SPECIALIZED CENTERS OF RESEARCH (SCOR) IN TRANSFUSION BIOLOGY AND MEDICINE Release Date: August 2, 1999 RFA: HL-99-023 National Heart, Lung, and Blood Institute Letter of Intent Receipt Date: December 1, 1999 Application Receipt Date: January 14, 2000 PURPOSE The objectives of the Specialized Centers of Research (SCOR) program in Transfusion Biology and Medicine are to improve the safety and efficacy of blood and blood components, to determine the indications for their use, to evaluate and possibly modify immunological responsiveness following their administration, and to develop and evaluate alternative treatment strategies that substitute for certain of their functions or stimulate their endogenous production so as to reduce transfusion needs. This initiative encourages the use of new and innovative technologies to conduct quality basic research and facilitate the transfer of the basic knowledge to the clinical area. The ultimate goals of this program are to make optimal use of blood and blood components and to improve transfusion practice. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This initiative, Specialized Centers of Research (SCOR) in Transfusion Biology and Medicine, is related to the priority areas of heart disease and stroke, and cancer. Potential applicants may obtain a copy of "Healthy People 2000," (Full Report: Stock No. 017-001- 00474-0 or Summary Report: Stock No. 017-001-00473-01) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402- 9325 (telephone 202-512-1800). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic for-profit and non-profit institutions, public and private, such as universities, colleges, hospitals, and laboratories. This RFA is intended to support SCOR grants for basic and clinical investigations. Applications that include only basic or only clinical research will not be responsive to this RFA. In addition, clinical research projects focused on large epidemiologic studies or large clinical trials will be considered unresponsive to this RFA. Foreign institutions are ineligible from receiving awards under this solicitation. Under exceptional circumstances, a foreign component critical to a project may be included as a part of that project. Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as Principal Investigators or responsible project investigators. The Principal Investigator should be an established research scientist with the ability to ensure quality control and the experience to administer effectively and integrate all components of the program. A minimum time commitment of 25 percent is expected for this individual. The Principal Investigator must also be the project leader of one of the component research projects. If, through peer review, this project is determined to be of low scientific merit, the overall SCOR application will not be considered further. If this project is judged by peer review to be of low scientific merit, it will markedly reduce the overall scientific merit ranking assigned to the entire application by the review committee. Project leaders must agree to commit at least 20 percent effort to each project for which they are responsible. MECHANISM OF SUPPORT This RFA will use the National Institutes of Health (NIH) specialized centers (P50) mechanism to support this research program. Responsibility for planning the proposed project will be solely that of the applicant. The total project period for applications submitted in response to the present RFA may not exceed five years. The anticipated start date of award is January 2001. Although multidisciplinary approaches are required, it is not the intent of this announcement to solicit applications for large clinical trials or large epidemiologic studies. In general, funds will not be provided for the purchase and installation of expensive, new equipment. Upon initiation of the program, there will be required communications between SCORs, usually in the setting of a biennial combined meeting of SCOR participants. Applicants should request travel funds for this purpose in fiscal years 2002, 2004, and 2006 of the budget. Applicants should also include a statement in their applications indicating their willingness to participate in these meetings. Basic and Clinical Research The overall concept of a SCOR program focuses on scientific issues related to diseases relevant to the mission of the National Heart, Lung, and Blood, Institute (NHLBI). It is essential, therefore, that all applications include both basic and clinical research projects. Interactions between basic and clinical scientists are expected to strengthen the research, enhance transfer of fundamental research findings to the clinical setting, and identify new research directions. Plans for transfer of findings from basic to clinical studies should be described. Each SCOR grant application and award must include research involving human patients/subjects, which is defined as research conducted with human patients/subjects or on material of human origin such as tissue or other specimens for which an investigator directly interacts with human patients/subjects. Support may be provided for human biomedical and behavioral studies of etiology, pathogenesis, prevention and prevention strategies, diagnostic approaches, and treatment of diseases, disorders or conditions. Small population-based epidemiologic studies, where the research can be completed within five years, may also be proposed. In addition, basic research projects must be included that relate to the clinical focus. A SCOR may also contain one or more core units that support the research projects. Length of SCOR Programs Each NHLBI SCOR program is limited to ten years of support. Exceptions to this policy will be made only if a thorough evaluation of needs and opportunities, conducted by a committee composed of non-federal experts, determines that there are