RFA-HL-04-018: SPECIALIZED CENTERS OF CLINICALLY ORIENTED RESEARCH (SCCOR) IN TRANSFUSION BIOLOGY AND MEDICINE

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SPECIALIZED CENTERS OF CLINICALLY ORIENTED RESEARCH (SCCOR) IN TRANSFUSION BIOLOGY AND MEDICINE RELEASE DATE: March 02, 2004 RFA Number: RFA-HL-04-018 EXPIRATION DATE: September 22, 2004 Department of Health and Human Services (DHHS) PARTICIPATING ORGANIZATION: National Institutes of Health (NIH) (http://www.nih.gov/) COMPONENT OF PARTICIPATING ORGANIZATION: National Heart, Lung, and Blood Institute (NHLBI) (http://www.nhlbi.nih.gov/) CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S): 93.839 LETTER OF INTENT RECEIPT DATE: August 17, 2004 APPLICATION RECEIPT DATE: September 21, 2004 THIS RFA CONTAINS THE FOLLOWING INFORMATION o Purpose of this RFA o Research Objectives o Mechanism of Support o Funds Available o Eligible Institutions o Individuals Eligible to Become Principal Investigators o Special Requirements o Where to Send Inquiries o Letter of Intent o Submitting an Application o Peer Review Process o Review Criteria o Receipt and Review Schedule o Award Criteria o Required Federal Citations PURPOSE OF THIS RFA The primary objective of the Specialized Centers of Clinically Oriented Research (SCCOR) programs is to foster multidisciplinary research on clinically relevant questions enabling basic science findings to be more rapidly applied to clinical problems. The clinical and basic research supported through this RFA program in transfusion biology and medicine is to support the development and application of new knowledge essential for improved safety, efficacy, and availability of blood, blood components, and plasma derivatives, and to transfer these research findings into clinical evaluation and application. RESEARCH OBJECTIVES The National Heart, Lung, and Blood Institute (NHLBI) revised the Specialized Centers of Research (SCOR) program, based primarily on recommendations from the National Heart, Lung, and Blood Advisory Council. The new program is called the Specialized Centers of Clinically Oriented Research (SCCOR) program. The original SCOR program required both basic and clinical research, but the preponderance of funded projects were in the basic science arena. The new title and the revisions to the program reflect the Institute's desire to capitalize on basic research advances by encouraging their translation to the clinical arena. The guiding principle of the new SCCOR program is the central focus on clinically relevant research, and the key change to achieve this goal is the requirement that at least one-half of funded projects be clinical. The specific components of the new SCCOR program are detailed in this RFA. Special instructions for preparing a SCCOR application are available from the program contact listed under WHERE TO SEND INQUIRIES or at http://www.nhlbi.nih.gov/funding/policies/sccor_desc.htm. Opportunities for research in transfusion medicine are increasing and have expanded to include any blood component or bone marrow derived cell. There continues to be a substantial need for performing evidence-based studies to evaluate the best approaches to provide blood and bone marrow derived components to patients. Listed below are four general areas of emphasis and specific examples are outlined for which studies would be considered to be responsive to this RFA announcement. The different research topics and approaches described below in the four areas of emphasis provide potential applicants with examples of topics that interest the NHLBI. These examples, however, are not meant to be all inclusive. Investigators are encouraged to consider pursuing other important and innovative research topics as well. It should be emphasized, however, that the topics chosen must relate directly to the four areas of emphasis identified in this initiative. Furthermore, topics may address more than one area of emphasis. For example, it would be appropriate for an application to propose projects that address research issues pertaining to one area of interest such as immunologic responses to blood components or platelet storage or a combination such as immunologic responses to blood components and platelet substitutes. It should be noted, however, that SCCOR investigations which focus exclusively on cellular therapy will not be considered responsive to this RFA. I. MANAGEMENT OF THE BLOOD SUPPLY Maintaining an adequate supply of blood components to meet patient needs for transfusion involves many factors including a broad donor base, methods of storing blood components, and determining appropriate indications for their use to avoid unnecessary and/or ineffective transfusions. Areas for research questions include: Donors o Determine the benefits of iron supplementation to donors; o Evaluate donor safety issues such as: frequency of donations, quantity of blood components removed, and effects of cytokines given to donors to enhance the collection of blood components; o Recruitment and retention of donors. o Storage and Utilization of Blood Components o Determine optimal transfusion triggers for cellular and plasma blood components to reduce ineffective use; o Assess the appropriate transfusion dose for each blood component; o Evaluate methods of extending