Committee.  
Other responsibilities of the Network Chair include: building community 
awareness and participation in the network, assisting in obtaining 
Institutional Review Board (IRB) approval for PBRN protocols, assisting 
investigator-practitioners and participating practices in obtaining a 
Federal Wide Assurance from the Office of Human Research Protection
(http://www.hhs.gov/ohrp) and preparing budgets and annual reports. 
The practitioner-investigators will be supported as subcontractors to 
the Network Chair.

Coordinating Center (CC)

The Coordinating Center will have both scientific and administrative 
functions.  The CC will arrange for meetings and conference calls of 
the DSMB.  CC staff will develop a database management system, informed 
consent procedures, a quality assurance program, and assist with IRB 
approvals. The CC will assist in the preparation of study protocols and 
Manuals of Procedures including the statistical design of each study. 
The CC will also develop data collection systems, assist in developing 
materials to aid recruitment of practitioner-investigators and 
patients, analyze study results, and review all manuscripts for 
statistical considerations.  The Principal Investigator of the CC will 
be a member of the Executive Committee. Other specific responsibilities 
of the CC will be to: coordinate site visits, prepare site visit 
agendas, prepare site visit reports, review performance of all 
participating practices, coordinate activities of the DSMB, develop and 
implement a system for adverse event reporting, create/maintain modular 
standardized protocols for study procedures, and conduct data analyses 
for the DSMB.  

While the initial focus of the PBRN is on forming a network of general 
dentists, the Network Chair and CC PI should also be prepared to 
recruit and coordinate ad-hoc networks of dental specialists as needed 
for specific study questions.  

The CC will establish an IRB that will meet all federal requirements 
and regulations and will serve as the IRB of record for all of the 
participating practices.

Data and Safety Monitoring Board (DSMB)

The DSMB will be composed of individuals not directly involved in 
patient care or data collection in the network.  The DSMB will be 
responsible for periodically reviewing accumulated data for evidence of 
adverse or beneficial treatment effects; for initiating recommendations 
for modification of study protocols, including termination of the 
treatment protocol when appropriate; and for assessing data quality and 
clinic performance.  The DSMB will operate in a manner consistent with 
the NIDCR guidelines for Data and Safety Monitoring of Clinical Trials 
(http://www.nidcr.nih.gov/clinicalTrials/data_Safety_Guidelines.asp).
  
Executive Committee (EC)

The Executive Committee will be composed of the Network Chair, who 
serves as Chair of the EC; the Principal Investigator of the 
Coordinating Center; the NIDCR Staff person; and five to six 
representative practitioner-investigators from the practice-based 
network who will serve for a fixed term of three years upon election by 
the full group of PBRN practitioner-investigators.  The EC will act as 
the administrative and executive arm of the PBRN and as the main 
governing body of the network.  The EC will prioritize research topics 
for protocol development, review protocols prior to submission to the 
Protocol Review Committee, and may make suggestions for submission of 
manuscripts.  The EC will make decisions on operational issues; consider 
and adopt changes in study procedures as necessary; review and implement 
recommendations from the IRB(s) and DSMB; review the progress of studies 
in achieving their main goals and take steps required to enhance 
likelihood of success; and review data collection practices and 
procedures as summarized in performance monitoring reports from the 
Coordinating Center to identify and correct remediable deficiencies.  
The EC will meet once per year in person and two or three times each 
year via teleconference.  

Protocol Review Committee (PRC)

A Protocol Review Committee composed of approximately eight individuals 
with expertise in clinical research, dental research, biostatistics, 
PBRNs, and clinical trial design and methodology will be organized by 
the NIDCR, with input from the Network Chair and Principal Investigator 
of the Coordinating Center.  It will include NIDCR representatives as 
well as extramural scientists independent of the network.  The PRC will 
give final approval to the therapeutic agents and procedures to be 
tested and approve study protocols prior to submission to the DSMB.  The 
Network Chair will serve as the non-voting Executive Secretary of the 
PRC.  Protocols will be open in the network for patient accrual only 
after approval by the PRC, IRB(s) and the DSMB.  The PRC will have an 
initial orientation meeting in the Washington, D.C. area during the 
first year.  Thereafter, annual meetings will be held.  Conference calls 
to review protocols, proposed protocol changes, and to discuss inclusion 
of new agents and/or procedures in the network will be held as needed 
via teleconference.