extraordinarily important reasons to continue a specific SCOR program. Under this policy, a given SCOR grant is awarded for a five-year project period following an open competition. Only one five-year competing renewal is permitted, for a total of ten years of support, unless the SCOR program is recommended for extension. The SCOR program in Transfusion Biology and Medicine is in the initial five-year project period and this competition is for the second five-year competition. The comprehensive evaluation of this SCOR Program will be conducted during the second project period according to the following timetable. Announcement of SCOR renewal competition FY 1999 Project Period (Second Competition) FY 2001 to FY 2005 Letter to SCOR Directors regarding SCOR FY 2002 (mid-way through year -02 evaluation plans of the second project period) SCOR Evaluation Meeting FY 2002 (late in year -02 of the second project period) Notification of SCOR Directors of NHLBI FY 2003 (mid-way through year -03 Decision of second project period) The NHLBI does not limit the number of SCOR applications in a given SCOR program from one institution provided there is a different SCOR principal investigator for each application and each application is self-contained and independent of the other(s). This does not preclude cooperation, planned or possible, among participants of SCORs after awards are made. Scientific overlap among applications will not be accepted. If more than one application is envisioned from an institution, the institution is encouraged to discuss its plans with the NHLBI SCOR program administrator. Consortium Arrangements If a grant application includes research activities that involve institutions other than the grantee institution, the program is considered a consortium effort. Such activities may be included in a SCOR grant application and can provide scientific expertise in areas and topics that may not be readily available at the applicant institution. However, the consortium projects must not constitute greater than 50 percent of the proposed projects. It is also imperative that a consortium application be prepared so that the programmatic, fiscal, and administrative considerations are explained fully. Applicants should exercise great diligence in preserving the interactions of the participants and the integration of the consortium project(s) with those of the parent institution, because synergism and cohesiveness can be diminished when projects are located outside the group at the parent institution. Facilities and Administrative costs paid as part of a consortium agreement are excluded from the limit on the amount of direct 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-aid. Consult the latest published policy governing consortia before developing the application. If clarification of the policy is needed, contact Ms. Jane Davis, Grants Operations Branch, NHLBI, (301) 435-0166. FUNDS AVAILABLE Applicants may request up to $1.28 million in direct costs, not including Facilities and Administrative costs for collaborating institutions, in the first year. Competing renewal applicants may request an increase in their budget in the first competing year (Year 06), not to exceed ten percent of the costs awarded in the last noncompeting award year (Year 05) or $1.28 million, whichever is greater (excluding Facilities and Administrative costs on subcontracts). Applicants may request up to a three percent increase for subsequent noncompeting years. The specific number to be funded will, however, depend on the merit and scope of the applications received and on the availability of funds. Award of grants pursuant to this RFA is contingent upon receipt of funds for this purpose. Designated funding levels are subject to change at any time prior to final award, due to unforeseen budgetary, administrative, and/or scientific developments. Equipment is included in the budget limitation. However, requests for expensive special equipment that cause an application to exceed this limit may be permitted on a case-by-case basis following staff consultation. Such equipment requires justification. Final decisions will depend on the nature of the justification and the availability of funds. BACKGROUND AND RESEARCH OBJECTIVES Background During the past two decades, significant scientific advances have been made in transfusion medicine which have improved the safety and efficacy of blood, blood components and plasma derivatives and have changed transfusion practices. Advances have been made in detecting viral pathogens in donated blood such as HIV-l, HIV-2, HTLV-I/HTLV-II and hepatitis C, thus preventing such agents from entering the blood supply. Moreover, procedures have been developed to inactivate viruses in plasma derivatives. Improved apheresis technologies have been developed that permit more efficient collection and manipulation of blood components and stem cells. Techniques have been developed which may lead to the use of stem cells from umbilical cord blood for bone marrow reconstitution. As a result, the importance of blood transfusion has been greatly expanded through the use of components and derivatives in increasingly specialized and effective forms of therapy. The use of blood and blood components continues to increase. Improved patient care, including aggressive cancer chemotherapy programs, bone marrow and peripheral blood stem cell transplantation and sophisticated surgery procedures have contributed heavily to this growth. Consequently, the implementation of research programs to determine the optimal use of this valuable resource is important and timely. Blood centers, as well as medical centers with large transfusion services, provide an important environment for research in transfusion medicine. These centers also provide a variety of education opportunities aimed at several groups, both within and outside the