the storage time for cellular components, particularly platelets; o Determine how to judge the safety and efficacy of blood component therapy. II. INCOMPATIBILITY AND BLOOD SAFETY IN TRANSFUSION MEDICINE Substantial progress has been made over the last several years in the identification of and testing for viruses that are capable of being transmitted by transfusion. The following areas of blood transfusion safety have received little emphasis and now represent the biggest transfusion risks for patients: Safety of blood products o Develop methods of blood product and recipient identification to ensure the correct product is given to the designated recipient; o Identify processes to either detect bacterial contamination or inhibit the growth of bacteria in transfused blood products B particularly platelets; o Identify ligands and/or receptors on erythrocytes for microbe binding. Blood Group Incompatibility o Develop improved methods of antigen typing to insure a compatible transfusion; o Identify systems to reduce alloimmunization in transfusion dependent patients; o Determine the pathophysiological events in Hemolytic Disease of the Newborn and identify preventative clinical intervention. III. IMMUNOLOGIC RESPONSES TO BLOOD COMPONENTS OR MARROW DERIVED CELLS There are both desirable and undesirable immunologic consequences of the transfusion of blood components or marrow derived cells. For all of these transfusion related effects, additional studies are needed to understand the factors associated with their development. These factors include the influence of the type, amount, and timing of transfusions on their occurrence, ways that desirable effects can be enhanced while undesirable effects are eliminated, and the pathophysiologic events associated with these conditions. Topics include: Desirable Effects o Graft vs. Leukemia; o Induction of tolerance to organ grafts. Undesirable Effects o Alloimmunization and refractoriness to platelet transfusions; o Alloimmunization to red cells with reduction in the available compatible donor pool; o Transfusion associated acute lung injury (TRALI); o Immunomodulatory effects of transfusion such as infection and tumor recurrence/metastasis; o GVHD IV. CELLULAR THERAPY Transfusion medicine has traditionally been involved in the production and storage of red cells, platelets, granulocytes, and plasma components. Another topic of interest has been the evaluation of their use in transfusions. However, it has become clear that there are many other types of blood and bone marrow derived cells that have important biologic functions. Therefore, of substantial interest are studies on the characterization of these cell types by exploring their role in the pathophysiology of human diseases, and methods for the manipulation and transfusion of these cells to provide a therapeutic benefit to patients. Examples of these therapies are listed below: Mononuclear Cell Fractions o Identify and characterize the stem cells that are associated with rapid and long term engraftment; o Develop methods for proliferation of stem cells in vitro; o Characterize the cells associated with GVHD and determine how this adverse effect can be eliminated/modified; o Identify factors associated with the development of peripheral blood stem cells as well as other blood cells. Pluripotent Stem Cells o How can the use of marrow derived cells in organogenesis be potentiated; o What factors are associated with the development of "plasticity" and how can this be facilitated; o What governs the trafficking of cells to desired locations. Cellular Engineering of New Blood Components o Develop blood "substitutes" which can take the place of "classic" blood component transfusions. Modification of Leukocytes to Act as Vaccines for the Treatment of Malignancies or Infectious Diseases o What are the best cells to use for targeted vaccine therapy; o What are the best ways to develop "vaccinated cells"; o How should they be used, and how is their effectiveness determined. Gene Therapy o Use cells to "cure" genetic diseases by inserting into cells the genetic material of interest; o Identify the most appropriate cells to use as the hosts for genetic material; o Determine how should the genetic material be inserted; o Determine how should genetically modified cells be infused (locally or systemically), the frequency of administration; o Establish ways to monitor the effectiveness of this therapy. Treatment of Autoimmune Diseases by Cellular Therapy Adoptive Immunotherapy o Peripheral blood mononuclear cells can be manipulated ex vivo and transfused to decrease or enhance immune function. Clinical Research Skills Development Core The newly developed Specialized Centers of Clinically Oriented Research (SCCOR) program mechanism requires clinical and basic scientists with a broad range of skills to work together on a unified theme. It, therefore, presents a rich environment for young clinical investigators to be exposed to and develop additional research skills. The individual centers can be expected to include among their research staffs clinical personnel who are newly trained and relatively inexperienced in research. To assist the SCCOR grants in enhancing the developmental environment for their new clinical investigators, the NHLBI will permit