From owner-sci-resources@net.bio.net Tue Dec 01 22:00:00 1992 Path: biosci!NET.BIO.NET!kristoff From: kristoff@NET.BIO.NET (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: No NIH Guide on 4 December Message-ID: Date: 2 Dec 92 15:38:52 GMT Sender: kristoff@net.bio.net Distribution: bionet Lines: 10 $$MAIL BEGIN *********************************************************** NOTE: The NIH Guide for Grants and Contracts will not be published on December 4. The next issue will be on December 11, 1992. Please inform your colleages who receive the paper copy of the NIH Guide for Grants and Contracts that there will not be an issue for the week of December 4. $$MAIL END************************************************************** From owner-sci-resources@net.bio.net Mon Dec 07 22:00:00 1992 Path: biosci!NET.BIO.NET!kristoff From: kristoff@NET.BIO.NET (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NSF - Summary of new documents on STIS - 6 December 1992 Message-ID: Date: 8 Dec 92 00:05:00 GMT Sender: kristoff@net.bio.net Distribution: bionet Lines: 59 ** NEW DOCUMENTS ON STIS ** Document Type: Program Guideline Title: FY93 RESEARCH EQUIPMENT GRANT PROGRAM (REG) File size (bytes): 27941 STIS Filename: nsf90146 ------------------------------------------------------------------------ ** UPDATES TO EXISTING STIS DOCUMENTS ** Document Type: Program Guideline Title: FY93 RESEARCH EQUIPMENT GRANT PROGRAM (REG) File size (bytes): 27941 STIS Filename: nsf90146 ------------------------------------------------------------------------ ** FOR YOUR REFERENCE ** ------------------------------------------------------------------------ HOW TO OBTAIN DOCUMENTS The above files can be retrieved in electronic form using the STIS system. If you don't know how to use STIS, send an E-mail message to stisinfo@nsf.gov (Internet) or stisinfo@NSF (BITNET). You will receive a copy of the STIS flyer via E-mail. If you are already using STIS, you can use the information above to retrieve these files: Documents via E-mail: Send a message to stisserv@nsf.gov (Internet) or stisserv@NSF (BITNET). Use the "STIS Filename" shown above in the "get" command. For example, to retrieve nsf90146, the text of your message should be as follows: get nsf90146 Anonymous FTP: FTP to stis.nsf.gov. Use the "STIS Filename" shown above to retrieve a file. For example, to retrieve nsf90146, you would enter: ftp> get nsf90146 WAIS or Gopher: Do a word search on the filename as shown in the summary. If you want a *printed* copy of a document: Send your name and postal mailing address, and the document title and number to "pubs@nsf.gov" (Internet) or "pubs@nsf" (BITNET). If you have problems with the above procedures: Send a message to "stis@nsf.gov" (Internet) or "stis@NSF" (BITNET). From owner-sci-resources@net.bio.net Wed Dec 09 22:00:00 1992 Path: biosci!NET.BIO.NET!kristoff From: kristoff@NET.BIO.NET (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 21, no. 44, pt. 5, 11 December 1992 Message-ID: Date: 10 Dec 92 00:49:09 GMT Sender: kristoff@net.bio.net Distribution: bionet Lines: 1352 $$XID RFA AR9301 AR-93-01 P1O1 ***************************************** JUVENILE RHEUMATIC DISEASES RESEARCH CENTER PLANNING GRANT NIH GUIDE, Volume 21, Number 44, December 11, 1992 RFA: AR-93-01 P.T. 34; K.W. 0715170, 0715010, 0710030 National Institute of Arthritis and Musculoskeletal and Skin Diseases Letter of Intent Receipt Date: March 1, 1993 Application Receipt Date: April 20, 1993 PURPOSE The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) invites applications for a planning grant for a juvenile rheumatic diseases research center. The goal of the planning grant is to establish a Juvenile Rheumatic Diseases Research Center (JRDRC). The JRDRC planning grant will allow the applicant to develop key multidisciplinary research areas needed to establish a JRDRC. A JRDRC is envisioned to be a resource center for research in juvenile arthritis and musculoskeletal diseases. This center will be associated with a major medical complex or consortium and dedicated to furthering the research effort related to juvenile arthritis and musculoskeletal diseases. 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 Request for Applications (RFA), Juvenile Rheumatic Diseases Research Center Planning Grant, is related to the priority area of chronic disabling conditions. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic, for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government that have an established program for pediatric rheumatology and a relevant research base. Foreign research organizations are ineligible. International collaborations in domestic applications will only be accepted if the resources are clearly shown to be unavailable in the United States. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT This RFA will use the National Institutes of Health (NIH) planning grant (P20). Responsibility for the planning, direction, and execution of the proposed program will be solely that of the applicant. The total project period for applications submitted in response to the present RFA should be three years. The anticipated award date is September 30, 1993. The direct costs requested cannot exceed $200,000 each year. The award will not be renewed, but may be converted to another funding mechanism. FUNDS AVAILABLE The estimated funds (total costs) available for the first year of support for a JRDRC planning grant is $300,000. One award is anticipated. Funding will depend on receiving applications judged highly meritorious by peer review. RESEARCH OBJECTIVES Chronic rheumatic diseases represent an important entity among chronic conditions affecting children. Among the rheumatic diseases seen in juvenile populations are rheumatoid arthritis, chronic arthritis (systemic, polyarthritic, and pauciarticular), spondyloarthropathy, systemic lupus erythematosus, dermatomyositis, scleroderma and other vasculopathies and connective tissue disorders. Many childhood rheumatic diseases have orthopaedic aspects. A research agenda for the genetic, infectious, and immunologic aspects of juvenile rheumatic diseases will benefit from a multidisciplinary approach. Because the research issues for juvenile arthritis and musculoskeletal diseases are complex, the NIAMS seeks to use a planning grant to explore the potential for establishing a JRDRC through a planning grant. Applications for a JRDRC planning grant should propose a program of multidisciplinary research development as a resource for research in arthritis and musculoskeletal diseases in children and for research to develop effective education programs for children, their families, and the public. The goal of the planning grant will be to develop those areas needed at the applicant institution or consortium. The applicant should outline the areas that may be part of a future JRDRC and the research projects presented in the planning grant should relate to the development of key areas in that center. A major goal of a JRDRC is to promote bench to bedside application of research. Clinical projects are required. The planning grant will provide funds for an Administrative and Planning Core and for Pilot Studies to develop and expand the research base. An Administrative and Planning Core will manage the overall activities related to developing the JRDRC. There must be a Director (Principal Investigator of the planning grant), a discrete administrative structure, and an Advisory Committee. The Core may also include the administration of shared resources, such as data sets or community or clinical research facilities, or provide research design and data analysis/statistical service. The Director will be the key figure in the scientific administration and management of the planning grant. The Director must be an experienced researcher with demonstrated leadership appropriate to the coordination and development of a Center. Although the final administrative structure of a Center will be left to the discretion of the applicant institution, experience demonstrates that effective development of Center programs requires interaction among the Director, the Principal Investigators of the pilot studies, appropriate institutional administrative personnel, and the staff of the NIAMS. Like other interdisciplinary grant programs, the success of a Center is dependent upon the involvement of scientific and professional personnel representing a variety of disciplines who must be willing to relate to and collaborate with each other in order to facilitate the development of new knowledge. The Advisory Committee assists the Director in making the scientific and administrative decisions relating to a Center. With the Director, the Advisory Committee will have the responsibility of evaluating the pilot studies proposed in the initial application and to be developed during subsequent years. (This does not preclude the applicant institution from developing a separate external review process to evaluate the scientific merit of the individual pilot studies developed during subsequent years. The final evaluation of the pilot studies, however, will rest with the Advisory Committee and the Director). The Advisory Committee may perform other duties as deemed appropriate by the applicant institution. The Advisory Committee must be composed of scientists and administrators with expertise and experience relevant to the Center's scientific program. Members may be employees of the applicant institution or of other institutions. However, at least two members of this committee must be from outside the Director's supervision (i.e., either at the applicant institution or another institution). The program areas of a JRDRC are to be related to arthritis and musculoskeletal diseases in children and may include treatment strategies. In the planning grant, pilot studies are to be proposed to expand the research base at the applicant institution. The P20 funding mechanism is intended to furnish modest support that will allow the investigators the opportunity to develop preliminary data sufficient to provide the basis for applications for independent research through conventional granting mechanisms. Pilot studies are typically limited to a nonrenewable period of one to two years. Applications submitted in response to this RFA must propose a minimum of three pilot studies to be supported during at least the first year of the award. Subsequent preliminary research projects may be developed during the course of the award. The Advisory Committee will have final approval for future pilot studies after a local peer review of the proposals. Appropriate research areas may include, but are not limited to: o Basic and clinical research leading to understanding the cause(s), diagnoses, improved treatment, and ultimate prevention of arthritis and musculoskeletal diseases in children is a critical aspect of the JRDRC. Clinical studies may address such research areas as: providing critical data for the design of larger clinical trials, testing the feasibility of new pharmacologic interventions, and devising improved diagnostic strategies. Studies integrating physical therapy and/or orthopaedic research with functional outcome may be included, as may epidemiologic studies that offer new insights. o Research development and evaluation of new programs, techniques or methodologies for the education of health professionals, patients, families of patients, and the public are appropriate. Evaluation and validation of patient assessment tools for the pediatric population may be proposed. Psychosocial research leading to improved intervention strategies, counseling, and enhancing the coping skills of children and their families are appropriate. SPECIAL REQUIREMENTS Investigators will be asked to meet periodically with NIAMS staff in Bethesda to review progress and plans for future work. Applicants from institutions that 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. Details of the interaction of the planning center staff and pilot study members with the GCRC staff and research personnel may be provided in a statement describing the collaborative linkages being developed. A letter of agreement from the GCRC Program Director must be included with the application. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements are required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis must be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale must be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues must be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information must be included in the form PHS 398 (rev. 9/91) in Sections 1-4 of the Research Plan AND summarized in Section 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., Native Americans [including American Indians or Alaskan Natives], Asian/Pacific Islanders, Blacks, Hispanics). The rationale for studies on single minority population groups should be provided. For the purpose of this policy, clinical research is defined as human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including, but not limited to, clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded. However, every effort should be made to include human tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. If the required information is not contained within the application, the application will be returned. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. LETTER OF INTENT Prospective applicants are asked to submit, by March 1, 1993 a letter of intent that includes a descriptive title of the proposed research projects, 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, the information that it contains allows NIAMS 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. Julia B. Freeman Centers Program, Extramural Programs National Institute of Arthritis and Musculoskeletal and Skin Diseases Westwood Building, Room 403 Bethesda, MD 20892 Telephone: (301) 402-3348 FAX: (301) 480-7881 APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 9/91) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research; from the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone 301/496-7441; and from the NIAMS program administrator listed under INQUIRIES. Special guidelines have been developed for the JRDRC planning grant. These guidelines must be used in writing and assembling the application. The guidelines may be obtained by contacting the Centers Program Director listed under INQUIRIES. The RFA label available in the application form 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 and number must be typed on line 2a of the face page of the application form and the YES box must be marked. Submit a signed, typewritten original of the application, including the Checklist, and three signed, photocopies, in one package to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** At the time of submission, two additional copies of the application must also be sent to: Dr. Tommy L. Broadwater Chief, Review Branch National Institute of Arthritis and Musculoskeletal and Skin Diseases Westwood Building, Room 405 Bethesda, MD 20892 Applications must be received by April 20, 1993. If an application is received after that date, it will be returned to the applicant without review. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by the DRG and responsiveness by the NIAMS. Incomplete applications will be returned to the applicant without further consideration. Applications may be triaged by an NIAMS peer review group on the basis of relative competitiveness. The NIH will withdraw from further competition those applications judged to be non-competitive for award and notify the applicant Principal Investigator and institutional official. Those applications judged to be competitive will undergo further scientific merit review. Those applications that are complete and responsive will be evaluated in accordance with the criteria stated below for scientific/technical merit by an appropriate peer review group convened by the NIAMS. The second level of review will be provided by the National Arthritis and Musculoskeletal and Skin Diseases Council. Review criteria for RFAs are generally the same as those for unsolicited research grant applications: o scientific, technical, or medical significance and originality of proposed research; o appropriateness and adequacy of the experimental approach and methodology proposed to carry out the research; o qualifications and research experience of the Director (Principal Investigator) and staff, particularly, but not exclusively, in the area of the proposed research; o availability of the resources necessary to perform the research; and o appropriateness of the proposed budget and duration in relation to the proposed research. Additional scientific/technical merit criteria specific to the objectives of a JRDRC program include: o qualifications, experience and commitment of the Director (Principal Investigator) and his/her ability to devote time and effort to provide effective leadership; o scientific and administrative structure, including internal and external procedures for monitoring and evaluating the proposed research and for providing ongoing quality control and scientific review; o adequacy of plans for interaction among investigators, and the integration of the various projects; o potential for developing a JRDRC from the resources and projects described; and o commitment to developing a JRDRC as a national resource. AWARD CRITERIA The anticipated date of award is September 30, 1993. The primary factors determining the award will be the priority score and the availability of funds. Since the NIAMS is interested in funding only the best research, individual research projects of lesser quality may not be funded, even if approved, under the "umbrella" of the planning grant (P20) mechanism. INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Dr. Julia B. Freeman Centers Program, EP National Institute of Arthritis and Musculoskeletal and Skin Diseases Westwood Building, Room 403 Bethesda, MD 20892 Telephone: (301) 402-3348 FAX: (301) 480-7881 Direct inquiries regarding fiscal matters to: Mara H. DeKemper Grants Management Officer National Institute of Arthritis and Musculoskeletal and Skin Diseases Westwood Building, Room 732 Bethesda, MD 20892 Telephone: (301) 496-0552 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.846, Arthritis, Musculoskeletal and Skin Diseases Research. Awards will be made under the authority of the Public Health Service Act, Title III, Section 301 (Public Law 410, 78th Congress, as amended, 42 USC 241) and administered under PHS grant policies and Federal regulations 42 CFR Part 52 and 45 CFR Part 74. This program is not subject to intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$XID RFA HL9312 HL-93-12 P1O1 ***************************************** EXPRESSION OF TUBERCULOSIS IN THE LUNG NIH GUIDE, Volume 21, Number 44, December 11, 1992 RFA: HL-93-12L P.T. 34; K.W. 0715165, 0715125, 1002004, 0710070, 1002027, 1002019 National Heart, Lung, and Blood Institute Letter of Intent Receipt Date: February 15, 1993 Application Receipt Date: April 13, 1993 PURPOSE The National Heart, Lung and Blood Institute (NHLBI) invites grant applications for support of research on the expression of tuberculosis (TB) in the lung. The primary objectives of this grant program are to encourage research on elucidating the factors involved in disease expression following infection by Mycobacterium tuberculosis (Mtb) and to determine the mechanisms by which such factors exert their influence on the lung. 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 Request for Applications (RFA), Expression of Tuberculosis in the Lung, is related to the priority areas of HIV infection, and immunization and infectious diseases. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Among the disciplines and expertise that may be appropriate for this research program are cell biology, immunology, infectious diseases, microbiology, molecular biology, molecular immunology, pathology, genetics, and pulmonary medicine. Applications may be submitted by for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Foreign institutions are not eligible for First Independent Research Support and transition (FIRST) (R29) award. Applications from minority individuals and women are encouraged. All current policies and requirements that govern the research grant programs of the National Institutes of Health (NIH) will apply to grants awarded under this RFA. Awards under this announcement to foreign institutions will be made only for research of very unusual merit, need, and promise, and in accordance with PHS policy governing such awards. MECHANISMS OF SUPPORT The support mechanisms for this program will be the individual research grant (R01) and the FIRST award (R29). While multidisciplinary approaches are encouraged, it is not the intent of this announcement to solicit applications for large studies encompassing a variety of individual subprojects, i.e., program projects. If collaborative arrangements through subcontracts with other institutions are planned, consult the program staff listed below. Upon initiation of the program, the NHLBI will sponsor periodic meetings to encourage exchange of information among investigators who participate in this program. In the budget for the grant application, applicants should request travel funds for a one-day meeting each 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. Applicants (who will plan and execute their own research programs) are expected to furnish their own estimates of time required to achieve the objectives of the proposed research project. Up to five years of support may be requested for R01s; five years are required for FIRST awards. Requested budgets for FIRST awards may not exceed those specified in the FIRST award guidelines. At the end of the initial award period, renewal applications may be submitted for peer review and competition for support through the regular grant program of the NIH. It is anticipated that support for this program will begin in September 1993. Administrative adjustments in project period and/or amount may be required at the time of the award. Since a variety of approaches would represent valid responses to this announcement, it is anticipated that there will be a range of costs among individual grants awarded. This RFA is a one-time solicitation. Future unsolicited competing continuation applications will compete with all investigator-initiated applications and will be reviewed according to the customary NIH peer review procedures. FUNDS AVAILABLE Although approximately $1,500,000 for this program is included in the financial plans for fiscal year 1993, award of grants pursuant to this RFA is contingent upon receipt of funds for this purpose. It is anticipated that six to eight new grants will be awarded under this program. The specific number to be funded will, however, depend on the merit and scope of the applications received and the availability of funds. RESEARCH OBJECTIVES Background The Centers for Disease Control estimates that since 1984 nearly 39,000 excess cases of TB have accumulated in the United States. This recent change in the TB morbidity trend appears attributable, in large part, to TB occurring in persons infected with the Human Immunodeficiency Virus (HIV), although increasing homelessness and immigration from regions of the world where TB is endemic are also contributing factors. Currently a number of general approaches are being actively pursued in basic research related to TB. Efforts are ongoing to define mycobacterial antigens involved in T-lymphocyte-dependent protective immunity. Gamma-delta-T-cells appear to be important in the immunologic response to Mtb and are under vigorous investigation. Research is being pursued in studies of the immunology of TB in the context of mammalian heat shock proteins; to date four such proteins have been identified. The lung is the portal of entry for Mtb and local defenses in the lung, including the mucociliary clearance mechanisms and bronchus-associated lymphoid tissue (BALT), are involved in processes that limit spread of infection within the lung as well as to extrapulmonary sites. However, most current research on TB delves into the systemic immune response to mycobacteria and basic mycobacteriology. By contrast, there is little research on specific pulmonary defenses or on TB as a disease of the lungs. Almost nothing is known about the basic mechanisms of protective immunity against Mtb in the lung and the local factors that contribute to lung injury, damage, or fibrosis. Furthermore, little is known about the breakdown of the lung defenses that allow the rapid progression and unusual, extrapulmonary patterns of primary and reactivation TB that are now being observed in HIV-infected patients who have depressed immune function. Little or no effort has been directed at the molecular and cellular mechanisms of TB, disease expression in the lung or the events that relate to host defenses in the human lung. Beyond descriptive clinical information on the pathology of TB, almost no new information has been obtained on the basic mechanisms of protective immunity and the immune factors that contribute to the natural history of Mtb infection. A number of factors are thought to influence susceptibility, resistance, and severity of disease when the lung responds to infection with Mtb. Data from clinical studies suggest a role for innate factors which might include such things as age, gender, ethnicity, and acquired conditions such as associated disease states. Aside from identifying such factors, there has been no recent progress on obtaining information about the mechanisms by which they exert their influence on susceptibility/resistance or severity of TB disease. Objectives and Scope The overall objective of this initiative is to encourage research directed at gaining a better understanding of disease expression in the lung following infection with Mtb. Applications are invited for innovative multidisciplinary approaches to identify the factors involved in disease expression, to determine their relationship to other factors of disease, and to better understand how such factors exert their influence on pathogenesis. Several topics relevant to the objectives of this RFA are described below in order to provide a perspective of the scope of the research that would meet the goals of the program. Studies in humans are encouraged where possible. Investigators are also encouraged to consider other approaches that meet the goals of this program in addition to those cited below. More information is clearly needed to clarify the specific and non-specific host defenses against Mtb in the lung, the local anatomic and immunologic factors that influence the natural history of pulmonary infection, with particular emphasis on the molecular basis for the generation of immunopathology. Acquired resistance to TB following primary infection is known to directly involve the immune system such that the ability of activated macrophages to ingest and kill virulent Mtb organisms is influenced by the function and number of T-helper lymphocytes. This is of particular interest in the context of HIV infection where T-helper cells are known to be adversely affected, and where the pathogenesis of TB in HIV-infected patients has been observed to differ from the classic granulomatous processes seen in HIV-negative individuals. Research directed at obtaining more detail about the mechanisms of TB pathogenesis and the factors affecting susceptibility/resistance and severity in the presence of HIV infection are of particular interest in response to this initiative. Another area that deserves further study concerns the genetically determined and acquired local and systemic factors that affect immunity and disease expression in the lung. Studies in inbred mice have revealed a genetic locus that modulates the innate resistance to mycobacterial infection. There appears to be a human homolog to this non-Major Histocompatibility locus. Various studies have suggested an association between HLA-type and pulmonary TB. Epidemiology and clinical/pathologic studies have indicated that certain racial groups such as African Americans develop more extensive lung damage from pulmonary TB. Basic research that addresses these aspects of TB could be considered in responding to this initiative. Little is known about the mechanisms of reactivation of TB in the lung. The development of animal models that simulate reactivation disease would permit exploration of areas of research on reactivation that are not easily addressed in human studies. Studies in humans that provide insights into the basic mechanisms of this aspect of disease expression would also be a desirable approach. Local factors in the lung such as underlying bronchiectasis or silicosis are known to influence fibrosis and other sequelae of TB. In cases where extensive fibrosis occurs, the mechanisms involved remain unexplored. In most cases of TB extensive fibrosis is not seen, yet when bronchiectasis is present fibrosis is a common occurrence. Studies elucidating the relationship between TB complicated by bronchiectasis and/or silicosis, and fibrosis is another example of research that would meet the goals of this program. SPECIAL REQUIREMENTS Applications that propose descriptive studies in humans only and do not contain studies directed at uncovering mechanisms of disease or supporting hypotheses related to mechanisms of disease expression will not be acceptable. This program will not support studies directed at development of animal models alone. Models must be applied to the study of disease mechanisms associated with expression of TB in the lung and whenever possible, the testing of hypothesis in the animal model should carry over to human studies. Applications that focus on molecular biology and molecular immunology of disease expression are of particular interest. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements will be required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis should be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale should be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues should be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information should be included in the form PHS-398 in Sections 1-4 of the Research Plan AND summarized in Section 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., Native Americans [including American Indians or Alaskan Natives], Asian/Pacific Islanders, Blacks, Hispanics). The rationale for studies on single minority population groups should be provided. For the purpose of this policy, clinical research includes human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including but not limited to clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are not subject to these policies. However, every effort should be made to include human tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. For foreign awards, the policy on inclusion of women applies fully; since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. If the required information is not contained within the application, the application will be returned. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design in inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and will be reflected in assigning the priority score to the application. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. LETTER OF INTENT Prospective applicants are asked to submit, by February 15, 1993, a letter of intent that includesa descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, the names of any other participating institutions or investigators, and the number and title of the RFA in response to which the application may be submitted. A letter of intent is not binding, will not enter into the review of any application subsequently submitted, and is not a requirement for application. Such letters are requested for the purpose of obtaining an indication of the number of applications to be received. The NHLBI will not provide a response to a letter of intent. The letter is to be received no later than February 15, 1993 and sent to: Chief, Centers and Special Projects Review Section Review Branch, Division of Extramural Affairs National Heart, Lung, and Blood Institute Westwood Building, Room 553 Bethesda, MD 20892 Telephone: (301) 496-7351 FAX: (301) 402-1660 APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 9/91) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research; from the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone 301-496-7441; and from the NIH program administrator named below. Use the conventional format for research project grant applications and ensure the points identified in the section Review Procedures and Criteria are fulfilled. To identify the application as a response to this RFA, check "yes" on item 2a of page 1 of the application and enter the title, Expression of Tuberculosis in the Lung, HL-93-12L. The RFA label available in the application kit must be affixed to the bottom of the face page of the original completed 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. Send or deliver the completed application and three signed and completed photocopies to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** Send two additional copies of the application to the Chief, Centers and Special Projects Review Section 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 Division of Research Grants (DRG). Otherwise the NHLBI cannot guarantee that the application will be reviewed in competition for this RFA. Applications must be received by April 13, 1993. If an application is received after this date, it will be returned to the applicant without review. The DRG will not accept any application in response to this announcement that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. The DRG 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 the DRG and responsiveness to the objectives of this RFA by the NHLBI. Incomplete applications will be returned withoug further consideration. If an application is judged unresponsive, the applicant will be contacted and given an opportunity to withdraw the application or to have it considered for the regular, investigator-initiated grant program of the NIH. Applications judged to be responsive will be reviewed for scientific and technical merit by an initial review group, convened by the Division of Extramural Affairs, NHLBI, solely to review these applications. This initial review will include a preliminary evaluation to determine scientific merit relative to the other applications received in response to this RFA (triage); the NIH will withdraw from further consideration applications judged to be noncompetitive and promptly notify the principal investigator and the official signing for the applicant organization. Those applications judged to be competitive will be further evaluated for scientific/technical merit by the usual peer review procedures. Review Criteria. The factors to be considered in the evaluation of scientific merit of each application will be similar to those used in the review of traditional research project grant applications including the novelty, originality, and feasibility of the approach; the training, experience, and research competence of the investigator(s); the adequacy of the experimental design; the suitability of the facilities; and the appropriateness of the requested budget to the work proposed. AWARD CRITERIA The anticipated date of award is September 30, 1993. In addition to the scientific merit of the applications, awards will be based on responsiveness to the RFA and the availability of resources. INQUIRIES Direct inquiries regarding programmatic issues to: Hannah H. Peavy, M.D. Interstitial Lung Diseases Branch Division of Lung Diseases National Heart, Lung, and Blood Institute Westwood Building, Room 6A09 Bethesda, MD 20892 Telephone: (301) 496-7034 FAX: (301) 496-9886 Direct inquiries regarding review matters to: Chief, Centers and Special Projects Review Section Review Branch, Division of Extramural Affairs National Heart, Lung, and Blood Institute Westwood Building, Room 553 Bethesda, MD 20892 Telephone: (301) 496-7351 FAX: (301) 402-1660 Direct inquiries regarding fiscal matters to: Raymond L. Zimmerman Grants Operations Branch Division of Extramural Affairs National Heart, Lung, and Blood Institute Westwood Building, Room 4A17 Bethesda, MD 20892 Telephone: (301) 496-4970 FAX: (301) 402-1200 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance, No. 93.838. Grants will be awarded under the authority of the Public Health Service Act, Title III, Section 301 (Public Law 78-410, as amended: 42 USC 241) and administered under PHS grants policies and Federal Regulations 42 CFR Part 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or to review by a Health Systems Agency. $$XID RFA DK9310 DK-93-10 P1O1 ***************************************** HUMAN GENES FOR NON-INSULIN DEPENDENT DIABETES MELLITUS NIH GUIDE, Volume 21, Number 44, December 11, 1992 RFA: DK-93-10 P.T. 34; K.W. 0715075, 0755035, 0755040, 0760015 National Institute of Diabetes and Digestive and Kidney Diseases Letter of Intent Receipt Date: February 18, 1993 Application Receipt Date: March 17, 1993 PURPOSE The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the American Diabetes Association (ADA) invite investigator-initiated research grant applications to identify specific genes responsible for non-insulin dependent diabetes mellitus (NIDDM) in humans. It is anticipated that this identification will require an interdisciplinary approach to develop and utilize strategies that will elucidate genes responsible for NIDDM using appropriate family pedigrees. Applications will be submitted to the National Institutes of Health (NIH) and will be reviewed by NIH according to the usual NIH peer review procedures. Applications judged meritorious and designated for funding will be supported partially by the NIDDK and partially by the ADA through the issuance of coordinated but separate awards by the two funding organizations. In order to facilitate the coordination of the NIDDK and the ADA, applicants are requested to provide the NIDDK authorization to allow the NIDDK to provide a copy of their letter of intent, application, NIH-prepared summary statement of the initial review, and yearly progress reports (if the application is funded) to the ADA. Applicants wishing to be considered for funding only by the NIDDK should so indicate in their letter of authorization. Under these latter circumstances, no information pertaining to their application will be shared with the ADA. 