Practitioner-investigators
 
Practitioner-investigators are defined in the PBRN as dentists and 
dental hygienists who are engaged in the daily practice of dentistry and 
dental hygiene in the participating practices of the PBRN network. They 
will be responsible for suggesting ideas for studies to the Network 
Chair; for carrying out study protocols and for adhering to network 
rules on patient recruitment, retention, and randomization; for 
recording and reporting results, participating in training, conforming 
with IRB, DSMB and HIPPA regulations, reporting adverse events, and for 
attending the annual PBRN meeting for practitioner-investigators. 
Practitioner–investigators, either directly or through their elected 
representatives to the Executive Committee, will have an active role in 
all aspects of the project including suggesting ideas for study, 
protocol development and publication of results.  Up to six 
practitioner-investigators will serve on the Executive Committee for 3-
year terms.  The practitioner-investigators must be representative of 
the gender and racial/ethnic distribution of the dentists in the region 
from which the network is formed.  Participating practices must be also 
drawn from a region encompassing more than one state and one population 
center.  A limited number of practices may be located outside the 
United States, provided that the standard of dental care in their 
country is comparable to the standard of care in the U.S. Practitioner-
investigators will be supported as subcontractors to the Network Chair.

MECHANISM OF SUPPORT
 
This RFA will use the NIH UO1 award mechanism.  As an applicant you 
will be solely responsible for planning, directing, and executing the 
proposed project.  This RFA is a one-time solicitation.  Future 
unsolicited, competing-continuation applications based on this project 
will compete with all investigator-initiated applications and will be 
reviewed according to the customary peer review procedures. The 
earliest anticipated start date is March 2005. 

This RFA uses just-in-time concepts.  This program does not require 
cost sharing as defined in the current NIH Grants Policy Statement at 
http://grants.nih.gov/grants/policy/nihgps_2001/part_i_1.htm.

The NIH U01 is a cooperative agreement award mechanism.  In the 
cooperative agreement mechanism, the Network Chair and the Coordinating 
Center PI retain the primary responsibility and dominant role for 
planning, directing, and executing the proposed project, with NIH staff 
being involved as a partner with them, as described under the section 
"Cooperative Agreement Terms and Conditions of Award"  
 
FUNDS AVAILABLE
 
Applicants may request a project period of up to 7 years. The NIDCR 
intends to commit approximately $2 million (direct costs) in FY 2005, 
$4 million (direct costs) in FY 2006 and 2007, and $5 million (direct 
costs) in FY 2008, 2009, 2010, and 2011 to fund this RFA. The available 
funds will be used to support the Coordinating Center, Network Chair, 
and practitioner-investigators for each PBRN. The number of PBRNs that 
will be supported by the NIDCR under this RFA has not been established 
and will depend on: 1) the merit of submitted applications as evaluated 
by peer review, 2) secondary review by the National Advisory Dental & 
Craniofacial Research Council, 3) budgetary requirements of submitted 
applications, and 4) programmatic priorities of the NIDCR. Although the 
financial plans of the NIDCR provide support for this program, awards 
pursuant to this RFA are contingent upon the availability of funds and 
the receipt of a sufficient number of meritorious applications.  
 
There will be an administrative review organized by the NIDCR after 
approximately four years to determine if the network(s) and each of its 
components have been performing as envisioned in terms of patient 
recruitment and implementation of protocols of importance to the field.  
Based on this review, a decision will be made by the NIDCR whether to 
continue the research activities as planned, to refocus the activities, 
or to plan for an orderly closeout of the network(s).
 
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 institutions/organizations
o Foreign institutions are not eligible to apply.  
 
INDIVIDUALS ELIGIBLE TO BECOME NETWORK CHAIRS 

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.  