applicants for a new SCCOR to request up to $100,000 in direct costs per year for a Clinical Research Skills Development Core. The objective of the Core is to support activities to assist new clinical investigators in progressing to more senior status by enhancing their research skills. This support is in addition to the usual cap on the SCCOR mechanism that is updated annually. A Clinical Research Skills Development Core is not required, however, and its absence will not disadvantage an applicant. The quality of the Clinical Research Skills Development Core, if proposed, will be evaluated based on the specific components listed below. The priority score on the Core will have no effect on the overall score of an application. Developmental opportunities that provide experience with new technologies and skills are encouraged for inclusion in the Core. Innovative strategies should be proposed for cross-disciplinary career development to achieve the goal of exposing new clinical investigators to additional research techniques and opportunities. Examples include a program of seminars focusing on scientific topics that include an integration of basic and clinical studies or an "exchange" program wherein clinical investigators spend time in basic science laboratories. In addition to developing the research skills of new clinical investigators, the Cores must ensure that the participating new clinical investigators receive the mentoring they need to foster their research careers. The Clinical Research Skills Development Core is intended for staff investigators with limited clinical research experience, including fellows and junior faculty members. Investigators who have had a previous K series award are not eligible to participate as new investigators under this program. Individuals with an active K grant can participate until the end of the award period for the K grant, but may not receive salary on the Skills Development Core. The Core should also address other skills necessary for a successful research career, such as grant writing, ethical conduct of research, and clinical trial design. If a Clinical Research Skills Development Core is proposed, it must be directed by an investigator with strong educational and mentoring credentials who will devote a minimum of 5 percent effort as its Leader. To facilitate mentoring and multidisciplinary developmental activities, active involvement by the principal investigator and other senior investigators within the SCCOR is strongly encouraged. An application for a Clinical Research Skills Development Core will be evaluated in terms of its potential effectiveness in developing the skills and research capabilities of new clinical investigators as reflected in the following required elements of the application: o A summary of the types of skills that would be developed and a description of proposed project-specific activities; o A detailed discussion of how mentoring and the professional development of the new clinical investigators will be achieved, including their progression to more independent status; o The credentials and track records of the Clinical Research Skills Development Core Leader, the Principal Investigator, and other participating senior staff in developing new investigators; o A plan for coordinating the activities of participating senior investigators; o A plan for monitoring the progress of the new clinical investigators; o A description of existing opportunities within the applicant's institution for supporting investigator development and steps taken to avoid overlap with or duplication of these efforts; o A detailed development plan for each proposed new investigator (or a representative plan and proposals for tailoring it to needs of multiple new investigators) including required course work and scientific enrichment activities such as special lectures, visiting scientist symposia, seminars, and workshops. Costs allowable for inclusion within the $100,000 direct costs per year limit for the Clinical Research Skills Development Core include salary support for the Core Leader and other participating senior investigators and staff, travel costs for new investigators, supplies and equipment to be used in support of developmental activities, and costs for courses, seminars, workshops, and other activities directly related to the development plan. All costs requested in this Core must be justified with respect to developmental activities and may not be used to supplement the costs of research proposed in the rest of the SCCOR. Since the Core is intended to serve new clinical investigators who occupy positions and receive salary support from the SCCOR grant, salary support for the new investigators is neither needed nor allowable as a Core cost. All new clinical investigators supported by the SCCOR grant should be eligible to participate in Core- sponsored activities so long as they have not attained independent status. However, attaining independent status should be an objective of the Core activities so participating new investigators should be encouraged to apply for either a Career Development Award, a patient-oriented regular research grant, or any other source of independent research or career development support. Although the participating new investigators will be