special blood bank community, including laboratory technicians, undergraduate and graduate students, and practicing physicians. The SCOR mechanism is a very important and vital approach to address issues and problems confronting transfusion medicine today. Some of the advantages of this mechanism are listed below: o The SCOR brings together multidisciplinary groups of investigators with valuable expertise to transfusion medicine. With its mix of basic, applied, and clinical research, the SCOR offers investigators invaluable resources for research through coordinated interactions. o The information that emerges from the research program of a SCOR may be useful in addressing important national policy issues in transfusion medicine. In the past, the SCOR program made important contributions to the NHLBI and other federal agencies. This involvement was particularly important during the turbulent times brought about by the AIDS epidemic. For example, investigators in a SCOR research project were the first to demonstrate unequivocally the value of hepatitis B core antigen antibody assay as a surrogate test for screening blood donors at increased risk for HIV infection. The Transfusion Medicine SCOR program, like the subspecialty which it serves, is in a continually evolving state of development. Nevertheless, in the brief history of the program there have been major accomplishments in basic and clinical research which include: o A series of knockout mice have been developed that contain deletions in one or several members of the family of tyrosine kinases to determine what effect these mutations have on hematopoietic cell development and function. These studies are helping to define the roles played by tyrosine kinases in hematopoietic signal transduction The potential to use this knowledge to modulate immune responses, both in auto-immune disease or in relation to transfusion-induced immunity, is enormous. o Studies on the kinetics of clearance of donor leukocyte subpopulations in transfusion recipients have shown a surprisingly prolonged, high-level microchimerism in massively transfused trauma patients This long-term multilineage microchimerism in trauma patients seems to be due to engraftment of donor stem cells in recipients with mutual tolerance between recipient and donor leukocytes. Preliminary clinical studies characterizing the survival of specific donor leukocyte subsets in massively transfused trauma patients revealed prolonged, high-level microchimerism. Multilineage persistence of four donor leukocyte subsets for six months to 1.5 years has been observed, suggesting engraftment of donor stem cells in recipients with mutual tolerance between recipient and donor leukocytes. Studies are in progress to understand the factors determining clearance versus chimerism of transfused leukocytes. These studies should yield critical insights relevant to prevention of alloimmunization and transfusion-induced graft-versus-host disease, as well as approaches toward induction of tolerance for tissue and organ transplantation and active immunotherapy. o Mapping of the Plasmodium vivax binding site within the Duffy antigen on the surface of red cells has enabled the synthesis of this epitope. Subsequent creation of a transgenic mouse model expressing human Duffy in their red cells has provided investigators with means to evaluate the potential therapeutic value of the synthetic polypeptide to prevent in vivo P. vivax invasion of red cells and interrupt the progression of malaria. o Since inception of the Transfusion Medicine SCOR program in 1985, a large proportion of studies in this program have dealt with transfusion-transmitted infectious diseases, particularly AIDS. This focus on infectious disease was in part a response to the recognition that HIV-l could be transmitted by blood transfusion. The multidisciplinary configuration of the SCOR program was ideally suited to meet the challenge of transfusion-associated AIDS. As a consequence, significant contributions were made in the understanding of HIV-l, HIV-2 and other human retroviruses. The knowledge gained from the Transfusion Medicine SCOR program contributed significantly, for example, to the selection, design and development of specific assays to detect the presence of human retroviruses in blood donors. Areas to be Addressed by this Initiative With implementation of donor screening procedures that virtually eliminate HIV-l and significantly reduce the likelihood of other transfusion-transmitted viruses from entering the blood supply, the National Heart, Lung, and Blood Institute (NHLBI) redirected its SCOR program in 1996 to address other important areas of scientific need and opportunity in Transfusion Biology and Medicine. Five areas of special emphasis were identified that are essential for the optimal use and improvement of transfusion therapy. Recent progress in our understanding in such areas as immune regulation and hematopoiesis make this an opportune time to encourage research in the following areas of emphasis: Immunomodulatory Aspects of Transfusion The immune system occupies a central role in the safety and efficacy of transfusion therapy. One of the major problems in transfusion therapy is alloimmunization. In some situations, the occurrence may be of little consequence, but as a general problem, alloimmunization is of great importance as it limits the effectiveness of transfusions and in some cases results in death of the patient. The target antigens to which these alloimmune responses are directed have been well defined and include epitopes on red blood cells, white blood cell specific antigens, platelet antigens, and HLA antigens. In other instances, such as graft-versus-leukemia mediated by transfusion of allogeneic T-cells, the target antigens are not known. Investigators in this SCOR program are encouraged to pursue studies that