COOPERATIVE MULTICENTER TRAUMATIC BRAIN INJURY CLINICAL TRIALS NETWORK Release Date: March 26, 2001 RFA: RFA-HD-01-007 National Institute of Child Health and Human Development (http://www.nichd.nih.gov) Letter of Intent Receipt Date: August 10, 2001 Application Receipt Date: October 17, 2001 PURPOSE The National Center for Medical Rehabilitation Research (NCMRR) at the National Institute of Child Health and Human Development (NICHD) invites applications from investigators interested in participating with the NICHD under a Cooperative Agreement (U01) in a multicenter clinical trials research Network program. This research Network is focused on Traumatic Brain Injury (TBI), and is designed to evaluate the relationship between acute care practice and rehabilitation strategies, to the long-term functional outcome of TBI patients. The objective of this program is to facilitate study of these clinical practices by establishing a Network of Clinical Network Sites and a Data Coordinating Center (DCC) that, by rigorous patient evaluation using common protocols, can study the required numbers of patients and can provide answers more rapidly than individual centers acting alone. 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 Request for Applications (RFA) is related to one or more priority areas. Potential applicants may obtain "Healthy People 2010" at http://www.health.gov/healthypeople. ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic, for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. The need for continuous and active communication among sites dictates that only institutions in the United States are eligible to apply. Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as Principal Investigators. MECHANISM OF SUPPORT This RFA will use the National Institutes of Health (NIH) Cooperative Research Project Grant (U01) award mechanism, an assistance mechanism (rather than an acquisition mechanism) in which substantial NIH scientific and/or programmatic involvement with the awardee is anticipated during performance of the activity. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients activity by involvement in the activity and otherwise working jointly with the award recipients in a partner role, but it is not to assume direction, prime responsibility, or a dominant role in the activity. Details of the responsibilities, relationships and governance of the studies to be funded under cooperative agreements are discussed below under Terms and Conditions of Award. FUNDS AVAILABLE The NICHD intends to commit approximately $5 million in total costs [direct plus Facilities and Administrative (F&A) costs] in FY 2002 to support up to eight Clinical Network Sites and one Data Coordinating Center Site. Applicants for the DCC may request a project period of up to five years and a budget for direct costs of up to $1.2 million for the first year. For Years 02 through 05, applications for the DCC may request direct costs of up to $750,000 per year. Applicants for the Clinical Network Sites may request a project period of up to five years and a budget for direct costs of up to $150,000 per year. Because the nature and scope of the research proposed may vary, it is anticipated that the size of awards also will vary. Although the financial plans of NICHD 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. At this time, the NICHD has not determined whether or how this program will be continued beyond the present solicitation. RESEARCH OBJECTIVES Background Traumatic Brain Injury (TBI) is a leading cause of death and disability in children and adults. An estimated two million head injuries occur in the United States each year. The number of treated cases of TBI has increased over the past 25 years as earlier and more specialized emergency treatment, especially at the accident scene, has saved individuals who might otherwise have died before reaching the hospital. Approximately 50 thousand of these individuals will have persistent physical, cognitive, behavioral and social deficits that may compromise their quality of life, as a result of their injury. This increase in the rate of survival from severe brain injury means that there will be an increasing number of patients in need of effective treatment to help them attain a satisfactory long-term life adjustment and quality of life following their injury. The size of this population argues for the importance of determining the most effective treatment and rehabilitation practices. During the past two decades, understanding of the pathophysiology of TBI has increased dramatically. It is now recognized that all neurologic damage does not occur at the moment of injury, but rather evolves over the ensuing minutes, hours and days. It is well established that a combination of early imaging in the emergency room, removal of extra-axial masses, support of blood pressure, ventilation as well as monitoring of intracranial pressure (American Association of Neurological Surgeons and the American Academy of Neurology, 1995) produces improved survival rates. Equally well established is the role of aggressive follow-on intensive care treatment. In addition, a growing literature suggests that adjunctive pharmacological treatment facilitates behavioral management during the rehabilitation process, and may result in a better functional outcome. Despite these advances, much remains to be learned about the underlying damage and pathophysiology of the deficits associated with TBI, and to link acute care, rehabilitation and long term patient