expected to devote essentially full-time effort to research during this period, they may devote an appropriate percentage of their time to maintaining clinical skills. An application for a Clinical Research Skills Development Core will be evaluated in terms of its potential effectiveness in developing the skills and research capabilities of new clinical investigators as reflected in the required application components identified above. MECHANISM OF SUPPORT This RFA will use the NIH P50 award mechanism. All applications received in response to the Transufsion Biology and Medicine Diseases SCCOR program will be considered as new applications and must meet the requirements for the new SCCOR program. As an applicant you will be solely responsible for planning, directing, and executing the proposed project. The anticipated award date is February 1, 2006. Each NHLBI SCCOR program is limited to 10 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 SCCOR program. Under this policy, a given SCCOR grant is awarded for a 5-year project period following an open competition. Only one 5-year competing renewal is permitted, for a total of 10 years of support, unless the SCCOR program is recommended for extension. The NHLBI comprehensive evaluation of the Transfusion Biology and Medicine SCCOR program will be conducted during the second project period according to the following timetable: Program Announced: FY 2004 Project Period (First Competition): FY 2006 through FY 2011 Program Reannounced: FY 2009 Project Period (Second Competition): FY 2011 through FY 2016 Letter to Principal Investigators Regarding SCCOR Evaluation Plans: FY 2012 (mid-way through year 02 of 2nd project period) SCCOR Evaluation Meeting: FY 2013 (late in year 02 of 2nd project period) The NHLBI does not limit the number of applications for a given SCCOR program from one institution. However, each SCCOR application from the institution must have a different principal investigator and must be self-contained and independent of other SCCOR applications from the same institution. Institutions envisioning more than one application are encouraged to discuss their plans with the program contact listed under Where to Send Inquiries. FUNDS AVAILABLE The NHLBI intends to commit approximately $4.0 million in FY 2006 to fund 2 to 3 new grants in response to this RFA. An applicant may request a project period of up to 5 years and a budget for direct costs up to $2.0 million not including Facilities and Administrative (F&A) costs for collaborating institutions, in the first year. In addition, applicants for a new SCCOR may request up to $100,000 in direct costs per year above the usual cap ($2.0 million direct costs) for a Clinical Research Skills Development Core. All applications will be considered as new applications. An increase of no more than 3 percent may be requested in each additional year. Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. Although the financial plans of the NHLBI 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. Consortium Arrangements If a grant application includes research activities that involve institutions other than the grantee institution, the application will be considered a consortium effort. Such applications are permitted, but it is imperative that the application be prepared so that programmatic, fiscal, and administrative considerations are explained fully. At least 50 percent of projects (including at least one clinical project) and 50 percent of the cores must be located at the applicant institution. The NIH published policy governing consortia is available in the business offices of institutions that are eligible to receive Federal grants-in-aid and should be consulted before developing the application. For clarification of the policy, contact Mr. Anthony Agresti, Grants Operation Branch, NHLBI, (301) 435-0171. Applicants for SCCOR grants should exercise great care in preserving the interactions of the participants and the integration of the consortium project (s) with those of parent institution, because synergism and cohesiveness can be diminished when projects are located outside the group at the parent institution. Indirect costs paid as part of a consortium agreement are excluded from the limit on the amount of direct costs that can be requested. ELIGIBLE INSTITUTIONS You may submit (an) application(s) if your institution has any of the following characteristics: o For-profit or non-profit organizations o Public or private institutions, such as universities, colleges, hospitals, and laboratories o Units of State and local governments o Eligible agencies of the Federal government o Foreign institutions are not eligible to apply. INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS Individuals with the skills, knowledge, and resources necessary to carry out the proposed research are invited to work with their institution to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH programs. SPECIAL REQUIREMENTS 1. The overall concept of a SCCOR program focuses on clinical and basic scientific issues related to diseases and disorders relevant to the mission of the NHLBI. To be considered responsive to this announcement, all applications must include both clinical and basic research. In addition, interactions between clinical and basic scientists are expected to strengthen the research, enhance the translation of fundamental research findings to the clinical setting, and identify new research directions. Translation of findings from basic to clinical studies is an important focus of the SCCOR program. 