KOSEN 한인과학기술자네트워크

Comprehensive Sickle Cell Centers Primary Sponsor: National Heart, Lung, and Blood Institute Deadline: 3/20/2001; 9/25/2001 KEYWORDS RFA: HL-01-015 Letter of Intent Receipt Date: March 20, 2001 Application Receipt Date: September 25, 2001 PURPOSE The National Heart, Lung, and Blood Institute (NHLBI) invites applications for support as Comprehensive Sickle Cell Centers that will offer interactive, state-of-the-art programs in basic and translational sickle cell disease research. The primary objective of this Request for Applications (RFA) is to support ten Comprehensive Sickle Cell Centers, and a Statistics and Data Management Center, to carry out research focused on the development of cures or significantly improved treatments for sickle cell disease. This research will include basic research efforts, inter-center collaborative clinical research, and local clinical research, with all three focused on the most promising therapeutic modalities on the horizon today, and each interactive with the others. In addition to their primary focus in research, Comprehensive Sickle Cell Centers will also support career development of young investigators in sickle cell disease research, and support patient service activities that are focused on the implementation into clinical practice of the best current models of care and treatment for sickle cell disease. 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, Comprehensive Sickle Cell Centers, is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at 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. At least one, and preferably more than one organization listed on each application must be associated with an established medical institution with facilities and patient populations available for clinical investigations in sickle cell disease. Underrepresented minority individuals, women, and persons with disabilities are encouraged to apply as Principal Investigators. Awards will not be made to foreign institutions. However, basic science or clinical projects from foreign institutions may be submitted as subcontracts if they have unusual scientific merit, unique resources, or documented evidence of successful collaborative arrangements. In accordance with NIH policy, facilities and administrative (F&A) costs will not be paid to a foreign institution. All current policies and requirements that govern the research grant programs of the National Institutes of Health (NIH) will apply to grants awarded under this RFA. Among the disciplines and expertise that may be appropriate for this program are hematology, pediatrics, medical genetics, pharmacology, therapeutic development, and clinical trials management. Awards for a Comprehensive Sickle Cell Center and for the Statistics and Data Management Center made under this RFA will not be made to the same Principal Investigator to ensure that data analysis is done independently of data acquisition. The same institution may apply for both a Comprehensive Sickle Cell Center and Statistics and Data Management Center award, but the applications for each must be from different Principal Investigators. The Principal Investigator of a Statistics and Data Management Center application cannot be listed in any capacity under personnel on a Center application. Statistics and Data Management Center applications need not be from an institution submitting a Center application. MECHANISM OF SUPPORT This RFA will use the NIH cooperative agreement (U54) administrative and funding mechanism of support. Under the cooperative agreement, the NIH assists, supports, and/or stimulates, and is substantially involved with recipients in conducting a study by facilitating performance of the effort in a "partner" role. Details of the responsibilities, relationships, and governance of a study or research funded under a cooperative agreement are discussed later in this document under the section entitled SPECIAL REQUIREMENTS (Terms and Conditions of Award). Comprehensive Sickle Cell Centers are identifiable units within sponsoring institutions that are organized around a group of investigators and other health professionals engaged in ongoing basic and clinical research and community service related to sickle cell disease. Centers provide support for multidisciplinary programs of basic, clinical and behavioral research; for core resources such as laboratory and data analysis; and for quality service activities including counseling, education, and community outreach. A Center is headed by a Program Director who is responsible for and provides leadership to all Center components, and who may also be Principal Investigator on one or more of the projects contained within the Center. Although individual components may be somewhat autonomous in the conduct of a specific project, each is directly accountable to the Center Program Director, who has overall responsibility for program coordination, implementation, and evaluation. The Program Director must maintain close contact with NHLBI program administrators and grants management specialists responsible for each grant. Committees, internal and external, which provide scientific and fiscal overview of Center activities are required. In addition, a formal ongoing agreement between the sponsoring institution and the Center must be developed with an explicit statement of the commitment of each to the other. In particular, the sponsoring institution should make a formal commitment of financial support to all components of a proposed Center specifically defining the resources for the salaries, equipment, supplies, and facilities that will be available to the investigators for the entire project period. Under the guidance of the Program Director, each of the required program components and services (research, education, and counseling) should be coordinated and integrated to strengthen the overall program, enhance transfer of new findings to the clinical setting, and identify new research directions. Such interaction should be frequent, formalized, and documented to facilitate continuous exchange of relevant information between projects and components, thus contributing to greater program productivity and effectiveness. Regular meetings of project principal investigators, seminars, poster sessions, and staff lectures are excellent mechanisms for fostering communication and interaction among Center staff. Finally, each Program Director will be expected to develop a mechanism for the ongoing evaluation of the effectiveness and impact of the activities constituting the Center program. While the NHLBI will continue to assess the quality and performance characteristics of the program through periodic outside review and staff evaluation, each of the Centers must consider approaches by which it can demonstrate how the local program has