INDIVIDUALS ELIGIBLE TO BECOME COORDINATING CENTER PIs 

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

Cooperative Agreement Terms and Conditions of Award

These special Terms and Conditions of Award are in addition to and not 
in lieu of otherwise applicable Office of Management and Budget 
administrative guidelines, Department of Health and Human Services 
(DHHS) grant administration regulations at CFR Parts 74 and 92, as 
applicable, and other DHHS, PHS, and NIH Grant Administration policy 
statements.

The administrative and funding instrument used for this program will be 
the cooperative agreement, an “assistance” mechanism (rather than an 
“acquisition” mechanism), in which substantial NIH programmatic 
involvement with the awardees is anticipated during performance of the 
activities.  Under the cooperative agreement mechanism, the NIDCR’s 
purpose is to support and stimulate the recipients’ activities by 
involvement in and otherwise working jointly with the award recipients 
in a partnership role as described below; it is not to assume 
direction, prime responsibility, or a dominant role in the activities.  
Consistent with this concept, the dominant role and primary 
responsibility resides with the awardees for the project as a whole.

1.  Awardee Rights and Responsibilities

o Awardees have primary authorities and responsibilities to define 
objectives and approaches, and to plan, conduct, analyze, and publish 
results, interpretations, and conclusions of their studies in 
conjunction with NIDCR, who will be a partner in all analyses and 
publications, and in accordance with the oversight roles of the EC and 
the Protocol Review Committee.

o The design, methods, and procedures of the operation of the network 
and the studies conducted will be detailed in an awardee-prepared and 
maintained, study-adopted Manual of Procedures (MOP) for each study in 
the PBRN.  The awardees will have the responsibility of following the 
MOP.

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 DHHS, PHS, and NIH policies.  

o The Network Chair is responsible for the overall conduct of the 
network and for providing scientific, technical, and administrative 
leadership.  She/he will have lead responsibility for planning and 
directing all phases of each study and for using the network's 
resources.  In carrying out these responsibilities, the network Chair 
will actively seek advice from all of the network's components, 
including the representative of the NIDCR.

o The Network Chair agrees to the governance of the network through an 
EC. The Executive Committee voting membership will consist of the 
Network Chair, who serves as Chair; the Principal Investigator of the 
Coordinating Center; the NIDCR Staff person; and five to six 
investigators from the practice based network who will serve for a 
fixed term of three years upon election by the full group of PBRN 
Investigators.

o The Coordinating Center Principal Investigator (CC PI) may be 
involved in performing specified support functions such as training and 
certification of coordinating center staff, and designing and 
maintaining quality assurance programs, managing data, analyzing data, 
and preparing publications.  The CC PI is responsible for all aspects 
of the operations of the Coordinating Center and for the local 
implementation of study protocols.

o At their practices, practitioner-investigators have the primary 
responsibility, as specified in each study protocol, of identifying and 
recruiting eligible patients, carrying out study protocols, overseeing 
procedures and follow-up for each patient enrolled in clinical studies, 
and for submitting required data to the Coordinating Center.  
Practitioner-investigators are also responsible for ensuring that their 
practice personnel are trained and certified to carry out study 
procedures.  

2.  NIDCR Staff Responsibilities

The appropriate NIDCR staff person whose name appears on the Notice of 
Grant Award will be responsible for normal stewardship responsibilities 
such as routine performance monitoring of the network, including 
matters of quality control within and among various components, and in 
evaluating patient recruitment and compliance with protocol of studies 
conducted in the network.

In addition, the named NIDCR staff person will have substantial 
programmatic involvement, above and beyond normal stewardship, and will 
participate with and assist, but not direct:

o the Network Chair and the Coordinating Center PI in the nomination 
and selection of an independent DSMB,

o the Network Chair, Coordinating Center PI, and Executive Committee in 
assuring that patient information handbooks, recruitment information, 
press releases, and publicity exhibits are properly prepared and 
disseminated,

o the Network Chair and the Coordinating Center PI in identifying 
additional participating practices and practitioner-investigators when 
needed to enhance patient recruitment,

o the Executive Committee in routine performance monitoring of the 
entire study including matters of quality control within and among 
various components, and in the determination of inadequate patient 
recruitment or failure to comply with the protocol on the part of 
individual practitioner-investigators,

o the Executive Committee in prioritizing research topics for protocol 
development and  review of protocols prior to submission to the 
Protocol Review Committee, and 

o the DSMB as an ex officio member and will participate in all 
deliberations of the DSMB, such as decisions to proceed from one phase 
of the study to the next, implementation of protocol changes, 
evaluation of patient recruitment, approval of any ancillary studies, 
planning data analyses, announcing study findings, and determining the 
timing of release of any reports.