2. The number of clinical research projects in each NHLBI SCCOR must be equal to or greater than the number of basic science projects, at the time of submission, award, and throughout the 5-year project period. For example, if an application has a total of three projects, two of the projects must be clinical research projects. Neither a clinical component in a basic science project nor a clinical core fulfills the requirement for a clinical project. However, a single project can integrate basic and clinical research. If the majority of the research within a project is clinical, it will be considered a clinical project; if the majority of the research within a project is basic, it will be considered a basic project. Because a SCCOR grant is a 5- year program, an applicant should submit a 5-year plan for all the projects. 3. In order for a project to be considered clinical research for the purposes of responsiveness to this RFA, the research must be patient-oriented research. Patient- oriented research is research in which an investigator (or colleague) directly interacts with patients having a disease or condition of interest. Normal healthy subjects may be included, but only in combination with studies involving patients. In studies involving the use of human specimens, the investigators must have direct interaction with the patient from whom the specimen is obtained and relate the research results to the patient status or outcome for this to be considered a clinical project. It is intended that the requirement for investigator interaction with the study participants will eliminate research involving archived tissue. Applicants are encouraged to pursue patient-oriented research on topics related to health disparities and the translation of this research to clinical practice for affected minority populations. At a minimum, clinical research projects must include women and minorities in the study population in representative numbers, unless such inclusion can be demonstrated to be inappropriate. Clinical studies involving interventions or treatments must give consideration to including sufficient numbers of women and minorities to conduct valid analyses of subgroup effects. Epidemiologic studies or Phase III clinical trials will be considered unresponsive to this RFA. 4. Each awarded SCCOR must consist of three or more projects, all of which are directly related to the overall clinical focus of the SCCOR. At least 50 percent of the projects and 50 percent of the cores must be located at the applicant institution and at least one of the clinical projects must be at the applicant institution. Component projects not located at the applicant institution may be at a foreign institution, but must conform to NIH policy regarding the protection of human subjects. Each component project, whether clinical or basic, requires a well-described clinically relevant hypothesis, preliminary data, and a time-table for conducting the proposed investigations. 5. The relationship of each core to each component project should be described. A core must provide services to two or more projects. 6. Each SCCOR must have a well-delineated organizational structure and administrative mechanism that foster interactions between investigators, accelerate the pace of research, enable translation of basic research findings to clinical applications, and ensure a productive research effort. 7. Applicants should provide a detailed data and safety monitoring plan for the clinical research proposed; the monitoring plan will be considered as part of peer review of the application. This plan should address informed consent, recruitment, reporting of adverse events, patient safety, oversight of clinical issues in the protocols, storage and analysis of confidential data, and dissemination of any research results. After a decision has been made regarding SCCOR awards, the Institute will determine whether to convene a Data and Safety Monitoring Board to oversee one or more clinical projects in a SCCOR program. 8. The principal investigator should be an established research scientist with the ability to ensure quality control and the experience to administer both clinical and basic research effectively and integrate all components of the program. A minimum time commitment of 25 percent is required for this individual. The principal investigator must be the project leader of one of the component research projects. If this project is not recommended by peer review, the overall SCCOR application will not be considered further. If this project is judged by peer review to be of low scientific merit, this will markedly reduce the overall scientific merit ranking assigned to the entire application. 9. Project leaders should have significant research experience and must agree to commit at least 20 percent effort to each project for which they are responsible. Leaders of clinical projects should have experience in clinical research as defined in Item 2, above. Investigators with minimal research experience, but promising credentials, may participate; however, it is expected that most of the project leaders will be investigators with significant research experience. 