focus on the mechanisms involved in these alloimmune reactions. The ultimate goal is to develop better strategies for the prevention and modulation when alloimmunity is undesired. Alternatively, better approaches could be developed to enhance the efficacy of alloimmune cellular therapies for graft-versus-tumor effect and cancer vaccine development. Development of Novel Cell Therapies and Cytokine Therapies Recent developments in the understanding of hematopoiesis and stem cell biology, in the identification of hematopoietic growth factors and cytokines, and in cell culture technology hold promise for the creation of novel cellular components and transfusion therapies. Studies are needed on the identification, collection, purification, manipulation, and preservation of hematopoietic stem cells for use in transplantation. Studies on the in vitro expansion of hematopoietic stem cells are also encouraged. Significant advances have been made which create realistic prospects for the establishment of in vitro culture systems for production of stem cells for transplantation and for the production of specific cell populations for transfusion therapy. It is important to better understand the molecular and genetic events that accompany stem cell proliferation and expansion, so that their manipulation will allow the therapeutic use of the derivative cells. A further objective of this SCOR program is to develop the requisite bioengineering and delivery strategies to apply this new understanding to patient care, hopefully minimizing the prolonged periods of severe pancytopenia that accompany modern hematologic and oncologic therapies. In addition to the use of cytokines to support the in vitro expansion of cells, studies are also needed to determine the optimal use of cytokines in vivo to reduce transfusion needs. Studies might address the identification of those disease states where cytokine therapy might be of use. Studies are needed on the dose and timing of cytokine therapy. Research studies on the regulation of endogenous cytokine production are important and could eventually lead to clinical therapies. Structure/Function Relationships of Human Blood Cell Surface Antigens Studies are needed to better understand the relation of structure to function in human blood cells, particularly red blood cells and platelets. There is a need for studies on the characterization and biological significance of blood cell surface antigens, particularly as they relate to the structural integrity of the cells, to specific cell functions, and to specific disease processes. Until recently, the major reasons for identifying blood group antigens and antibodies have been their importance in assuring safe and effective blood transfusions. In recent years, however, clinical information regarding the relation of blood cell antigens to disease has accumulated, as has knowledge of blood cell membrane structure and function. The primary structure of many of the red cell membrane proteins have been deduced by cloning of genes that encode these proteins. Significant progress has also been made in defining polymorphisms in individual protein sequences responsible for various antigenic determinants. These accomplishments have opened new research opportunities in red cell and transfusion medicine. Platelet antigens are known to be associated with functional glycoproteins on platelet membranes and platelet antibodies have been shown to affect platelet function. Similar studies are needed to determine what role antibodies may play in altering red blood cell function. The emerging research issues in this area include: 1) defining the physiologic function of cell membrane proteins, 2) identifying the contribution of these membrane proteins and their homologues to various disorders, hematological as well as nonhematological and, 3) using of novel approaches such as phage-display systems, transgenic mice, and transfected cell lines to develop monoclonal antibodies for use as typing reagents and for use as therapeutic agents. Blood Substitutes/Platelet Substitutes Research on oxygen-carrying red cell substitutes could lead to the development of products that provide short or even possibly long-term support for anemic patients with the advantages of being universally compatible, pathogen free, and without the requirement for cross-matching. They would ideally have a long shelf-life and offer convenient storage. There are currently several human safety trials of artificial oxygen carriers in various stages of study. Most results reported thus far have been disappointing as unexpected toxicities have been observed. Thus, studies are needed to understand the mechanisms of toxicity of hemoglobin-based oxygen carriers. Projects might address the apparent vasoactivity of these preparations. Animal models or in vitro models need to be developed to reliably predict human toxic reactions. Furthermore, the long-term (metabolic and pharmacologic) effects of oxygen carriers need to be delineated. Studies on the efficacy of artificial oxygen carriers also need to be conducted under the experimental conditions that reflect the intended clinical use. Of particular importance are the function of artificial oxygen carriers in the presence of red cells; the measurement of tissue and organ function as an indication of efficacy; and the comparison of the efficacy of artificial oxygen carriers with that of red cells. Much effort has also been expended on the development of novel methods to prepare safer, hemostatically efficacious platelet products or substitutes with longer shelf-lives than currently provided by conventional liquid-stored platelets. These include storage in the frozen state; storage in cold (4 degrees C) in the liquid state; use of infusible platelet membrane fragments or microparticles; use of rehydrated lyophilized platelets; as well as the use of