outcomes. Because of the subtle and delayed sequelae associated with TBI, determining the most appropriate medical, rehabilitative and educational services for children and young adults with brain injury is especially difficult. Personality changes that appear to be independent of severity of injury are common long-term consequences of TBI, and may become more pronounced over time. Such long-term residual psychiatric sequelae pose challenges to community re-entry and to quality of life and are often viewed as more seriously handicapping than the cognitive and physical aspects of the injury itself. While there has been substantial improvement in the outcome from severe head injury, there remains a great deal of variability in the care of these patients across the country. Current medical management of TBI has, in some instances, adopted principles of care and employed pharmaceuticals and methodologies without rigorous use of evidence-based research necessary for their objective evaluation. Clinically important variations may occur because there is no efficacious standard of practice, linked to long-term outcomes, to guide treatment. Similarly, there has been little systematic study of the variables that influence the course and effectiveness of rehabilitation after brain injury. Comprehensive rehabilitation programs typically address areas of cognitive processes, behavioral and social interactions, speech, language and communication, mobility and activities of daily living. Depending on the particular focus of the program, certain areas may receive greater emphasis. The precise format and intensity of the interventions required for a given patient remain highly variable. Few programs have been subjected to the degree of scientific scrutiny (e.g., case definition, stratification by age and severity, standardized patient inclusion criteria, standardized and quantitative measurement of treatment and outcome) needed to draw conclusions about the efficacy of various treatment methods. As a result, it is difficult to determine which approaches are the most effective in returning TBI patients to maximum levels of community or vocational integration. Objectives The primary scientific objective of the TBI Clinical Trials Network will be to identify which intervention variables result in improvements in long-term outcome. It is the objective of this RFA to establish a Network of clinical sites that will work together and, in conjunction with NICHD staff, design clinical intervention protocols and measures of outcome. Applicants should describe their ability to identify TBI patient populations, to provide acute care, and to provide post-rehabilitation follow-up. Additionally, applicants should describe their approaches to the sharing of data and design of comprehensive databases that will allow comparisons of procedures and interventions. Proposed interventions may be designed for multiple points of care including the accident scene, emergency room, intensive care unit, rehabilitation and long-term follow up. Goals of the TBI Clinical Trials Network will include: o Recruitment of clinical trauma centers and rehabilitation/post rehabilitation programs to participate in cooperative research. o Establishment of uniform case definitions and standards of care among participating centers that will permit quantitative evaluation of interventions. o Development of training programs for management of intracranial pressure. o Development of a database for collection and management of data, including development of web-based support and data sharing among and between Network participants. o Determine if predictor variables ("proxy measures") can predict long-term outcome. o Recommend improved treatment methods. These research goals will be achieved through a TBI Network that will include approximately eight Clinical Network Sites and a Data Coordinating Center (DCC), supported by U01 awards. The Clinical Network Sites will recruit, evaluate and treat the participants in any or all of the clinical studies supported by the TBI Network. The DCC will have primary responsibility for data collection and management of each trial. NICHD program staff serving as a Project Scientist will cooperate with the funded Principal Investigators (PI) in designing and executing protocols to optimize management in these areas. Role of the Clinical Network Sites The Clinical Network Sites will work in collaboration with each other and with NICHD staff to: o Recruit patients into TBI Network clinical studies. o Evaluate and treat the participants in any or all of the clinical studies supported by the TBI Network. o Design clinical intervention protocols. o Design outcome measures. Research conducted within the Network will encompass primarily cooperative Network protocols. It is expected that the composite research plan will encompass projects that address each aspect of the TBI Clinical Trials Network goals for acute care treatment, rehabilitation, and long-term functional outcome. Limited funds may be available during grant Years 04 and 05 to allow the Principal Investigator of each Clinical Network Site to propose an individual research plan to accomplish his/her personal research interests. The proposal will be required to have the same degree of specificity and format as a regular research grant application. The TBI Network Steering Committee will review these projects and make decisions regarding approval. Proposals for individual research projects will be requested at the time funds become available. They