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 Request for Applications (RFA), Human Genes for Non-Insulin Dependent Diabetes Mellitus, is related to the priority area of diabetes and chronic disabling conditions. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications for research grants may be made by public and private, foreign and domestic, for-profit and non-profit organizations, such as universities, colleges, hospitals and laboratories, units or State and local governments, and authorized units of the Federal Government. Women and minority investigators are encouraged to apply. MECHANISM OF SUPPORT This RFA will use the NIH research project grant (R01). Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. The total project period for an application submitted in response to the present RFA may not exceed five years. The anticipated award date is September 30, 1993. For the purpose of cost-containment, requested direct costs must not exceed $160,000 per year for any single application. Applications exceeding this limit will not be reviewed as part of this RFA. The average award made by the NIDDK is expected to be approximately $200,000 in total costs. This RFA is a one-time solicitation. Future unsolicited competing continuation applications will compete with all investigator-initiated applications and be reviewed according to the customary peer review procedures. FUNDS AVAILABLE Highly meritorious applications in response to this solicitation will be partially funded by the NIDDK and partially funded by the ADA if permission is given by the applicant. The NIDDK will commit up to $2 million for first-year expenses and additional funds for approved expenses in subsequent years for up to five years to fund applications submitted in response to this RFA. The ADA anticipates support of up to 20 percent of recommended direct costs for each funded application per year. The NIDDK and the ADA plan to make approximately 10 to 12 awards in FY 1993 contingent on the receipt of highly meritorious applications in response to this solicitation. With respect to post-award administration, the current policies and requirements that govern the research grant programs of the NIH will prevail for awards made by the NIDDK. Applicants should note that funds from the ADA will be subject to the indirect cost policy and post-award administration policies of the ADA. The award of grants pursuant to this RFA is contingent on the availability of funds for this purpose. RESEARCH OBJECTIVES Background The term "diabetes" encompasses a number of different diseases, and hence, a number of different genes may be involved. Because of the potential for complex interplay between several genes, novel approaches may be necessary to ascertain the genes involved in the etiology of diabetes. The NIDDK recognizes this area as a high priority for research and has taken steps to stimulate research in genetics and molecular biology. In addition, the National Diabetes Advisory Board, in its "Long-Range Plan to Combat Diabetes, 1987," made several recommendations to the NIDDK directed at increasing progress in this area, including an increased emphasis on interdisciplinary research collaboration. In 1990, the NIDDK convened a scientific workshop to address opportunities in the search for the diabetes genes. The participants analyzed the current state of knowledge and endorsed a multifaceted and concerted effort to discover the genetic basis of diabetes and its complications. The NIDDK is coordinating efforts with the ADA to expeditiously and efficiently achieve the goal of both organizations: identify genes responsible for NIDDM. Toward this end, the ADA has recently embarked on the development of family pedigrees and the acquisition of genetic resources to aid in the elucidation of human genes responsible for NIDDM. The last decade has witnessed an expansion in knowledge and scientific methods allowing the isolation of genes responsible for a few but growing number of severe human diseases, such as Duchenne muscular dystrophy and Huntington's disease. Most recently, a five-year effort has culminated in the cloning and sequencing of the gene responsible for cystic fibrosis. This achievement has had a dramatic effect on research into the cause and cure for cystic fibrosis. Similar scientific approaches are being directed toward the search for the diabetes genes. NIDDM affects approximately 13 million Americans. It is the predominant form of the disease and severely impacts upon U.S. minority populations. This clustering of prevalence among ethnic/racial groups along with twin and family studies and animal models points to the genetic nature of this disease. Several genetic markers have been described as being associated with a rare form of NIDDM called Maturity Onset Diabetes of the Young (MODY) that shows autosomal dominant inheritance. One of these genetic markers is the gene for glucokinase, a key enzyme of glucose homeostasis found in the insulin-secreting beta cell of the pancreas and in the liver. This is the first evidence that a gene involved in glucose metabolism could be implicated in the pathogenesis of NIDDM. A variety of other genes may be related to the long-term complications suffered by those with all forms of diabetes. It will be worthwhile to apply a wide array of molecular biological techniques to explore genes related to insulin secretion, insulin action and key metabolic processes that regulate the body's metabolism. It is important to identify specific genetic markers/elements that are relevant to diabetes and its complications. These markers can take the form of genetic-susceptibility markers identifying the presence of specific genetic loci that predispose an individual to the disease and/or genetic mutations in key metabolic elements involved in the pathogenesis of NIDDM. Scope Through this solicitation, the NIDDK and the ADA intend to stimulate investigator-initiated research designed to develop and utilize new molecular genetic strategies to provide a better understanding of the major genes involved in NIDDM in humans. To achieve this objective, appropriate family pedigrees may need to be collected as a prerequisite for the identification or for the verification of specific gene involvement. Since a large number of families may need to be recruited, accumulation of these families must be included within the framework of the proposed research plan. Utilization of existing sources of genetic material is encouraged. For example, the ADA is developing a repository of data, DNA, and cell lines of family pedigrees with NIDDM. This repository will be completed by the spring of 1995 but data and cell samples will likely become available much sooner. It is anticipated that these results will elucidate mechanisms involved in disease onset, thus enabling the development of specific intervention therapies and the identification of individuals at risk for the development of NIDDM. Relevant research topics listed below are examples and should not be construed as required or limiting. Responsive applications to this solicitation include: o development of gene mapping strategies for the specific identification and localization of genes for NIDDM o utilization of subtractive hybridization techniques to identify pathophysiologic processes in NIDDM o employment of highly informative polymorphic markers such as variable number repeat polymorphisms or microsatellite markers to evaluate relevant family pedigrees. Applications must propose the testing of an hypothesis rather than the establishment of, for example, a genetic resource. SPECIAL REQUIREMENTS Upon initiation of this program, the NIDDK and the ADA will sponsor periodic meetings to encourage exchange of information among investigators, to foster collaborative efforts between program grantees, and to identify resources that would enhance the productivity of grantees. For this purpose, requests for travel funds for a one day meeting each year, probably to be held in the Washington, DC metropolitan area, must be included in the budget section of the application. It is anticipated that the first meeting will be held soon after the award of grants in order to discuss and establish the nature and extent of possible collaboration among the group of investigators. Applicants should also include a statement in their applications indicating their willingness to participate in such meetings. Letter of Authorization Each applicant must submit a brief statement to the NIDDK indicating whether or not they wish their application to be considered for coordinated funding by the ADA. Although applicants may request that their applications be considered only by the NIDDK and not by the ADA, it is necessary that the record indicate the applicant's consideration of this opportunity. For each applicant who wishes to have the ADA consider their application for coordinated funding, all materials relating to the application will be promptly forwarded to that organization by the NIDDK, and the summary statement for the application will be shared with the ADA at the time of their availability. The NIDDK will provide no information to the ADA, nor any other non-governmental agency, related to applications from any applicant who requests that the ADA not consider their application. Letters of authorization should be prepared by the Principal Investigator and co-signed by the official signing for the applicant organization. This must be submitted as a cover letter accompanying the application. Whether or not an applicant wishes to be considered for coordinated funding by the ADA will not effect the funding decisions of the NIDDK. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDIES NIH policy is that applicants for NIH clinical research grants and cooperative agreements are required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis should be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale should be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues must be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information must be included in the form PHS 398 (rev. 9/91) in Sections 1-4 of the Research Plan AND summarized in Section 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., Native Americans (including American Indians or Alaskan Natives), Asian/Pacific Islanders, Blacks, Hispanics). The rationale for studies on single minority population groups should be provided. For the purpose of this policy, clinical research is defined as human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventative strategies), diagnosis, or treatment or diseases, disorders or conditions, including but not limited to clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded. However, every effort should be made to include human tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. For foreign awards, the policy on inclusion of women applies fully; since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. If the required information is not contained within the application, the application will be returned. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. LETTER OF INTENT Potential applicants are strongly encouraged to submit a letter of intent by February 18, 1993. The letter of intent is to include: (1) names of the Principal Investigator/program director and principal collaborators, (2) descriptive title of the potential application, (3) identification of the organization(s) involved, and (4) 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, the information that it contains is helpful in planning for the review of applications. It allows NIDDK 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: Chief, Review Branch National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 605 5333 Westbard Avenue Bethesda, MD 20892 APPLICATION PROCEDURES Applications are to be submitted on form PHS 398 (rev. 9/91), that is available from an applicant institution's office of sponsored research and from the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone (301) 496-7441. Use the conventional format for research project grant applications. To identify the application as a response to this RFA check "yes" on item 2a of page one of the application and enter the title "Human Genes for NIDDM" and the RFA number DK-93-10. The RFA label included in the PHS 398 application package must be affixed to the face page to assist in the processing of the application. Failure to use this label could result in the delayed processing of the application such that it may not reach the review committee in time for review. Applicants from institutions that have a General Clinical Research Center (GCRC) funded by the NIH National Center of Research Resources may wish to identify the Center as a resource for conducting the proposed research. If so, a letter of agreement from the GCRC Program Director should be included in the application material. Applications must be received by March 17, 1993. If an application is received after that date, it will be returned to the applicant without review. The original, including the Checklist, and three signed photocopies of the application must be submitted in one package to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** At the time of submission, two additional copies of the application must be sent under separate cover to: Review Branch National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 605 5333 Westbard Avenue Bethesda, MD 20892 The Division of Research Grants (DRG) will not accept any application in response to this announcement that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. The DRG 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 by DRG staff for completeness and by NIDDK staff for responsiveness. Incomplete applications will be returned to the applicant without further consideration. If the application is not responsive to the RFA, NIDDK staff will contact the applicant to determine whether to return the application to the applicant or submit it for review in competition with unsolicited applications at the next review cycle. Applications may be triaged by an NIDDK peer review group on the basis of relative competitiveness. The NIH will withdraw from further competition those applications judged to be non-competitive for award and notify the applicant Principal Investigator and institutional official. Those applications judged to be competitive will undergo further scientific merit review. Those applications that are complete and responsive will be evaluated in accordance with the criteria stated below for scientific/technical merit by an appropriate peer review group convened by the NIDDK. The second level of review will be provided by the National Diabetes and Digestive and Kidney Diseases Advisory Council. Applications in response to this RFA will be reviewed using the usual NIH peer review procedures. The factors to be considered in the evaluation of scientific merit of each application will be those used in the review of traditional research project grant applications, including the novelty, originality, and feasibility of the approach; the training, experience, and research competence of the investigator(s); the adequacy of the experimental design; the suitability of the facilities; the appropriateness of the requested budget to the work proposed; and the adherence, whenever appropriate, to NIH guidelines concerning clinical research involving minorities and women. AWARD CRITERIA The anticipated date of award is September 30, 1993. The following will be considered in making funding decisions: o Quality of the proposed project as determined by peer review o Availability of funds o Scientific interrelationships among the proposed projects. INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Joan T. Harmon, Ph.D. Executive Director, Diabetes Research Program Division of Diabetes, Endocrinology and Metabolic Diseases National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 622 Bethesda, MD 20892 Telephone: (301) 496-7731 Direct inquiries regarding fiscal matters to: Betty E. Bailey Grants Management Branch Division of Extramural Activities National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 649 Bethesda, MD 20892 Telephone: (301) 496-7467 Schedule: Letter of Intent: February 18, 1993 Application Receipt Date: March 17, 1993 Initial Review: June/July 1993 NIDDK Advisory Council Review: September 1993 Anticipated Award Date: September 30, 1993 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.847, Diabetes, Endocrinology and Metabolism Research. Awards are made under 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 requirements of Executive Order 12372 or Health Systems Agency review. From owner-sci-resources@net.bio.net Wed Dec 09 22:00:00 1992 Path: biosci!NET.BIO.NET!kristoff From: kristoff@NET.BIO.NET (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 21, no. 44, pt. 2, 11 December 1992 Message-ID: Date: 10 Dec 92 00:41:45 GMT Sender: kristoff@net.bio.net Distribution: bionet Lines: 1500 $$XID NIHGUIDE 19921211 V21N44 P2O4 ************************************ returned to the applicant without further consideration. If the application is not responsive to the RFA, NHLBI staff will contact the applicant to determine whether to return the application or submit it for review in competition with unsolicited applications at the next review cycle. Applications judged to be responsive will be reviewed for scientific and technical merit by an initial review group, convened by the Division of Extramural Affairs, NHLBI, solely to review these applications. Review criteria for this RFA are generally the same as those for unsolicited research grant applications. INQUIRIES Written and telephone inquiries regarding 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 the RFA to: Hannah H. Peavy, M.D. Division of Lung Diseases National Heart, Lung, and Blood Institute Westwood Building, Room 6A09 Bethesda, MD 20892 Telephone: (301) 496-7034 FAX: (301) 496-0886 Direct inquiries regarding review matters to: Chief, Centers and Special Projects Review Section Review Branch, Division of Extramural Affairs National Heart, Lung, and Blood Institute Westwood Building, Room 553 Bethesda, MD 20892 Telephone: (301) 496-7351 FAX: (301) 402-1660 Direct inquiries regarding fiscal matters to: Raymond L. Zimmerman Division of Extramural Affairs National Heart, Lung, and Blood Institute Westwood Building, Room 4A17 Bethesda, MD 20892 Telephone: (301) 496-4970 FAX: (301) 402-1200 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance, No. 93.838. Grants will be awarded under the authority of the Public Health Service Act, Title III, Section 301 (Public Law 78-410, as amended: 42 USC 241) and administered under PHS grants policies and Federal Regulations 42 CFR Part 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or to review by a Health Systems Agency. $$R7 END ************************************************************ $$R8 BEGIN AR-93-01 FULL-TEXT *************************************** JUVENILE RHEUMATIC DISEASES RESEARCH CENTER PLANNING GRANT NIH GUIDE, Volume 21, Number 44, December 11, 1992 RFA AVAILABLE: AR-93-01 P.T. 34; K.W. 0715170, 0715010, 0710030 National Institute of Arthritis and Musculoskeletal and Skin Diseases Letter of Intent Receipt Date: March 1, 1993 Application Receipt Date: April 20, 1993 THE REQUEST FOR APPLICATIONS (RFA) ANNOUNCED IN THIS NOTICE CONTAINS ESSENTIAL INFORMATION FOR THE PREPARATION OF AN APPLICATION. POTENTIAL APPLICANTS MAY OBTAIN THE RFA AND GUIDELINES FROM THE CONTACT NAME IN INQUIRIES, BELOW. PURPOSE The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) invites applications for a planning grant for a juvenile arthritis and musculoskeletal diseases center. The goal of the planning grant is to explore the potential for establishing a Juvenile Rheumatic Diseases Research Center (JRDRC). The JRDRC planning grant will support development of key multidisciplinary research areas needed to establish a JRDRC. A JRDRC is envisioned to be a resource center for research in juvenile arthritis and musculoskeletal diseases. This center will be associated with a major medical complex or consortium and will work in furthering the research effort related to juvenile arthritis and musculoskeletal diseases. 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 RFA, Juvenile Rheumatic Diseases Research Center Planning Grant, is related to the priority area of chronic disabling conditions. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic, for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments and eligible agencies of the Federal government. An established clinical and research program in areas pertaining to juvenile arthritis and musculoskeletal diseases should be present. MECHANISM OF SUPPORT This RFA will use the National Institutes of Health (NIH) planning grant (P20). Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. The total project period for applications submitted in response to the present RFA should be three years. The anticipated award date is September 30, 1993. The direct costs requested cannot exceed $200,000 each year. The award will not be renewed, but may be converted to another funding mechanism. FUNDS AVAILABLE The estimated funds (total costs) available for the first year of support for the JRDRC planning grant is $300,000. One award is anticipated. Funding will depend on receiving applications judged highly meritorious by peer review. RESEARCH OBJECTIVES Chronic rheumatic diseases represent an important entity among chronic conditions affecting children. Among the rheumatic diseases seen in juvenile populations are rheumatoid arthritis, chronic arthritis (systemic, polyarthritic, and pauciarticular), spondyloarthropathy, systemic lupus erythematosus, dermatomyositis, scleroderma and other vasculopathies and connective tissues disorders. Many childhood rheumatic diseases have orthopaedic aspects. A research agenda for the genetic, infectious, and immunologic aspects of juvenile rheumatic diseases will benefit from a multidisciplinary approach. Because the research issues are complex for juvenile arthritis and musculoskeletal diseases, the NIAMS seeks to explore the potential for establishing a JRDRC through a planning grant. The planning grant for a JRDRC will provide funds for an administrative and planning core and for pilot studies to develop and expand the research base. Appropriate research areas include basic, clinical, and epidemiologic research as well as educational and psychosocial research. SPECIAL REQUIREMENTS Investigators will be asked to meet periodically with NIAMS staff in Bethesda to review progress and plans for future work. The planning center will work with the NIAMS to hold a workshop to review the research agenda for juvenile arthritis. Applicants should include in the budget plans, appropriate travel costs for these meetings. STUDY POPULATIONS SPECIAL INSTRUCTIONS FOR INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDIES For projects involving clinical research, NIH requires applicants to give special attention to the inclusion of women and minorities in study populations. If women or minorities are not included in the study populations for clinical studies, a specific justification for this exclusion must be provided. Applications without such documentation will not be accepted for review. LETTER OF INTENT Prospective applicants are asked to submit, by March 1, 1993, a letter of intent that includes a descriptive title of the proposed research projects, 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, the information that it contains allows NIAMS 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. Julia B. Freeman at the address listed under INQUIRIES. APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 9/91) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research and from the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone 301/496-7441. Special guidelines have been developed for the JRDRC planning grant. These guidelines must be used in writing and assembling the application. The guidelines may be obtained by contacting the Centers Program Director listed under INQUIRIES. Applications must be received by April 20, 1993. The RFA label available in the application form 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 and number must be typed on line 2a of the face page of the application form and the YES box must be marked. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by Division of Research Grants (DRG) and responsiveness by the NIAMS. Incomplete applications will be returned to the applicant without further consideration. Applications may be triaged by an NIAMS peer review group on the basis of relative competitiveness. The NIH will withdraw from further competition those applications judged to be non-competitive for award and notify the applicant Principal Investigator and institutional official. Review criteria for RFAs are generally the same as those for unsolicited research grant applications. Additional scientific/technical merit criteria specific to the objectives of the JRDRC program include: o qualifications, experience and commitment of the Director (Principal Investigator) and his/her ability to devote time and effort to provide effective leadership; o scientific and administrative structure, including internal and external procedures for monitoring and evaluating the proposed research and for providing ongoing quality control and scientific review; o adequacy of plans for interaction among investigators, and the integration of the various projects and core units; and o potential for developing a JRDRC from the resources and projects described. AWARD CRITERIA The anticipated date of award is September 30, 1993. INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Dr. Julia B. Freeman Centers Program, Extramural Programs National Institute of Arthritis and Musculoskeletal and Skin Diseases Westwood Building, Room 403 Bethesda, MD 20892 Telephone: (301) 402-3348 FAX: (301) 480-7881 Direct inquiries regarding fiscal matters to: Mara H. DeKemper Grants Management Officer National Institute of Arthritis and Musculoskeletal and Skin Diseases Westwood Building, Room 732 Bethesda, MD 20892 Telephone: (301) 496-0552 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.846, Arthritis, Musculoskeletal and Skin Diseases Research. Awards will be made under the authority of the Public Health Service Act, Title III, Section 301 (Public Law 410, 78th Congress, as amended, 42 USC 241) and administered under PHS grant policies and Federal regulations 42 CFR Part 52 and 45 CFR Part 74. This program is not subject to intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$R8 END ************************************************************ $$R9 BEGIN AR-93-03 FULL-TEXT *************************************** SKIN DISEASES RESEARCH CORE CENTERS NIH GUIDE, Volume 21, Number 44, December 11, 1992 RFA AVAILABLE: AR-93-03 P.T. 04; K.W. 0715185, 1003002, 0710070, 0710030 National Institute of Arthritis and Musculoskeletal and Skin Diseases Letter of Intent Receipt Date: May 10, 1993 Application Receipt Date: June 18, 1993 THE REQUEST FOR APPLICATIONS (RFA) ANNOUNCED IN THIS NOTICE CONTAINS ESSENTIAL INFORMATION FOR THE PREPARATION OF AN APPLICATION. POTENTIAL APPLICANTS MAY OBTAIN THE RFA FROM THE CONTACT NAMED IN INQUIRIES, BELOW. PURPOSE The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) invites applications for research core centers in skin diseases. The Skin Diseases Research Centers (SDRCs) will provide the resources for a number of established, currently funded investigators, often from different disciplines, to adopt a multidisciplinary approach to common research problems in skin diseases and to ensure greater productivity than from each of the separate projects. 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 RFA, Skin Diseases Research Core Centers, is related to the priority area of chronic disabling conditions. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal Government. A strong clinical and research program in skin diseases should be present. Foreign organizations are not eligible. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT This RFA will use the National Institutes of Health (NIH) core research center grant (P30). Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. The total project period for applications submitted in response to this RFA should be five years. The direct costs requested cannot exceed $400,000 each year. The anticipated award date is March 1, 1994. FUNDS AVAILABLE The NIAMS intends to fund two SDRCs in FY 1994, subject to the availability of resources and receipt of sufficiently meritorious applications. The estimated funds (total costs) available for the first year of support is $1.0 million. RESEARCH OBJECTIVES Research in skin diseases is at a stage where broad advances can be effectively fostered by research core centers. Examples of these areas include, but are not limited to: o stratum corneum: biochemistry, structure, function o epidermis: differentiation, keratinization, cellular constituents o dermal-epidermal junction: structure, functions, diseases o skin as an immunological organ o autoimmune skin diseases o dermis: structural components, diseases The choice of research problem upon which the SDRC would focus is made by the principal and collaborating currently funded investigators. The SDRC (P30) is a mechanism for integrating, coordinating, and fostering the interdisciplinary cooperation of a group of established investigators conducting programs of active, high-quality research that relate to a common theme. The SDRC provides support for: 1. Core resources and facilities to be used by investigators of individually supported research projects in order to enhance and coordinate their activities. This support may include personnel, equipment, supplies, services, and facilities. 2. Limited funds for pilot and feasibility studies. 3. Program enrichment activities. SPECIAL REQUIREMENTS Specific guidelines have been developed for the SDRC application and program. These guidelines may be obtained from the contact person listed under INQUIRIES. STUDY POPULATIONS SPECIAL INSTRUCTIONS FOR INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDIES For projects involving clinical research, NIH requires applicants to give special attention to the inclusion of women and minorities in study populations. If women or minorities are not included in the study populations for clinical studies, a specific justification for this exclusion must be provided. Applications without such documentation will not be accepted for review. LETTER OF INTENT Prospective applicants are asked to submit, by May 10, 1993, a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, the identities of other key personnel and participating institutions, and the number and title of 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, the information that it contains allows the NIAMS staff to estimate the potential review workload and to avoid possible conflict of interest in the review. The letter of intent is to be sent to: Dr. Julia B. Freeman Centers Program, EP National Institute of Arthritis and Musculoskeletal and Skin Diseases Westwood Building, Room 403 Bethesda, MD 20892 Telephone: (301) 402-3348 FAX: (301) 480-7881 APPLICATION PROCEDURES Special guidelines have been developed for the SDRC program in NIAMS. These guidelines must be used in assembling the application. These guidelines may be obtained by contacting the Centers Program Director listed above. The research grant application form PHS 398 (rev. 9/91) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research and from the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone 301/496-7441. Applications must be received by June 18, 1993. The RFA label available in the PHS 398 application form must be affixed to the bottom of the face page of the application. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by the DRG and responsiveness by NIAMS. Incomplete applications will be returned to the applicant without further consideration. Applications may be triaged by an NIAMS peer review group on the basis of relative competitiveness. The NIAMS will withdraw from further competition those applications judged to be noncompetitive for award and notify the applicant Principal Investigator and institutional official. Those applications judged to be competitive will undergo further scientific merit review. This review will be for scientific/technical merit by an appropriate peer review group convened by the NIAMS. The second level of review will be provided by the National Arthritis and Musculoskeletal and Skin Diseases Advisory Council. AWARD CRITERIA The primary factors determining the award will be the priority score and the availability of funds. Since the NIAMS is interested in funding only the best research, individual research projects of lesser quality may not be funded, even if approved, under the "umbrella" of the SDRC mechanism. INQUIRIES Written and telephone requests for the RFA and the opportunity to clarify any issues or questions from potential applicants are welcome. Direct requests for the RFA and inquiries regarding programmatic issues to: Dr. Julia B. Freeman Centers Program, EP National Institute of Arthritis and Musculoskeletal and Skin Diseases Westwood Building, Room 403 Bethesda, MD 20892 Telephone: (301) 402-3348 FAX: (301) 480-7881 Direct inquiries regarding fiscal matters to: Mary L. Graham Grants Management Officer National Institute of Arthritis and Musculoskeletal and Skin Diseases Westwood Building, Room 722A Bethesda, MD 20892 Telephone: (301) 402-3361 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.846, Arthritis, Musculoskeletal and Skin Diseases Research. Awards will be made under the authority of the Public Health Service Act, Title III, Section 301 (Public Law 410, 78th Congress, as amended, 42 USC 241) and administered under PHS grants policies and Federal regulations 42 CFR Part 52 and 45 CFR Part 74. This program is not subject to intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$R9 END ************************************************************ $$R10 BEGIN HL-93-07 FULL-TEXT ************************************** MONOENERGETIC X-RAY SYSTEMS FOR CARDIOVASCULAR IMAGING NIH GUIDE, Volume 21, Number 44, December 11, 1992 RFA AVAILABLE: HL-93-07-H P.T. 34; K.W. 0706030, 0705015 National Heart, Lung, and Blood Institute (NHLBI) Letter of Intent Receipt Date: July 5, 1993 Application Receipt Date: October 13, 1993 THE REQUEST FOR APPLICATIONS (RFA) ANNOUNCED IN THIS NOTICE CONTAINS ESSENTIAL INFORMATION FOR THE PREPARATION OF AN APPLICATION. POTENTIAL APPLICANTS MAY OBTAIN THE RFA FROM THE CONTACT NAMED IN INQUIRIES, BELOW. PURPOSE This solicitation will support grants for research and development of monoenergetic (10-20 eV) x-ray sources that can be hospital based and are clinically applicable for imaging cardiovascular structures. It is desirable that the proposed imaging system be tuneable with spectral concentration in a narrow band and at an intensity appropriate for specific cardiovascular imaging applications. A principal objective is to achieve improved image quality at lower radiation dose as compared with conventional x-ray imaging systems. 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 RFA, Monoenergetic X-ray Systems for Cardiovascular Imaging is related to the priority area of cardiovascular imaging. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-002-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Federal agencies must ensure that their own authorizing legislation will allow them to respond to this solicitation and to receive a PHS grant. Applications from minorities and women are encouraged. MECHANISM OF SUPPORT This RFA will use the National Institutes of Health (NIH) individual research grant (R01). Responsibility for the planning, direction, and execution of 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. This RFA is a one-time solicitation. Future unsolicited competing continuation applications will compete with all investigator-initiated applications and be reviewed according to customary peer review procedures. Because the nature and scope of the research proposed in response to this RFA may vary, it is anticipated that the size of an award will vary also. FUNDS AVAILABLE Approximately $1.5 million in total costs will be provided for the first year of support for the entire program. It is anticipated that three to four new grants will be awarded under this program. This level of support is dependent on the receipt of a sufficient number of applications of high scientific merit. Although this program is provided for in the financial plan of the National Heart, Lung, and Blood Institute (NHLBI), awards pursuant to this RFA are contingent upon the availability of funds for this purpose. Administrative adjustments in project period and/or amount of support may be required at the time of the award. RESEARCH OBJECTIVES The proposed RFA seeks to support grant applications to study, develop, and evaluate minimally invasive x-ray systems using monoenergetic radiation to achieve improved resolution and image quality. Complete systems would need to be described, including both source and detector. Grant applications should propose a specific application, such as coronary artery imaging without intraarterial injection of contrast material, and include quantitative objectives for resolution, patient dose, and image quality. Grant applications should also emphasize close collaboration among physicists, biophysicists, radiologists, cardiologists, and bioengineers with both a theoretical basis and an experimental plan for the proposed system. Grant applications may propose research in imaging systems for cardiovascular application utilizing monoenergetic or nearly monoenergetic x-ray sources and detector systems, including, but not limited to, the following technologies: o Transition x-ray sources o Channeling radiation sources o Cerenkov radiation sources o Smith-Purcell radiation sources o Parametric conversion systems o Coherent superlattice radiation systems o Free electron Laser systems Each application must provide evidence that the proposed system is feasible as a hospital based facility, with size and cost estimates based upon calculations and experimental data. SPECIAL INSTRUCTIONS FOR INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDIES For projects involving clinical research, NIH requires applicants to give special attention to the inclusion of women and minorities in study populations. If women or minorities are not included in the study populations for clinical studies, a specific justification for this exclusion must be provided. Applications without such documentation will not be accepted for review. LETTER OF INTENT Prospective applicants are asked to submit, by July 5, 1993, a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, the identities of other key personnel and participating institutions, and the number and title of this RFA. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information that it contains allows 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: Chief, Centers and Special Projects Section Review Branch Division of Extramural Affairs National Heart, Lung and Blood Institute Westwood Building, Room 553A Bethesda, MD 20892 Telephone: (301) 496-7351 FAX: (301) 402-1660 APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 9/91) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research and may be obtained from the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone 301/496-7441. Send or deliver a signed, typewritten original of the application, including the checklist, and three signed photocopies, in one package to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** Send two additional copies of the application to the Chief, Centers and Special Projects Section, at the address listed under LETTERS OF INTENT. Applications must be received by October 13, 1993. REVIEW CONSIDERATIONS Those applications that are complete and responsive will be evaluated for scientific/technical merit by an appropriate peer review group convened by the NHLBI. The second level of review will be provided by the National Heart, Lung, and Blood Advisory Council. Review criteria for RFAs are generally the same as those for unsolicited research grant applications. Although multidisciplinary approaches are encouraged, it is not the intent of this announcement to solicit applications for large studies that encompass a variety of independent projects, i.e., program projects. AWARD CRITERIA The most important criterion in selecting awardees will be the scientific merit. However, factors such as program balance and available funds may enter into selection from among competing applications. The anticipated date of award is April 1, 1994 INQUIRIES Inquiries regarding programmatic issues and requests for the RFA document be directed to: Dr. Alan Berson or Dr. Rosalie Dunn Devices and Technology Branch Division of Heart and Vascular Diseases National Heart, Lung and Blood Institute Federal Building, Room 312 Bethesda, MD 20892 Telephone: (301) 496-1586 Direct inquiries regarding fiscal and administrative matters to: Mr. William Darby Grants Operations Branch Division of Extramural Affairs National Heart, Lung and Blood Institute Westwood Building, Room 4A11 Bethesda, MD 20892 Telephone: (301) 496-7536 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.837, Heart and Vascular Diseases. Awards will be made under the authority of the Public Health Service Act, Section 301 (42 USC 241) and administered under PHS grants policies and Federal Regulations, most specifically 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or to Health Systems Agency review. $$R10 END *********************************************************** ONGOING PROGRAM ANNOUNCEMENTS $$P1 BEGIN PA-93-27 ************************************************* PSYCHOTHERAPY, BEHAVIOR THERAPY, AND COUNSELING IN DRUG DEPENDENCE TREATMENT NIH GUIDE, Volume 21, Number 44, December 11, 1992 PA NUMBER: PA-93-27 P.T. 34; K.W. 0745060, 0404009, 0414014 National Institute on Drug Abuse PURPOSE The purpose of this Program Announcement (PA) is to encourage the study of psychotherapy, behavior therapy, drug abuse counseling, and other psychosocial interventions in the treatment of drug abuse and dependence. Studies involving the use of controlled clinical trials or other scientifically established research methods are encouraged. A secondary aim is to encourage the development of instruments to measure the process and outcome of psychotherapy/counseling of drug addicts and instruments that may be useful in determining therapist and patient characteristics predictive of treatment outcome. This announcement is intended to encourage the investigation of the treatment of individuals who are dependent upon cocaine, opiates, and other types of drugs (including polydrug abusers). This announcement is not intended to support therapy development research. 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 PA, Psychotherapy, Behavior Therapy, and Counseling in Drug Dependence Treatment, is related to the priority area of alcohol and other drugs. Potential applicants may obtain a copy of Healthy People 2000 (Full Report: Stock No. 017-001-00474-0 or Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by foreign and domestic, for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Applications from minority individuals and women are encouraged. Foreign applicants are not eligible for First Independent Research Support and Transition (FIRST) awards (R29). MECHANISM OF SUPPORT Support mechanisms include: research projects (R01), small grants (R03), and FIRST awards (R29). Most investigator-initiated research is supported by regular research grants. Research grants are awarded to institutions on behalf of Principal Investigators who have designed and will direct a specific project or set of projects. Except for small grants (R03) and FIRST awards (R29), investigator(s) may apply for a renewal (competing continuation) of the project by submitting an application for further support, including a report of progress and including specific plans for future work. For details on a particular support mechanism or program, contact the program staff listed under INQUIRIES. RESEARCH OBJECTIVES Background Some form of psychotherapy, behavior therapy, or drug abuse counseling occurs in virtually every type of drug abuse/dependence treatment. Even where effective pharmacological treatments exist, such as the use of methadone for opiate dependence, they are usually administered with appropriate psychosocial/behavioral interventions (Grabowski et al., 1984). Numerous behavioral interventions have been studied in attempts to improve the efficacy of drug abuse treatment. Contingency management has been shown to have some efficacy in medically withdrawing patients from methadone (Higgins et al., 1986) for some methadone-maintained individuals, but not all (Stitzer et al., 1986; Iguchi et al., 1988; Stitzer et al., 1992). Where the methadone dose has been decreased as a consequence to drug positive urine specimens, treatment dropout has been exacerbated (Stitzer et al., 1986; Iguchi et al., 1988). While it has been suggested that the use of "negative incentives" increases dropout rate, the extent to which the observed increases in dropout rate are due to methadone dose reduction per se has not been established. Operant behavioral interventions appear to be most effective when integrated into a complete treatment package, as in the Community Reinforcement Approach (Hunt & Azrin, 1973; Azrin, 1976). This approach, originally developed for alcoholics, has been modified for cocaine abusers and has shown promise (Higgins et al., 1991). Behavioral interventions based upon principles of classical conditioning, such as cue exposure, are also believed to have promise. When used as an adjunct to a comprehensive outpatient cocaine treatment program, patients given repeated cue exposure (to induce "extinction" to cocaine-related cues) evidenced better retention in treatment and fewer cocaine-positive urine specimens than patients not receiving the cue exposure (Childress, et al., 1992). Individual cognitive-behavioral and psychodynamic as well as family approaches have all been demonstrated to have some efficacy (Stanton et al., 1982; Woody et al., 1983, 1987; Rounsaville et al., 1983; Carroll et al., 1991), but none has been demonstrated consistently to be more effective than another. This is congruent with findings in the psychotherapy research field at large; that is, it has not been consistently demonstrated that one type of psychotherapy is more effective than another (Luborsky et al., 1975; Smith & Glass 1977; Lambert et al., 1986; Stiles et al., 1986). For particular subgroups of patients, however, there is reason to believe that particular types of therapies may be more useful than others. For example, there is some evidence that a structured, behavioral therapy may be more effective for substance abusers with sociopathic characteristics than an interactionally focused therapy (Kadden et al., 1989). In subgroups of patients with antisocial personality disorder who have an additional diagnosis of depression, cognitive-behavioral and supportive-expressive psychotherapy appears to be of some benefit. However, antisocial personality disorder alone appears to be a negative indicator for response to psychotherapy (Woody et al., 1985). There is also some evidence that the addition of psychotherapy to drug abuse counseling may be necessary for other subgroups of addicts. For example, in a methadone-maintenance program, drug abuse counseling is a sufficient complement to the treatment of opiate addicts with low levels of psychiatric severity. Providing psychotherapy to low psychiatric severity methadone-maintained opiate addicts who are already receiving drug abuse counseling does not appear to yield any further benefit (Woody et al., 1984). However, in methadone-maintained opiate addicts with high levels of psychiatric severity, psychotherapy in addition to drug abuse counseling is significantly more effective than drug counseling alone (Woody et al., 1984). Inherent in doing research on psychosocial treatments for drug dependence are substantial methodological difficulties. Attrition is a problem in any form of behavioral treatment research, but especially so in drug dependence treatment. While there are numerous statistical procedures for dealing with the problem of attrition (Howard et al., 1990), none can replace lost data. It is, therefore, important to be aware of the ramifications of utilizing the array of available statistical techniques that are sometimes used to partially "correct" for lost data. Defining and including control groups as opposed to comparison groups (Borkovec, 1990) also presents a dilemma in comparative psychosocial treatment research. While there is no "perfect" design in such research, there are more or less perfect designs depending upon the research question we are asking. Other methodological and statistical issues, such as those dealing with therapist/counselor variance (Crits-Christoph et al., 1990) and choosing appropriate outcome measures (Lambert, 1990) are also important considerations and have been discussed at length elsewhere (Onken and Blaine, 1990). Additional research is needed to answer a number of questions in this field such as: 1. Are certain strategies of drug abuse counseling/psychotherapy more effective than others in helping individuals achieve treatment goals? 2. In what way are various immediate treatment goals related to long-term outcome goals? 3. What is the relative efficacy of drug abuse counseling versus psychotherapy, and when and with whom is drug abuse counseling sufficient? 4. What populations of drug addicts (e.g., the dually diagnosed, racial and ethnic minorities, women, adolescents, etc.) require what types of counseling or psychotherapy? 5. How is the process of psychotherapy or counseling related to outcome in drug dependence treatment? 6. What are the characteristics of successful therapists, patients, and therapist/patient pairs? Specific Areas of Interest: 1. Development of Psychotherapy/Counseling Instruments and Research Methods. Psychotherapy research, particularly with drug addicts, is in an early stage of development. The development and the refinement of instruments and methods that measure the theoretical constructs in the fields of psychotherapy and counseling are needed. Without instruments that measure these constructs in a valid and reliable manner, the controlled, scientific study of psychotherapy and counseling is impossible. Investigators are encouraged to develop new instruments and refine existing instruments from the mental health field that can be used in controlled psychotherapy/counseling research studies with drug addicts. The development of valid and reliable instruments that measure various aspects of the process and strategies of psychotherapy/counseling, the immediate goals and outcome of these treatments, therapist characteristics predictive of treatment outcome, and patient characteristics predictive of outcome are encouraged. 2. Comparative Psychosocial Treatment Research with Drug Addicts. Controlled clinical trials that examine the relative efficacy of psychotherapy, behavior therapy, counseling, pharmacotherapy, and the many combinations of these forms of treatment with various populations of drug addicts are encouraged. The goal of such comparative treatment research is not to determine which treatments "win," but, rather to determine which treatments are most efficacious with which populations, and under what conditions. Studies that investigate the relative efficacy of individual, group, or family psychotherapy, behavior therapy, and drug abuse counseling in patients with various co-morbid Axis I and Axis II disorders are particularly encouraged. Investigations that compare the efficacy of one form or combination of psychotherapy, behavior therapy, or counseling to another in other subpopulations of drug addicts (e.g., racial and ethnic minorities, pregnant women, and individuals who abuse cocaine intravenously) are also encouraged. Where effective pharmacotherapies are available, research projects that attempt to maximize the efficacy of that pharmacotherapy through integration with psychosocial treatment are encouraged. Applicants proposing comparative psychosocial treatment research studies are encouraged to examine the interactions of relevant therapist/patient characteristics with therapy type and to assess the relative contribution of therapist, patient, and type of therapy to treatment outcome. For these studies, it is imperative that investigators accurately measure and control for the psychiatric diagnosis and problem severity level of the patients. It is also necessary that clear definitions of treatment outcome variables be specified, and that valid and reliable measures of outcome be used. It is recommended that therapists/counselors providing the treatment be systematically trained, that manuals be used to guide the treatments, that valid and reliable therapist competence and adherence scales be used, and that the treatment process be measured accurately. For all efficacy studies, it is recommended that adequate followup assessments be planned. It is also important that these studies use procedures and methods that can be replicated. It is strongly suggested that pilot data showing that a counseling or psychotherapy strategy is promising be provided when proposing comparative research involving this treatment. These pilot data should indicate that the utilization of the therapy approach shows promise in its ability to produce a decrease in drug use, dropout rate, or psychiatric symptoms. 3. Research on Therapist and Patient Variables in Psychotherapy and Counseling. Researchers have highlighted the importance of individual differences among therapists and counselors independent of the form of treatment. Some studies have shown that certain therapists/counselors are more successful than others, and that this success is more related to the treatment provider than to the type of treatment provided (e.g., McLellan et al., 1988). Studies are sought that assess therapist and/or counselor characteristics and relate these characteristics to effective treatment. Studies that examine the interaction of therapist/counselor and patient variables as related to outcome are also encouraged. Additionally, studies that link the characteristics of patients with successful psychotherapeutic, behavioral, or drug abuse counseling treatment are desired. Measurements of therapist and patient characteristics should be obtained using psychometrically sound instruments. These studies should control for the type of treatment offered and should use objective, empirical measures of the treatment process that occurs. 4. Short-Term vs. Long-Term Goals of Drug Abuse Counseling/Psychotherapy/Behavior Therapy. The treatment process may be viewed as having two distinctive but interrelated sets of goals. One set involves long-term objectives to be achieved as a result of involvement in the treatment program. These goals include reduction in illicit drug use, reduction in illegal activities, improvement in social adjustment, etc. The other set of goals involves specific objectives to be achieved within the treatment program that, it is assumed, will allow clients to attain the long-term treatment goals. These immediate goals include assisting the client in recognizing the harm caused by drug dependence, developing personal strategies for reducing or avoiding stress, recognizing irrational ideas or beliefs, developing realistic strategies for interpreting life events, etc. Research is needed to determine how immediate treatment goals are related to long-term treatment goals (i.e., how success in achieving goals within treatment is related to success in achieving goals that result from treatment). For example, investigators may wish to establish different measures of immediate treatment goals, evaluate clients on success in achieving those goals, and then relate success in attaining immediate treatment goals to outcome measures of drug use or social adjustment. Research is also needed to identify, operationally define, and compare the efficacy of different strategies for attaining immediate treatment goals. For example, investigators may wish to establish different measures of immediate treatment goals, evaluate clients on success in achieving those goals, and then relate success in attaining immediate treatment goals to outcome measures of drug use or social adjustment. Also, investigators may wish to establish two distinctive procedures for achieving stress management (or employment) by clients and then compare the efficacy of the two procedures in terms of stress management. Controlled clinical trials or other rigorous research methods should be used. 5. Component Analysis Research. Knowing the effective components of treatment can greatly aid in improving the quality of treatment. Theoretically based research that attempts to determine the effective components or combination of components in drug dependence psychotherapies, behavior therapies, or counseling strategies is encouraged. Where there is more than one way to answer a proposed research question, investigators are urged to state their theoretical, ethical, and practical reasons for choosing one research design over another (see Borkovec, 1990). Investigators should address the issues of selection bias and attrition (Howard et al., 1990), and any other pertinent methodological issues (see Onken and Blaine, 1990). If a subject is identified as being at risk for HIV acquisition and/or transmission, HIV testing and counseling should be offered to the subject in accordance with current guidelines. Furthermore, in high-risk populations, investigators are encouraged to assess the effect of the new therapy on the acquisition/ transmission of associated infectious disease, including HIV. STUDY POPULATION SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements will be required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis should be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale should be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues should be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information should be included in the form PHS 398 in Sections 1-4 of the Research Plan AND summarized in Section 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., Native Americans (including American Indians or Alaskan Natives), Asian/Pacific Islanders, Blacks, Hispanics). The rationale for studies on single minority population groups should be provided. For the purpose of this policy, clinical research includes human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including but not limited to clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded. However, every effort should be made to include human tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. For foreign awards, the policy on inclusion of women applies fully; since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. If the required information is not contained within the application, the application will be returned. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and will be reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. APPLICATION PROCEDURES Applications are to be submitted on the grant application form PHS 398 (rev. 9/91) and will be accepted at the standard application deadlines as indicated in the application kit. The receipt dates for applications for AIDS-related research are found in the PHS 398 instructions. Application kits are available at most institutional offices of sponsored research and may be obtained from the Office of Grant Inquiries, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone (301) 496-7441. The title and number of the announcement must be typed in Section 2a on the face page of the application. FIRST award applications must include at least three sealed letters of reference attached to the face page of the original application. FIRST award applications submitted without the required number of reference letters will be considered incomplete and will be returned without review. The completed original application and five legible copies must be sent or delivered to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** REVIEW PROCEDURES Applications will be assigned on the basis of established PHS referral guidelines. Applications will be reviewed for scientific and technical merit by an initial review group in accordance with the standard NIH peer review procedures. Following scientific-technical review, the applications will receive a second-level review by the appropriate national advisory council. Small grant applications (R03) do not receive a second-level review. AWARD CRITERIA Applications will compete for available funds with all other approved applications assigned to that Institute/Center/Division. The following will be considered in making funding decisions: o Scientific and technical merit of the proposed project as determined by peer review o Availability of funds o Institute program needs and balance INQUIRIES Written and telephone inquiries are encouraged. The opportunity to clarify any issues or questions from potential applications is welcome. Direct inquiries regarding programmatic issues to: Dr. Lisa Onken Treatment Research Branch National Institute on Drug Abuse 5600 Fishers Lane, Room 10A-30 Rockville, MD 20857 Telephone: (301) 443-4060 Direct inquiries regarding fiscal matters to: Mrs. Shirley Denney, Chief Grants Management Branch National Institute on Drug Abuse 5600 Fishers Lane, Room 8A-54 Rockville, MD 20857 Telephone: (301) 443-6710 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.279. Awards are made under authorization of the Public Health Service Act, Section 301 and administered under PHS grants policies and Federal Regulations at Title 42 CFR Part 52, Grants for Research Projects, Title 45 CFR part 74 and 92, Administration of Grants, and 45 CFR Part 46, Protection of Human Subjects. Title 42 CFR Part 2, Confidentiality of Alcohol and Drug Abuse Patient Records, may also be applicable to these awards. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. Sections of the Code of Federal Regulations are available in booklet form from the U.S. Government Printing Office. Awards must be administered in accordance with the PHS Grants Policy Statement, (rev. 10/90), which is available from institutional offices of sponsored research. REFERENCES Azrin, N., "Improvements in the community reinforcement approach to alcoholism," Behavior Research and Therapy, 14: 339-348, 1976. Borkovec, T.D., "Control groups and comparison groups in psychotherapy outcome research," In Onken, L. Simon and Blaine, J.D. (Eds.) Psychotherapy and counseling in the treatment of drug abuse, NIDA Research Monograph #104, Department of Health and Human Services Publication Number (ADM)90-1722, 1990. Carroll, K., Rounsaville, B., and Gawin, F., "A comparative trial of psychotherapies for ambulatory cocaine abusers: Relapse Prevention and Interpersonal Psychotherapy," American Journal of Drug and Alcohol Abuse, 17: 229-247, 1991. Childress, A.R., Ehrman, R., McLellan, A.T., and O'Brien, C.P., "Cue reactivity assessment and a cue exposure intervention in cocaine dependence," American Journal of Psychiatry, under review. Crits-Christoph, P., Beebe, K., and Connolly, M.B. "Therapists effects in the treatment of drug dependence: Implications for conducting comparative treatment studies," In Onken, L. Simon and Blaine, J.D. (Eds.) Psychotherapy and counseling in the treatment of drug abuse, NIDA Research Monograph #104, Department of Health and Human Services Publication Number (ADM)90-1722, 1990. Grabowski, J., Stitzer, M.L., and Henningfeld, J.E., "Therapeutic applications of behavioral techniques: An overview,". In Behavioral Intervention Techniques in Drug Abuse Treatment, Grabowski, J., Stitzer, M.L., and Henningfeld, J.E.(Eds.) NIDA Research Monograph #46, Department of Health and Human Services Publication Number (ADM)86-1282, 1984. Higgins, S.T., Stitzer, M.L., Bigelow, G.E. and Liebson, I.A., "Contingent methadone delivery: Effects on illicit opiate use," Drug and Alcohol Dependence; 17: 311-322, 1986. Higgins, S.T., Delaney, D.D., Budney, A.J., Bickel, W.K., Hughes, J.R., Foerg, F., and Fenwick. J.W., "A behavioral approach to achieving initial cocaine abstinence," American Journal of Psychiatry, 148,9: 1218-1224, 1991. Howard, K.I., Cox, M., and Saunders, S.M., "Attrition in substance abuse comparative treatment research: The illusion of randomization," In Onken, L. Simon and Blaine, J.D. (Eds.) Psychotherapy and counseling in the treatment of drug abuse, NIDA Research Monograph #104, Department of Health and Human Services Publication Number (ADM)90-1722, 1990. Hunt, G.M., and Azrin, N., A community reinforcement approach to alcoholism. Behavior Research and Therapy, 11: 91-104, 1973. Iguchi, M.Y., Stitzer, M.L., Bigelow, G.E., and Liebson, I.A., "Contingency management in methadone maintenance: Effects of reinforcing and aversive consequences on illicit polydrug use," Drug and Alcohol Dependence; 22: 1-7, 1988. Kadden, R.M., Cooney, N.L., Getter, H., and Litt, M.D., "Matching alcoholics to coping skills or interactional therapies: Posttreatment results," Journal of Consulting and Clinical Psychology, 57: 698-704, 1989. Lambert, M.J., Shapiro, D.A., and Bergin, A.E., "The effectiveness of psychotherapy," In Garfield, S.L. and Bergin, A.E. (Eds.) Handbook of Psychotherapy and Behavior Change. New York: Wiley, 157-211, 1986. Lambert, M.J., "Conceptualizing and selecting measures of treatment outcome: Implications for drug abuse outcome studies," In Onken, L. Simon and Blaine, J.D. (Eds.) Psychotherapy and counseling in the treatment of drug abuse, NIDA Research Monograph #104, Department of Health and Human Services Publication Number (ADM)90-1722, 1990. Luborsky, L., Singer, B., and Luborsky, L., "Comparative studies of psychotherapies: Is it true that "everyone has won and all must have prizes?" Archives of General Psychiatry 32: 995-1007, 1975. McLellan, A.T., Woody, G.E., Luborsky, L, and Goehl, L., "Is the counselor an 'active ingredient' in substance abuse rehabilitation? An examination of treatment success among four counselors," The Journal of Nervous and Mental Disease, 176: 423-430, 1988. Onken, L. Simon and Blaine, J.D. (Eds.) Psychotherapy and counseling in the treatment of drug abuse, NIDA Research Monograph #104, Department of Health and Human Services Publication Number (ADM)90-1722, 1990. Rounsaville, B.J., Glazer, W., Wilbur, C.H., Weissman, M.M., and Kleber, H.D., "Short-term interpersonal psychotherapy in methadone maintained opiate addicts," Archives of General Psychiatry 40: 629-636, 1983. Smith, M.L. and Glass, G.V., "Meta-analysis of psychotherapy outcome studies," American Psychologist 32: 752-760, 1977. Stanton, M.D., and Todd, T.C. and Associates, The Family Therapy of Drug Abuse and Addiction. New York: The Guilford Press, 1982. Stiles, W.B., Shapiro, D.A., and Elliott, R., "Are all psychotherapies equivalent?" American Psychologist 41: 165-180, 1986. Stitzer, M.L., Bickel, W.K., Bigelow, G.E., and Liebson, I.A., "Effect of methadone dose contingencies on urinalysis results of polydrug-abusing methadone-maintenance patients," Drug and Alcohol Dependence; 18: 341-348, 1986. Stitzer, M.L., Iguchi, M.Y., and Felch, L.J., "Contingent take-home incentive: Effects on drug use of methadone maintenance patients," Journal of Consulting and Clinical Psychology, In press. Woody, G.E., Luborsky, L., McLellan, A.T., O'Brien, C.P., Beck, A.T., Blaine, J., Herman, I., and Hole, A., "Psychotherapy for opiate addicts- Does it help?" Archives of General Psychiatry 40: 639-645, 1983. Woody, G.E., McLellan, A.T., Luborsky, L., and O'Brien, C.P., Blaine, J., Fox, S., Herman, I., and Beck, A.T., "Severity of psychiatric symptoms as a predictor of benefits from psychotherapy: The Veterans Administration-Penn Study," American Journal Of Psychiatry 141: 1172-1177, 1984. Woody, G.E., McLellan, A.T., Luborsky, L., and O'Brien, C.P., "Sociopathy and psychotherapy outcome," Archives of General Psychiatry 42: 1081-1086, 1985. Woody, G.E., McLellan, A.T., Luborsky, L., and O'Brien, C.P., "Psychotherapy and counseling for methadone-maintained opiate addicts: Results of research studies," In Psychotherapy and Counseling in Drug Abuse Treatment, Onken, L. Simon and Blaine, J.D., NIDA Research Monograph #104, Department of Health and Human Services Publication Number (ADM)90-1722, 1990. $$P1 END ************************************************************ $$P2 BEGIN PA-93-28 ************************************************* RESEARCH TO IMPROVE DRUG ABUSE TREATMENT ENTRY, RETENTION, COMPLIANCE, AND EFFECTIVENESS NIH GUIDE, Volume 21, Number 44, December 11, 1992 PA NUMBER: PA-93-28 P.T. 34; K.W. 0404009, 0415001, 0404000 National Institute on Drug Abuse PURPOSE The purpose of this announcement is to encourage research to investigate entry, retention, and compliance in drug abuse treatment, and research on strategies to improve entry and retention in treatment, and to bring about compliance with program expectations and effectiveness of drug abuse treatment. An important focus of these studies will be on the various environmental and intrapersonal factors that promote drug abuse treatment entry, retention, compliance, and effectiveness. Research may be conducted in conjunction with clinical trials, evaluation studies, or through separate epidemiological and ethnographic studies. 