photochemical methods for the inactivation of viruses, bacteria, and protozoa. Other approaches have attempted to make artificial platelet substitutes that are capable of in vivo hemostasis. These include liposomes bearing hemostatically active agents on their surface; fibrinogen-coated albumin microspheres; and red blood cells bearing RGD peptides or fibrinogen on their surfaces. Considerable challenges, however, still exist. The major problem is the lack of appropriate methodology for assessing in vitro and in vivo the hemostatic function of such alternative platelet products and substitutes. Thus, this program encourages the development of definitive criteria to evaluate the hemostatic efficacy as well as the mechanism of action of preparations with potential use as platelet substitutes. Indications for Red Blood Cell or Platelet Transfusion Despite the obvious advantages of blood transfusion, there is concern that blood components such as red blood cells and platelets are at times given to patients who do not really need them, are given too frequently to patients who do need them, and occasionally, either are not given or are given in insufficient quantities when treatment is urgently required. Clinical decisions regarding red blood cell and platelet transfusions are hampered by a general lack of clinical studies, by imprecise methods of evaluating clinical need and by uncertain methods for measuring effects. The time-honored and useful measurements of hemoglobin concentration and hematocrit are clearly not sufficient, by themselves, for many patients much of the time. Research studies are clearly needed to improve knowledge in these areas. Studies might focus on the development of predictors that better define the need for red blood cell transfusion. The identification of organs that are specifically at risk during acute anemia and the development of clinical monitors that measure the state of perfusion and the presence of cellular hypoxia in those organs that are specifically sensitive to low hemoglobin values may be promising approaches. Studies are also needed to determine the appropriate indications for platelet transfusions. The platelet levels that predispose thrombocytopenic patients to hemorrhage and the efficacy of therapeutic modalities other than transfusion are not well understood and require investigation. The development of a practical test that predicts the likelihood of clinically significant platelet-related bleeding would be extremely useful. An area in transfusion of special interest to the Institute is neonatal transfusion therapy. Dramatic advances in the care of infants of low to extremely low birth weight have resulted in survival beyond the immediate intrapartum period. Current practice often includes transfusions with red blood cells as part of the therapy for most of these infants. However, adequacy of red blood cell transfusion in the premature infant is most often assessed by measuring hemoglobin and hematocrit, two parameters that, as in adults, have limited correlation with both the need to transfuse as well as transfusion outcome. Research is needed to establish quantitative, clinically useful criteria to be used in addition to or instead of hemoglobin and hematocrit measurements in determining when to begin and end blood transfusions in newborns. There is a need for new, innovative methods to assess oxygen delivery in the newborn. Furthermore, studies to determine transfusion outcomes in this population are also needed. The different research topics and approaches described in the five areas of emphasis are intended to provide potential applicants with examples of the types of topics that are of interest to the NHLBI and worthy of pursuit. These examples, however, are not meant to be all inclusive. Investigators are encouraged to consider pursuing other important and innovative scientific topics as well. It should be emphasized, however, that THE TOPICS CHOSEN MUST RELATE DIRECTLY TO THE FIVE AREAS OF EMPHASIS IDENTIFIED IN THIS INITIATIVE. Furthermore, the topics may address one or more than one area of emphasis. For example, it would be appropriate for a SCOR applicant to propose projects that address research issues pertaining to one area of interest such as structure/function relationships of human blood cell surface antigens or a combination such as structure/function relationships of human blood cell surface antigens and immunomodulatory aspects of transfusion. Applicants should also note that a SCOR program must meet the following criteria: (1) address areas of significant national need and clinical importance; (2) attract talented investigators who foster the development of a multidisciplinary and collaborative synergistic approach; (3) include both basic and clinical components with at least one of the projects in the SCOR dealing exclusively with clinical issues or in which clinical parts of two or more projects would, in aggregate, constitute at least one project relative to resources and personnel; and, most importantly; (4) have the potential to accelerate the transfer of basic research to clinical application. APPLICANTS ARE REQUESTED TO CONTACT THE PROJECT OFFICER OF THIS INITIATIVE PRIOR TO PREPARING A SCOR APPLICATION TO MAKE CERTAIN THAT THEIR PROPOSED PROGRAM IS COMPATIBLE WITH THE OBJECTIVES OF THIS SOLICITATION. The major emphasis of this SCOR program is on basic, applied and clinical research in transfusion biology and medicine, the nature of which will depend upon the interests and areas of expertise of its investigators, as well as on the physical resources and population available. However, each institution requesting SCOR support should have a basic range of competence and potential that will enable it to develop a program addressing the objectives and goals of this initiative. SCORs should also provide a challenging environment for attracting