should not be included in the applications submitted in response to this RFA. Role of the Data Coordinating Center The DCC will work in collaboration with the Clinical Network Site Principal Investigators to: o Establish data sets for acute TBI care. o Establish data sets for rehabilitation. o Establish data sets for one-year follow-up. o Establish web-based data tools. o Establish imaging data collection. o Establish and conduct education and training procedures for all research coordinators involved in the Network. o Provide data analysis for all clinical protocols. Domestic organizations with capacity to maintain close communication with NIH and with prior expertise as a research support services provider, and as a statistical coordinating and assistance center for multi-center research (including randomized controlled trials and observational studies of both medical and behavioral nature), are encouraged to submit applications under this RFA for establishment and operation of a DCC. Guidance and Management Structure The overall guidance and management of the TBI Network will be provided by a Steering Committee, a Network Advisory Board, and a Data Safety and Monitoring Committee (DSMC). In addition, the Network will establish Policies and Procedures that govern its operations, including publications. These documents will be reviewed periodically and may be amended at the discretion of the Steering Committee and the NICHD. SPECIAL REQUIREMENTS Minimum Application Requirements for Clinical Network Site Applications: o The Principal Investigator and research team at each Clinical Network Site must have a history of previous successful clinical research. o Applicant Clinical Network Sites must have a minimum of 100 moderate-to- severe TBI admissions annually. o Applicant Clinical Network Sites must have an established follow-up program with experience in following patients and a designated facility must be in place. Eighty percent of patients entered into the acute care database must have rehabilitation follow-up. This must include data related to acute care rehabilitation, intermediate care, community-based care and long-term care. In addition, one-year post-trauma center discharge information must be available. o Each participating site must designate a research coordinator with adequate percent effort. Description of this individual’s training, experience and involvement in clinical research should be provided. o The Clinical Site must demonstrate willingness and ability to participate in a cooperative manner with other Clinical Network Sites, with the DCC, and with NICHD in the delineation of research protocols, statistical methods, uniform data collection and data transfer. o The departmental and institutional commitment to collaborative TBI research should be clearly documented by providing letters to the Principal Investigator, and by citing evidence of past support. o The application must provide evidence of recent research productivity by the applicant Clinical Network Site in previous or present clinical trials, especially of a cooperative multicenter nature. Specifically, contributions in key areas such as protocol design, patient recruitment, data analysis and interpretation, and publication are important. o Proposed Network Concept Protocol Because protocols for investigation will not be written until after awards are made, it is not possible for applications to propose the exact work that they will carry out if funded. Therefore, to provide peer reviewers and NICHD staff with sufficient information regarding the capabilities of the investigators, each applicant for a Clinical Network Site must submit a concept protocol. The applicant should note carefully that the concept study proposed may or may not be adopted by the TBI Network as one of its protocols. The proposal is requested to serve as an indicator of the applicant’s ability to participate in the development and design of protocols for cooperative clinical investigations. Principal Investigators should propose a cooperative research protocol that reflects research efforts transcending his/her individual research programs. The protocol should be written specifically for this TBI Network and will be a key factor in evaluation of the application. Applicants should briefly (two to three pages) outline the rationale and background of the proposed study, study design and protocol, eligibility criteria and initial sample size and power analysis. The cooperative research plan should propose questions that will be examined cooperatively. Applicants should indicate how their disciplinary and methodological perspectives could contribute to a cooperative research effort. Applicants should also address how they might cooperate in the continuing business of the TBI Clinical Trials Network described above, and should propose projects that would expand the research agenda of the Network. It is anticipated that the Steering Committee and Advisory Board will include the concept protocols submitted by the funded Clinical Network Sites in their consideration of topics for actual studies. Research conducted during the first three years of funding will be limited to common Network protocols. Minimum Application Requirements for Data Coordinating Center Applications: o The applicant must have demonstrated prior experience as a coordinating center in multicenter studies. o The Principal Investigator, with other staff, must have appropriate biostatistical, data management and coordination expertise. o The applicant