influenced understanding and practice in matters related to sickle cell disease. The total project period for an application submitted in response to this RFA will be five years. The anticipated award date is April 1, 2003. FUNDS AVAILABLE The NHLBI intends to commit approximately $22,000,000 in FY 2003 to fund ten grants for Comprehensive Sickle Cell Centers, one new grant for a Statistics and Data Management Center, and per-patient costs for inter-Center collaborative clinical studies in response to this RFA. Comprehensive Sickle Cell Center applicants may request a project period of five years and a budget for total costs (direct costs plus facilities and administrative (F&A) costs) of up to $1,770,000 per year. Because the nature and scope of the research proposed may vary, it is anticipated that the size of each award will also vary. Statistics and Data Management Center applicants may request a project period of up to five years and a budget for total costs (direct costs plus facilities and administrative (F&A) costs) of up to $700,000. Statistics and Data Management Center applications must be submitted separately from Comprehensive Sickle Cell Center applications. In addition to the $1,770,000 in total costs per year that may be requested in the application, approximately $3,600,000 of additional total costs per year will be available program-wide for reimbursement of Comprehensive Sickle Cell Centers based on patient entry into inter- Center collaborative clinical studies (see Program Structure below for additional funding caps for required program components). Although the financial plans of the NHLBI provide support for this program, awards pursuant to this RFA are contingent upon the availability of funds. Requests for expensive pieces of equipment that cause the application to exceed the budget limits cited above will be considered on an individual basis. However, applicants should make every attempt to include all equipment in the ceiling amount and must discuss any equipment requests that cause the application to exceed the ceiling with NHLBI staff early in the planning phase of the application. Such requests for equipment will require in-depth justification and will be carefully considered during the review process. Final decisions will depend on the nature of the justification and the Institute's fiscal situation. Consortium Arrangements When a grant application includes research activities that involve institutions other than the grantee institution, it is considered a consortium effort. Such activities may be included in a grant application, but it is imperative that a consortium application be prepared so that the programmatic, fiscal, and administrative considerations are explained fully. Facilities and Administrative costs paid as a part of a consortium agreement are included in the limit on the amount of total costs that can be requested. The published policy governing consortia is available in the business offices of institutions that are eligible to receive Federal grants-in-iad. Consult the latest published policy governing consortia before developing the application. If clarification of the policy is needed, contact Ms. Mary Page at the address listed under INQUIRIES. RESEARCH OBJECTIVES Background Sickle cell disease is a worldwide health problem and is one of the most common inherited disorders of man. This genetic blood disorder is probably the best understood disease at the molecular level and Linus Pauling coined the term "molecular disease" over forty-five years ago in ascribing the abnormality to the globin portion of the hemoglobin molecule. Almost ten years later, the specific molecular defect was identified as a single amino acid substitution of valine for glutamic acid at position 6 of the beta-globin polypeptide chain. With the advent of recombinant DNA technology, investigators were able to further define this genetic mutation in the globin gene as a change in the codon GAG to GTG. The substitution of glutamic acid by valine results in a loss of two negative charges on the surface of the molecule making sickle hemoglobin less soluble than normal hemoglobin upon deoxygenation. This abnormal hemoglobin aggregates and forms fibers within the red cells, leading to morphological changes that subsequently affect the ability of the cells to traverse the microvasculature, causing occlusion of these small vessels that results in acute pain, and acute as well as chronic organ damage. In addition, sickle red cells are less resilient than normal cells, leading to their early destruction and thus a chronic anemia. This cascade of events caused by the abnormal cell morphology affects the structure and function of the red cells, blood flow through tissues and organs throughout the body, and abnormal interaction of these cells with the microvasculature. The complex pathophysiology of this disorder is a direct consequence of the change in morphology of red cells containing sickle hemoglobin. Despite the distinction of being the first described molecular disease, there is no cure or effective treatment currently available. The NIH established the Comprehensive Sickle Cell Center Program in 1972, in response to a Presidential initiative and Congressional mandate. After an open competition, ten Centers were funded in 1972 and five additional Centers in 1973. Subsequent RFAs were funded in 1977, 1978, 1983, 1988, 1993, and 1998. Ten Comprehensive Sickle Cell Centers are currently funded. With this RFA, the Sickle Cell Disease Scientific Research Group, Blood Diseases Program, Division of Blood Diseases and Resources, National Heart, Lung, and Blood Institute, announces its plan to fund ten Comprehensive Sickle Cell Centers, for the period 2003-2008. INQUIRIES Inquiries concerning this RFA are strongly encouraged. The opportunity to clarify any issues or answer questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Greg Evans, Ph.D. Division of Blood Diseases and Resources National Heart, Lung, and Blood Institute 6701 Rockledge Drive, Room 10152, MSC 7950 Bethesda, Maryland 20892-7950 Telephone: (301) 435-0055 FAX: (301) 480-0868 E-Mail: EvansG@ nih.gov Direct inquiries regarding review matters, address the letter of intent, and send two copies of the application to: Deborah Beebe, Ph.D. Division of Extramural Affairs National Heart, Lung, and Blood Institute 6701 Rockledge Drive, Room 7178, MSC 7924 Bethesda, Maryland 20892-7924 Telephone: (301) 435-0270 FAX: (301) 480-3541 E-mail: BeebeD@nhlbi.nih.gov Direct inquiries regarding fiscal matters to: Mary Page Grants Operations Branch National Heart, Lung, and Blood Institute 6701 Rockledge Drive, Room 7162, MSC 7926 Bethesda, MD 20892- 7926 Telephone: (301) 435-0152 FAX: (301) 480-3310 E-mail: PageM@nih.gov National Heart, Lung, and Blood Institute (www.nhlbi.nih.gov)