A Protocol Review Committee (PRC) composed of approximately eight 
individuals with appropriate expertise will be organized by the NIDCR 
with input from the Network Chair and Coordinating Center PI. This 
Committee will give final approval to the therapeutic agents and 
procedures to be tested and approve study protocols prior to submission 
to the Data and Safety Monitoring Board (DSMB).  Protocols will be open 
in the network for patient accrual only after approval by the PRC, 
DSMB, and IRBs.  

The NIDCR reserves the right to curtail, withhold, or terminate support 
for the study; for an individual award; or for support of a 
participating consortium in situations involving: inadequate patient 
recruitment, follow up, data reporting or quality control; a major 
breach of the study protocol; a substantive change in the set protocol 
to which the NIDCR does not agree; statistical evidence that the major 
study endpoint has been reached ahead of schedule; or human subject 
ethical issues that dictate a premature termination.  Prior to taking 
such actions, NIDCR will consult with and receive recommendations from 
the DSMB.

3.  Collaborative Responsibilities

Data and Safety Monitoring Board (DSMB): A group composed of 
individuals not directly involved in patient care or data collection in 
the trial, who are responsible for periodically reviewing accumulated 
data for evidence of adverse or beneficial treatment effects; for 
initiating recommendations for modification of the study protocol, 
including termination of the treatment when appropriate; and for 
assessing data quality and clinic performance.  The NIDCR, in 
collaboration with the Network Chair and Coordinating Center Principal 
Investigator, will appoint the DSMB.  The DSMB will operate in a manner 
consistent with the NIDCR guidelines for Data and Safety Monitoring of 
Clinical Trials 
(http://www.nidcr.nih.gov/clinicalTrials/data_Safety_Guidelines.asp).

Executive Committee (EC): This committee will be composed of the 
Network Chair, who serves as Chair; the Principal Investigator of the 
Coordinating Center; the NIDCR Staff person; and five to six 
investigators from the practice based network who will serve for a 
fixed term of three years upon election by the full group of PBRN 
Investigators.  It acts as the administrative and executive arm of the 
PBRN and as the main governing body of the network. It makes decisions 
on day-to-day operational issues; considers and adopts changes in study 
procedures as necessary; reviews and implements recommendations from 
the IRB and DSMB; reviews progress of studies in achieving their main 
goals and takes steps required to enhance likelihood of success; and 
reviews data collection practices and procedures as summarized in 
performance monitoring reports from the Coordinating Center to identify 
and correct remediable deficiencies.
 
4.  Outside Participation

Support or other involvement of industry or any other third party in 
the study--e.g., participation by the third party; involvement of study 
resources or citing the name of the study or NIDCR support; or special 
access to study results, data, findings, or resources--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 of and concurrence by NIDCR.

5.  Arbitration

Any disagreement that may arise on scientific/technical matters within 
the scope of the award between award recipients and the NIDCR may be 
brought to arbitration.  An arbitration panel will be composed of three 
members, one member selected by the Network Chairperson, a second 
member selected by the NIDCR, and a third member selected by the two 
prior selected members.  This special arbitration procedure in no way 
affects the awardee's rights to appeal an adverse action that is 
otherwise appealable in accordance with PHS regulations at 42 CFR Part 
50, subpart D, and DHHS regulations at 45 CFR Part 16.

DATA AND SAFETY MONITORING IN CLINICAL TRIALS

Applicants are directed to the full text of the NIH Policies regarding 
Data and Safety Monitoring and Reporting of Adverse Events that are 
found in the NIH Guide for Grants and Contracts Announcements at the 
following web sites:
http://grants.nih.gov/grants/guide/notice-files/not98-084.html; 
http://grants.nih.gov/grants/guide/notice-files/not99-107.html;
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-038.html

All applicants receiving an award under this RFA must comply with the 
NIH policy cited in these NIH Announcements and any other data safety 
and monitoring requirements found elsewhere in this RFA.