10. Applicants are encouraged to establish links and utilize existing resources, including the NHLBI Program in Genomic Applications, NHLBI clinical research networks, and General Clinical Research Centers, as feasible and appropriate. If applicants propose to utilize such resources, a letter of agreement from the program director or principal investigator of the resource should be included with the application. WHERE TO SEND INQUIRIES We encourage inquiries concerning this RFA and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into three areas: scientific/research, peer review, and financial or grants management issues: o Direct your questions about scientific/research issues to: Dr. Luiz H. Barbosa Division of Blood Diseases and Resources National Heart, Lung, and Blood Institute Building Two Rockledge Center, Room 10140 Bethesda, MD 20892 Telephone: (301) 435-0075 FAX: (301) 480-1060 Email: BarbosaL@nhlbi.nih.gov o Direct your questions about peer review issues to: Dr. Anne P. Clark Division of Extramural Affairs National Heart, Lung, and Blood Institute 6701 Rockledge Drive, Room 7214, MSC 7924 Bethesda, MD 20892-7924 Telephone: (301) 435-0270 Fax: (301) 480-0730 Email: ac42y@nih.gov o Direct your questions about financial or grants management matters to: Ms. Shelia L. Ortiz Division of Extramural Affairs National Heart, Lung & Blood Institute 6701 Rockledge Drive, Suite 7044 Bethesda, MD 20892-7926 (301)435-0166 FAX (301)480-3310 ortizs@nhlbi.nih.gov LETTER OF INTENT Prospective applicants are asked to submit a letter of intent that includes the following information: o Descriptive title of the proposed research o Name, address, and telephone number of the Principal Investigator o Names of other key personnel o Participating institutions o Number and title of this RFA Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review. The letter of intent is to be sent by the date listed at the beginning of this document. The letter of intent should be sent by mail or email to Dr. Anne Clark at the address listed under Where to Send Inquiries . SUBMITTING AN APPLICATION Applications must be prepared using the PHS 398 research grant application instructions and forms (rev. 5/2001). Applications must have a DUN and Bradstreet (D&B) Data Universal Numbering System (DUNS) number as the Universal Identifier when applying for Federal grants or cooperative agreements. The DUNS number can be obtained by calling (866) 705-5711 or through the web site at http://www.dunandbradstreet.com/. The DUNS number should be entered on line 11 of the face page of the PHS 398 form. The PHS 398 document is available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. For further assistance contact GrantsInfo, Telephone (301) 710-0267, Email: GrantsInfo@nih.gov. SUPPLEMENTARY INSTRUCTIONS: Because of the size and complexity of a SCCOR, prospective applicants are urged to consult with the staff of the Division of Blood Diseases and Resources early in the preparation of the application (see INQUIRIES Section). Special instructions are needed for preparing a SCCOR application and are available from the program contact listed under WHERE TO SEND INQUIRIES, or at http://www.nhlbi.nih.gov/funding/policies/sccor_desc.htm. Each NHLBI SCCOR program is limited to 10 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 SCCOR program. Under this policy, a given SCCOR grant is awarded for a 5-year project period following an open competition. Only one 5-year competing renewal is permitted, for a total of 10 years of support, unless the SCCOR program is recommended for extension. The NHLBI does not limit the number of applications for a given SCCOR program from one institution. However, each SCCOR application from the institution must have a different principal investigator and must be self-contained and independent of other SCCOR applications from the same institution. Institutions envisioning more than one application are encouraged to discuss their plans with the program contact listed under Where to Send Inquiries. USING THE RFA LABEL: The RFA label available in the PHS 398 (rev. 5/2001) application form must be affixed to the bottom of the face page of the application. Type the RFA number on the label. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2 of the face page of the application form and the YES box must be marked. The RFA label is also available at: http://grants.nih.gov/grants/funding/phs398/label-bk.pdf. SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten original of the application, including the Checklist, and three signed, photocopies, in one package to: Center For Scientific Review National Institutes Of Health 6701 Rockledge Drive, Room 1040, MSC 7710 Bethesda, MD 20892-7710 Bethesda, MD 20817 (for express/courier service) At the time of submission, two additional copies of the application and all copies of the appendix material must be sent to: Anne P. Clark, Ph.D. Chief, Review Branch Division of Extramural Affairs National Heart, Lung, and Blood Institute 6701 Rockledge Drive, Room 7214, MSC 7924 Bethesda, MD 20892-7924 Bethesda, MD 20817 (for express/courier