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: email@example.com 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) 710-0267, 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. References de Bont LGM, Dijkgraaf LC, Stengenga B. Epidemiology and natural progression of articular temporomandibular disorders. Oral Surg Oral Med Oral Pathol Oral Radio Endod 1997;83:72-6. Carlsson GE, LeResche L. Epidemiology of Temporomandibular Disorders. Temporomandibular Disorders and Related Pain Conditions. Progress in Pain Research and Management, Vol. 4, edited by B.J. Sessle, P.S. Bryant and R.A. Dionne, IASP Press, Seattle, 1995. Drangsholt M, LeResche L. Temporomandibular Disorder Pain. Epidemiology of Pain, edited by I.K. Crombie, IASP Press, Seattle, 1999. Eisenberg DM, Kessler RC, Foster C, et. al. Unconventional medicine in the United States. Prevalence, costs, and patterns of use. New Engl J Med 1993;328:246-52. Gran JT. The epidemiology of chronic generalized musculoskeletal pain. Best practice & Research Clinical Rheumatology 2003;17:547-61. Kuttila M, Kuttila S, LeBell Y, Alanan P. Association between TMD treatment need, sick leaves and use of health care services for adults. Journal of Orofacial Pain 1997;11:242-8 Lawrence RC, Helmick CG, Arnett FC. Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States. Arthritis Rheum 1998;41:778-99. LeResche L. Epidemiology of temporomandibular disorders: implications for the investigation of etiologic factors. Crt Rev Oral Biol Med 1997;8:291-305; Lipton JA, Ship JA, Larach-Robinson D. Estimated prevalence and distribution of reported orofacial pain in the United States. J Am Dent Assoc 1993;124:115-21. Locker D, Slade G. Prevalence of symptoms associated with temporomandibular disorders in a Canadian population. Community Dent Oral Epidemiol 1998;16:310-43. Locker D, Grushka M. The impact of dental and facial pain. J Dent Res 1987;66:1414-7. National Institutes of Health Technology Assessment Conference Statement: Management of temporomandibular disorders, April 29 – May 1, 1996. Oral Surg Oral Med Oral Pathol Oral Radiol Endo; 1997. p. 177-83. Oral Health in America: A Report of the Surgeon General. Rockville, MD: U.S. Department of Health and Human Services; 2000. Schwartz BS, Stewart WF, Simon D, Lipton RB, Epidemiology of tension- type headache. JAMA 1998;279:381-3. Von Korff M, LeResche L, Dworkin SF. First onset of common pain symptoms: a prospective study of depression as a risk factors. Pain 1993;55:251-58. Zakrzewska JM, Hamlyn PJ. Facial Pain. Epidemiology of Pain, edited by I.K. Crombie, IASP Press, Seattle, 1999.
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