PROSPECTIVE STUDIES ON CRANIOFACIAL PAIN AND DYSFUNCTION
 
RELEASE DATE:  February 17, 2004
 
RFA Number:  RFA-DE-05-007 (See issuance of PAR-11-348)


(see clarification NOT-DE-04-005)

EXPIRATION DATE:  November 17, 2004

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(S) 93.121 Oral Diseases 
and Disorders Research
 
LETTER OF INTENT RECEIPT DATE: October 15, 2004
APPLICATION RECEIPT DATE: November 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 Principal Investigators
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 applications for a Cooperative Agreement (U01) to support a 
multi-site prospective cohort study of craniofacial pain and 
dysfunction.  For the purpose of this RFA, craniofacial pain and 
dysfunction will be defined as one or a combination of symptoms such as 
pain in the muscles of mastication, pain in the temporomandibular 
joint, facial neuropathies, locking and/or limitation of jaw opening. 

The primary purpose of this RFA is to encourage experienced and 
established investigators in the area of epidemiology to submit 
proposals for a prospective cohort study that will identify the 
incidence of craniofacial pain and dysfunction and its risk factors.   
Available cohort studies of craniofacial pain and dysfunction have 
several limitations including the lack of standardized procedures for 
measuring pain and/or dysfunction, study populations that consist of 
only people with pain, poor retention rates, cross-sectional or 
retrospective sampling and data analysis, and relatively short follow-
up time (3 years or less).  Applications responsive to this RFA must 
propose a prospective cohort study that addresses these limitations.
   
RESEARCH OBJECTIVES
 
Background

Chronic pain is a disabling and costly condition.  Headache, facial 
pain and craniofacial pain and dysfunction are highly prevalent in the 
general population and can lead to impaired quality of life, reduced 
effectiveness at work, home and school and may have social and economic 
impact including substantial use of health care resources for 
diagnostic and treatment procedures.   

Musculoskeletal diseases broadly present a major public health problem 
but prevalence data available for most of these conditions are 
extremely limited. According to several studies in the United States 
and Western Europe, approximately 38-57% of the population reports 
musculoskeletal pain. Craniofacial pain and dysfunction that affect the 
muscles and joints of the face, much like other painful musculoskeletal 
conditions such as fibromyalgia, are thought to have a multifactorial 
etiology that often makes diagnosis and management difficult. In 
addition, similar to painful musculoskeletal conditions, craniofacial 
pain and dysfunction lack objective diagnostic criteria that can easily 
and clearly differentiate people with the condition from those without 
it. 

To date, most epidemiologic studies of craniofacial pain and 
dysfunction only report prevalence rates. A review of the literature on 
craniofacial pain and dysfunction identified 11 studies that estimated 
the prevalence of pain in the face or jaws in children, adolescents and 
young adults.  In these studies, the prevalence of pain ranged from 0-
18% with a median value of 3%. However, only four of the studies were 
population-based and all of them were conducted outside of the U.S 
(Japan and Sweden). Overall, these population-based studies showed that 
although reported pain increased with age, craniofacial pain and 
dysfunction is relatively uncommon in children aged 7 through 17.  

Data from NHANES (1989) indicated that the prevalence of craniofacial 
pain and dysfunction ranged from 5% to 12% in the general population.  
In the US, approximately 10.8 million adults experience symptoms 
associated with craniofacial pain and nearly 2% of the general 
population seeks treatment for their symptoms.  The highest prevalence 
is observed in young adults (18-43 years) and declines rapidly in later 
years (55-74 years). Studies have indicated that both sexes are 
affected, but the majority of individuals seeking treatment are women.  

Prospective cohort studies are necessary to determine the incidence and 
risk factors for craniofacial pain and dysfunction.   Very few cohort 
studies have reported the incidence of craniofacial pain or even 
provided enough data to calculate it, but available data indicate that 
the incidence varies from 1.6% to 3.9% per year.  Only one study 
reported that the incidence was higher in women than in men and 
available prevalence and incidence data suggest that the age and gender 
of affected individuals may be similar to those of migraine; i.e. 
greater in females than in males, with incidence peaking in the teens 
and declining with increasing age. 

Several obstacles in determining the incidence of craniofacial pain and 
dysfunction exist. First, the incidence of this condition appears to be 
about two to three new cases per 100 people per year. To allow for 
sufficient cases, a large group of people without any initial history 
of craniofacial pain and dysfunction must be recruited and followed for 
a relatively long period of time.  Second, craniofacial pain and 
dysfunction is a recurrent condition and the case definition used in 
longitudinal studies is extremely important.  Similar problems are 
faced by longitudinal studies of other chronic musculoskeletal 
conditions such as low back pain, migraine and osteoarthritis.  