talented young scientists into biomedical research -and offering opportunities for career development. SPECIAL REQUIREMENTS Special features of SCOR grants are: o They provide opportunities for young and established investigators with mutual or complementary interests to engage in multidisciplinary basic and clinical research in a synergistic fashion such that major therapeutic advances will be realized. o A SCOR has a central theme to which all research projects pertain. In addition, a SCOR may include core units to provide services to the various research projects and to support the organizational and administrative aspects of the program. o Inherent in the SCOR program is a special interaction between the SCOR director, the grantee institution, and the Division of Blood Diseases and Resources (DBDR). Upon initiation of the program, DBDR will hold periodic meetings to encourage exchange of information among investigators who participate in this program and to stimulate collaboration. Applicants should include travel funds for a two-day meeting every other year, most likely to be held in Bethesda, Maryland. Applicants should also include a statement in their applications indicating their willingness to participate in these meetings. o The Division's overall SCOR program and each SCOR grant undergo periodic evaluation. The progress reports are prepared for the information of the National Heart, Lung, and Blood Advisory Council, the Division of Blood Diseases and Resources staff, and ad hoc members of SCOR evaluation groups. Requirements of SCOR grants: o The overall concept of a SCOR program focuses on scientific issues related to the mission of the NHLBI. It is essential, therefore, that all applications include both basic and clinical research projects. Interactions between basic and clinical scientists are expected to strengthen the research, enhance transfer of fundamental research findings to the clinical setting, and identify new research directions. Plans for transfer of findings from basic to clinical studies should be described. o Each SCOR must have a well-delineated organizational structure and administrative mechanism that foster interactions between investigators, accelerate the pace of research, and ensure a productive research effort. o Each SCOR grant application and award must include research involving human patients/subjects, which is defined as research conducted with human patients/subjects or on material of human origin such as tissue or other specimens for which an investigator directly interacts with human patients/subjects. Support may be provided for human biomedical and behavioral studies of etiology, pathogenesis, prevention and prevention strategies, diagnostic approaches, and treatment of diseases, disorders, or conditions. Small population-based studies, where the research can be completed within five years, may also be proposed. In addition, basic research projects must be included that relate to the clinical focus. Each component project requires a well-described hypothesis, preliminary data and a time-table for conducting the proposed investigations. A SCOR may also contain one or more core units that support the research projects. The relationship between each research project and one or more core units should be described. o Applications from institutions which have a General Clinical Research Center (GCRC) funded by the NIH National Center for Research Resources may wish to identify the GCRC as a resource for conducting the proposed research. In such a case, a letter of agreement from the GCRC program director/principal investigator could be included with the application. o The principal investigator should be an established scientist with the ability to ensure quality control and the experience to administer effectively and integrate all components of the program. A minimum time commitment of 25 percent is expected for this individual. The principal investigator must also be the project leader of one of the component research projects. If, through peer review, this project is not recommended for further consideration, the overall SCOR application will not be considered further. If this project is judged by peer review to be of low scientific merit, it will markedly reduce the overall scientific merit ranking assigned to the entire application by the review committee. o Project leaders must agree to commit at least 20 percent effort to each project for which they are responsible. Investigators with minimal research experience, but promising credentials, may participate; however, it is expected that most of the project directors will be investigators with significant research experience. o If a project director transfers to another institution, support for the project will normally not be continued as a consortium. 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 subpopulations must be included in all NIH supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification is provided that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This new 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 "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research", which have been published in the Federal Register of March 28, 1994 (F59 14508-14513), and in the NIH Guide for Grants and Contracts of March 18, 1994, Volume 23, Number 11. Investigators may obtain copies from these sources or from the program staff or contact person listed under Inquiries. Program staff may also provide additional relevant information concerning the policy. INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of the NIH 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 was published in the NIH Guide for Grants Contracts, March 6, 1998, and is available at the following URL address: https://grants.nih.gov/grants/guide/notice-files/not98-024.html. LETTER OF INTENT Prospective