must have the ability to assist in designing protocols and the data collection system, including transmission via the Internet. o The applicant must demonstrate the willingness and ability to cooperate with the Clinical Network Sites and NICHD staff in all design, data collection and analysis functions. o The DCC must have an established data system to collect and tabulate statistics. Meetings Each PI should plan and budget for four Steering Committee meetings per year in the Washington, DC area. Each meeting will be approximately two days in length. During these meetings, the Steering Committee will determine the operating policies of the Network, discuss on-going research, formulate the collaborative research plan, and discuss the implications of their research with interested parties outside of the Network who may be invited by the Steering Committee as the occasion warrants. Departmental and Institutional Commitments The department and institutional commitment to collaborative TBI research and to prioritization of TBI Network research should be clearly documented by providing letters to the Principal Investigator and by citing evidence of past support. This institutional assurance to provide support should address areas such as fiscal administration, personnel management, space allocation, procurement, planning, equipment and budgeting. Expectation of Cooperation Applicants should indicate their willingness and ability to participate in these stated aspects of the Network. The statement of willingness to cooperate should be included under Consortium/Contractual Arrangements, item h of the Research Plan in the application. Budget Requirements All applications must include an adequately justified year-by-year budget, reflecting the changes in proposed activities as the studies progress. In addition, a composite budget should be submitted. Applicable facilities and administrative costs will be provided. Budgets will be reviewed on the basis of appropriateness for the work proposed. Allowable costs and policies governing the research grant program of the NIH will prevail. Budget Requirements for the Clinical Network Site Applications: o For Clinical Network Sites, the first-year budget at the time of application will be limited to a BASE BUDGET. This budget should reflect Base Budget support for the minimum number of full-time and/or part-time staff necessary to successfully carry out the proposed trial. The personnel list should include a Principal Investigator, co-investigator(s), study coordinator, and data entry staff. When an application has been funded, the Principal Investigator will be required to complete protocol budgets for those studies planned within the TBI Network. These budgets will consist of specific protocol-related costs and the anticipated number of subjects to be enrolled in the study at the applicant Clinical Network Site. The Principal Investigator will be required to project patient enrollment for a specific protocol during a specified time frame. Ongoing annual budgets of each Clinical Network Site will be based on specific protocols. Protocol funds will be awarded separately. Future years budgets should be limited to base budget costs, with an annual increment of base salary and travel costs not to exceed three percent (the maximum amount available for equipment and supplies will not increase). Applicants shall use the negotiated rates for Facilities and Administrative (F&A) costs in effect at the time of the initial award throughout the each competitive segment of the project. Award levels for sponsored agreements may not be adjusted in future years as a result of changes in negotiated rates. o Each investigator should budget for travel costs and related expenses for travel to required meetings (four meetings a year) in the Washington, DC area. Each meeting will be approximately two days in length. Budget Requirements for DCC Applications: DCC applicants should provide a BASE BUDGET, presented with precision and clarity, that includes at a minimum, the following: o Salary and administrative support for the Principal Investigator, Project Coordinator, and other staff as required to meet the first-year responsibilities of the DCC. o Estimated travel costs and related expenses for the Principal Investigator and other DCC staff for travel to required meetings. o Travel and logistical support expenses for members of the DSMC and the Network Advisory Group. For the purposes of this RFA, applicants should estimate three meetings per year for the DSMC and one meeting per year for the Network Advisory Group. o Expenses related to communications, supplies, equipment, and other items identified as essential to the establishment and operation of the DCC. o Clearly specified plans and procedures for monitoring of DCC budgetary expenditures. Terms and Conditions of Award Cooperative agreements are assistance mechanisms and are subject to the same administrative requirements as grants. The following terms and conditions will be incorporated into the award statement and provided to each Principal Investigator as well as the institutional officials at the time of the award. These terms are in addition to, and not in lieu of, otherwise applicable OMB guidelines, HHS Grant Administration Regulations at 45 CFR Part 74 and 92, and other HHS, HS, and NIH grant administration policies. The NICHD Grants Management Branch in accordance with HHS, PHS, and NIH Grant Administration policies will administer business management aspects of these awards. The cooperative agreement funding mechanism will require collaboration among the NICHD Project Scientist, the DCC Principal Investigator, and the Principal Investigators of the TBI Clinical Network Sites. The NICHD Project Scientist will coordinate the activities of the TBI Network, and will facilitate communication and the exchange of information. 