service) Telephone: (301) 435-0270 FAX: (301) 480-0730 Email: ac42y@nih.gov APPLICATION PROCESSING: Applications must be received on or before the application receipt date listed in the heading of this RFA. If an application is received after that date, it will be returned to the applicant without review. The Center for Scientific Review (CSR) will not accept any application in response to this RFA that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. However, when a previously unfunded application, originally submitted as an investigator-initiated application, is to be submitted in response to an RFA, it is to be prepared as a NEW application. That is, the application for the RFA must not include an Introduction describing the changes and improvements made, and the text must not be marked to indicate the changes from the previous unfunded version of the application. Principal investigators should not send supplementary material without first contacting the Scientific Review Administrator (SRA). The SRA will be identified in the letter sent to you indicating that your application has been received. If you have not received such a letter within three weeks after submitting the application, contact Dr. Anne Clark at the address listed under Where to Send Inquiries . PEER REVIEW PROCESS Upon receipt, applications will be reviewed for completeness by the CSR and responsiveness by the NHLBI. 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 NHLBI in accordance with the review criteria stated below. As part of the initial merit review, all applications will: o Undergo a process in which only those applications deemed to have the highest scientific merit, generally the top half of the applications under review, will be discussed and assigned a priority score o Receive a written critique o Receive a second level review by the National Heart, Lung, and Blood Advisory Council. REVIEW CRITERIA The goals of NIH-supported research are to advance our understanding of biological systems, improve the control of disease, and enhance health. Factors to be considered in the evaluation of each application will be similar to those used in the review of traditional clinical and basic research grant applications and, in addition, will include overall proposed interactions between clinical and basic research projects. The review panel will include a majority of clinical researchers who will receive special instructions to place emphasis on strong clinical components. Major factors to be considered in the evaluation of applications include: o Scientific merit of the proposed clinical and basic research projects including significance, importance, clinical relevance and appropriateness of the theme; innovation, originality, and feasibility of the approach; and adequacy of the experimental design. o Leadership, scientific expertise, experience, and commitment of the principal investigator; competence of the investigators to accomplish the proposed research goals and their time commitment to the program; clinical research experience among the investigators; and the feasibility and strength of consortium arrangements. o Collaborative interaction between clinical and basic research components and the adequacy of 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; quality of the support cores; proposed instrumentation; quality controls; administrative structure; institutional commitment; and, when needed, data management systems. o Adequacy of the data and safety monitoring plan for the clinical research proposed. Each project will receive a priority score. Each core (except the Clinical Research Skills Development Core) will be Recommended or Not Recommended based on whether the core is essential for the proposed research and has the capability to fulfill the proposed function. Reviewers will evaluate the number of projects serviced by the core; strengths and weaknesses of the proposed approaches, resources, and interactions; whether the investigators are qualified for their role(s) in the core; and whether the proposed budget for the core is appropriate. Each application will receive an overall priority score based on the review criteria listed above. The Clinical Research Skills Development Core will receive a priority score based on the review criteria below, but the priority score will not enter into the overall priority score. Review Criteria for Clinical Research Skills Development Core The Clinical Research Skills Development Core will be evaluated for its effectiveness in developing the skills and clinical research capabilities of new investigators. This will include an evaluation of: o Credentials and track record of the Principal Investigator, Clinical Research Skills Development Core Project Leader, and other participating senior investigators. o Methods by which new investigators are to be recruited and selected including plans to recruit women and minority individuals. o Plans for developing the skills of new investigators; the types of skill and technologic development proposed. o Means by which the new investigators' professional development will be achieved. ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, your application will also be reviewed with respect to the following: o PROTECTIONS: The adequacy of the proposed protection for humans, animals, or the environment, to the extent they may be adversely affected by the project proposed in the application. o INCLUSION: The adequacy of plans to include subjects from both genders, all racial and ethnic groups (and subgroups), and children as appropriate for the scientific goals of the research. Plans for the recruitment and retention of subjects will also be evaluated. (See Inclusion Criteria included in the section on Federal Citations, below) o DATA SHARING: The adequacy of the proposed plan to share data. o BUDGET: The reasonableness of the proposed budget and the requested period of support in relation to the proposed research. RECEIPT AND REVIEW SCHEDULE Letter of Intent Receipt Date: August 17, 2004 Application Receipt Date: September 21 , 2004 Peer Review Date: January / February 1, 2005 Council Review: May/September, 2005 Earliest Anticipated Start Date: January 1, 2006 AWARD CRITERIA Award criteria that will be used to make award decisions include: o Scientific merit (as determined by peer review) o Availability of funds o Programmatic priorities. REQUIRED FEDERAL CITATIONS MONITORING PLAN AND DATA SAFETY AND MONITORING BOARD: Research Components involving Phase I and II clinical trials must include provisions for assessment of patient eligibility and status, rigorous data management, quality assurance, and auditing procedures. In addition, it is NIH policy that all clinical trials require data and safety monitoring, with the method and degree of monitoring being commensurate with the risks (NIH Policy for Data Safety and Monitoring, NIH Guide for Grants and Contracts, June 12, 1998: http://grants.nih.gov/grants/guide/notice-files/not98-084.html). INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH: It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH-supported clinical research projects unless a clear and compelling justification is provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing clinical research should read the AMENDMENT "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research - Amended, October, 2001," published in the NIH Guide for Grants and Contracts on October 9, 2001 (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines are available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the new PHS Form 398; and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences. INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS: The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all human subjects research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them. This policy applies to all initial (Type 1) applications submitted for receipt dates after October 1, 1998. All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines" on the inclusion of children as participants in research involving human subjects that is available at http://grants.nih.gov/grants/funding/children/children.htm. REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS: NIH policy requires education on the protection of human subject participants for all investigators submitting NIH proposals for research involving human subjects. You will find this policy announcement in the NIH Guide for Grants and Contracts Announcement, dated June 5, 2000, at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html. HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (see http://escr.nih.gov). It is the responsibility of the applicant to provide, in the project description and elsewhere in the application as appropriate, the official NIH identifier(s) for the hESC line(s)to be used in the proposed research. Applications that do not provide this information will be returned without review. PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT: The Office of Management and Budget (OMB) Circular A-110 has been revised to provide public access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are (1) first produced in a project that is supported in whole or in part with Federal funds and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this PA in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award. URLs IN NIH GRANT APPLICATIONS OR APPENDICES: All applications and proposals for NIH funding must be self-contained within specified page limitations. Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) should not be used to provide information necessary to the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site. HEALTHY PEOPLE 2010: The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This RFA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople. AUTHORITY AND REGULATIONS: This program is described in the Catalog of Federal Domestic Assistance No. 93.837, and is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. 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 described at http://grants.nih.gov/grants/policy/policy.htm and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. The PHS strongly encourages all grant recipients to provide a smoke-free workplace and discourage the use of all tobacco products. In addition, Public Law 103-227, the Pro- Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care, or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.

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NIH Funding Opportunities and Notices