Factors that may be implicated in the etiology of craniofacial pain and 
dysfunction are: age, gender, stress, depression, presence of multiple 
somatic symptoms, orthodontic treatment, occlusal or masticatory 
dysfunction, extraction of third molars, facial trauma, and 
degenerative arthritis.  Tension-type headaches and fibromyalgia also 
have been associated with craniofacial pain and dysfunction.  

Because few prospective cohort studies assessing the onset of 
craniofacial pain and dysfunction have been conducted, definitive data 
on risk factors for these conditions are lacking. Therefore, it is 
important that well-designed prospective observational studies be 
conducted to gain a better understanding of the etiology, pathogenesis, 
and impact of these disorders on oral and general health so that 
effective preventive and treatment strategies can be developed.  

Scientific Aims

The overall aim of this RFA is to support a multi-site prospective 
cohort study of craniofacial pain and dysfunction.  For the purpose of 
this RFA, craniofacial pain and dysfunction will be defined as one or a 
combination of symptoms such as pain in the muscles of mastication, 
pain in the temporomandibular joint, facial neuropathies, locking 
and/or limitation of jaw opening. 

The multi-site study will consist of one Coordinating Center (CC) and 
at least two participating research sites.  The principal investigator 
will direct the Coordinating Center and should be an individual with 
extensive training or experience in epidemiology and the design of 
prospective cohort studies. 

It is expected that findings from this study will identify risk factors 
and document the incidence of craniofacial pain and dysfunction. The 
Coordinating Center (CC) will provide leadership in study design and 
analysis for the participating research sites. This study will assess 
risk factors for craniofacial pain and dysfunction and will include a 
clinical oral examination and collection of baseline blood samples for 
subsequent analysis. Participants will then be followed over time to 
identify risk factors that are associated with or predict the onset of 
craniofacial pain and dysfunction. The CC will provide overall study 
management, coordination, and data quality assurance. 

Research Scope

The Coordinating Center (CC) will have primary responsibility for: 1) 
study design and management, and 2) coordination and quality assurance 
of data.  The CC will have a leadership role in scientific and 
administrative matters such as development of study design, determining 
sample size and characteristics of the population to be included in the 
study, recommending recruitment strategies, and recruiting research 
sites to participate in the study.        

The CC staff will develop a database management system, informed 
consent procedures and a quality assurance program.  The CC will 
establish the study protocol and prepare a Manual of Procedures.  The 
CC also will develop data collection systems, assist in developing 
material to aid recruitment of participants, analyze study results, and 
review all manuscripts for statistical considerations.  The CC and 
research sites will develop a plan to store and retrieve blood samples 
collected from participants.  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 research 
sites, coordinate yearly meetings of all sites, create/maintain 
standardized protocols for study procedures, and conduct data analyses. 

The research sites will work with the CC in developing the protocol and 
Manual of Procedures to be used for the study.  It is their 
responsibility to adhere to all procedures as specified in the protocol 
and Manual of Procedures, i.e., patient recruitment, data and specimen 
collection, informed consent materials, etc., provide technical and 
administrative oversight and transmit accurate clinical data to the CC.   

To stimulate communications among the CC and the research sites, an 
Executive Committee (EC) must be established.  The EC will be composed 
of the Principal investigator of the CC (Chair), a NIDCR staff person 
and one key person from each of the participating research sites. The 
EC will review the study protocol and manuscripts; make decisions on 
operational issues; consider and adopt changes in study procedures as 
necessary; review the progress of the study in achieving its main 
goals; recommend necessary steps to enhance the likelihood of success; 
and review data collection practices and procedures as summarized in 
performance monitoring reports from the CC to identify and correct 
remediable deficiencies.  The EC will meet once per year in person and 
two times each year via teleconference.

Proposals responding to this RFA must provide a comprehensive plan that 
addresses the study design and statistical analysis, plans to insure 
adequate cohort size throughout the course of the study, data 
management and quality assurance, and overall coordination of the 
study.  The study design should include details regarding sample size 
estimates, population to be recruited, questionnaires to be 
administered, description of the clinical examinations to be done at 
baseline, description of collection of blood samples, intervals for 
follow-up and data to be collected in the follow-up visits.  Also, the 
proposal should identify the participating research sites and provide 
justification for their selection.  An outline of the proposed Manual 
of Procedures must be included in an Appendix to the application.  

MECHANISM OF SUPPORT
 
This RFA will use NIH U01 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 award date is August 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/archive/grants/policy/nihgps_2001/part_i_1.htm.  

The NIH U01 is a cooperative agreement award mechanism. In the 
cooperative agreement mechanism, the Principal Investigator retains the 
primary responsibility and dominant role for planning, directing, and 
executing the proposed project, with NIH staff being substantially 
involved as a partner with the Principal Investigator, as described 
under the section "Cooperative Agreement Terms and Conditions of 
Award".    