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 Program Announcement (PA), Research to Improve Drug Abuse Treatment Entry, Retention, Compliance, and Effectiveness, is primarily related to the priority area of alcohol and other drugs. Potential applicants may obtain a copy of Healthy People 2000 (Full Report: Stock No. 017-001-00474-0, or Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by foreign and domestic, non-profit and for-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal Government. Women and minority investigators are encouraged to apply. Foreign applicants are not eligible for the First Independent Research Support and Transition (FIRST) awards (R29). MECHANISM OF SUPPORT Mechanisms available for support of this program include individual research applications (R01s), FIRST awards (R29s), and small grants (R03s). Small grants (R03s) and FIRST awards (R29s) may not apply for a renewal (competing continuation) of the project. For details on a particular support mechanism or program, contact the program staff listed under INQUIRIES. RESEARCH OBJECTIVES The treatment of drug abuse and addiction is a key part of the President's national drug control strategy. Two factors significantly affecting treatment outcomes are the length of time spent in treatment and the patient's during-treatment performance. Given the adverse health and other consequences of drug use and the scarcity of treatment resources, it is imperative that treatment effectiveness is improved by increasing patient retention and improving patient compliance with treatment. The amount of time spent in treatment is one of the most significant predictors of favorable treatment outcomes. Research has shown that patients under legal sanction are likely to stay in treatment longer. Research has also addressed compliance with treatment expectations. Provision of enhanced services to treatment patients has also been shown to improve outcomes. Recent research has found that setting behavioral contingencies for take-home methadone privileges is an effective means of improving compliance with program expectations. As with other chronic diseases, there are compliance issues that interact with medication and behavior. Given high demand for drug abuse treatment relative to existing capacity and the need to improve drug abuse treatment outcomes, this announcement seeks to stimulate research projects that will increase knowledge about treatment compliance and retention. Description of Program Applications submitted under this announcement should focus on (1) research to understand factors and processes related to patient retention in treatment or compliance with program expectations; (2) research to test treatment innovations or strategies to enhance the ability of programs to retain patients or increase rates of program completion; and/or (3) strategies to improve patient compliance with program rules, expectations, and treatment goals. Studies under this announcement may involve analyses of existing data bases, collection of new data in programs, development and testing of identification and assessment methodologies to improve retention and compliance, or program-based studies of strategies for improvement in these areas. Investigation is encouraged in all treatment modalities (including methadone maintenance, medically supervised withdrawal from methadone with transition to counseling or self-help programs, drug-free outpatient, and therapeutic community or short-term residential/inpatient programs), although short-term treatment should be effectively linked to aftercare or continuing care arrangements. Compliance strategies that address aftercare are encouraged. Studies of interventions may be comparative or controlled studies, but should utilize the best available and most appropriate research methodologies. Controlled studies should be based on well-defined patient groups entering treatment and treatment models that take into account identifiable stages of treatment at which program modifications are most likely to be needed in order to increase retention and compliance. Interventions can be pharmacological or nonpharmacological and may be based in a variety of settings (e.g., hospitals, residential programs, outpatient programs, correctional settings). Retention in treatment. Although research has shown that successful outcomes are more likely if patients stay in treatment for 90 days or longer, early dropout rates in many drug abuse treatment programs are high. Research focused on studies of retention in treatment and strategies to improve retention, such as tailored interventions to reduce dropout in the critical induction period, is needed, as are studies to clarify the relationship between length of treatment and treatment outcome. Also of interest are studies to determine the roles of legal coercion, social supports and/or pressure, and other external factors that influence retention in treatment. Compliance in treatment. Research indicates that during-treatment performance is predictive of post-treatment outcomes. New studies to examine strategies to improve treatment performance by reducing problematic use of alcohol and other drugs, by improving participation in treatment, or by improving compliance with other treatment program goals are encouraged. Investigations may also focus on improving the operation or organization of treatment programs to increase compliance and retention. Studies may be of single interventions such as behavioral contingencies, combinations of interventions, program structure interventions combining targeted services and behavioral contingencies, and/or the use of medications in conjunction with program structure. Examples of program structure factors include negotiation of behavioral expectations (e.g., job search, participation in training), monitoring program-relevant behavior, participation in individual and group counseling or therapy as a condition for remaining enrolled in treatment, tracking and outreach to reduce treatment dropout, and From owner-sci-resources@net.bio.net Wed Dec 09 22:00:00 1992 Path: biosci!NET.BIO.NET!kristoff From: kristoff@NET.BIO.NET (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 21, no. 44, pt. 1, 11 December 1992 Message-ID: Date: 10 Dec 92 00:40:47 GMT Sender: kristoff@net.bio.net Distribution: bionet Lines: 1506 NOTE: The NIH Guide may be split into more than one mail message to avoid truncation during e-mail distribution. The first message always begins with the RFP/RFA summary sections followed by the appended texts of the full RFP/RFAs. ---------------------------------------------------------------------- $$XID NIHGUIDE 19921211 V21N44 P1O4 ************************************ X-comment: RFAS described: AI-93-06, CA-93-01, DK-93-10, OD-93-01, HL-93-12, AR-93-01, AR-93-03, HL-93-07 NIH GUIDE - Vol. 21, No. 44 - December 11, 1992 $$INDEX BEGIN ******************************************************* NOTICES $$INDEX N1 ********************************************************** WORLD AIDS FOUNDATION Fogarty International Center INDEX: FOGARTY INTERNATIONAL CENTER $$INDEX N2 ********************************************************** NATIONAL CANCER INSTITUTE BRIEFING ON "THERAPEUTIC STUDIES OF PRIMARY CENTRAL NERVOUS SYSTEM MALIGNANCIES IN ADULTS" National Cancer Institute INDEX: CANCER $$INDEX N3 ********************************************************** PREAPPLICATION CONFERENCE FOR WOMEN'S INTERAGENCY HEALTH STUDY National Institute of Allergy and Infectious Diseases INDEX: ALLERGY, INFECTIOUS DISEASES $$INDEX N4 ********************************************************** MANAGEMENT AND OPERATION OF THE NCI FREDERICK CANCER RESEARCH AND DEVELOPMENT CENTER National Cancer Institute INDEX: CANCER NOTICES OF AVAILABILITY (RFPs AND RFAs) $$INDEX R1 ********************************************************** OPERATION OF THE NATIONAL ORGAN PROCUREMENT AND TRANSPLANTATION NETWORK (RFP HRSA-240-BHRD-2(3) Health Resources and Services Administration INDEX: HEALTH RESOURCES AND SERVICES ADMINISTRATION $$INDEX R2 ********************************************************** SCIENTIFIC REGISTRY FOR ORGAN TRANSPLANTATION (RFP HRSA-240-BHRD-3(3) Health Resources and Services Administration INDEX: HEALTH RESOURCES AND SERVICES ADMINISTRATION $$INDEX R3 03/11/93 ************************************************* RESEARCH LEADING TO IMPROVED MEASLES VACCINES (RFA AI-93-06) National Institute of Allergy and Infectious Diseases INDEX: ALLERGY, INFECTIOUS DISEASES $$INDEX R4 03/12/93 ************************************************* RADIOLOGIC DIAGNOSTIC ONCOLOGY GROUP V: STEREOTACTIC BREAST BIOPSY FOR NON-PALPABLE LESION CHARACTERIZATION (RFA CA-93-01) National Cancer Institute INDEX: CANCER $$INDEX R5 03/17/93 ************************************************* HUMAN GENES FOR NON-INSULIN DEPENDENT DIABETES MELLITUS (RFA DK-93-10) National Institute of Diabetes and Digestive and Kidney Diseases INDEX: DIABETES, DIGESTIVE, KIDNEY $$INDEX R6 03/30/93 ************************************************* EXTRAMURAL RESEARCH FACILITIES CONSTRUCTION PROJECTS (RFA OD-93-01) National Institutes of Health INDEX: NATIONAL INSTITUTES OF HEALTH $$INDEX R7 04/13/93 ************************************************* EXPRESSION OF TUBERCULOSIS IN THE LUNG (RFA HL-93-12) National Heart, Lung, and Blood and Institute INDEX: HEART, LUNG, BLOOD $$INDEX R8 04/20/93 ************************************************* JUVENILE RHEUMATIC DISEASES RESEARCH CENTER PLANNING GRANT (RFA AR-93- 01) National Institute of Arthritis and Musculoskeletal and Skin Diseases INDEX: ARTHRITIS, MUSCULOSKELETAL, SKIN DISEASES $$INDEX R9 06/18/93 ************************************************* SKIN DISEASES RESEARCH CORE CENTERS (RFA AR-93-03) National Institute of Arthritis and Musculoskeletal and Skin Diseases INDEX: ARTHRITIS, MUSCULOSKELETAL, SKIN DISEASES $$INDEX R10 10/13/93 ************************************************ MONOENERGETIC X-RAY SYSTEMS FOR CARDIOVASCULAR IMAGING (RFA HL-93-07-H) National Heart, Lung, and Blood Institute INDEX: HEART, LUNG, BLOOD ONGOING PROGRAM ANNOUNCEMENTS $$INDEX P1 ********************************************************** PSYCHOTHERAPY, BEHAVIOR THERAPY, AND COUNSELING IN DRUG DEPENDENCE TREATMENT (PA-93-27) National Institute on Drug Abuse INDEX: DRUG ABUSE $$INDEX P2 ********************************************************** RESEARCH TO IMPROVE DRUG ABUSE TREATMENT ENTRY, RETENTION, COMPLAINCE, AND EFFECTIVENESS (PA-93-28) National Institute on Drug Abuse INDEX: DRUG ABUSE $$INDEX P3 ********************************************************** KIDNEY DISEASE OF DIABETES MELLITUS: PATHOGENETIC MECHANISMS (PA-93- 29) National Institute of Diabetes and Digestive and Kidney Diseases INDEX: DIABETES, DIGESTIVE, KIDNEY $$INDEX P4 ********************************************************** RESEARCH ON RAYNAUD'S PHENOMENON AND SYSTEMIC SCLEROSIS (PA-93-30) National Institute of Arthritis and Musculoskeletal and Skin Diseases INDEX: ARTHRITIS, MUSCULOSKELETAL, SKIN DISEASES $$INDEX P5 ********************************************************** RESISTANCE TO ANTIVARALS TARGETED TO HUMAN IMMUNODEFICIENCY VIRUS (PA- 93-31) National Institute of Allergy and Infectious Diseases INDEX: ALLERGY, INFECTIOUS DISEASES $$INDEX P6 ********************************************************** INSTITUTIONAL RESEARCH TRAINING IN ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES (PA-93-32) National Institute of Arthritis and Musculoskeletal and Skin Diseases INDEX: ARTHRITIS, MUSCULOSKELETAL, SKIN DISEASES ERRATA $$INDEX E1 ********************************************************** RESEARCH USING THE UNITED STATES RENAL DATA SYSTEM (RFA DK-93-12) National Institute of Diabetes and Digestive and Kidney Diseases INDEX: DIABETES, DIGESTIVE, KIDNEY This publication is also available electronically to institutions via BITNET or INTERNET. Alternative access is through the NIH Grant Line using a personal computer. Contact Dr. John James at 301/496-7554 for details, or send an E-mail message to ZNS@NIHCU. $$INDEX END ********************************************************* NOTICES $$N1 BEGIN ********************************************************** WORLD AIDS FOUNDATION NIH GUIDE, Volume 21, Number 44, December 11, 1992 P.T. 34, 42; K.W. 0715008, 0502017 Fogarty International Center The World AIDS Foundation (WAF) announces its intent to support research and education relating to Acquired Immunodeficiency Syndrome (AIDS) in the developing world. The goal of the WAF is to facilitate information exchange and assist developing countries in responding to the AIDS pandemic. The WAF is particularly interested in projects that are catalytic and once in place could have a multiplicative effect. The WAF also is particularly interested in supporting applications that originate from developing countries and that emphasize collaboration between and among scientists from developed and developing countries. The main area of interest of the WAF is education for health professionals in developing countries, especially in-country training. This includes highly focused workshops that enhance the scientific process and transfer knowledge needed in the effort against the Human Immunodeficiency Virus (HIV) infection and AIDS. The limit of any single funding request to the WAF is $200,000. APPLICATION PROCEDURES Concept letters and applications may be prepared in either English or French. Applicants should submit concept letters for initial consideration. Following review of concept letters, applicants may be invited to submit complete proposals. The annual deadline for receipt of concept letters is February 1. INQUIRIES Concept letters and inquiries concerning the programs of the World AIDS Foundation are to be directed by mail or by FAX to: World AIDS Foundation Assistant Secretary for Health c/o Director, Fogarty International Center National Institutes of Health Building 31, Room B2C02 Bethesda, MD 20892, U.S.A. FAX: (301) 402-2056 or Fondation Mondiale SIDA c/o Directeur de l'Institut Pasteur 28 rue du Docteur Roux 75724 Paris, Cedex 15, FRANCE FAX: 0033-1-45688938 $$N1 END ************************************************************ $$N2 BEGIN ********************************************************** NATIONAL CANCER INSTITUTE BRIEFING ON "THERAPEUTIC STUDIES OF PRIMARY CENTRAL NERVOUS SYSTEM MALIGNANCIES IN ADULTS" NIH GUIDE, Volume 21, Number 44, December 11, 1992 P.T. 34; K.W. 0715035, 0705055, 0740015, 0740020 National Cancer Institute Request for Applications (RFA) CA-93-03, for cooperative agreements (U01) from consortia of institutions to perform Phase I and II clinical evaluations of promising new chemotherapeutic or biologic agents for the treatment of primary central nervous system (CNS) malignancies was published in the NIH Guide for Grants and Contracts, Vol. 21, No. 41, November 13, 1992. The National Cancer Institute (NCI) will hold a briefing session concerning this RFA on Tuesday, January 19, 1993 in Conference Room H, Executive Plaza North, 6130 Executive Boulevard, Rockville, MD to discuss this initiative and answer questions. Two sessions will be held from 9:00 a.m. to 11:00 a.m. and 2:00 p.m. to 4:00 p.m. Potential applicants may attend either session. All interested parties are invited to attend. INQUIRIES For further information and to register for the meeting, contact: Ms. Diane Bronzert Cancer Therapy Evaluations Program Division of Cancer Treatment National Cancer Institute Executive Plaza North, Room 734 Bethesda, MD 20892 Telephone: (301) 496-8866 FAX: (301) 480-4663 $$N2 END ************************************************************ $$N3 BEGIN ********************************************************** PREAPPLICATION CONFERENCE FOR WOMEN'S INTERAGENCY HEALTH STUDY NIH GUIDE, Volume 21, Number 44, December 11, 1992 P.T. 42, II; K.W. 0710030, 0785035 National Institute of Allergy and Infectious Diseases The National Institute of Allergy and Infectious Diseases (NIAID) is sponsoring a one-day preapplication conference concerning the Request for Applications (RFA) AI-92-12, Women's Interagency Health Study (WIHS). The conference is open to anyone interested in applying for a cooperative agreement award in response to this RFA. Issues to be discussed include application procedures, program goals and objectives, and award criteria. Time will be allocated for questions and answers. DATE: December 18, 1992 CONFERENCE SITE: Bethesda, MD INQUIRIES Briana Porte The Mayatech Corporation 1300 Silver Spring, MD 20910 Telephone: (301) 587-1600 $$N3 END ************************************************************ $$N4 BEGIN ********************************************************** MANAGEMENT AND OPERATION OF THE NCI FREDERICK CANCER RESEARCH AND DEVELOPMENT CENTER NIH GUIDE, Volume 21, Number 44, December 11, 1992 P.T. 34; K.W. 0780000, 1002002, 0780018, 0710030 National Cancer Institute The National Cancer Institute (NCI) is seeking sources to perform research, operation and technical support, animal production, computer services, and scientific library services at the NCI Frederick Cancer Research and Development Center (NCI-FCRDC), a government-owned, contractor-operated facility that is a designated Federally Funded Research and Development Center (FFRDC). The facility consists of approximately 100 buildings and structures on 69 acres in Frederick, Maryland. The NCI intends to recompete this requirement which is presently being performed under five separate contracts as follows: Research, Contract N01-CO-74101, Advanced BioScience Laboratories, Inc.; Operations and Technical Support, Contract N01-CO-74102, Program Resources, Inc.; Animal Production, Contract N01-CM-23911, Harlan Sprague Dawley, Inc.; Computer Services, Contract N01-CO-74103, Data Management Services, Inc.; Scientific Library Services, Contract N01-CO-23913, Data Management Services, Inc. All contracts are anticipated to be cost type, either cost-plus-fixed-fee or cost-plus-award-fee. Offerors will have the option of submitting multiple or combinatorial proposals. Anticipated beginning date of new contracts is September 26, 1994. Further notice will be published, including RFP availability, on or about March 1993. Term of resulting contract(s) is anticipated to be 10 years. Current annual negotiated amount for the last year of each contract: Research, $15,156,672; Operations and Technical Support, $155,588,664; Animal Production, $3,522,562; Computer Services, $1,457,207; Scientific Library Services, $985,476. This announcement is intended to apprise all interested organizations of this future full and open competition opportunity. INQUIRIES If additional information is required, contact John Baker, Contract Specialist Frederick Cancer Research and Development Center National Cancer Institute P.O. Box B, Building 427 Frederick, MD 21702-1201 Telephone: (301) 846-1112 No collect calls will be accepted. $$N4 END ************************************************************ NOTICES OF AVAILABILITY (RFPs AND RFAs) $$R1 BEGIN HRSA-240-BHRD-2(3) *************************************** OPERATION OF THE NATIONAL ORGAN PROCUREMENT AND TRANSPLANTATION NETWORK NIH GUIDE, Volume 21, Number 44, December 11, 1992 RFP AVAILABLE: HRSA-240-BHRD-2(3) P.T. 34; K.W. 0780025, 0710125 Health Resources and Services Administration The Division of Organ Transplantation has a requirement for an organization to operate and maintain the National Organ Procurement Transplant Network (OPTN). This acquisition will require that the organization have expertise in organ procurement and a board of directors that includes representatives of organ procurement organizations, transplant centers, voluntary health associations, and the general public to establish in one location or through regional centers a system to match organs and individuals included on the list, especially individuals whose immune system makes it difficult for them to receive organs. It is anticipated that only one award will be made to a private non profit organization. It is expected that the contract will have a three-year period of performance. Any responsible offeror may submit a proposal that will be considered by the government. Request for Proposals (RFP) HRSA-240-BHRD-2(3) will be issued on or about November 17, 1992. Proposals will be due on February 15, 1993. INQUIRIES To receive a copy of the RFP, supply this office with a request in writing and two self-addressed mailing labels addressed to: Ms. Ann Linkins, Contract Specialist Contract Procurement and Operations Branch Health Resources and Services Administration Parklawn Building, Room 13A-19 5600 Fishers Lane Rockville, MD 20857 This advertisement does not commit the government to make an award. $$R1 END ************************************************************ $$R2 BEGIN HRSA-240-BHRD-3(3) *************************************** SCIENTIFIC REGISTRY FOR ORGAN TRANSPLANTATION NIH GUIDE, Volume 21, Number 44, December 11, 1992 RFP AVAILABLE: HRSA-240-BHRD-3(3) P.T. 34; K.W. 0780030, 0780025 Health Resources and Services Administration The Division of Organ Transplantation has a requirement for the acquisition of Scientific Registry for Organ Transplantation. This acquisition will require maintenance of a computerized registry on all kidney, heart, liver, heart-lung, and pancreas transplant recipients at the time of transplant and periodically after transplant. It is anticipated that only one award will be made to a private non profit organization. It is expected that the contract will have a three-year period of performance. Any responsible offeror may submit a proposal that will be considered by the government. Request for Proposals (RFP) HRSA-240-BHRD-3(3) will be issued on or about November 17, 1992. Proposals will be due on February 15, 1993. INQUIRIES This advertisement does not commit the government to make an award. To receive a copy of the RFP, supply this office with a request in writing and two self-addressed mailing labels addressed to: Ms. Ann Linkins, Contract Specialist Contract Procurement and Operations Branch Health Resources and Services Administration 5600 Fishers Lane, Room 13A-19 Rockville, MD 20857 $$R2 END ************************************************************ $$R3 BEGIN AI-93-06 FULL-TEXT *************************************** RESEARCH LEADING TO IMPROVED MEASLES VACCINES NIH GUIDE, Volume 21, Number 44, December 11, 1992 RFA AVAILABLE: AI-93-06 P.T. 34; K.W. 0715125, 0740075 National Institute of Allergy and Infectious Diseases Letter of Intent Receipt Date: January 11, 1993 Application Receipt Date: March 11, 1993 THE REQUEST FOR APPLICATIONS (RFA) ANNOUNCED IN THIS NOTICE CONTAINS ESSENTIAL INFORMATION FOR THE PREPARATION OF AN APPLICATION. POTENTIAL APPLICANTS MAY OBTAIN THE RFA FROM THE CONTACT NAMED IN INQUIRIES, BELOW. PURPOSE Measles recently reemerged as a public health problem in the U.S. and measles continues to be a deadly disease in the developing world. The purpose of this RFA is to acquire the information needed for the development of safe new measles vaccines that are highly efficacious when administered in early infancy and that will aid in the control and eventual eradication of measles. An expanded research effort is needed for the rational development and evaluation of new vaccines and immunization strategies. The National Institute of Allergy and Infectious Diseases (NIAID) requests investigator-initiated research grant applications focused on the study of measles virus and the host's response to infection as it relates to the safe induction of long-lasting protective immunity in individuals, and the reduction of measles disease and infant deaths in populations. 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 RFA, Research Leading to Improved Measles Vaccine, is related to the priority area of immunization and infectious diseases. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Foreign institutions are not eligible for the First Independent Research Support and Transition (FIRST) (R29) award. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT This RFA will use the National Institutes of Health (NIH) individual research grant (R01) and the FIRST (R29) award mechanisms (if interinstitutional collaborations are anticipated, contact Dr. James M. Meegan at the address listed under INQUIRIES). The total project period for applications submitted in response to the present RFA may not exceed five years. Because the nature and scope of the research proposed in response to this RFA may vary, it is anticipated that the size of an award will also vary. If the proposed budget exceeds $200,000, the Principal Investigator must obtain a written waiver from Dr. James Meegan to submit with the grant application. This RFA is a one-time solicitation. Future unsolicited competing continuation applications will compete with all unsolicited investigator-initiated applications and be reviewed according to the customary NIH peer review procedures. FUNDS AVAILABLE There are $1.5 million available in total support (direct plus indirect costs) for this RFA for the first year. It is anticipated that six to eight new awards will be made, none to exceed $200,000 in total annual direct costs. RESEARCH OBJECTIVES A major epidemic of measles occurred in 1989-90, and measles reemerged as a significant health problem in the U.S. The major cause of the reemergence of measles in the U.S. was the failure to vaccinate children at the appropriate age, rather than failure of vaccine efficacy. However, current vaccines do have some deficiencies as public health tools, particularly in regard to efficacy in very young infants. Infants are at greatest risk during the interval between loss of maternal antibody and receipt of vaccine. Thus, both internationally and domestically, there is an urgent need for an efficacious vaccine that can be safely administered at six to nine months of age or earlier in infancy. Furthermore, future programs aimed to increase immunization coverage will emphasize administration at earlier ages in infancy of current as well as new, multiple combinations of vaccines. This announcement is intended to stimulate innovative research on measles across several research disciplines, with a strong emphasis on studies to develop improved vaccines that can safely overcome the maternal antibody barrier and induce long-lasting protective immunity. Research projects are sought that investigate topics including, but not limited to, those listed below. o Determination of which measles antigens are required to safely elicit long-lasting, protective humoral and cellular immunity in the developing immune system of the young infant. o Characterization of the quantitative and qualitative differences between vaccine-induced and naturally-induced protective immunity. o Elucidation of the impact of maternal antibody on infant immunization, and development of strategies to overcome maternal antibody as a block to immunization in very young infants. o Development of an animal model of measles virus infection and disease that parallels human disease and that could be used to study the many host and viral factors influencing establishment of protective immunity in the young infant. o Establishment of the viral correlates of virulence and attenuation. o Investigation of measles virus pathogenesis, including virus-induced immune suppression. o Elucidation of viral and host factors contributing to immunization-induced adverse events. o Pre-clinical development of highly efficient methods for the safe delivery of appropriate measles antigens leading to establishment of protective immunization. o Application of research on closely related viral systems, such as distemper, to address specific problems related to immunization of young infants. SPECIAL REQUIREMENTS Principal Investigators should budget for an annual one-day progress review meeting at the NIH. STUDY POPULATIONS SPECIAL INSTRUCTIONS FOR INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDIES For projects involving clinical research, NIH requires applicants to give special attention to the inclusion of women and minorities in study populations. If women or minorities are not included in the study populations for clinical studies, a specific justification for this exclusion must be provided. Applications without such documentation will not be accepted for review. LETTER OF INTENT Prospective applicants are asked to submit, by January 11, 1993, a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, the identities of other key personnel and participating institutions, and the number and title of 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, the information that it contains allows NIAID staff to estimate the potential review workload and to avoid possible conflict of interest in the review. The letter of intent is to be sent to Dr. James M. Meegan at the address listed under INQUIRIES. APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 9/91) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research and from the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone 301-496-7441. Applications must be received by the receipt date of this RFA. Applications not received by the receipt date will be considered nonresponsive to this RFA and the applicant will be contacted to determine whether to have the application returned to the applicant or be processed as an unsolicited application for the next DRG review cycle. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by the DRG and responsiveness by the NIAID. Incomplete applications will be returned to the applicant without further consideration. If the application is complete but not responsive to the RFA, it will undergo the same process as for late applications. Complete and responsive applications will be evaluated for scientific/technical merit by an appropriate scientific review group. The second level of review will be provided by the NIAID National Advisory Council. Review criteria to be used are generally the same as those for unsolicited research grant applications. AWARD CRITERIA The anticipated date of award is September 1993. Awards will be made solely on the basis of priority score, programmatic balance, and available funds. INQUIRIES Written and telephone requests for the RFA and the opportunity to clarify any issues or questions from potential applicants are welcome. Send the letter of intent, requests for the RFA, and inquiries regarding programmatic issues to: Dr. James M. Meegan Virology Branch, Division of Microbiology and Infectious Diseases National Institute of Allergy and Infectious Diseases Solar Building, Room 3A15 Bethesda, MD 20892 Telephone: (301) 496-7453 FAX: (301) 496-8030 Direct inquiries regarding fiscal matters to: Mr. Todd C. Ball Grants Management Branch, Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4B35 Bethesda, MD 20892 Telephone: (301) 496-7075 Schedule Letter of Intent Receipt Date: January 11, 1993 Application Receipt Date: March 11, 1993 Scientific Review Date: July 1993 Council Meeting Date: September 1993 Earliest Award Date: September 1993 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.856, Microbiology and Infectious Diseases Research. Awards are made under 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 requirements of Executive Order 12372 or Health Systems Agency review. $$R3 END ************************************************************ $$R4 BEGIN CA-93-01 FULL-TEXT *************************************** RADIOLOGIC DIAGNOSTIC ONCOLOGY GROUP V: STEREOTACTIC BREAST BIOPSY FOR NON-PALPABLE LESION CHARACTERIZATION NIH GUIDE, Volume 21, Number 44, December 11, 1992 RFA AVAILABLE: CA-93-01 P.T. 34; K.W. 0715035, 0706030, 0745020 National Cancer Institute Letter of Intent Receipt Date: January 12, 1993 Application Receipt Date: March 12, 1993 THE REQUEST FOR APPLICATIONS (RFA) ANNOUNCED IN THIS NOTICE CONTAINS ESSENTIAL INFORMATION FOR THE PREPARATION OF AN APPLICATION. POTENTIAL APPLICANTS MAY OBTAIN THE RFA FROM THE CONTACT NAMED IN INQUIRIES, BELOW. PURPOSE The Radiation Research Program (RRP), Division of Cancer Treatment (DCT) of the National Cancer Institute (NCI), invites applications for cooperative agreements to establish a multi-institutional scientific group in order to optimize a clinical algorithm for non-palpable breast lesion characterization. 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 RFA, Radiologic Diagnostic Oncology Group (RDOG) V: Stereotactic Breast Biopsy for Non-Palpable Lesion Characterization, is related to the priority area of cancer. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0, or Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Non-profit and for-profit organizations and institutions, governments and their agencies, and foreign and domestic institutions are eligible to apply. Applications from minority individuals and women are encouraged. Applications may be submitted from institutions that desire to be a participating clinical institution in a consortium and/or as a headquarters institution. The same institution may serve in both capacities within this cooperative agreement. MECHANISM OF SUPPORT Awards will be made as cooperative agreements (U01), a funding mechanism in which substantial NCI programmatic involvement with the recipients during performance of the planned activity is anticipated. Applicants will be responsible for the planning, direction, and execution of the proposed project. FUNDS AVAILABLE Approximately $1,500,000 in total costs per year for four years will be committed to fund applications that are submitted in response to this RFA. It is anticipated that a consortium of about ten clinical institutions and the headquarters component will be funded to establish the RDOG V. It is anticipated that approximately one-fourth of the total funds expended each year will be devoted to the headquarters function, and approximately three-quarters will be awarded to the participating Clinical Institutions. RESEARCH OBJECTIVES The objective of this RFA is to invite applications to perform centrally coordinated multi-institutional cooperative clinical trials to develop an optimal clinical algorithm for characterization of small non-palpable breast cancers. The successful applicants will form RDOG V. The results of the RDOG V studies should have a direct and immediate impact on management of minimal breast cancer. Sufficient numbers of patients must be available in each institution for successful completion of the proposed clinical trials. Background The RDOG was formed by the NCI in September 1987. The RDOG objective is timely evaluation of current and emerging imaging modalities in the management of patients with cancer. The development of multi-institutional clinical trial groups allows for rapid patient accrual within a short period of time. This in turn ensures rapid evaluation and optimization of imaging techniques for diagnosis, staging, and serial monitoring of cancer. The RDOG has had a significant impact on clinical research in radiology. This is the first time that multi-institutional clinical trials in diagnostic imaging have been conducted in a centrally coordinated fashion with strict quality control and analysis of cost-effectiveness. Ultimately, RDOG study findings would be useful for design of therapeutic protocols and formulating clinical and medical insurance reimbursement policy. Since the time of its establishment, RDOG clinical research has been important for the development of optimal imaging algorithms for prostate and lung cancer (RDOG I), pancreatic and colon cancer (RDOG II) and musculoskeletal and head and neck tumors (RDOG III). In the near future, RDOG IV will be established to study pediatric solid tumors and ovarian cancer. This RFA will establish RDOG V in order to evaluate stereotactic breast biopsy as a minimally invasive, low morbidity alternative for open surgical biopsy. SPECIAL REQUIREMENTS The administrative and funding mechanism to be used to support these awards will be a cooperative agreement (U01) between each awardee and the NCI. In a cooperative agreement there is substantial Federal programmatic involvement above and beyond the levels characteristic of traditional program management of grants. Prospective applicants must obtain a copy of the RFA for additional information. STUDY POPULATIONS SPECIAL INSTRUCTIONS FOR INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS For projects involving clinical research, NIH requires applicants to give special attention to the inclusion of women and minorities in study populations. If women and minorities are not included in the study populations, a specific and compelling justification for this exclusion must be provided. Applications that do not include women and minorities and that are without such documentation will not be accepted for review. LETTER OF INTENT Prospective applicants are asked to submit, by January 12, 1993, a letter of intent that includes a descriptive title of the proposed research, the name and address of the Principal Investigator, the names of other key personnel, the 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 is requested in order to provide an indication of the number and scope of applications to be reviewed. The letter of intent is to be sent to Dr. Faina Shtern at the address listed under INQUIRIES. APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 9/91) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research; from the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, Room 449, Westwood Building, 5333 Westbard Avenue, Bethesda, MD 20892, telephone (301) 496-7441; and from the NCI program director named below. Submit a signed, typewritten original of the application, including the Checklist, and three signed, exact photocopies, in one package to the address below. The photocopies must be clear and single sided. Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** At the time of submission, send two additional copies of the application to: Referral Officer Division of Extramural Activities National Cancer Institute Room 838, Westwood Building Bethesda, MD 20892 REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed by the DRG for completeness. Incomplete applications will be returned to the applicant without further consideration. Evaluation for responsiveness to the program requirements and criteria stated in the RFA is an NCI program staff function. Applications that are judged non-responsive will be returned to the applicant by the NCI, but may be submitted as investigator-initiated research grants at the next receipt date. Questions concerning the responsiveness of proposed research to the RFA may be directed to program staff listed under INQUIRIES. If the number of applications submitted is large compared to the number of awards to be made, the NCI may conduct a preliminary scientific peer review (triage) to eliminate those that are clearly not competitive. The NCI will remove from competition those applications judged to be noncompetitive for award and notify the applicant and institutional business official. Those applications judged to be both competitive and responsive will be further evaluated according to the review criteria stated in the RFA for scientific and technical merit by an appropriate peer review group convened by the Division of Extramural Activities, NCI. The second level of review by the National Cancer Advisory Board considers the special needs of the NCI and the priorities of the National Cancer Program. INQUIRIES Direct requests for the RFA and inquiries regarding programmatic issues to: Faina Shtern, M.D. Chief, Diagnostic Imaging Research Branch Radiation Research Program National Cancer Institute Executive Plaza North, Suite 800 Bethesda, MD 20892 Telephone: (301) 496-9531 Direct inquiries regarding fiscal matters to: Ms. Barbara Fisher Grants Management Coordinator Grants Administration Branch National Cancer Institute Executive Plaza South, Suite 242 6120 Executive Boulevard Rockville, MD 20852 Telephone: (301) 496-7800, Ext. 29 FAX: (301) 496-8601 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.395, Cancer Treatment Research. Awards are made under 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 requirements of Executive Order 12372 or Health Systems Agency review. $$R4 END ************************************************************ $$R5 BEGIN DK-93-10 FULL-TEXT *************************************** HUMAN GENES FOR NON-INSULIN DEPENDENT DIABETES MELLITUS NIH GUIDE, Volume 21, Number 44, December 11, 1992 RFA AVAILABLE: DK-93-10 P.T. 34; K.W. 0715075, 0755035, 0755040, 0760015 National Institute of Diabetes and Digestive and Kidney Diseases Letter of Intent Receipt Date: February 18, 1993 Application Receipt Date: March 17, 1993 THE REQUEST FOR APPLICATIONS (RFA) ANNOUNCED IN THIS NOTICE CONTAINS ESSENTIAL INFORMATION FOR THE PREPARATION OF AN APPLICATION. POTENTIAL APPLICANTS MAY OBTAIN THE RFA FROM THE CONTACT NAMED IN INQUIRES, BELOW. PURPOSE The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the American Diabetes Association (ADA) invites investigator-initiated research grant applications to identify specific genes responsible for non-insulin dependent diabetes mellitus (NIDDM) in humans. It is anticipated that this identification will require an interdisciplinary approach to develop and utilize strategies that will elucidate genes responsible for NIDDM using appropriate family pedigrees. Applications will be submitted to the National Institutes of Health (NIH) and will be reviewed by NIH according to the usual NIH peer review procedures. Applications judged meritorious and designated for funding will be supported partially by the NIDDK and partially by the ADA through the issuance of coordinated but separate awards by the two funding organizations. Applicants are requested to provide the NIDDK with a letter of authorization to allow the NIDDK to provide a copy of their letter of intent, application, NIH-prepared summary statement of the initial review, and yearly progress reports, if funded, to the ADA. Applicants wishing to be considered for funding only by the NIDDK should so indicate in their letter of authorization. Under these latter circumstances, no information pertaining to their applications will be shared with the ADA. 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 RFA, Human Genes for Non-Insulin Dependent Diabetes Mellitus, is related to the priority area of diabetes and chronic disabling conditions. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications for research grants may be made by public and private, foreign and domestic, for-profit and non- profit organizations, such as universities, colleges, hospitals and laboratories, units or State and local governments, and authorized units of the Federal government. Women and minority investigators are encouraged to apply. MECHANISM OF SUPPORT This RFA will use the NIH research project grant (R01). Responsibility for the planning, direction, and execution of 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 award date is September 30, 1993. For the purpose of cost-containment, requested direct costs must not exceed $160,000 per year for any single application. Applications exceeding this limit will not be reviewed as part of the RFA. FUNDS AVAILABLE The NIDDK will commit up to $2 million for first-year expenses, and additional funds for approved expenses in subsequent years for up to five years to fund applications submitted in response to this RFA. The ADA anticipates support of up to 20 percent of recommended direct costs for each funded application per year. The NIDDK and the ADA plan to make approximately 10 to 12 awards in FY 1993 contingent on the receipt of highly meritorious applications in response to this solicitation. With respect to post-award administration, the current policies and requirements that govern the research grant programs of the NIH will prevail for awards made by the NIDDK. Applicants should note that funds from the ADA will be subject to the indirect cost policy and post-award administration policies of the ADA. The award of grants pursuant to this RFA is contingent on the availability of funds for this purpose. SPECIAL REQUIREMENTS Letter of Authorization Each applicant must submit a brief letter to the NIDDK indicating whether or not they wish their application to be considered for coordinated funding by the ADA. Although applicants may request that their applications be considered only by the NIDDK and not by the ADA, it is necessary that the record indicate the applicant's consideration of this opportunity. For each applicant who wishes to have the ADA consider their application for coordinated funding, all materials relating to the application will be promptly forwarded to that organization by the NIDDK, and the summary statement for the application will be shared with the ADA at the time of their availability. The NIDDK will provide no information to the ADA, nor any other non-governmental agency, related to applications from any applicant who requests that the ADA not consider their application. Letters of authorization should be prepared by the Principal Investigator and co-signed by the official signing for the applicant organization. This letter must be submitted as a cover letter accompanying the application. RESEARCH OBJECTIVES NIDDM affects approximately 13 million Americans. It is the predominant form of the disease and severely impacts upon U.S. minority populations. This clustering of prevalence among ethnic/racial groups along with twin and family studies and animal models points to the genetic nature of this disease. Several genetic markers have been described as being associated with a rare form of NIDDM called Maturity Onset Diabetes of the Young (MODY) that shows autosomal dominant inheritance. One of these genetic markers is the gene for glucokinase, a key enzyme of glucose homeostasis found in the insulin-secreting beta cell of the pancreas and in the liver. This is the first evidence that a gene involved in glucose metabolism could be implicated in the pathogenesis of NIDDM. A variety of other genes may be related to the long-term complications suffered by those with all forms of diabetes. Through this solicitation, the NIDDK and the ADA intend to stimulate investigator-initiated research designed to develop and utilize new molecular genetic strategies to provide a better understanding of the major genes involved in NIDDM in humans. To achieve this objective, appropriate family pedigrees may need to be collected as a prerequisite for the identification or for the verification of specific gene involvement. Since a large number of families may need to be recruited, accumulation of these families must be included within the framework of the proposed research plan. Utilization of existing sources of genetic material is encouraged. For example, the ADA is developing a repository of data, DNA, and cell lines of family pedigrees with NIDDM. STUDY POPULATIONS SPECIAL INSTRUCTIONS FOR INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDIES For projects involving clinical research, NIH requires applicants to give special attention to the inclusion of women and minorities in study populations. If women or minorities are not included in the study populations for clinical studies, a specific justification for this exclusion must be provided. Applications without such documentation will not be accepted for review. LETTER OF INTENT Potential applicants are strongly encouraged to submit a letter of intent by February 18, 1993. The letter of intent is to include: (1) names of the Principal Investigator/program director and principal collaborators, (2) descriptive title of the potential application, (3) identification of the organization(s) involved, and (4) the number and title of the RFA in response to which the application may be submitted. The letter of intent is to be sent to: Chief, Review Branch National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 605 5333 Westbard Avenue Bethesda, MD 20892 APPLICATION PROCEDURES Applications are to be submitted on form PHS 398 (rev. 9/91), that is available from an applicant institution's office of sponsored research and from the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone (301) 496-7441. Use the conventional format for research project grant applications. To identify the application as a response to this RFA check "yes" on item 2a of page one of the application and enter the title "Human Genes for NIDDM" and the RFA number DK-93-10. Applications must be received by March 17, 1993. REVIEW CONSIDERATIONS Applications in response to this solicitation will be reviewed using the usual NIH peer review procedures. For further details, applicants are referred to the RFA document. INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct requests for the RFA and inquiries regarding programmatic issues to: Joan T. Harmon, Ph.D. Executive Director, Diabetes Research Program Division of Diabetes, Endocrinology and Metabolic Diseases National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 622 Bethesda, MD 20892 Telephone: (301) 496-7731 Direct inquiries regarding fiscal matters to: Betty E. Bailey Grants Management Branch Division of Extramural Activities National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 649 Bethesda, MD 20892 Telephone: (301) 496-7467 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.847, Diabetes, Endocrinology and Metabolism Research. Awards are made under 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 requirements of Executive Order 12372 or Health Systems Agency review. $$R5 END ************************************************************ $$R6 BEGIN OD-93-01 FULL-TEXT *************************************** EXTRAMURAL RESEARCH FACILITIES CONSTRUCTION PROJECTS NIH GUIDE, Volume 21, Number 44, December 11, 1992 RFA AVAILABLE: OD-93-01 P.T. 02; K.W. 0715035, 0715040, 0715032, 0715165, 0404009, 1002046 National Institutes of Health Letter of Intent Receipt Date: February 17, 1993 Application Receipt Date: March 30, 1993 THE REQUEST FOR APPLICATIONS (RFA) ANNOUNCED IN THIS NOTICE CONTAINS ESSENTIAL INFORMATION FOR THE PREPARATION OF AN APPLICATION. POTENTIAL APPLICANTS MAY OBTAIN THE RFA FROM THE CONTACT NAMED IN INQUIRES, BELOW. PURPOSE Public Law Number 102-394, the Appropriations Act for the Department of Health and Human Services for Fiscal Year 1993, provides $4,960,000 in the budget of the Office of the Director, National Institutes of Health (NIH) for extramural facilities construction grants, to be awarded competitively. The NIH announces the availability of an RFA, OD-93-01 for the construction of facilities of urgent national importance for biomedical/behavioral research and/or services to support such research. Applications for construction grants that were previously submitted to the NIH must recompete under this RFA. The main objective of this construction program is to facilitate the conduct of biomedical/behavioral research by providing funds for construction of new facilities and for the purchase of associated fixed research equipment essential for the operation of these facilities. Support may be requested for the construction of new facilities and additions or renovations to existing facilities to meet the biomedical/behavioral research and/or services to support such research needs of an institution, or of a research group at that institution or elsewhere that utilizes the resources of that institution. The purpose of the proposed facility must be within the scope of one of the statutes authorizing the awards. Those statutes authorize construction grants that would benefit the fields of cancer, vision, heart, lung and blood, AIDS research, and drug abuse, pharmacotherapeutic research. ELIGIBILITY REQUIREMENTS Domestic, non-Federal, public and private non-profit institutions, organizations, and associations that conduct or support biomedical/behavioral research are eligible to apply. An institution may submit only one application in response to this announcement. For example, a medical school and a dental school of the same institution, even when separated geographically, may not submit separate applications. MECHANISM OF SUPPORT The award mechanism will be the construction grant award (C06). Awards will be administered under Federal Regulation 45 CFR Part 74 - Administration of Grants, and for cancer construction projects, 42 CFR Part 52b will also apply. Up to 50 percent of the allowable costs of a project may be awarded, not to exceed $2,000,000. Prior to grant award, the applicant must provide an assurance of required matching funds and that additional funds will be secured to meet any projected costs in excess of the award amount. Requests of less than $500,000 will not be accepted. No indirect costs or continuation costs will be awarded. FUNDS AVAILABLE This one-time solicitation based on the Fiscal Year 1993 appropriation provides $4,960,000 for this initiative. It is anticipated that three to four awards will be made. LETTER OF INTENT Prospective applicants are asked to submit by, February 17, 1993, a letter of intent. The letter, requested for planning purposes only, must identify the RFA number, the proposed Principal Investigator, and include a brief title of the type(s) of research/research support to be conducted in the new facility. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information that it contains allows NIH staff to estimate the potential workload to avoid conflict of interest in the review. The letter of intent is to be addressed to Mr. Kenneth Brow at the address listed under INQUIRIES. APPLICATION PROCEDURES Applicants must use Standard Form 424, Application for Federal Assistance. Application forms and the complete RFA must be requested from the staff contact official listed under INQUIRIES. REVIEW CONSIDERATIONS Applications that are complete and responsive will be reviewed for scientific and technical merit by appropriate special peer review group(s) that will be convened by the Division of Research Grants, NIH. The second level of peer review will be conducted by the National Advisory Board or Council appropriate for the statutory authority that is applicable to the application. Detailed criteria on which the applications will be evaluated are discussed in the RFA. INQUIRIES For additional information, a copy of the RFA, and application Standard Form 424 materials, contact: Mr. Kenneth Brow Chief, Research Facilities Branch Division of Cancer Biology, Diagnosis, and Centers National Cancer Institute Executive Plaza North, Room 300 Bethesda, MD 20892 Telephone: (301) 496-8534 The programmatic and fiscal contacts are listed in the RFA. AUTHORITY AND REGULATIONS Grants for research facilities construction programs of the National Institutes of Health are subject to Executive Order 12372. Awards will be made under the construction grants authorities in the Public Health Service Act, Title IV, Sections 413(b)(6)(B), 421(b)(2)(B), 455, 464P(b)(3), and Title XXIII, Section 2351(a)(7)(B) and administered under PHS grants policies and Federal Regulations 45 CFR Part 74 and for cancer construction only, 42 CFR Part 52b . This program is described in the Catalog of Federal Domestic Assistance, Number 93.392, Cancer-Construction. $$R6 END ************************************************************ $$R7 BEGIN HL-93-12 FULL-TEXT *************************************** EXPRESSION OF TUBERCULOSIS IN THE LUNG NIH GUIDE, Volume 21, Number 44, December 11, 1992 RFA AVAILABLE: HL-93-12L P.T. 34; K.W. 0715165, 0715125, 1002004, 0710070, 1002027, 1002019 National Heart, Lung, and Blood Institute Letter of Intent Receipt Date: February 15, 1993 Application Receipt Date: April 13, 1993 THE REQUEST FOR APPLICATIONS (RFA) ANNOUNCED IN THIS NOTICE CONTAINS ESSENTIAL INFORMATION FOR THE PREPARATION OF AN APPLICATION. POTENTIAL APPLICANTS MAY OBTAIN THE RFA FROM THE CONTACT NAMED IN INQUIRIES, BELOW. PURPOSE The National Heart, Lung, and Blood Institute (NHLBI) invites grant applications for support of research on elucidating the factors that are involved in expression of tuberculosis (TB) in the lung. The primary objectives of this grant program are to encourage research on understanding the factors involved in disease expression following infection by Mycobacterium tuberculosis (Mtb) and to determine the mechanisms by which such factors exert their influence on the lung. 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 RFA, Expression of Tuberculosis in the Lung, is related to the priority areas of HIV infection, and immunization and infectious diseases. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Foreign institutions are not eligible for the First Independent Research Support and Transition (FIRST) (R29) awards. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT This mechanism of support for this RFA will be the research project grant (R01) or the FIRST (R29) award. Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. The total project period for applications submitted in response to this RFA may not exceed five years. Requested budgets for FIRST (R29) awards may not exceed those specified in the FIRST (R29) award guidelines. The anticipated award date is September 30, 1993. Since a variety of approaches would represent valid responses to this announcement, it is anticipated that there will be a range of costs among individual grants awarded. This RFA is a one-time solicitation. Future unsolicited competing continuation applications will compete with all investigator-initiated applications and be reviewed according to the customary peer review procedures. FUNDS AVAILABLE The estimated funds (total costs) available for the first year of support for the entire program is $1.5 million. The expected number of new awards is six to eight. The specific number to be funded will, however, depend on the merit and scope of the applications received and the availability of funds. RESEARCH OBJECTIVES The Centers for Disease Control estimates that since 1984 nearly 39,000 excess cases of TB have accumulated in the United States. This recent increase in TB morbidity is attributable, in large part, to TB occurring in persons infected with the Human Immunodeficiency Virus (HIV). General approaches are being actively pursued in basic tuberculosis research but there is little research that relates to host defenses in the human lung and little or no effort is directed at the molecular and cellular mechanisms of TB expression in the lung. Almost no new information has been obtained on the basic mechanisms of protective immunity and the immune factors that contribute to the natural history of Mtb infection. A number of innate factors (age, gender, ethnicity) and associated disease states are thought to influence susceptibility/resistance and severity of disease when the lung responds to infection with Mtb. There has been no recent progress on obtaining information about the mechanisms by which such factors exert their influence on susceptibility/resistance or severity of TB disease. The overall objective of this initiative is to encourage basic research on disease expression in the lung resulting from infection with Mtb. Applications are invited for innovative multidisciplinary approaches to identify the factors involved in disease expression, to determine their relationship to other factors of disease, and to better understand how such factors exert their influence on pathogenesis. Applications submitted in response to this announcement should clearly define the rationale, background, and specific aims of the proposed studies, and should provide a succinct description of the methods and procedures to be used. Among topics relevant to the objectives of this RFA is research on the basic mechanisms of protective immunity against Mtb in the lung, including local anatomic and immunologic factors that contribute to lung injury, damage, or fibrosis, with particular emphasis on the molecular basis for the generation of immunopathology. Another area of interest is acquired resistance to tuberculosis and the role of T-helper lymphocyte-macrophage interactions in the ability of activated macrophages to ingest and kill virulent Mtb organisms. Since T-helper cells are known to be adversely affected by HIV infection and since the pathogenesis of TB in HIV-infected patients has been observed to differ from the classic granulomatous processes seen in HIV-negative individuals, research directed at obtaining more detail about the mechanisms of TB pathogenesis and the factors affecting susceptibility/resistance and severity in the presence of HIV infection is of particular interest in response to this initiative. Since little is known about the mechanisms of reactivation of tuberculosis in the lung, the development of animal models that simulate reactivation disease and studies in humans that provide insights into the basic mechanisms of reactivation disease expression would also be desirable approaches. Basic research that addresses genetically determined and acquired local and systemic factors that affect immunity and disease expression in the lung would also be considered responsive to this initiative, as would studies elucidating the relationship between TB complicated by bronchiectasis and/or silicosis, and fibrosis. Studies in humans are encouraged where possible. Investigators are also encouraged to consider other approaches that meet the goals of this program in addition to those cited. SPECIAL REQUIREMENTS Applications that propose descriptive studies in humans only and do not contain studies directed at uncovering mechanisms of disease or supporting hypotheses related to mechanisms of disease will not be acceptable. This program will not support studies directed at development of animal models alone. Models must be applied to the study of disease mechanisms associated with expression of tuberculous disease in the lung and wherever possible, the testing of hypotheses in the animal model should carry over to human studies. Applications that focus on the molecular biology and molecular immunology of expression of tuberculosis in the lung are of particular interest. STUDY POPULATIONS SPECIAL INSTRUCTIONS FOR INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDIES For projects involving clinical research, NIH requires applicants to give special attention to the inclusion of women and minorities in study populations. If women and minorities are not included in the study populations for clinical studies, a specific justification for this exclusion must be provided. Applications without such documentation will not be accepted for review. LETTER OF INTENT Prospective applicants are asked to submit, by February 15, 1993, a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, the names of any other participating institutions or investigators, and the number and title of the RFA in response to which the application may be submitted. A letter of intent is not binding, will not enter into the review of any application subsequently submitted, and is not a requirement for application. Such letters are requested for the purpose of obtaining an indication of the number of applications to be received. The NHLBI will not provide a response to a letter of intent. The letter is to be received no later than February 15, 1993 and sent to: Chief, Centers and Special Projects Review Section Review Branch, Division of Extramural Affairs National Heart, Lung, and Blood Institute Westwood Building, Room 553 Bethesda, MD 20892 Telephone: (301) 496-7351 FAX: (301) 402-1660 APPLICATION PROCEDURES Applications must be received by April 13, 1993 The research grant application form PHS 398 (rev. 9/91) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research and from the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone (301) 496-7441. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed by NIH staff for completeness and responsiveness. Incomplete applications will be From owner-sci-resources@net.bio.net Wed Dec 09 22:00:00 1992 Path: biosci!NET.BIO.NET!kristoff From: kristoff@NET.BIO.NET (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 21, no. 44, pt. 4, 11 December 1992 Message-ID: Date: 10 Dec 92 00:47:07 GMT Sender: kristoff@net.bio.net Distribution: bionet Lines: 1237 $$XID NIHGUIDE 19921211 V21N44 P4O4 ************************************ o scientific and technical merit of the application as determined by peer review, o availability of funds, and o program balance. INQUIRIES For further information about these awards, contact: Richard W. Lymn, Ph.D. Program Director National Institute of Arthritis and Musculoskeletal and Skin Diseases Westwood Building, Room 403 Bethesda, MD 20892 Telephone: (301) 402-3346 For administrative and fiscal matters, contact: Diane Watson Grants Management Officer National Institute of Arthritis and Musculoskeletal and Skin Diseases Westwood Building, Room 732 Bethesda, MD 20892 Telephone: (301) 402-3352 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.846, Arthritis, Musculoskeletal and Skin Diseases Research. Awards will be made under the authority of the Public Health Service Act, Title III, Section 301 (Public Law 78-410, as amended; 42 USC 241) and administered under PHS grants policies and Federal Regulations 42 CFR Part 52, 45 CFR Part 74 and 42 CFR Part 66. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$P6 END ************************************************************ ERRATA $$E1 BEGIN R3 19921106 APPEND RFA DK-93-12 BOTH ************************ RESEARCH USING THE UNITED STATES RENAL DATA SYSTEM NIH GUIDE, Volume 21, Number 44, December 11, 1992 RFA: DK-93-12 P.T. 34; K.W. 0785095, 0755018 National Institute of Diabetes and Digestive and Kidney Diseases This erratum is issued for Request for Applications DK-93-12, published in the NIH Guide for Grants and Contracts, Vol. 21, No. 40, November 6, 1992. The section MECHANISM OF SUPPORT should be amended with the addition of the following sentence: "Each grant award will not be more than $50,000 total cost per year (direct and indirect) for a maximum of two years." $$E1 END ************************************************************ $$XID RFA AR9303 AR-93-03 P1O1 ***************************************** SKIN DISEASES RESEARCH CORE CENTERS NIH GUIDE, Volume 21, Number 44, December 11, 1992 RFA: AR-93-03 P.T. 04; K.W. 0715185, 1003002, 0710070, 0710030 National Institute of Arthritis and Musculoskeletal and Skin Diseases Letter of Intent Receipt Date: May 10, 1993 Application Receipt Date: June 18, 1993 PURPOSE The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) invites applications for research core centers (P30s) in skin diseases. The Skin Diseases Research Centers (SDRCs) will provide the resources for a number of established, currently funded investigators, often from different disciplines, to adopt a multidisciplinary approach to common research problems in skin diseases and to ensure greater productivity than from each of the separate projects. 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 Request for Applications (RFA), Skin Diseases Research Core Centers, is related to the priority area of chronic disabling conditions. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal Government. An established clinical and research program in skin diseases should be present. Foreign organizations are not eligible. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT This RFA will use the National Institutes of Health (NIH) core research center grant (P30). Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. The total project period for applications submitted in response to the present RFA is five years. The direct costs requested cannot exceed $400,000 each year. The anticipated award date is March 1, 1994. FUNDS AVAILABLE The NIAMS intends to fund three SDRCs from this RFA in FY 1994, subject to the availability of resources and receipt of sufficiently meritorious applications. The estimated funds (total costs) available for the first year of support of these centers are $1.0 million. RESEARCH OBJECTIVES Research in skin diseases is at a stage where a number of areas are making broad advances that can be effectively fostered by research core centers. Examples of these areas include, but are not limited to: o stratum corneum: biochemistry, structure, function o epidermis: differentiation, keratinization, cellular constituents o dermal-epidermal junction: structure, functions, diseases o skin as an immunological organ o autoimmune skin diseases o dermis: structural components, diseases The choice of research problem upon which the SDRC would focus is made by the principal and collaborating currently funded investigators. The SDRCs will provide support for: 1. Core resources and facilities to be used by investigators of individually supported research projects in order to enhance and coordinate their activities. This support may include personnel, equipment, supplies, services, and facilities. 2. Limited funds for pilot and feasibility studies. 