1. The Primary Rights and Responsibilities of the Awardees All awardees will agree to accept the participatory and cooperative nature of the group process. All awardees are required to submit annual progress reports to NICHD, as appropriate and to provide study and site performance information as stipulated by NICHD. The Principal Investigator of each Clinical Network Site and the DCC will play an important role in the design, implementation and execution of the clinical trial. Each Principal Investigator will have primary responsibility to define objectives and approaches, and to plan, conduct, analyze, and publish results, interpretations and conclusions of his/her studies. The TBI Network will retain custody of, and primary rights to their data developed under this award, subject to Government rights of access, consistent with current HHS, PHS, and NIH policies. Each investigator will have the right to publish based on the work of their individual research programs. Each Principal Investigator will also propose a cooperative research plan in which they will identify research questions, methodological research, protocols and data sets that they propose to work on cooperatively. Clinical Network Sites: The Clinical Network Sites specifically will: o Develop and implement research protocols, interventions, and evaluation strategies, with all protocol documents including, at a minimum, an introduction section with background and rationale, a statement of the study objectives, criteria for selection of subjects and enrollment procedures, clinical and laboratory evaluations to be performed, plans for data collection, management, and monitoring, and for reporting of adverse events, a complete description of the study treatment, and statistical considerations, including general design issues, endpoints, sample size, accrual and power, monitoring and analysis, and stopping rules. Some of these activities are shared with the DCC. o As a shared activity with the DCC, when appropriate, collect, analyze, and interpret data, and disseminate research results from TBI Network studies, while assuring quality control. o Be required to project patient enrollment for a specific protocol during a specified time frame, continuation and level of funding will be contingent on actual recruitment. o Present research concepts, plans, progress, and results to the Steering Committee. o Publish and disseminate results of both independent and shared research. When joint protocols are completed, publish in collaboration with other involved TBI Network Sites. o Collaborate with other awardees and the NIH. o Retain custody of and rights to data developed under these awards subject only to the Government rights of access consistent with current HHS, PHS, and NIH policies. o Implement any Network-approved shared study protocols, where feasible, including the recruitment and monitoring of study participants, associated data collection, and study-associated quality control measures at the study sites, in collaboration with the DCC. o Obtain local institutional review board (IRB) approval of all study protocols implemented at U.S. or foreign sites and comply with both IRB and TBI Network policies and procedures. o Generate, if feasible, additional research proposals, including shared protocols, for consideration for inclusion in the TBI Network. o Attend and participate in all Network conference calls and Steering Committee meetings. Data Coordinating Center: The DCC will provide research support services to the TBI Network. These will include establishment and maintenance of a centralized information management system to help the TBI Clinical Network Sites collect, edit, store, analyze, publish, and disseminate results from their individual projects as well as from shared research. It will assist the program staff of the NICHD in monitoring research progress, and will work to ensure data integrity, accuracy, and accessibility among all Network sites. It will offer technical assistance and analytical support for all sites, as needed. All activities of the DCC must be closely coordinated with the NICHD Project Scientist. In support of all research projects undertaken by the TBI Network, the DCC staff will: o Support the activities of the Network Advisory Group, Steering Committee, and the DSMC through provision of materials/documentation support, meeting planning and logistics, and conference call coordination. o Provide advice on study design, data collection, data analysis, and publication development to all TBI Network research projects. o Prepare, design, and disseminate operations manuals, data collection forms, databases, and results reporting summaries for TBI Network research projects. o Compile for the Network Advisory Group and Steering Committee, the DSMC and the NICHD site visit reports, monthly and quarterly subject enrollment reports, meeting summaries. o Prepare quarterly Clinical Network Site performance and progress reports, and other reports as needed. o Maintain or assure maintenance of high quality databases resulting from any collaborative research, supervise all data collection procedures, and arrange for the most efficient transfer of study data