FUNDS AVAILABLE 
 
NIDCR intends to commit approximately $2.5 million in FY 05 to fund one 
new grant in response to this RFA. An applicant may request a project 
period of up to 7 years and a budget of up to $2.5 million total cost 
in the first year.  Future year costs will be held to no more than a 3% 
increase in total costs per year. 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.  
 
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. However, 
collaborations with Foreign institutions are allowed.

INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS   

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 RFA. It is recommended 
that the principal investigator of the CC be an individual with an 
advanced degree in epidemiology who has extensive experience in 
designing and managing prospective cohort studies. 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.

o Establishing appropriate mechanisms for quality control and 
monitoring.

o The design, methods, and procedures of the operation of the study
will be detailed in an awardee-prepared and maintained, study-adopted 
Manual of Procedures (MOP).  The participant sites 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 Coordinating Center Principal Investigator (CC PI) may be 
involved in performing specified support functions such as training and 
certification of coordinating center staff, 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.

2. Responsibilities of Research Sites

The generation of high–quality data in a multi-site setting will require 
continuous feedback of the sites to the CC.  The sites will be 
responsible for:

o Daily recruitment and follow-up

o Data collection

o Providing adequate and timely response to all pertinent requests from 
the CC

o Immediate reporting of problems in data collection, information flow 
and staff changes

3.   NIDCR Staff Responsibilities

The appropriate NIDCR program 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 study, 
including matters of quality control within and among various 
components, and in evaluating subject recruitment and compliance with 
the protocol of the study.

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 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 Executive Committee in routine performance monitoring of the 
entire study including matters of quality control within and among 
various study components, and in the determination of inadequate patient 
recruitment or failure of the participating research sites to comply 
with the protocol.

The NIDCR reserves the right to curtail, withhold, or terminate support 
of 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 protocol 
to which the NIDCR does not agree; or human subject ethical issues that 
dictate a premature termination.

4.  Collaborative Responsibilities

Executive Committee (EC): This committee will be composed of the 
the Principal Investigator of the Coordinating Center that serves as the 
Chair; the NIDCR Staff person; and investigators from each of the 
participating research site.  The EC makes decisions on day-to-day 
operational issues; considers and adopts changes in study 
procedures as necessary; reviews and implements recommendations from 
IRBs; reviews progress of the study in achieving its main 
goals and takes necessary 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.
 
5.  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.

6.  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 EC 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.

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:

Maria Teresa Canto, DDS, MPH
Director, Population Sciences Research Program
Clinical, Epidemiology & Behavioral Research Branch
Division of Population and Health Promotion Sciences
National Institute of Dental & Craniofacial Research 
National Institutes of Health 
45 Center Drive, Room 4AS43B
Bethesda, MD  20892-6401
Telephone:(301) 594-5497
Fax: (301) 480-8319
E-mail: maria.canto@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:

Robert L. Tarwater
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: 301-594-4836
Fax: 301-480-3562
E-mail: Robert.Tarwater@nih.gov
 
LETTER OF INTENT
 
Prospective applicants are asked to submit a letter of intent that 
includes the following information:

o Descriptive title of the proposed research
o Name, address, and telephone number of the Principal Investigator
o Names of other key personnel 
o Participating institutions
o Number and title of this RFA 

Although a letter of intent is not required, is not binding, and does 
not enter into the review of a subsequent application, the information 
that it contains allows 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:

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.
 
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:

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 the 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 merit review, all applications will:

o Undergo a process in which only those applications deemed to have the 
highest scientific merit, generally the top half of the applications 
under review, will be discussed and assigned a priority score
o Receive a written critique
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 evaluate the 
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 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.  For example, an investigator may propose to carry out 
important work that by its nature is not innovative but is essential to 
move a field forward.

SIGNIFICANCE: Does this approach address the main objectives of this 
RFA? 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? 

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  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 
coordinating center 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 The experience and qualifications of the PI and key staff in 
serving as a Coordinating Center.

o Previous experience of the Principal Investigator and key staff in 
developing epidemiological studies, especially prospective cohort 
studies, and effectively managing and coordinating multiple site 
studies.

o Adequacy of proposed study design for conducting a prospective study 
of a chronic musculoskeletal condition.
  
o Adequacy of proposed systems to be used for data management, quality 
control, data analysis, monitoring, and preparation of scientific 
publications.

o  Adequacy of the outline for the proposed Manual of Procedures.

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).

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.

RECEIPT AND REVIEW SCHEDULE

Letter of Intent Receipt Date: October 15, 2004
Application Receipt Date: November 16, 2004
Peer Review Date: March 2005
Council Review: May 2005
Earliest Anticipated Start Date: August 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.
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm 

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.

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

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

Applicants may wish to place data collected under this 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.healthypeople.gov/.

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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