Data and Safety Monitoring is required for every clinical trial.  
Monitoring must be performed on a regular basis and the conclusions of 
the monitoring reported to the extramural Program Director.

The type of data safety and monitoring required will vary based on the 
type of clinical trial and the potential risks, complexity and nature 
of the trial.  A plan for data and safety monitoring is required for 
all clinical trials.

The DSMB/Plan is established at the time the protocol is developed and 
must be approved by both the Institutional Review Board (IRB) and the 
Government and be in place before the trial begins.  If the protocol 
will be developed during the research funded under this RFA, a general 
description of the data and safety monitoring plan must be submitted as 
part of the proposal and will be reviewed by the initial review group.  

Monitoring plans, at a minimum, must include the prompt reporting of 
adverse events to the IRB, Food and Drug Administration (if applicable) 
and NIH.  The frequency of reporting of the conclusions of the 
monitoring activities should also be described in the plan. Examples of 
monitoring activities to be considered are described in the NIH Policy 
for Data and Safety Monitoring at 
http://grants.nih.gov/grants/guide/notice-files/not98-084.html.

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:

Bruce Pihlstrom, D.D.S., M.S.
Division of Population Sciences and Health Promotion
National Institute of Dental and Craniofacial Research
National Institutes of Health
Building 45, Room 4AS-43G
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:

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:  George.Hausch@nih.gov

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

Mary Daley
Division of Extramural Activities
National Institute of Dental and Craniofacial Research
Building 45, Room 4AN-44B
Bethesda, MD  20892-6402
Telephone:  (301) 594-4800
FAX:  (301) 480-3562
Email:  daleym@mail.nih.gov   

Pre-application consultation with NIDCR staff is encouraged.  In 
addition, there will be at least one Technical Assistance Workshop 
conducted by NIDCR staff, currently planned for January or February, 
2004, that potential applicants may wish to attend. Topics to be 
discussed will include this RFA, the application procedure and review 
process. A notice will be placed in the NIH Guide announcing this 
workshop. 

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 Names, addresses, and telephone numbers of the Network Chair and 
Coordinating Center Principal Investigator
o Names of other key personnel 
o Number and title of this RFA 

Although a letter of intent is not required, is not binding, and does 
not enter into the review of a subsequent application, the information 
that it contains allows NIDCR staff to estimate the potential review 
workload and plan the review.
 
The letter of intent is to be sent by the date listed at the beginning 
of this document.  The letter of intent should 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
Telephone:  (301) 594-2904
FAX:  (301) 480-8303
Email:  George.Hausch@nih.gov

SUBMITTING AN APPLICATION

Applications must be prepared using the PHS 398 research grant 
application instructions and forms (rev. 5/2001). 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 DUNS number can be obtained by calling 
(866) 705-5711 or through the web site at 
http://www.dunandbradstreet.com/. The DUNS number should be entered on 
line 11 of the face page of the PHS 398 form. The PHS 398 document 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.
 
SUPPLEMENTARY INSTRUCTIONS: 

In order to be considered, applicants for the Network Chair and 
Coordinating Center must each prepare separate applications for peer 
review and must submit them jointly as a package together with a cover 
letter indicating that the applications are being submitted as a 
package in response to RFA-DE-05-006. See the description of the roles, 
responsibilities and requirements in the RESEARCH OBJECTIVES section 
that should be addressed in the applications.

Budgets should describe funding to be used to offset participation 
costs for the participating dentists and the cost of an annual meeting 
of the network. Funding may not be requested for the purchase of 
expensive equipment.

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/labels.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 and 
all copies of the appendix material 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
Telephone:  (301) 594-2904
FAX:  (301) 480-8303
Email:  George.Hausch@nih.gov
 
APPLICATION PROCESSING: Applications must be received on or before the 
application receipt date listed in the heading of this RFA.  If an 
application is received after that date, it will be returned to the 
applicant without review.  

