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) 710-0267, 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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