where indicated. o Ensure that all TBI Clinical Network Sites and investigators fully comply with NIH regulatory requirements, including informed consent, reporting of adverse events, human and animal subject safety and welfare provisions, and the requirements of international collaboration. o Provide training to all Clinical Network Site personnel as needed on data management and analysis, and quality control and quality assurance. o In coordination with the NICHD, provide periodic on-site monitoring of the Clinical Network Sites for those studies being performed at each site. o Provide monthly reports detailing the progress in patient recruitment as well as the percent effort spent on each specific research protocol for each Clinical Site. o Provide budget pages for each protocol in non-competing continuation (Type 5) applications. o Attend and participate in all Network conference calls and Steering Committee meetings. 2. NICHD Responsibilities NICHD Project Scientist: The NICHD TBI Network Project Scientist will be the Director of the Clinical Practices Research Program of the National Center for Medical Rehabilitation Research, NICHD. The Project Scientist is a partner within the Network representing the government"s interest in the substantive work of the Network. The primary role of the Project Scientist is to facilitate the work of the Network and to connect the Network to public policy operations within the government. He/she will: o Assist in all functions of the Steering Committee, including: reviewing and commenting on each stage of the program before subsequent stages are started, exercising the options of adding, modifying or terminating aspects of the program . o Assist with the development of common protocols. o Assist in the analysis, interpretation, and reporting of findings in the scientific literature and other media to the community at large and the public policy community within the Federal government. NICHD Project Officer: NICHD will appoint a Project Officer, apart from the Project Scientist, who will: o Have the option to withhold support to a participating institution if technical performance requirements, such as compliance with the protocol, are not met. o Carry out continuous review of all activities to ensure objectives are being met. The above responsibilities are in addition to, not in lieu of, the levels of involvement normally required for program stewardship of grants. 3. Collaborative Responsibilities The overall guidance and management of the TBI Network will be provided by a Steering Committee, a Network Advisory Board, and a Data Safety and Monitoring Committee (DSMC), as described below: Steering Committee Responsibilities Planning and implementation of the cooperative aspects of the study will be done by a Steering Committee consisting of the Principal Investigator from each participating awardee institution and the NICHD Project Scientist. The Steering Committee will formulate a research plan for cooperative research that will distill the several individual cooperative research plans into a coherent plan and will involve allocating resources among the participating cooperative agreements to implement it. The cooperative research plan will be agreed upon by majority vote of the Steering Committee, but each Principal Investigator will have the right of approval for any aspect of the cooperative research plan involving them. Due publication credit will be given to all work done cooperatively. The Steering Committee will: o Plan the design and implementation of the cooperative research protocols. o Participate in decision-making regarding allocation of funds for cooperative research protocols. o Participate in decision-making regarding allocation of funds for individual research protocols. o Publish results, conclusions, and interpretations of the cooperative protocols. o Formulate publication policy and appoint a Publication Subcommittee, as judged necessary by the Steering Committee. o Agree to accept the coordinating role of the committee and the cooperative nature of the group process. Network Advisory Board An Advisory Board will advise the Steering Committee in the identification and prioritization of topics for Network research. The Advisory Board, chosen by NICHD, will comprise senior scientists in the areas central to the work of the Network who are not affiliated with NICHD or part of the Network. As well as serving in an advisory capacity to the Steering Committee as deemed necessary, the Advisory Board will serve as the second level of review for projects approved by the Steering Committee as part of the research activities of the Network. The Network"s scope is defined as the sum of the approved individual and cooperative research plans of participating cooperative agreements in the Network. Data Safety and Monitoring Committee A Data Safety and Monitoring Committee (DSMC), established by NICHD, will advise the NIH and the TBI Network, including the DCC, on research design issues, data quality and analysis, and ethical and human subject issues. It also will monitor the safety of any ongoing clinical trials. DSMC membership will include, but not be limited to, individuals with expertise in clinical trial design and conduct, relevant basic, medical, rehabilitation and behavioral sciences research. The DCC will prepare reports and provide coordination, support, and funding for travel and logistics arrangements related to DSMC meetings and actions. 