Although there is no immediate acknowledgement of the receipt of an 
application, applicants are generally notified of the review and 
funding assignment within 8 weeks.
 
The Center for Scientific Review (CSR) will not accept any application 
in response to this RFA that is essentially the same as one currently 
pending initial review, unless the applicant withdraws the pending 
application.  However, when a previously unfunded application, 
originally submitted as an investigator-initiated application, is to be 
submitted in response to an RFA, it is to be prepared as a NEW 
application.  That is, the application for the RFA must not include an 
Introduction describing the changes and improvements made, and the text 
must not be marked to indicate the changes from the previous unfunded 
version of the application.  

PEER REVIEW PROCESS 
 
Upon receipt, applications will be reviewed for completeness by the CSR 
and responsiveness by NIDCR.  Incomplete and/or nonresponsive 
applications will not be reviewed.  

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 scientific review, all 
applications 
 
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 written critique
o Receive a second level review by the National Advisory Dental 
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 evaluate the paired 
Network Chair and Coordinating Center applications in order to judge 
the likelihood that the proposed approach will have a substantial 
impact on the pursuit of these goals.  The scientific review group will 
address and consider each of the following criteria in assigning the 
application’s overall score, weighting them as appropriate for each 
application.  

o Significance 
o Approach 
o Innovation
o Investigator
o Environment
 
The application does not need to be strong in all categories to be 
judged likely to have major scientific impact and thus deserve a high 
priority score.  

SIGNIFICANCE: Does this approach address the main objectives of the 
PBRN? If the aims of the application are achieved, how will scientific 
knowledge be advanced?
 
APPROACH: Are the conceptual framework, design, methods, and analyses 
adequately developed, well-integrated, and appropriate to the aims of 
the project? Does the applicant acknowledge potential problem areas and 
consider alternative tactics?

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

INVESTIGATOR: Are the investigators appropriately trained and well 
suited to carry out this work? Is the work proposed appropriate to the 
experience level of the Network Chair and Principal Investigator of the 
Coordinating Center and other researchers?

ENVIRONMENT: Does the scientific environment in which the work will be 
done contribute to the probability of success? Does the proposed 
network 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 considered in the determination of scientific 
merit and the priority score in determining the capability and capacity 
to carry out the required activities.

o Adequacy of the proposed methods for ensuring that the composition of 
the PBRN is representative of the gender and racial/ethnic distribution 
of the dentists in the state or states where they are forming the 
network.

Additional scientific/technical merit criteria specific to the 
objectives of this RFA for the Network Chair include:

o The likelihood that the PBRN will provide an infrastructure to 
conduct multiple clinical trials and prospective observational studies 
that will answer questions facing general dental practitioners in the 
routine care of their patients.

o The experience, qualifications, and administrative experience of the 
Network Chair and staff in conducting clinical trials and/or clinical 
research studies.  

o The experience and qualifications of the Network Chair and staff in 
clinical dental / oral health research.  

o Experience of the Network Chair in the effective management and 
coordination of a practice based research network or a multicenter 
trial or clinical research study.

o Adequacy of the proposed overall administrative organizational 
structure and procedures for managing and coordinating the network 
activities, committees, and collaborative arrangements.

o Capacity to recruit and retain practitioner-investigators into a 
PBRN, as well as the ability to recruit and retain specialty practices 
if needed.

Additional scientific/technical merit criteria specific to the 
objectives of this RFA for the Coordinating Center include:

o The experience and qualifications of the PI and key staff in 
conducting clinical trials and/or clinical research studies and serving 
as a Coordinating Center.

o Previous experience of the Principal Investigator and key staff in 
developing clinical trial protocols and effectively managing and 
coordinating multicenter clinical trials or clinical research studies.

o Adequacy of proposed systems to be used for randomization, data 
management, quality control, data analysis, clinic monitoring, and 
preparation of scientific publications.

o Adequacy of plans to provide a flexible and adaptable electronic 
communications network/platform that will provide a common means for 
connectivity, data sharing, and communication within the PBRN and with 
other medical and dental PBRNs currently in existence or that may be 
created in the future.  