applicants are asked to submit a letter of intent by December 1, 1999, 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 the RFA in response to which the application may be submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, it assists the NHLBI staff to estimate the potential review workload and to avoid conflict of interest in the review. The letter of intent is to be sent to: Dr. C. James Scheirer Division of Extramural Affairs National Heart, Lung and Blood Institute 6701 Rockledge Drive, Suite 7093, MSC 7924 Bethesda, MD 20892-7924 Telephone: (301) 435-0266 FAX: (301) 480-3541 Email: js110j@nih.gov 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 business offices of sponsored research or may be obtained 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; Email: GrantsInfo@nih.gov, and from the NIH program administrator listed under INQUIRIES. Specific instructions for preparing a SCOR application are also available from the program contact listed under INQUIRIES. The RFA label included in grant application PHS 398 (rev. 4/98) must be affixed to the bottom of the face page of the application. 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, SCOR in Transfusion Biology and Medicine and number, HL-99-023 must be typed on line 2 of the face page of the application form and the "YES" box must be marked. Send or deliver 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) Send two additional copies of the application to the Chief, Review Branch, at the address listed under LETTER OF INTENT. It is important to send these two copies at the same time as the original and three copies are sent to the Center for Scientific Review (CSR). Applications must be received by January 14, 2000. If an application is received after that date, it will be returned to the applicant without review. The 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. The 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 responsiveness by the NHLBI staff. Incomplete applications or applications deemed not responsive to the RFA 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 NHLBI in accordance with the review criteria stated below. Applicants should submit the highest quality applications possible to CSR as no site visits or reverse site visits will be held. As part of the initial merit review, a streamlined process may be used by the initial review group in which the scientific merit of applications relative to other applications received in response to the RFA will be determined. Applications judged to be of high scientific merit will be discussed and be assigned a priority score, and will also receive a second level of review by the National Heart, Lung, and Blood Advisory Council. Applications determined to be of low scientific merit will be withdrawn from further consideration and the principal investigator and the official signing for the applicant organization will be notified. Factors to be considered in the evaluation of each application will be similar to those used in review of traditional research grant applications and, in addition, will include overall proposed interactions among basic and clinical research projects. Major factors to be considered in the evaluation of applications include: o Scientific merit of the proposed basic and clinical research projects including significance, importance, and appropriateness of the theme; innovation, originality, and feasibility of the approach; and adequacy of the experimental design. o Leadership, scientific stature, and commitment of the program director; competence of the investigators to accomplish the proposed research goals and their time commitment to the program; and the feasibility and strength of consortium arrangements. o Collaborative interaction among basic and clinical research components, the balance between them, and plans for transfer of potential findings from basic to clinical studies. o Adequacy of the environment for performance of the proposed research including clinical populations and/or specimens; laboratory facilities; proposed instrumentation; quality controls; administrative structure; institutional commitment; and, when needed, data management systems. o Appropriateness of the budget for the proposed program. o Appropriateness of the central theme and coordination and interrelation of the research projects and core units. AWARD CRITERIA The anticipated date of award is January 1, 2001, for the SCORs in Transfusion Biology and Medicine. Awards will be made according to priority score, availability of funds, and programmatic priorities. 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 and requests for supplemental instructions to: George Nemo, Ph.D. Division of Blood Diseases and Resources National Heart, Lung, and Blood Institute 6701 Rockledge Drive, MSC 7950 Bethesda, MD 20892-7950 Telephone: (301) 435-0075 FAX: (301) 480-1046 Email: nemog@nih.gov Direct inquiries regarding fiscal and administrative matters to: Ms. Jane Davis Division of Extramural Affairs National Heart, Lung and Blood Institute 6701 Rockledge Drive, Suite 7174, MSC 7926 Bethesda, MD 20892-7926 Telephone: (301) 435-0166 FAX: (301) 480-3310 Email: davisj@nih.gov AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.839, Blood Diseases and Resources. Awards will be made under the authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirement of Executive Order 12372 or Health Systems Agency review. All current policies and requirements that govern the research grant programs of the NIH will apply to grants awarded under this RFA. 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.
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Office of Extramural Research (OER) |
National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892 |
Department of Health and Human Services (HHS) |
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