4. Arbitration Procedures When agreement between an awardee and NICHD staff cannot be reached on programmatic and scientific-technical issues that may arise after the award, an arbitration panel will be formed. The panel will consist of one person selected by the Principal Investigators, one person selected by the NICHD staff, and a third person selected by these two members. The decision of the arbitration panel, by majority vote, will be binding. These special arbitration procedures in no way affect the awardees right to appeal an adverse action in accordance with PHS regulations at 42 CFR Part 50, Subpart D, and HHS regulations at 45 CFR Part 16. INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS 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 biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification are 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 research involving human subjects should read the UPDATED "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research," published in the NIH Guide for Grants and Contracts on August 2, 2000 (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-048.html), a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_update.htm. The revisions relate to NIH-defined Phase III clinical trials and require: a) all applications or proposals and/or protocols to 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) all investigators to report accrual, and to conduct and report analyses, as appropriate, by sex/gender and/or racial/ethnic group differences. INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of NIH that children (i.e., individuals under the age of 21) must be included in all human subject 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," published in the NIH Guide for Grants and Contracts, March 6, 1998, and available on the Internet at: http://grants.nih.gov/grants/guide/notice-files/not98-024.html. Investigators may obtain copies of the policy from the program staff listed under INQUIRIES. Program staff also can provide additional relevant information concerning the policy. LETTER OF INTENT Prospective applicants are asked to submit a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, the identities of other key personnel and participating institutions, and the 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 NICHD staff to estimate the potential review workload and plan the review. The letter of intent is to be sent to Dr. Beth Ansel, at the address listed under INQUIRIES, below, by August 10, 2001. 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. Reviewers are cautioned that their anonymity may be compromised when they directly access an Internet site. APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 4/98) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research, on the Internet at http://grants.nih.gov/grants/funding/phs398/phs398.html, and from the Division of Extramural Outreach and Information Resources, National Institutes of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892- 7910, telephone 301-710-0267, E-mail: Grantsinfo@nih.gov. Application Instructions Instructions accompanying the PHS 398 (rev. 4/98) are to be followed in completing these applications. The research plan section of the application should conform to the guidelines of PHS-398. The cooperative research plan should be presented and should include Specific Aims, Background and Significance, Progress Report/Preliminary Studies, and Research Design and Methods, as in the standard Research Plan section. The budget for the application should be predicated on the requirements of the cooperative research plan. The standard 25-page limit for sections a d of the Research Plan will apply. Submission Instructions The RFA label available in the PHS 398 (rev. 4/98) application form must be stapled to the bottom of the face page of the application and must display the RFA number HD-01-007. A sample RFA label is available at http://grants.nih.gov/grants/funding/phs398/label-bk.pdf. Please note this is in the pdf format. 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. 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 should be sent to: L. R. Stanford, Ph.D. Director, Division of Scientific Review National Institute of Child Health and Human Development 6100 Executive Boulevard, Room 5E03F, MSC 7510 Bethesda, MD 20892-7510 Rockville, MD 20852 (for express/courier service) Applications must be received by October 17, 2001. If an application is received after that date, it will be returned to the applicant without review. 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. CSR will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of substantial revisions of applications already reviewed, but such applications must include an introduction addressing the previous critique. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by CSR and for responsiveness to this RFA by NICHD. Incomplete and/or non-responsive applications will be returned to the applicant without further consideration. 