PROTECTION OF HUMAN SUBJECTS FROM RESEARCH RISK: The involvement of 
human subjects and protections from research risk relating to their 
participation in the proposed research will be assessed.  (See criteria 
included in the section on Federal Citations, below).
 
INCLUSION OF WOMEN, MINORITIES AND CHILDREN IN RESEARCH: The adequacy 
of plans to include subjects from both genders, all racial and ethnic 
groups (and subgroups), and children as appropriate for the scientific 
goals of the research.  Plans for the recruitment and retention of 
subjects will also be evaluated.  (See Inclusion Criteria in the 
sections on Federal Citations, below).

CARE AND USE OF VERTEBRATE ANIMALS IN RESEARCH: If vertebrate animals 
are to be used in the project, the five items described under Section f 
of the PHS 398 research grant application instructions (rev.  5/2001) 
will be assessed.  

ADDITIONAL REVIEW CONSIDERATIONS

Sharing Research Data 
Applicants requesting $500,000 or more in direct costs in any year of 
the proposed research must include a data sharing plan in their 
application.  The reasonableness of the data sharing plan or the 
rationale for not sharing research data will be assessed by the 
reviewers.  However, reviewers will not factor the proposed data 
sharing plan into the determination of scientific merit or priority 
score.   

BUDGET: The reasonableness of the proposed budget and the requested 
period of support in relation to the proposed research will be 
evaluated. The Network Chair’s budget should include the estimated 
aggregate cost for support of the participating practices. After 
protocols have been developed NIDCR will work with the National Chair 
to determine core budgets and capitation rates for each practice.

RECEIPT AND REVIEW SCHEDULE

Letter of Intent Receipt Date: June 18, 2004
Application Receipt Date: July 16, 2004
Peer Review Date: October – November 2004
Council Review: January 2005
Earliest Anticipated Start Date: March 2005

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 

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.
/humansubjects/guidance/45cfr46.htm 

DATA AND SAFETY MONITORING PLAN: Data and safety monitoring is required 
for all types of clinical trials, including physiologic, toxicity, and 
dose-finding studies (phase I); efficacy studies (phase II); efficacy, 
effectiveness and comparative trials (phase III).  The establishment of 
data and safety monitoring boards (DSMBs) is required for multi-site 
clinical trials involving interventions that entail potential risk to 
the participants.  (NIH Policy for Data and Safety Monitoring, NIH 
Guide for Grants and Contracts, June 12, 1998: 
http://grants.nih.gov/grants/guide/notice-files/not98-084.html).  

SHARING RESEARCH DATA:  Starting with the October 1, 2003 receipt date, 
investigators submitting an NIH application seeking $500,000 or more in 
direct costs in any single year are expected to include a plan for data 
sharing or state why this is not possible.  
http://grants.nih.gov/grants/policy/data_sharing Investigators should 
seek guidance from their institutions, on issues related to 
institutional policies, local IRB rules, as well as local, state and 
Federal laws and regulations, including the Privacy Rule.  Reviewers 
will consider the data sharing plan but will not factor the plan into 
the determination of the scientific merit or the priority score.

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

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

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

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

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

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

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

STANDARDS FOR PRIVACY OF INDIVIDUALLY IDENTIFIABLE HEALTH INFORMATION: 
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).  
Those who must comply with the Privacy Rule (classified under the Rule 
as “covered entities”) must do so by April 14, 2003 (with the exception 
of small health plans which have an extra year to comply).  

Decisions about applicability and implementation of the Privacy Rule 
reside with the researcher and his/her institution.  The OCR website 
(http://www.hhs.gov/ocr/) 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 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.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.  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 at http://www.cfda.gov/ and is not subject 
to the intergovernmental review requirements of Executive Order 12372 
or Health Systems Agency review.  Awards are made under the 
authorization of Sections 301 and 405 of the Public Health Service Act 
as amended (42 USC 241 and 284)  and under Federal Regulations 42 CFR 
52 and 45 CFR Parts 74 and 92 .  All awards are subject to the terms 
and conditions, cost principles, and other considerations described in 
the NIH Grants Policy Statement.  The NIH Grants Policy Statement can 
be found at http://grants.nih.gov/grants/policy/policy.htm  

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

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