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 NICHD in accordance with the review criteria stated below. As part of the initial merit review, all applications will receive a written critique and may undergo a process in which only those applications deemed to have the highest scientific merit will be discussed, assigned a priority score, and receive a second level review by the National Advisory Child Health and Human Development Council. Review Criteria Criteria for the Evaluation of Clinical Site Applications: 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 review, comments on the following aspects of the application will be made in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in the assignment of the overall score, which is to reflect the overall impact of the project on the field, weighing the criteria appropriately for each application. An application does not need to be strong in all categories to be judged likely to have a major scientific impact and thus deserve a high merit rating. For example, an investigator may propose to carry out important work, which by its nature is not innovative, but is essential to move a field forward. (1) Significance: Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge be advanced? What will be the effect of these studies on the concepts or methods that drive this field? (2) 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? Does the research plan consider and address the course of TBI treatment and care? (3) 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? (4) Investigator: Is the investigator appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the Principal Investigator and other researchers (if any)? Do the Principal Investigators and associated team members have experience with the clinical management of TBI patients? (5) Environment: Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed analyses take advantage of unique features of the scientific environment or employ useful collaborative arrangements? Is there evidence of institutional support? Have the Clinical Network Centers established a cooperative participation with acute rehabilitation and long-term care sites? Criteria for Evaluation of DCC applications: (1) Does the applicant possess the knowledge necessary to contribute meaningfully to final study design, including understanding of the scientific, ethical and practical issues underlying the type of research to be conducted by the Network? (2) Does the applicant demonstrate knowledge of the potential problems associated with the conduct of the research to be conducted by the Network, and identify solutions or alternatives? (3) Does the application provide specific evidence of experience and qualifications of team members who would be responsible for data quality and management activities? (4) Does the application document knowledge and experience in areas relevant to the conduct of collaborative clinical research? This includes the adequacy of the approach to developing a cooperative relationship among the Clinical Sites and exercising appropriate leadership in matters of study design, data acquisition, data management, data quality and data analysis. (5) Is there evidence of experience of DCC personnel in using procedures that ensure the safety and confidentiality of all records? In addition to the above criteria, all applications for the TBI Clinical Network will also be reviewed with respect to the following: o Commitment to the cooperative nature of the program. o The adequacy of plans to include both genders, minorities and their subgroups, and children as appropriate for the scientific goals of the research. Plans for the recruitment and retention of subjects will also be evaluated. o The reasonableness of the proposed budget and duration in relation to the proposed research. o The adequacy of the proposed protection for humans or the environment, to the extent they may be adversely affected by the project proposed in the application. SCHEDULE Letter of Intent Receipt Date: August 10, 2001 Application Receipt Date: October 17, 2001 Peer Review Date: February/March 2002 Council Review: June 2002 Earliest Anticipated Award Date: July 2002 AWARD CRITERIA Applications recommended by the National Advisory Child Health and Human Development Council will be considered for award based primarily on scientific and technical merit, as determined by peer review. Program balance, that is, the scope and variety of research strengths to enable a successful collaborative program, will be considered. Final selection of Clinical Sites for funding may be based partly on the need for diversity in the study population. Awards will be contingent upon availability of funds. INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Beth M. Ansel, Ph.D., CCC-SLP National Center for Medical Rehabilitation Research National Institute of Child Health and Human Development 6100 Executive Boulevard, Room 2A03, MSC 7510 Bethesda, MD 20892-7510 Telephone: (301) 402-2242 FAX: (301) 402-0832 E-mail: Beth_Ansel@nih.gov Direct inquiries regarding fiscal matters to: Christopher Myers Grants Management Branch National Institute of Child Health and Human Development 6100 Executive Boulevard, Room 8A17H, MSC 7510 Bethesda, MD 20892-7510 Telephone: (301) 435-6996 FAX: (301) 402-0915 E-mail: cm143g@nih.gov AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance Nos. 93.929. Awards are made under authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and administered under NIH grants policies and Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. The PHS strongly encourages all grant and contract recipients to provide a smoke-free workplace and promote the non-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.

Weekly TOC for this Announcement
NIH Funding Opportunities and Notices


NIH Office of Extramural Research Logo
   Department of Health and Human Services (HHS) - Home Page Department of Health
and Human Services (HHS) 		  USA.gov - Government Made Easy
NIH... Turning Discovery Into Health®


Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files.