3. Program enrichment activities. An SDRC should be an identifiable organizational unit within a university-affiliated medical center. An Administrative Core should be proposed to coordinate the Center and administer the program enrichment activities. One or more research cores may be proposed. A research core is a facility shared by two or more Center investigators that enables them to conduct their independently funded individual research projects more efficiently and/or more effectively. Cores generally fall into one of four categories: (1) provision of a technology that lends itself to automation or preparation in large batches (e.g., histology and tissue culture); (2) complex instrumentation (e.g., electron microscopy); (3) animal preparation and care; and (4) service and training (e.g., molecular biology, biostatistics). A pilot and feasibility study program provides modest research support for a limited time (three years or less) to enable eligible investigators to explore the feasibility of a skin diseases-related concept and amass sufficient data to pursue it through other funding mechanisms. Eligible investigators include: 1. an established investigator in skin diseases or related areas with a proposal for testing the feasibility of a new or innovative idea that is skin diseases-related but represents a clear and distinct departure from the investigator's ongoing research interest; 2. an established, supported investigator with no previous work in skin diseases or related areas who is willing to test the applicability of his/her expertise on a skin diseases-related problem; and 3. a new investigator who has not been a principal investigator in a past or current NIH research project grant (R01, R29, P01). New investigators should be clearly independent and have a faculty appointment higher than that of postdoctoral fellow or research associate. SPECIAL REQUIREMENTS Specific guidelines have been developed for the SDRC application and program. These guidelines may be obtained from the contact person listed under INQUIRIES. Applicants from institutions that 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. Details of the interactions of the SDRC staff with the GCRC staff and research personnel may be provided in a statement describing the collaborative linkages being developed. A letter of agreement from the GCRC Program Director must be included with the application. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements are required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis must be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale must be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues must be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information must be included in the form PHS 398 (rev. 9/91) in Sections 1-4 of the Research Plan AND summarized in Section 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., Native Americans [including American Indians or Alaskan Natives], Asian/Pacific Islanders, Blacks, Hispanics). The rationale for studies on single minority population groups should be provided. For the purpose of this policy, clinical research is defined as human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including, but not limited to, clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded. However, every effort should be made to include human tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. For foreign awards, the policy on inclusion of women applies fully; since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. If the required information is not contained within the application, the application will be returned. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. LETTER OF INTENT Prospective applicants are asked to submit, by May 10, 1993, a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, the identities of other key personnel and participating institutions, and the number and title of 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, the information that it contains allows NIAMS 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. Julia B. Freeman Centers Program, EP National Institute of Arthritis and Musculoskeletal and Skin Diseases Westwood Building, Room 403 Bethesda, MD 20892 Telephone: (301) 402-3348 FAX: (301) 480-7881 APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 9/91) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research and from the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone 301/496-7441. Special guidelines have been developed for the SDRC program in the NIAMS. These guidelines must be used in assembling the application. The guidelines may be obtained by contacting the Centers Program Director listed under INQUIRIES. The RFA label available in the application form 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 and number must be typed on line 2a of the face page of the application form and the YES box must be marked. Submit a signed, typewritten original of the application, including the Checklist, and three signed, photocopies, in one package to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** At the time of submission, two additional copies of the application must also be sent to: Dr. Tommy L. Broadwater Chief, Review Branch National Institute of Arthritis and Musculoskeletal and Skin Diseases Westwood Building, Room 405 Bethesda, MD 20892 Applications must be received by June 18, 1993. If an application is received after that date, it will be returned to the applicant without review. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by the Division of Research Grants (DRG) and responsiveness by the NIAMS. Incomplete applications will be returned to the applicant without further consideration. Applications that are received after the June 18, 1993, receipt date, that exceed the budget limit of $400,000 in direct costs, or that are otherwise unresponsive to the major criteria of the RFA will be returned to the applicant. Applications may be triaged by an NIAMS peer review group on the basis of relative competitiveness. The NIH will withdraw from further competition those applications judged to be non-competitive for award and notify the applicant Principal Investigator and institutional official. Those applications judged to be competitive will undergo further scientific merit review. It is unlikely that a site visit will be conducted. Each proposal should therefore be complete in itself and be prepared as if no site visit is expected. Those applications that are complete and responsive will be evaluated in accordance with the criteria stated below for scientific/technical merit by an appropriate peer review group convened by the NIAMS. The second level of review will be provided by the National Arthritis and Musculoskeletal and Skin Diseases Advisory Council. Review criteria for RFAs are generally the same as those for unsolicited research grant applications. o scientific, technical, or medical significance and originality of proposed research; o appropriateness and adequacy of the experimental approach and methodology proposed to carry out the research; o qualifications and research experience of the Principal Investigator and staff, particularly, but not exclusively, in the area of the proposed research; o availability of the resources necessary to perform the research; o appropriateness of the proposed budget and duration in relation to the proposed research. Factors to be considered in evaluation of the scientific merit of each application will include an evaluation of the independently funded biomedical research base, the appropriateness of the proposed cores, the quality of the proposed pilot and feasibility studies, and their proposed management. The evaluation of the biomedical research base will encompass the record of research training and the institution's commitment to the Center program. AWARD CRITERIA The anticipated date of award is March 1, 1994. The primary factors determining the award will be the priority score and the availability of funds. Since the NIAMS is interested in funding only the best research, individual research projects of lesser quality may not be funded, even if approved, under the "umbrella" of the SDRC mechanism. INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Dr. Julia B. Freeman Centers Program, EP National Institute of Arthritis and Musculoskeletal and Skin Diseases Westwood Building, Room 403 Bethesda, MD 20892 Telephone: (301) 402-3348 FAX: (301) 480-7881 Direct inquiries regarding fiscal matters to: Mary L. Graham Grants Management Officer National Institute of Arthritis and Musculoskeletal and Skin Diseases Westwood Building, Room 722A Bethesda, MD 20892 Telephone: (301) 402-3361 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.846, Arthritis, Musculoskeletal and Skin Diseases Research. Awards will be made under the authority of the Public Health Service Act, Title III, Section 301 (Public Law 410, 78th Congress, as amended, 42 USC 241) and administered under PHS grants policies and Federal regulations 42 CFR Part 52 and 45 CFR Part 74. This program is not subject to intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$XID RFA AI9306 AI-93-06 P1O1 ***************************************** RESEARCH LEADING TO IMPROVED MEASLES VACCINES NIH GUIDE, Volume 21, Number 44, December 11, 1992 RFA: AI-93-06 P.T. 34; K.W. 0715125, 0740075 National Institute of Allergy and Infectious Diseases Letter of Intent Receipt Date: January 11, 1993 Application Receipt Date: March 11, 1993 PURPOSE Measles recently reemerged as a public health problem in the U.S. and measles continues to be a deadly disease in the developing world. The purpose of this Request for Application (RFA) is to acquire the information needed for the development of safe new measles vaccines that are highly efficacious when administered in early infancy and that will aid in the control and eventual eradication of measles. An expanded research effort is needed for the rational development and evaluation of new vaccines and immunization strategies. The National Institute of Allergy and Infectious Diseases (NIAID) requests investigator-initiated research grant applications focused on the study of measles virus and the host's response to infection as it relates to the safe induction of long-lasting protective immunity in individuals, and the reduction of measles disease and infant deaths in populations. 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 RFA, Research Leading to Improved Measles Vaccine, is related to the priority area of immunization and infectious diseases. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Research grant applications may be submitted by domestic and foreign, for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal Government. Foreign institutions are not eligible for the First Independent Research Support and Transition (FIRST) (R29) award. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT This RFA will use the National Institutes of Health (NIH) individual research grant (R01) and the FIRST award (R29) programs (if interinstitutional collaborations are anticipated, please contact Dr. James M. Meegan at the address listed under INQUIRIES). The total project period for applications submitted in response to the present RFA may not exceed five years. Because the nature and scope of the research proposed in response to this RFA may vary, it is anticipated that the size of the award will vary also. This RFA is a one-time solicitation. Future unsolicited competing continuation applications will compete with all unsolicited investigator-initiated applications and be reviewed according to the customary peer-review procedures. FUNDS AVAILABLE There are $1.5 million available in total support (direct plus indirect costs) for this RFA for the first year. It is anticipated that six to eight new awards will be made, none to exceed $200,000 in total annual direct costs. If the proposed budget exceeds $200,000, the Principal Investigator must obtain a written waiver from Dr. James Meegan to submit with the grant application. RESEARCH OBJECTIVES Background In the U.S. from 1981 to 1988, approximately 3,000 cases of measles occurred each year. This represents a reduction of more than 99 percent from the annual number of cases reported before the introduction of measles vaccine in 1963. However, a major epidemic of measles occurred in 1989-90, and measles reemerged as a significant health problem in the U.S. In 1990, there were 27,672 cases, which represented the largest number of cases since 1977, and included the largest number of deaths (89) since 1971. Fifty-five percent of the deaths occurred in children less than five years old. Of the reported cases, 22.7 percent experienced complications and 21.1 percent required hospitalization. The major cause of the reemergence of measles in the U.S. was the failure to vaccinate children at the appropriate age, rather than failure of vaccine efficacy. However, currently licensed vaccines do have some deficiencies as public health tools, particularly in regard to efficacy in very young infants. The U.S. program in response to the reemergence of measles includes increasing vaccine coverage rates by recommending immunization against measles using the measles, mumps and rubella vaccine (MMR) at 15 months of age, followed by a booster MMR immunization as the child enters school. The vaccine used in the U.S. has a primary failure rate of about five percent, but this rate is higher if the vaccine is given to children less than 15 months of age because residual, maternally-derived measles antibody interferes with infant immunization rates. In developing countries, measles continues to be a deadly disease, causing over one and a half million deaths each year. In those areas, infants also are at greatest risk during the interval between loss of maternal antibody and receipt of vaccine. Thus, both internationally and domestically, there is an urgent need for an efficacious vaccine that can be safely administered at six-nine months of age or earlier in infancy. This need was underscored in the 1990 U.S. epidemic in which 17 percent of cases and 16.9 percent of deaths occurred in infants under one year of age. Furthermore, future programs aimed at increasing immunization coverage will emphasize administration at earlier ages in infancy of current, as well as new, combinations of vaccines. With regard to safety, it is important to note that the use of inactivated measles vaccine in the 1960s was followed by atypical measles in some individuals naturally exposed to measles in later life. Moreover, recent studies of some candidate live virus vaccines raise concerns about possible immunosuppression-associated adverse consequences. The goal is to avoid similar problems with future vaccines, through research to understand the biological factors that underlie these observations. Scope of Research This announcement is intended to stimulate innovative research on measles across several research disciplines, with a strong emphasis on studies to develop improved vaccines that can safely overcome the maternal antibody barrier and induce long-lasting protective immunity. Research projects are sought that investigate topics including, but not limited to, those listed below. o Determination of which measles antigens are required to safely elicit long-lasting, protective humoral and cellular immunity in the developing immune system of the young infant. o Characterization of the quantitative and qualitative differences between vaccine-induced and naturally-induced protective immunity. o Elucidation of the impact of maternal antibody on infant immune response, and development of strategies to overcome maternal antibody as a block to effective immunization in very young infants. o Development of an animal model of measles virus infection and disease that parallels human disease and that could be used to study the many host and viral factors influencing establishment of protective immunity in the young infant. o Establishment of the viral correlates of virulence and attenuation. o Investigation of measles virus pathogenesis, including virus-induced immune suppression. o Elucidation of viral and host factors contributing to immunization-induced adverse events. o Pre-clinical research leading to development of highly efficient methods for the safe delivery of measles antigens required for the establishment of protective immunity. o Application of research on closely related viral systems, such as distemper, to address specific problems related to immunization of young infants. SPECIAL REQUIREMENTS Principal Investigators should budget for an annual one-day progress review meeting at the NIH. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements are required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis must be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale must be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues must be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information must be included in the form PHS 398 (rev. 9/91) in Sections 1-4 of the Research Plan AND summarized in Section 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., Native Americans [including American Indians or Alaskan Natives], Asian/Pacific Islanders, Blacks, Hispanics). The rationale for studies on single minority population groups should be provided. For the purpose of this policy, clinical research is defined as human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including but not limited to clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are exempt. However, every effort should be made to include human tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. For foreign awards, the policy on inclusion of women applies fully; since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. If the required information is not contained within the application, the application will be returned. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and reflected in the priority score. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. LETTER OF INTENT Prospective applicants are asked to submit, by January 11, 1993, a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, the identities of other key personnel and participating institutions, and the number and title of 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, the information that it contains allows NIAID 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. James Meegan at the address listed under INQUIRIES. APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 9/91) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research and from the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone 301/496-7441. The RFA label available in the application form 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 and number must be typed on line 2a of the face page of the application form and the "YES" box must be marked. Submit a signed, typewritten original of the application, including the Checklist, and five signed, photocopies, in one package to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** FIRST (R29) award applications must include at least three sealed letters of reference attached to the face page of the original application. FIRST award applications submitted without the required number of reference letters will be considered incomplete and will be returned without review. Applications must be received by the receipt date of this RFA. Applications not received by the receipt date will be considered non-responsive and the applicant will be contacted to determine whether the application will be returned to the applicant or be processed as an unsolicited application for the next Division of Research Grant (DRG) review cycle. The DRG will not accept any application in response to this announcement that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. The DRG 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 the DRG and responsiveness by the NIAID. Incomplete applications will be returned to the applicant without further consideration. If the application is complete but not responsive to the RFA, it will undergo the same process as for late applications above. Complete and responsive applications will be evaluated in accordance with the criteria stated below for scientific/technical merit by an appropriate scientific review group. The second level of review will be provided by the NIAID Council. Review criteria for applications responsive to this RFA are generally the same as those for unsolicited research grant applications: o scientific, technical, or medical significance and originality of proposed research; o potential contribution to the development of new measles vaccines; o appropriateness and adequacy of the experimental approach and methodology proposed to carry out the research; o qualifications and research experience of the Principal Investigator and staff, particularly but not exclusively in the area of the proposed research; o availability of resources necessary to perform the research; o appropriateness of the proposed budget and duration in relation to the proposed research; Applicants from institutions that 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. If so, a letter of agreement from either the GCRC program director or Principal Investigator could be included with the application. AWARD CRITERIA The anticipated date of award is September 1993. Awards will be made on the basis of priority score, programmatic balance, and available funds. INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Send letters of intent and direct inquiries regarding programmatic issues to: Dr. James M. Meegan Virology Branch, Division of Microbiology and Infectious Diseases National Institute of Allergy and Infectious Diseases Solar Building, Room 3A15 Bethesda, MD 20892 Telephone: (301) 496-7453 FAX: (301) 496-8030 If express mail or courier service is to be used, use the following address for the Solar Building: 6003 Executive Blvd, Rockville, MD 20852. Direct inquiries regarding fiscal matters to: Mr. Todd C. Ball Grants Management Branch, Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4B35 Bethesda, MD 20892 Telephone: (301) 496-7075 Schedule Letter of Intent Receipt Date: January 11, 1993 Application Receipt Date: March 11, 1993 Scientific Review Date: July 1993 Council Meeting Date: September 1993 Earliest Award Date: September 1993 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.856, Microbiology and Infectious Diseases Research. Awards are made under 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 requirements of Executive Order 12372 or Health Systems Agency review. $$XID RFA HL9307 HL-93-07 P1O1 ***************************************** MONOENERGETIC X-RAY SYSTEMS FOR CARDIOVASCULAR IMAGING NIH GUIDE, Volume 21, Number 44, December 11, 1992 RFA: HL-93-07-H P.T. 34; K.W. 0706030, 0705015 National Heart, Lung, and Blood Institute Letter of Intent Receipt Date: July 5, 1993 Application Receipt Date: October 13, 1993 PURPOSE This solicitation will support grants for research and development of monoenergetic and/or nearly monoenergetic x-ray sources that can be hospital based and clinically applicable for imaging cardiovascular structures. It is desirable that the proposed imaging system be tuneable so as to achieve spectral concentration in a single line or very narrow band to deliver energy in a band and at an intensity appropriate for specific cardiovascular imaging applications. 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 Request for Applications (RFA), Monoenergetic X-ray Systems for Cardiovascular Imaging, is related to the priority area of cardiovascular imaging. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-002-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Federal agencies must also ensure that their own authorizing legislation will allow them to respond to this solicitation and to receive a PHS grant. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT This RFA will use the National Institutes of Health (NIH) individual research grant (R01). Responsibility for the planning, direction, and execution of 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. This RFA is a one-time solicitation. Future unsolicited competing continuation applications will compete with all investigator-initiated applications and be reviewed according to the customary peer review procedures. The anticipated award date is April 1, 1994. Because the nature and scope of the research proposed in response to this RFA may vary, it is anticipated that the size of an award will vary also. FUNDS AVAILABLE Approximately $1.5 million in total costs will be provided for the first year of support for the entire program. It is anticipated that three to four new grants will be awarded under this program. This level of support is dependent on the receipt of a sufficient number of applications of high scientific merit. Although this program is provided for in the financial plan of the National Heart, Lung, and Blood Institute (NHLBI), awards pursuant to this RFA are contigent upon the availability of funds for this purpose. Administrative adjustments in project period and/or amount of support may be required at the time of the award. RESEARCH OBJECTIVES Background Biomedical imaging with x-ray systems continues to be widely used. Despite exposing subjects to undesirable ionizing radiation, the resolution and image quality obtained with x-ray systems surpasses other imaging modalities for many applications. In a number of instances, however, the benefits of repeated x-ray procedures are offset by the risks of exposure. Examples are angiography, mammography, and fluoroscopy during ablation of cardiac conduction tissue, especially for children. A new type of x-ray source with characteristics that reduce exposure but maintain or improve image quality would provide broad biomedical benefits. A monoenergetic or nearly monoenergetic x-ray source with certain special characteristics is desirable, e.g., spectral concentration, high brightness, tunable, and highly directional and polarized. An x-ray source with a narrow frequency range, ideally at a single frequency, would be advantageous because it would allow x-rays only at the desired frequency to be produced, eliminating radiation outside of the spectrum necessary for imaging. In angiography, for example, an iodinated agent is injected into the arterial system to provide contrast. The attenuation of x-rays by iodine changes by orders of magnitude for x-rays just below approximately 33.2 kiloelectron volts (keV) as compared with x-rays just above 33.2 keV. By eliminating x-ray frequencies outside of the range required for a specific application, the dose may be significantly reduced. It has been estimated that mammographic examinations performed with near monoenergetic x-rays will deliver a dose to the patient that will be from one-tenth to one-fiftieth as much as the dose delivered with a conventional x-ray system. This estimate is similarly applicable to angiography studies. Over the past nine years, the NHLBI has been supporting research in energy subtraction imaging with monoenergetic radiation generated from the synchrotron source at Stanford University. In the original design, two images bracketing 33.2 keV were required to be obtained sequentially before subtracting them, which is the way this is accomplished with conventional x-ray sources. An innovation developed at Stanford is the use of two detectors, allowing simultaneous image acquisition before subtraction, thus effectively eliminating effects of patient motion, an important concept for coronary artery visualization. Using the synchrotron facility at Brookhaven National Laboratory, images of coronary arteries have now been obtained, but only at an experimental level. The crystal monochromatization required for detection entails a significant diminution in beam intensity. Further, a synchrotron is very costly and limits the accessibility of the system. Other issues Several processes for producing monoenergetic x-rays without the need for a large, expensive linear accelerator such as a synchrotron have been reported, all of which require that relativistic electrons be produced, i.e., electrons traveling at nearly the speed of light. Most of these processes have been theoretically described and some have been demonstrated experimentally. Channeling radiation, transition radiation, parametric conversion, and free electron laser production are examples of such processes. Although each of these processes requires that electrons be accelerated to near the speed of light, a synchrotron or similar very large and expensive linear accelerator may not be needed. A major goal of this solicitation is to demonstrate whether or not monoenergetic x-rays can be produced with a clinically applicable, hospital based system. This RFA seeks to support grant applications to study, develop and evaluate minimally invasive x-ray systems using monoenergetic radiation to achieve improved resolution and image quality. Complete systems would need to be described, including both source and detector. Grant applications should propose a specific application, such as coronary artery imaging without intraarterial injection of contrast material, and include quantitative objectives for resolution, patient dose, and image quality. Grant applications should also emphasize close collaboration among physicists, biophysicists, radiologists, cardiologists, and engineers with both a theoretical basis and an experimental plan for the proposed system. Proposed Research Grant applications may propose research in imaging systems for cardiovascular application utilizing tuneable monoenergetic x-ray sources and detector systems to deliver energy at appropriate intensities, including, but not limited to, the following technologies: o Transition x-ray sources o Channeling radiation sources o Cerenkov radiation sources o Smith-Purcell radiation sources o Parametric conversion systems o Coherent superlattice radiation systems It is desirable that each application provide evidence that the proposed system is feasible as a hospital based facility, with size and cost estimates based upon calculations and experimental data. SPECIAL REQUIREMENTS Awardees will be requested to meet twice annually to exchange information and to report on progress, including coordination of activities in appropriate areas. Applicants are advised to include such plans in their budget requests, including their willingness to participate in such activities. SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements are required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis must be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale must be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues must be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information must be included in the form PHS 398 (rev. 9/91) in Sections 1-4 of the Research Plan AND summarized in Section 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including adequate numbers of women. For the purpose of this policy, clinical research is defined as human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies, diagnosis, or treatment of diseases, disorders or conditions, including, but not limited to, clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded. However, every effort should be made to include human tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. For foreign awards, the policy on inclusion of women applies fully; since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States populations, including minorities. If the required information is not contained within the application, the application will not be accepted for review. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. LETTER OF INTENT Prospective applicants are asked to submit, by July 5, 1993, a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, the identities of other key personnel and participating institutions, and the number and title of 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, the information that it contains allows 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: Chief, Centers and Special Projects Section Review Branch, Division of Extramural Affairs National Heart, Lung and Blood Institute Westwood Building, Room 553A Bethesda, MD 20892 Telephone: (301) 496-7351 FAX: (301) 402-1660 APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 9/91) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research and from the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone (301) 496 7441. The RFA label available in the application form 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, to identify the application as a response to this RFA, check "YES", enter the title Monoenergetic X-Ray Systems for Cardiovascular Imaging, and the RFA number HL-93-07-H on line 2a of the face page of the application. Send or deliver a signed, typewritten original of the application, including the Checklist, and three signed photocopies to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** Send two additional copies of the application to the Chief, Centers and Special Projects Section, 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 Division of Research Grants (DRG), otherwise the NHLBI cannot guarantee the the application will be reviewed in competition for this RFA. Applications must be received by October 13, 1993. If an application is received after that date, it will be returned to the applicant without review. The DRG will not accept any application in response to this announcement that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. The DRG 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 by the DRG staff for completeness and by the NHLBI for responsiveness. Incomplete applications will be returned to the applicant without further consideration. If the application is not responsive to the RFA, NHLBI staff will contact the applicant to determine whether to return the application to the applicant or submit it for review in competition with unsolicited applications at the next review cycle. Applications may be triaged by an NHLBI peer review group on the basis of relative competitiveness. The NIH will withdraw from further competition those applications judged to be non-competitive for award and notify the applicant Principal Investigator and institutional official. Those applications judged to be competitive will undergo further scientific merit review. Those applications that are complete and responsive will be evaluated in accordance with the criteria stated below for scientific/technical merit by an appropriate peer review group convened by the NHLBI. The second level of review will be provided by the National Heart, Lung and Blood Advisory Council. Review criteria for RFAs are generally the same as those for unsolicited research grant applications. o the novelty, originality and feasibility of the approach and the adequacy of the experimental design o the competence of the principal investigator and collaborators to accomplish the proposed research, and the commitment and time they will devote to the project o the suitability of the facilities to perform the proposed research, including laboratories, instrumentation, and data management systems o the appropriateness of the requested budget and duration for the proposed research o adequate plans for interaction and communication of information and concepts among investigators involved in collaborative studies AWARD CRITERIA Although multidisciplinary approaches are encouraged, it is not the intent of this announcement to solicit applications for large studies that would encompass a variety of independent projects, i.e., program projects. This program will not support clinical trials or large epidemiological studies. In general, funds will not be provided for the purchase and installation of expensive, new equipment. Awards under this announcement to foreign institutions will be made only for research of very unusual merit, need and promise, and in accordance with PHS policy governing such awards. Upon initiation of the program, the Division of Heart and Vascular Diseases will sponsor periodic meetings to encourage exchange of information among investigators who participate in this program, and to stimulate collaboration. INQUIRIES Inquiries regarding this announcement may be directed to: Dr. Alan Berson or Dr. Rosalie Dunn Devices and Technology Branch Division of Heart and Vascular Diseases National Heart, Lung and Blood Institute Federal Building, Room 312 Bethesda, MD 20892 Telephone: (301) 496-1586 Direct inquiries regarding fiscal and administrative matters to: Mr. William Darby Grants Operations Branch Division of Extramural Affairs National Heart, Lung and Blood Institute Westwood Building, Room 4A11 Bethesda, MD 20892 Telephone: (301) 496-7536 FAX: (301) 402-1200 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.837., Heart and Vascular Diseases. Awards will be made under the authority of the Public Health Service Act, Section 301 (42 USC 241) and administered under PHS grants policies and Federal Regulations, most specifically 42 CFR Part 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency Review. From owner-sci-resources@net.bio.net Wed Dec 09 22:00:00 1992 Path: biosci!NET.BIO.NET!kristoff From: kristoff@NET.BIO.NET (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 21, no. 44, pt. 3, 11 December 1992 Message-ID: Date: 10 Dec 92 00:42:58 GMT Sender: kristoff@net.bio.net Distribution: bionet Lines: 1499 $$XID NIHGUIDE 19921211 V21N44 P3O4 ************************************ linking social incentives such as social services or job training/placement to treatment enrollment and participation. Strategies to increase compliance may include improving the staff/patients therapeutic relationship, assessing and meeting patient needs (e.g., medical/dental care, child care), improving the effectiveness of drug abuse counselors in meeting patient needs, and pharmacological and behavioral strategies alone or in combination. Investigators may wish to consider compliance strategies in patient subgroups based on diagnostic criteria and stages of recovery. Research that examines fundamental questions of program philosophy and patient-treatment interactions (including matching) are encouraged. Specific Areas of Interest Research priorities include the need to characterize better the individuals who stay in or leave treatment, to examine the decision process leading to remaining in treatment, and to assess program factors that may inhibit or facilitate treatment compliance. Also relevant are the potential influences of concurrent psychiatric and other medical disorders (e.g., AIDS) on treatment retention and compliance. Research is needed on how patient personality, perceptions, expectations, and beliefs affect treatment retention and the effect of program organization, leadership, and context on the retention process. The role social networks play in the decision to remain in treatment and in compliance with treatment also should be explored. Since drug dependence is a chronic relapsing disorder, more needs to be learned about persistent drug-induced neuropsychological changes that may be involved in leaving treatment or failures to comply with treatment. Also, there should be study of the effects of drug availability and other environmental factors on retention. To clarify intrapersonal and environmental factors associated with treatment retention and compliance, studies of untreated drug dependent persons, as well as those in treatment, are strongly encouraged. Thus, epidemiological and ethnographic studies are needed to complement what can be learned through studies of interventions. Research on the natural history of drug disorders should be particularly helpful in clarifying the role of a variety of treatments in retention as well as factors associated with compliance. To facilitate this research, methodological approaches for assessing the long-term course of drug disorders need to be refined. Archival and secondary analyses are encouraged to exploit the potential of existing data sets. Development of compatible data bases across programs are encouraged to facilitate replication across settings, with different populations, and over time. Examples of research areas identified above include the following: o Factors associated with treatment retention and compliance (e.g., patient personality, perceptions, expectations, and beliefs) should be explored explicitly in treatment research studies. Comorbidity studies could be informative. o The role of social networks in affecting treatment retention and compliance should be studied. Examination of gender, ethnic, and educational differences and examination of differences in social competence are particularly important. o The characteristics of individuals who stay in or leave treatment should be studied to determine how they differ and possible ways in which those who leave treatment can be induced to remain in treatment. The decision-making process leading to decision to leave treatment--including the roles of factors such as drug- related neuropsychological deficits, family members, and coercion in deciding to seek treatment--should be studied. o Treatment retention failures should be studied to determine why treatment retention does not occur. This should include why persons fail to invest in treatment. o The effect of program organization, leadership, and context on treatment retention should be studied. Research should include studying the impact of program type (e.g., directive-nondirective, medical-nonmedical orientation, residential-nonresidential), perceived staff caring (the so-called "smile factor"), and cultural aspects of the program (race, ethnicity, language) on retention. o Better methods to assess and evaluate the probability of leaving treatment are needed (e.g., employing measures of drug craving, drug availability, stage(s) in drug abuse history, cognitive deficits, availability of support systems). o Neuropsychological factors, including those that are drug induced, may increase the likelihood in some persons to leave treatment and these factors should be studied. Cognitive deficits of drug abusers in treatment may preclude treatment compliance and their role in the treatment retention process needs to be assessed. Cross-Institute/Intra-Institute Areas of Interest Projects may be submitted under this announcement that address issues in common with, for example, the National Institute on Alcohol Abuse and Alcoholism (NIAAA), the National Institute of Mental Health (NIMH), and various programs within NIDA. Also, applicants may wish to collaborate with the Center for Substance Abuse Treatment (CSAT) or the Center for Substance Abuse Prevention (CSAP) grantees who deal with the types of environmental and social factors addressed by this announcement. It is conceivable that an applicant could carry out the research in the context of a CSAP Community Partnership grant, a CSAT Target Cities grant, a CSAP High Risk Youth grant or other initiative. This would have the benefit of providing a potential applicant with a pool of patients and a primed community. Preapplication consultation with the individual listed below is strongly encouraged. Applications are considered for acceptance and assigned according to standard NIH/PHS referral guidelines. International Comparative Studies It is recognized that some treatment research issues related to such areas as retention in treatment, program completion, and compliance with treatment expectations lend themselves to comparative multi-site study, especially where environmental differences and available treatment options are concerned. Well-designed comparative multi-site studies may include program sites in foreign countries, provided that the foreign program site is justified in terms of the research objectives. Such studies may include a collaborating scientist or clinical researcher affiliated with the foreign program sites. However, foreign institutions are not eligible for FIRST awards (R29s). STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements will be required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis should be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale should be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues should be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information should be included in the form PHS 398 in Sections 1-4 of the Research Plan AND summarized in Section 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., Native Americans (including American Indians or Alaskan Natives), Asian/Pacific Islanders, Blacks, Hispanics). The rationale for studies on single minority population groups should be provided. For the purpose of this policy, clinical research includes human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including but not limited to clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded. However, every effort should be made to include human tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. For foreign awards, the policy on inclusion of women applies fully; since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. If the required information is not contained within the application, the application will be returned. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and will be reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. APPLICATION PROCEDURES Applications are to be submitted on the grant application form PHS 398 (rev. 9/91) and will be accepted at the standard application deadlines as indicated in the application kit. The receipt dates for applications for AIDS-related research are found in the PHS 398 instructions. Application kits are available at most institutional offices of sponsored research and from the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone 301/496-7441. The title and number of the announcement must be typed in Item 2a of face page of the application. FIRST award applications must include at least three sealed letters of reference attached to the face page of the original application. FIRST award applications submitted without the required number of reference letters will be considered incomplete and will be returned without review. The completed original and five permanent, legible copies of the PHS 398 form must be sent or delivered to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** REVIEW PROCEDURES The Division of Research Grants (DRG), NIH, serves as a central point for receipt of applications for most discretionary HHS grant programs. Applications received under this announcement will be assigned to an initial review group (IRG) in accordance with established PHS referral guidelines. The IRGs, consisting primarily of non-Federal scientific and technical experts, will review the applications for scientific and technical merit in accordance with the standard NIH peer review procedures. Notification of the review recommendations will be sent to the applicant after the initial review. Applications will receive a second-level review by an appropriate national advisory council, whose review may be based on policy considerations as well as scientific merit. Only applications recommended for further consideration by the council may be considered for funding. Small grants (R03s) do not receive a second level review. AWARD CRITERIA Applications will compete for available funds with all other approved applications assigned to the Institute/Center/Division. The following will be considered when making funding decisions: o Quality of the proposed project as determined by peer review o Availability of funds o Program balance among research areas of the announcement INQUIRIES Written and telephone inquiries are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Frank M. Tims, Ph.D. Treatment Research Branch Division of Clinical Research National Institute on Drug Abuse 5600 Fishers Lane, Room 10A-30 Rockville, MD 20857 Telephone: (301) 443-4060 Direct inquires regarding fiscal issues to: Mrs. Shirley A. Denney Chief, Grants Management Branch National Institute on Drug Abuse 5600 Fishers Lane, Room 8A-54 Rockville, MD 20857 Telephone: (301) 443-6710 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.279. Awards are made under authorization of the Public Health Service, Sections 301 and 405, and administered under PHS policies and Federal Regulations at Title 42 CFR 52, Grants for Research Projects, Title 45 CFR Part 74 & 92, Administration of Grants, and 45 CFR Part 46, Protection of Human Subjects. Title 42 CFR Part 2, Confidentiality of Alcohol and Drug Abuse Patient Records may also be applicable to these awards. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. Sections of the Code of Federal Regulations are available in booklet form from the U.S. Government Printing Office. Grants must be administered in accordance with the PHS Grants Policy Statement, (rev. 10/90), which is available from institutional offices of sponsored research. $$P2 END ************************************************************ $$P3 BEGIN PA-93-29 ************************************************* KIDNEY DISEASE OF DIABETES MELLITUS: PATHOGENETIC MECHANISMS NIH GUIDE, Volume 21, Number 44, December 11, 1992 PA: PA-93-29 P.T. 34; K.W. 0715075, 0785095, 0765033, 0411005, 0755030 National Institute of Diabetes and Digestive and Kidney Diseases PURPOSE The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) invites research applications for studies related to Kidney Disease of Diabetes Mellitus (KDDM). This Program Announcement (PA) invites submission of individual research grant applications focusing primarily on basic research into the pathogenetic mechanisms of KDDM. 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 PA, Kidney Disease of Diabetes Mellitus: Pathogenic Mechanisms, is related to the priority area of diabetes and chronic disabling diseases. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone (202) 783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign for-profit or non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Minority individuals and women are encouraged to apply. Foreign institutions are not eligible for the First Independent Research Support and Transition (FIRST) (R29) awards. MECHANISM OF SUPPORT Support of this program will be through the traditional NIH grant-in-aid research project grant (R01) and First Independent Research Support and Transition (FIRST) award (R29). Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. Except as otherwise stated in this announcement, awards will be administered under PHS grants policy as stated in the PHS Grants Policy Statement. It should be noted that FIRST (R29) awards are restricted to domestic institutions only. A maximum of three years may be requested for foreign awards. FIRST award applications should request five years. Annual awards will be made, subject to continued availability of funds and progress achieved. Although this program is provided for in the financial plans of the NIDDK, the award of grants pursuant to this PA is contingent upon the availability of funds for this purpose. It is anticipated that the average size of an award made in response to this PA will be about $180,000 per year including both direct and indirect costs; however, considerable variability around this average is expected. RESEARCH OBJECTIVES This PA is intended to encourage new fundamental studies of KDDM. The aim is to stimulate investigator-initiated research protocols designed to further the understanding of the pathogenetic mechanisms and genetic determinants of KDDM, as well as to address issues concerning risk factors, co-morbidity, and causes of excess incidence of diabetic end-stage renal disease (ESRD) in certain minority populations. Kidney disease of diabetes mellitus (KDDM) continues to be the most frequent cause of ESRD in the USA and the largest single cause of renal disease. This is true for Caucasians, African Americans, Hispanics, and Native Americans. Even though progress has been made in understanding some of the mechanisms leading to the development of KDDM and its progression to ESRD, the pathogenesis of KDDM still remains largely undefined. Examples of representative research topics that would be considered responsive to this solicitation include the following: o Characterization of the pathogenetic mechanisms and the genes associated with KDDM, including the role of the genes in the immune response in insulin-dependent diabetes mellitus (IDDM), and genetic and environmental determinants in non-insulin dependent diabetes mellitus (NIDDM). o Identification of the role, pathways, and interaction of biochemical and metabolic factors in KDDM. o Comparison of KDDM in IDDM vs NIDDM. o Biochemical characterization of the changes observed in glomerular basement membrane. o Morphologic and morphometric studies of, e.g., the glomeruli, including basement membrane thickening, extent of mesangial expansion, and quantitation of capillary surface area with disease progression. o Studies addressing risk factors and co-morbidity in KDDM. o Studies of the pathophysiology of hyperfiltration and its linkage to subsequent morphologic injury. o Investigation of the possible causes of the excess incidence of KDDM in Blacks, Hispanics, and Native Americans, including genetic and environmental factors. o Studies examining the etiology of KDDM including non-enzymatic glycation, aldose reductase activity, hyperinsulinemia, and hyperglycemia, that may serve as a model for understanding KDDM and other complications of diabetes. SPECIAL REQUIREMENTS Interdisciplinary approaches may be needed and are encouraged for these studies. For example, collaborations among the following disciplines may be productive: molecular and cell biology, genetics, immunology, pathology, biochemistry/metabolism, nephrology, endocrinology, physiology, and pharmacology. SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements are required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis must be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which disproportionally affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale must be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues must be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information must be included in the form PHS 398 (rev. 9/91) in Item 4 (Research Design and Methods) of the Research Plan and summarized in Item 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations i.e., Native Americans [including American Indians or Alaskan Natives], Asian/Pacific Islanders, Blacks, Hispanics. The rationale for studies on single minority population groups should be provided. For the purpose of this policy, clinical research is defined as human biomedical and behavioral studies of etiology, epidemiology, prevention [and preventive strategies], diagnosis, or treatment of diseases, disorders or conditions, including but not limited to clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded. However, every effort should be made to include human tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. For foreign awards, the policy on inclusion of women applies fully; since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. If the required information is not contained within the application, the application will be returned without review. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. APPLICATION PROCEDURES The research grant application form PHS 398 (rev.9/91) is to be used in applying for these grants. The form is available from most institutional offices of sponsored research and from the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone (301) 496-7441. The PA title and number must be typed on line 2a of the face page of the application form and check the YES box. Submit a signed, typewritten original of the application, including the Checklist, and five signed, exact photocopies, in one package to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** FIRST (R29) award applications must include at least three sealed letters of reference attached to the face page of the original applications. FIRST (R29) award applications submitted without the required numbered of reference letters will be considered incomplete and will be returned without review. The Division of Research Grants (DRG) will not accept any application in response to this announcement that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. However, it is allowable to submit the same project as both an R01 and as a component project of a program project. The DRG 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 previously reviewed. Such applications must not only include an introduction addressing the previous critique, but also be responsive to this PA. REVIEW CONSIDERATIONS Applications received in response to this PA will be assigned to an initial review group and to an awarding Institute/Center for possible funding on the basis of established PHS referral guidelines. A review for scientific and technical merit will be conducted by an initial review group convened by the DRG in accordance with the standard NIH peer review procedures. Following this review, the applications will be given a secondary review by the National Diabetes and Digestive and Kidney Diseases Advisory Council or the corresponding Advisory Council/Board of another funding component (unless the application is not recommended for further consideration by the initial review group). Review criteria for application submits in response to a PA are generally the same as those for unsolicited research grant applications. Review criteria include: o Scientific, technical, or medical significance and merit specific to the objectives of the PA and originality of the proposed research o Appropriateness and adequacy of the experimental approach and methodology proposed to carry out the research o Qualifications and research experience of the Principal Investigator and staff, particularly but not exclusively in the area of the proposed research o Availability of resources necessary to perform the research o Appropriateness of the proposed budget and duration in relation to the proposed research AWARD CRITERIA Applications received in response to this PA will compete for available funds with other applications recommended for funding. The following will be considered in making funding decisions: o quality of the proposed project as determined by peer review, o availability of funds, and o program balance among research areas of the announcement. INQUIRIES NIDDK staff are available for consultation concerning application development before or during the process of preparing an application. Potential applicants are advised to contact NIDDK staff as early as possible for information or assistance in initiating the application process and developing an application. Direct inquiries regarding programmatic issues to: Gladys H. Hirschman, M.D. Director, Chronic Renal Diseases Program Division of Kidney, Urologic and Hematologic Diseases National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 3A-07 Bethesda, MD 20892 Telephone: (301) 496-8218 or Charles A. Wells, Ph.D. Director, Diabetes Complications Program Division of Diabetes, Endocrinology and Metabolic Diseases National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 622 Bethesda, MD 20892 Direct inquiries regarding fiscal matters to: Aretina D. Perry Grants Management Specialist Division of Extramural Activities National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 639 Bethesda, MD 20892 Telephone: (301) 496-7467 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance Nos. 93.849 and 93.847. Awards are made under 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 requirements of Executive Order 12372 or Health Systems Agency review. $$P3 END ************************************************************ $$P4 BEGIN PA-93-30 ************************************************* RESEARCH ON RAYNAUD'S PHENOMENON AND SYSTEMIC SCLEROSIS NIH GUIDE, Volume 21, Number 44, December 11, 1992 PA NUMBER: PA-93-30 P.T. 34; K.W. 1002004, 0765033 National Institute of Arthritis and Musculoskeletal and Skin Diseases PURPOSE The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) invites research grant applications for studies of basic biological and clinical aspects of Raynaud's phenomenon, focusing particularly on microvascular control mechanisms, collagen synthesis, and other aspects of fibroblast biology, endothelial cell function, and immunological abnormalities associated with Raynaud's phenomenon. The goal of this program announcement (PA) is to promote research that contributes to the understanding the pathogenesis of Raynaud's phenomenon and its relationship to other pathogenetic mechanisms in systemic sclerosis. 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 PA, Research on Raynaud's Phenomenon and Systemic Sclerosis, is related to the priority area of chronic disabling conditions. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001- 00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by foreign and domestic, for-profit and non-profit organizations, public and private institutions, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Applications from minority individuals and women are encouraged. Foreign institutions are not eligible for First Independent Research Support and Transition (FIRST) awards (R29). MECHANISM OF SUPPORT Applications are requested under the following mechanisms: traditional research grants (R01), FIRST awards (R29). Because the nature and scope of the research proposed in response to this RFA may vary, it is anticipated that the size of an award will vary also. RESEARCH OBJECTIVES The goal of this PA is to encourage research that will elucidate the relationship between Raynaud's phenomenon and systemic rheumatic illness. Raynaud's phenomenon consists of intermittent blanching, reactive hyperemia, and cyanosis of fingers, toes, ears, and nose in response to cold, emotion, and other external events. More than 90 percent of patients with scleroderma (systemic sclerosis) and approximately 25 percent of patients with systemic lupus erythematosus develop Raynaud's phenomenon, often as the first symptom, but the relationship between this abnormality and the associated rheumatic illness remains unknown. Recent studies have suggested that the primary abnormality may reside in control mechanisms for microvascular blood flow, endothelial cell injury, or pathologic biology of endothelial cells or fibroblasts. In scleroderma, Raynaud's phenomenon is closely associated with excessive skin fibroblast synthesis of skin collagen. Several autoantibodies occur in patients with scleroderma and with systemic lupus erythematosus; whether these autoantibodies cause, follow, or are unrelated to the occurrence of Raynaud's phenomenon is unknown. Research proposed in response to this Program Announcement may be at any level of biological organization, but must in some way address the pathophysiology of Raynaud's phenomenon and/or its relationship to systemic sclerosis or other rheumatic disease. Possible topics include, but are not limited to, the following: o Up- and down-regulator mechanisms of microvascular blood flow; o Neurogenic mechanisms in microcirculatory abnormalities; o Immunologically-mediated endothelial cell injury; o Control mechanisms of fibroblast function as it relates to the occurrence of scleroderma; and o Relationship of specific autoantibodies to Raynaud's phenomenon. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements are required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis must be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale must be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues should be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information must be included in the form PHS 398 (rev. 9/91) in Sections 1-4 of the Research Plan AND summarized in Section 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., Native Americans [including American Indians or Alaskan Natives], Asian/Pacific Islanders, Blacks, Hispanics). The rationale for studies on single minority population groups must be provided. For the purpose of this policy, clinical research is defined as human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including but not limited to clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded. However, every effort should be made to include human tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. For foreign awards, the policy on inclusion of women applies fully; since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. If the required information is not contained within the application, the review will be deferred until the information is provided. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and will be reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. APPLICATION PROCEDURES Applications are to be submitted on the grant application form PHS 398 (rev. 9/91) and will be accepted at the standard application deadlines as indicated in the application kit. Application kits are available at most institutional offices of sponsored research and may be obtained from the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone 301/496-7441. The title and number of the PA must be typed in Section 2a on the face page of the application. The completed original application and five legible copies must be sent or delivered to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** REVIEW PROCEDURES Applications will be assigned on the basis of established PHS referral guidelines. Applications will be reviewed for scientific and technical merit by initial review groups (study sections) of the Division of Research Grants (DRG), NIH, in accordance with the standard NIH peer review procedures. Following scientific-technical review, the applications will receive a second-level review by the National Arthritis and Musculoskeletal and Skin Diseases Advisory Council or by other relevant advisory boards and/or councils. AWARD CRITERIA Applications will compete for available funds with all other approved applications assigned to NIAMS. The following will be considered in making funding decisions: o quality of the proposed project as determined by peer review; o availability of funds; and o program balance among research areas of the announcement. INQUIRIES Written and telephone inquiries are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Director, Arthritis Program National Institute of Arthritis and Musculoskeletal and Skin Diseases Westwood Building, Room 405 Bethesda, MD 20892 Telephone: (301) 402-3340 Direct inquiries regarding fiscal matters to: Diane M. Watson Chief, Grants Management Branch National Institute of Arthritis and Musculoskeletal and Skin Diseases Westwood Building, Room 732A Bethesda, MD 20892 Telephone: (301) 402-3352 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.846, Arthritis, Musculoskeletal and Skin Diseases Research. Awards will be made under the authority of the Public Health Service Act, Title III, Section 301 (Public Law 410, 78th Congress, as amended, 42 USC 241) 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 requirements of Executive Order 12372 or Health Systems Agency review. $$P4 END ************************************************************ $$P5 BEGIN PA-93-31 ************************************************* RESISTANCE TO ANTIVIRALS TARGETED TO HUMAN IMMUNODEFICIENCY VIRUS NIH GUIDE, Volume 21, Number 44, December 11, 1992 PA NUMBER: PA-93-31 P.T. 34; K.W. 0715008, 0740012, 0765012, 0755060 National Institute of Allergy and Infectious Diseases Application Receipt Dates: January 2, May 1, September 1, 1993 PURPOSE This Program Announcement (PA) is designed to stimulate research to: (1) elucidate mechanisms of Human Immunodeficiency Virus (HIV) drug resistance, (2) determine the effects of viral drug resistance in lentivirus pathogenesis, (3) identify improved methods to screen for drug resistant HIV and animal lentivirus variants, and (4) design and evaluate novel therapies for treating or preventing drug resistance, utilizing in vitro and animal model systems as applicable. 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 PA, Resistance to Antivirals Targeted to HIV, is related to the priority area of HIV infection. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000: (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic, foreign, for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Foreign institutions are not eligible for First Independent Research Support and Transition (FIRST) (R29) awards. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT This PA solicits R01 and R29 applications. While no funds have been set aside specifically for supporting applications submitted in response to this PA, the NIAID regards additional quality research in this area to be of high programmatic priority. The total project period for awards made in response to this PA will not exceed four years for domestic institutions and three years for foreign institutions. If an R29 application is submitted, three reference letters are required to be submitted with the application and stapled to the face page of the original application. RESEARCH OBJECTIVES Background The Developmental Therapeutics Branch (DTB), Basic Research and Development Program (BRDP), Division of AIDS (DAIDS), National Institute of Allergy and Infectious Diseases (NIAID) supports basic and applied research grants leading to the discovery of new therapies for the treatment of HIV infection and the opportunistic infections (OIs) associated with AIDS. This goal is accomplished through: (1) management of investigator-initiated research for HIV; (2) fostering of innovative, multidisciplinary efforts leading to the discovery and design of new anti-HIV and anti-OI therapies through the National Cooperative Drug Discovery Group programs for treatment of HIV infection (NCDDG-HIV) and for treatment of the OIs associated with AIDS (NCDDG-OI); and (3) preclinical drug development contract resources to confirm activity of anti-HIV and anti-OI compounds, and to evaluate combination and immune-based therapies in vitro and in animal models. The DTB released a Request for Applications (RFA) entitled "Drug Resistance and the Human Immunodeficiency Virus" in 1989. Applications funded in response to that RFA focused predominantly on methodologies for detecting HIV variants with reduced susceptibility to antivirals. During the past few years, our understanding of the emergence of drug-resistant HIV has increased dramatically. For example, diminished in vitro susceptibility of HIV clinical isolates from patients undergoing treatment with AZT for as few as six to twelve months is well documented. Associated with this phenotype of reduced susceptibility to AZT is a characteristic pattern of genetic alterations at codons 41, 67, 70, 215, and 219 of reverse transcriptase (RT) that appear to emerge in a temporal fashion conferring progressively increasing resistance. The complex interplay among these mutations as evidenced by (1) the disappearance of the codon 70 mutation in sequential clinical isolates that show increased resistance and (2) the stability of the mutation at codon 215 in isolates from patients switched to ddI therapy that have reverted to AZT susceptibility is not well understood. The precise mechanism by which these mutations confer the resistant phenotype in cell culture remains unknown. More recently, a decrease in in vitro sensitivity to ddI of HIV isolates obtained from patients who changed to ddI therapy after prolonged treatment with AZT has been reported. An initial report describing resistance to ddC in one patient has also appeared. In addition, preliminary results from clinical trials indicate that HIV drug resistance to several non-nucleoside RT (NNRT) inhibitors, as determined in vitro, develops rapidly in patients. Novel mutations in HIV RT that correlate with in vitro resistance to ddI, ddC and the NNRT inhibitors have been identified in clinical isolates. Introduction of these specific mutations into the genetic background of a replication competent, fully susceptible virus confers a resistant phenotype that mimics the susceptibility profile of the original clinical isolates. In summary, characteristic patterns of mutations in HIV-1 RT have been identified at the molecular level in resistant variants and genetic signatures appear to be distinct for each inhibitor or class of inhibitors. These observations notwithstanding, the exact mechanism(s) by which the resistant phenotype is manifested in vivo via these alterations is not known, and the clinical significance of HIV-related drug resistance remains unknown at this time. Research Scope Molecular, enzymatic and biologic effects of drug resistance: Given the precedence of resistance to several nucleoside analogs and to NNRT inhibitors in clinical isolates, it is expected that resistance to inhibitors directed against other viral targets is likely to occur. With the introduction of anti-HIV agents other than RT inhibitors into clinical trials and the preclinical development of others, studies involving therapeutic modalities directed against non-RT targets, e.g., protease, TAT, myristoylation, as well as against RT, are urgently needed. Crucial clinical studies to determine whether or not emergence of drug resistant variants is correlated with disease progression are underway. Of equal importance are studies that decipher the molecular, enzymatic and biological aspects of HIV drug resistance that can serve as the basis for developing therapeutic strategies to overcome or delay the emergence of drug resistant HIV in the clinic. While clinical relevance awaits further corroboration, research focussed on understanding the mechanisms underlying resistance and the biological properties of the resistant virus that are implicated in disease progression is encouraged. As mentioned above, in spite of the identification of characteristic genetic alterations conferring a drug resistant phenotype on HIV, the precise mechanism(s) by which these mutations mediate their enzymatic and biological impact on the resistant phenotype is unknown. The following areas of research are particularly encouraged: o Elucidation of the basis for the apparent inability of cell-free assays to distinguish RT purified from AZT-resistant vs. AZT-sensitive isolates may shed additional light on this dilemma. This is contrasted by retention of the drug resistant phenotype in RT purified from NNRT- resistant HIV. o Structure/function studies of drug resistant viral targets in the presence and absence of drug may also contribute to delineating the mechanisms by which genetic alterations result in loss of drug effect. o The biological effects the genetic alterations conferring the resistant phenotype have on the properties of the virus in terms of its pathogenicity and capacity to accelerate or attenuate disease progression are not well studied. Information is also incomplete regarding the relationship between HIV variants capable of forming syncytium upon cocultivation of infected patient peripheral blood lymphocytes with MT-2 cells, viral drug resistance and clinical progression. o The effect of drug resistance on viral transmission needs to be elucidated. If drug resistant HIV variants are transmitted, is the frequency comparable to that of their drug sensitive counterparts? Phenotypic and genotypic detection of drug resistance: Sensitive and reproducible methods for (1) detection of drug resistant HIV mutants, including primary isolates within phenotypic mixtures and (2) quantitation of levels of drug resistance and proportion of resistant HIV variants are urgently needed to delineate the mechanism(s) and impact of resistance and to predict the efficacy of new therapies. Methods for the expansion of primary HIV isolates to adequate titers with minimal selection for specific viral variant(s) are also critical. Recent evidence suggests that passage of clinical isolates in cell lines may rapidly select for specific genotypes. Specifically o Additional culture systems should be developed that closely model the in vivo situation. Currently, assays utilizing fresh peripheral blood mononuclear cells (PBMC) have received the predominant focus. However, variable infectability of donor cells may preclude the standardization of this assay system. Methods for expansion of primary HIV isolates to adequate titers with minimal selection for specific viral variant(s) are also critically needed. o Genotypic assays also suffer from certain limitations, particularly those imposed by the possibility that the genetic signature of resistance associated with a specific therapeutic may not yet be comprehensive. Technical difficulties also exist in designing polymerase chain reaction primers that can accurately, specifically, and reproducibly amplify the associated mutations. Because of these current limitations and deficiencies in evaluating HIV drug resistance, development of novel and/or validation of existing assays to measure viral susceptibility to antivirals is/are strongly encouraged. For example, innovative, highly sensitive biophysical methods recently developed may be modified and implemented to identify alterations previously undetectable at the protein level that correspond to mutations conferring the resistant phenotype. Such changes may represent markers for HIV resistance to drugs or may, themselves, be directly responsible for the drug resistant phenotype. Animal models of drug resistance: Development and implementation of relevant animal models of lentivirus infection are critically needed to address these resistance issues. Efforts to establish an animal model of viral drug resistance may include development of protocols for detection and quantitation as well as expansion of isolates, as the problems addressed above for HIV-specific susceptibility assays are likely to be similar. Animal models of lentiviral infection (e.g., SIV and FIV) of potential relevance are available. Thus, systematic evaluation of virus isolates from drug-treated animals may define an animal model that parallels documented resistance in HIV-infected patients. Once developed, such model(s) may be exploited for assessing drug therapy and drug resistance. Novel strategies for circumventing HIV drug resistance: The ultimate goal of these studies is to design novel strategies to circumvent and/or delay the development of viral drug resistance. As an example, one approach can focus on highly conserved functional domains identified in several HIV proteins (RNA-dependent and DNA-dependent activities, and RNaseH and RNaseD activities of RT; transactivation, nuclear-targeting, and RNA/protein binding activities of Tat). The observation that these domains are spared from sequence variations suggests that most mutations in these regions would be lethal to the virus and, therefore, to have no or minimal consequence on drug treatment. This and other research objectives include, but are not limited to: o Exploiting other viral targets believed to be essential for viral survival, and thus incompatible with resistance-conferring mutations o Investigating combination therapies designed to inhibit more than one distinct step in the HIV infectious cycle that may delay the development of viral drug resistance by virtue of a multipronged action o Designing studies to reduce the overall rate at which HIV mutates. While not specifically addressed in this PA, evaluation of the role of host-mediated processes in the resistant phenotype may also provide insight into developing new therapeutic approaches. The rationale for any potential approach should first be tested and analyzed in an appropriate in vitro system, if applicable. For example, a new therapeutic regimen may be evaluated for its effect on in vitro emergence of resistant HIV variants. Alternatively, a novel therapeutic strategy may be tested for its activity against established resistant mutants. Subsequent evaluation of new drug strategies in relevant animal models should yield important information on the applicability of the proposed strategies to the clinical setting. The approaches outlined above are examples of potential research directions bearing on the emergence of HIV drug resistance and are not intended to be comprehensive. STUDY POPULATIONS SPECIAL INSTRUCTIONS FOR INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDIES NIH policy is that applicants for NIH clinical research grants and cooperative agreements will be required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis should be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale should be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group, together with a rationale for its choice. In addition, gender and racial/ethnic issues should be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information should be included in the form PHS 398 in Items 1-4 of the Research Plan AND summarized in Item 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., Native Americans (including American Indians or Alaskan Natives), Asian/Pacific Islanders, Blacks, Hispanics). The rationale for studies on single minority population groups must be provided. For the purpose of this policy, clinical research is defined as human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including but not limited to clinical trials. The usual NIH policies concerning research involving human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded. However, every effort should be made to include tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. For foreign awards, the policy on inclusion of women applies fully; since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. If the required information is not contained within the application, the application will be deferred until the information is provided. Peer review will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in the study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and will be reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. APPLICATION PROCEDURES Applications are to be submitted on grant application form PHS 398 (rev. 9/91). Receipt dates are January 2, May 1, and September 1. Application kits are available at most institutional offices of sponsored research and may be obtained from the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone 301/496-7441. The title and number of the announcement must be typed in Section 2a on the face page of application and the "YES" box marked. The completed original application and five legible copies must be sent or delivered to Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** REVIEW PROCEDURES Applications in response to this announcement are expected to be assigned to the NIAID. However, whenever there is inter-institute programmatic overlap in the proposed research, the PHS Referral Guidelines will prevail in the assignment of applications to the different institutes. Applications will be reviewed for scientific and technical merit by study sections of the Division of Research Grants, NIH, in accordance with the standard NIH peer review procedures. Applications focusing on AIDS will be assigned to study sections constituted to review AIDS-related grant applications. Following scientific-technical review, the applications will receive a second-level review by an appropriate national advisory council. For AIDS-related applications, the earliest award date for successful applications will be no more than six months from the receipt date. AWARD CRITERIA Applications will compete for available funds with all other approved applications. The following criteria will be considered in making funding decisions: o Quality of the proposed project as determined by peer review o Availability of funds o Program balance among research areas of the announcement. Applications from institutions that have a General Clinical Research Center (GCRC) funded by the NIH National Center for Research Resources may identify the GCRC as a resource for conducting the proposed research by including a letter of agreement from either the GCRC program director or the principal investigator. INQUIRIES Written and telephone inquiries are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries of a scientific nature to: Roberta Black, Ph.D. Basic Research and Development Program, Division of AIDS National Institute of Allergy and Infectious Diseases Solar Building, Room 2C12 Bethesda, MD 20892 Telephone: (301) 496-8197 FAX: (301) 480-5703/402-3211 Direct inquiries regarding fiscal matters to: Ms. Jane Unsworth Chief, AIDS Grants Management Section National Institute of Allergy and Infectious Diseases Solar Building, Room 4B22 Bethesda, MD 20892 Telephone: (301) 496-7075 FAX: (301) 480-3780 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance, 93.856 - Microbiology and Infectious Diseases Research and 93.855 - Immunology, Allergy and Transplantation Research. Awards are made under 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 Part 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$P5 END ************************************************************ $$P6 BEGIN PA-93-32 ************************************************* INSTITUTIONAL RESEARCH TRAINING IN ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES NIH GUIDE, Volume 21, Number 44, December 11, 1992 PA NUMBER: PA-93-32 P.T. 44; K.W. 0715020, 0705050, 0715140, 0715010, 0715170, 0715185, 0720005 1002004, 0790000, 0710070 National Institute of Arthritis and Musculoskeletal and Skin Diseases PURPOSE The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) invites applications to develop or enhance research training for individuals who conduct basic and clinical research on the tissues and diseases within its mandate. The proposed training plan may include short-term training for health professionals as well as full time predoctoral and post-doctoral positions. The purpose of this announcement is to ensure a cadre of well trained scientists interested in pursuing research careers in areas relevant to the mission of the NIAMS. 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 program announcement, Institutional Research Training Awards in Arthritis and Musculoskeletal and Skin Diseases, is related to the priority areas of chronic disabling conditions and physical activity and fitness. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325, (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic, non-profit, private and public institutions to support research training programs. The applicant institution must have, or be able to develop, the staff and facilities required for the proposed program. The training program director at the institution will be responsible for the selection and appointment of trainees to receive support and for the overall direction of the program. The individuals to be trained on a National Research Service Award (NRSA) training grant must be citizens or non-citizen nationals of the United States or have been lawfully admitted for permanent residence (i.e., in possession of the Alien Registration Receipt Card I-551 or I-151) at the time of appointment. Individuals on temporary or student visas are not eligible. NRSA research training grants may not be used to support studies leading to the M.D., D.O., D.D.S., D.V.M., or other similar health-professional degree. Individuals holding an M.S., a Ph.D, or M.D./Ph.D. or an equivalent graduate level research degree, are not eligible for short term training positions. Programs able to provide postdoctoral training to both M.D.s and Ph.D.s are encouraged. Institutions are encouraged to develop multi-year plans that provide strong research training for health professionals, while cognizant of requirements for board certification. MECHANISM OF SUPPORT The mechanism of support for this program announcement will be the NRSA institutional training grant (T32). Institutions may request support for predoctoral students, postdoctoral trainees, and short- term research training. Stipends will be awarded at levels commensurate with NIH policy at the time of award and may be supplemented from non-Federal sources. Training related expenses, tuition and fees, and travel expenses may also be requested for trainees, although the levels vary depending on the type of training to be supported. Postdoctoral trainees should be appointed for at least two years. RESEARCH OBJECTIVES The NIAMS is committed to increasing the number of well-trained health professionals and basic scientists interested in conducting high quality research in areas of its mission and able to both compete successfully for NIH grant support and provide leadership in the areas of clinical research. The research program of training grant applications should be related to the mission of the NIAMS. Major areas of interest to the NIAMS, with respect to institutional awards, include: o Arthritis and Other Rheumatic Diseases o Muscle Biology and Muscle Diseases o Musculoskeletal Diseases and Disorders, including Orthopaedic Research o Skin Biology and Skin Diseases o Bone Biology and Bone Diseases o Rheumatic Diseases in Children o Epidemiology of Arthritis, Bone, Muscle, and Skin Diseases o Multidisciplinary Approaches Due to the complexity of the tissues and diseases, it is becoming increasingly clear that research excellence in arthritis, muscle biology, musculoskeletal disorders, bone and skin diseases requires interdisciplinary approaches. Thus, the NIAMS encourages institutions to develop training programs that support individuals in acquiring expertise in several disciplines such as molecular biology, cell biology, structural biology, biophysics, immunology, developmental biology, genetics, and epidemiology. Additionally, research training programs may be strengthened by combining or crossing traditional departmental or specialty divisions. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements are required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis must be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale must be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues should be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information must be included in the form PHS 398 (rev. 9/91) in Sections 1-4 of the Research Plan AND summarized in Section 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., Native Americans (including American Indians or Alaskan Natives), Asian/Pacific Islanders, Blacks, Hispanics). The rationale for studies on single minority population groups must be provided. For the purpose of this policy, clinical research is defined as human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including but not limited to clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded. However, every effort should be made to include human tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. If the required information is not contained within the application, the review will be deferred until the information is provided. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and will be reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. APPLICATION PROCEDURES Applications are to be submitted on the grant application form PHS 398 (rev. 9/91). Application kits are available from most institutional offices of sponsored research and may be obtained from the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone (301) 496-7441. Prior to preparing an application, prospective applicants should consult the "National Research Service Award Guidelines for Individual Awards - Institutional Awards," available from most grantee offices of sponsored research and from the Office of Grants Inquiries at the address listed above. Applicants should note the "Modification of Existing Review Criteria for NRSA Institutional Research Training Grants" issued in the NIH Guide for Grants and Contracts, Vol. 21, No. 11, March 20, 1992. Institutional Research Training Grant Applications may be submitted on January 10, May 10, and September 10 of each year. Applications submitted in response to this announcement must be identified by typing PA-INSTITUTIONAL RESEARCH TRAINING IN NIAMS and PA-93-32 on line 2a of the face page, below the title of the project. The typed original application and five signed exact single-sided photocopies must be submitted or delivered to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** Applicants from institutions that have a General Clinical Research Center (GCRC) funded by the NIH National Center for Research Resources may identify the GCRC as a resource for conducting the proposed activity. In such a case, a letter of agreement from either the GCRC program director or Principal Investigator should be included with the application. REVIEW PROCEDURES Upon receipt, applications will be reviewed initially by the Division of Research Grants (DRG) for completeness. Incomplete applications will be returned to the applicant without further consideration. All applications responding to this announcement that are assigned to the NIAMS will be reviewed for scientific and technical merit by the AMS initial review group (IRG), followed by a second level review by the National Arthritis and Musculoskeletal and Skin Diseases Advisory Council. Applications not recommended for further consideration by the IRG will not undergo secondary review. Applications assigned to Institutes/Centers other than the NIAMS will undergo a similar two-level review process within the designated Institute/Center. Review criteria used by initial review groups in reviewing NRSA Institutional Training applications are given in the booklet "National Research Service Award Guidelines for Individual Awards - Institutional Awards," dated March 20, 1992, available from the Office of Grants Inquiries at the address listed under APPLICATION PROCEDURES. AWARD CRITERIA Applications will compete for available funds with other approved applications. The following will be considered in making funding decisions: From owner-sci-resources@net.bio.net Wed Dec 09 22:00:00 1992 Path: biosci!NET.BIO.NET!kristoff From: kristoff@NET.BIO.NET (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 21, no. 44, pt. 6, 11 December 1992 Message-ID: Date: 10 Dec 92 00:49:55 GMT Sender: kristoff@net.bio.net Distribution: bionet Lines: 1412 $$XID RFA OD9301 OD-93-01 P1O1 ***************************************** EXTRAMURAL RESEARCH FACILITIES CONSTRUCTION PROJECTS NIH GUIDE, Volume 21, Number 44, December 11, 1992 RFA: OD-93-01 P.T. 02; K.W. 0715035, 0715040, 0715032, 0715165, 0404009, 1002046 National Institutes of Health Letter of Intent Receipt Date: February 17, 1993 Application Receipt Date: March 30, 1993 PURPOSE Public Law Number 102-394, the Appropriations Act for the Department of Health and Human Services for Fiscal Year 1993, provides $4,960,000 in the budget of the Office of the Director, National Institutes of Health (NIH), for extramural facilities construction grants, to be awarded competitively. In response, the NIH is issuing a Request for Applications (RFA) OD-93-01 for the construction of facilities of urgent national importance for biomedical/behavioral research and/or services to support such research. Applications for construction grants that were submitted previously to the NIH may be resubmitted if the applicant wishes to recompete under this RFA. The main objective of this construction program is to facilitate the conduct of biomedical/behavioral research by providing funds for construction of new facilities and for the purchase of fixed research equipment essential for the operation of these facilities. Support may be requested for the construction of new facilities and additions or renovations to existing facilities to meet the biomedical/behavioral research and/or research support needs of an institution, or of a research group at that institution or elsewhere that utilizes the resources of that institution. The purpose of the proposed facility must be within the scope of one of the statutes authorizing the awards. Those statutes authorize construction grants for the National Cancer Program [Title IV, Section 413(b)(6)(B), PHS Act], construction grants for the National Heart, Blood Vessel, Lung and Blood Diseases and Blood Resources Program [Title IV, Section 421(b)(2)(B), PHS Act], construction grants for the vision research program of the National Eye Institute [Title IV, Section 455, PHS Act] construction grants for the NIH AIDS research programs [Title XXIII, Section 2351(a)(7)(B), PHS Act], and construction grants for the drug abuse, pharmacotherapeutic research program of the National Institute on Drug Abuse [Title IV, Section 464P(b)(3), PHS Act]. ELIGIBILITY REQUIREMENTS Domestic, non-Federal, public and private non-profit institutions, organizations, and associations that conduct or support biomedical/behavioral research are eligible to apply. An institution may submit only one application in response to this announcement. For example, a medical school and a dental school of the same institution, even if separated geographically, may not submit separate applications. MECHANISM OF SUPPORT The award mechanism will be the construction grant award (C06). Awards will be administered under Federal Regulation 45 CFR Part 74 - Administration of Grants, and for cancer construction projects, 42 CFR Part 52b will also apply. Up to 50 percent of the allowable costs of a project may be awarded, not to exceed $2,000,000 per award. Prior to grant award, the applicant must provide an assurance of required matching funds and that additional funds will be secured to meet any projected costs in excess of the award amount. Requests of less than $500,000 will not be accepted. FUNDS AVAILABLE This one-time solicitation based on the Fiscal Year 1993 appropriation provides $4,960,000 for this initiative. It is anticipated that three to four awards will be made. No indirect costs or continuation costs will be awarded. OBJECTIVES AND SCOPE Support may be requested for the costs of constructing non-Federal facilities to meet the biomedical/behavioral research, and/or services to support such research, needs of an institution or of a research group at that institution or elsewhere that utilizes the resources of that institution. The purpose of the proposed facility must be within the scope of one of the statutes authorizing the awards. Those statutes authorize construction grants that would benefit the fields of cancer, vision, heart, lung, and blood, AIDS research, and drug abuse, pharmacotherapeutic research. Associated fixed research equipment necessary for operation of these facilities may also be requested as part of the application. Instrumentation that usually would be requested as part of a research project will not be provided as part of this construction award. Facility construction that may be supported under this program includes: o Construction of new facilities o Additions to existing buildings o Completion of uninhabitable "shell" space in new or existing buildings o Major alterations and renovations LETTER OF INTENT Prospective applicants are asked to submit, by February 17, 1993, a letter of intent. The letter, requested for planning purposes only, should identify the RFA number noted above, the Principal Investigator, and include a brief title of the type(s) of research/research support to be conducted in the new facility. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information that it contains allows NIH staff to estimate the potential workload and to avoid conflict of interest in the review. The letter of intent is to be addressed to: Mr. Kenneth Brow Chief, Research Facilities Branch Division of Cancer Biology, Diagnosis, and Centers National Cancer Institute Executive Plaza North, Room 300 Bethesda, MD 20892 Telephone: (30l) 496-8534 APPLICATION PROCEDURES o Intergovernmental-Review -- Executive Order 12372 Applicants are required to comply with Executive Order 12372 as supplemented by DHHS 45 CFR Part l00, Intergovernmental Review of Department of Health and Human Services Programs and Activities. Standard Form 424 meets the reporting requirements of Executive Order 12372. The purposes of this review are to: 1. Identify the relationship of any proposed project to State or area-wide comprehensive plans and evaluate the significance of these projects for the plans or programs of particular State agencies or local governments; and 2. Ensure that public agencies responsible for environmental standards and civil rights have an opportunity to review and comment upon proposed projects. Each applicant is encouraged to discuss projects with the Single Point of Contact (SPOC) at the earliest time possible and to provide the SPOC with required information in a timely manner. (The State Single Point of Contact List is included as an attachment in the special instructions accompanying the application Standard Form 424 package.) The SPOC must be given 60 days to review a construction grant application. Applications submitted to NIH in response to this solicitation must contain either SPOC comments or documentation indicating the date on which the application was submitted to the SPOC for review. The SPOC comment period ends 60 days after the application receipt date. Applicants are to provide the SPOC with a copy of the application NOT LATER THAN the time the application is submitted to the Division of Research Grants, NIH. Applicants required to submit applications for review to a Health Systems Agency (HSA), or Statewide Health Planning and Development Agency (SHPDA), must contact the SPOC/HSA/SHPDA to determine what coordination has been agreed to by those agencies. The NIH is required to notify the SPOC whenever an application is received without an indication that the application has been provided to the SPOC for review. All SPOC comments must be forwarded to both the applicant and to the NIH Institute to which the application is assigned. If comments are provided by the SPOC, the applicant may wish to submit to the NIH a statement of its reaction to the comments and any appropriate changes to its application. If no response is received from the SPOC by the end of the 60 days allotted for review of the application, the applicant must notify the NIH that no response was received. o Public Disclosure Applicants must also make a public disclosure of the project by publication and describe its environmental impact at the time the SPOC is notified. It is suggested that the notice be published in a large-circulation newspaper in the area. This public disclosure is required by Section 102 of the National Environmental Policy Act (NEPA) of l969 and by Federal Executive Order 11514. One example of a suitable disclosure statement follows: "PUBLIC NOTICE "Notice is hereby given that the Uptown Medical School proposes to construct additional space, partially utilizing Federal funds. The proposed construction project is the addition of 2,700 square feet connected to the existing Allen Building, which is located at 5333 Main Street, Downtown, Ohio." "The Medical School has evaluated the environmental and community impact of the proposed construction. There will be construction noise and increased construction traffic during the construction period, 1993-1994. No significant permanent environmental impacts are foreseen. All building permits and zoning approvals have been obtained." "In accordance with Federal Executive Order 11514, which implements the NEPA of 1969, any individual or group may comment on, or request information concerning, the environmental implications of the proposed project. Communications should be addressed to the Office of Planning, Uptown Medical School, and be received by (date). The Federal grant application may be reviewed at the Office of the Dean, School of Medicine, 5333 Main Street, during working hours." o Design Standards Design requirements are imposed to protect the health and safety of persons using the proposed facility, control the project's impact on the natural environment, conserve energy resources, achieve economy in construction costs, and protect against natural disasters such as earthquake and flood. Therefore, the documents listed under REFERENCES at the end of the RFA must be consulted, and the design requirements incorporated in the development, review, and evaluation of all drawings and specifications. Application Applicants must use Standard Form 424, Application for Federal Assistance. Application forms and special instructions for completing the forms relevant to this RFA must be requested from the staff contact official noted below. Those responsible for preparing the application are advised to consult with appropriate institutional officials before completing the application forms. An institution may submit only one application in response to this specific announcement. An original and two copies of the application including appendices must be submitted to: Application Receipt Office Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** Applications must be received at NIH by March 30, 1993. To insure against carrier delays, retain a legible proof-of-mailing receipt from the carrier, dated no later than one week prior to the receipt date. Applications received after the receipt date will not be accepted for review in this competition and will be returned to the applicant. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed by NIH staff for completeness and responsiveness and to verify application and award eligibility. Those applications judged to be unresponsive, incomplete, or ineligible will be returned to the applicant. Applications that are complete and responsive will be reviewed for scientific and technical merit by appropriate special peer review group(s) that will be convened by the Division of Research Grants (DRG), NIH. The second level of peer review will be conducted by the National Advisory Board or National Advisory Council appropriate for the statutory authority that is applicable to the application, (i.e., the National Cancer Advisory Board, the National Heart, Lung, and Blood Advisory Council, the National Advisory Eye Council, the National Advisory Research Resources Council, or the National Advisory Council on Drug Abuse) in September 1993 to assess the relevance of all applications to the objectives described above. In addition, each application that receives a priority score will be reviewed by NIH staff and consultants for adherence to Government regulations and sound engineering practice. Final award decisions will be made by the Director, NIH. Awards will be made on or before September 30, 1993. Applications will be evaluated on the basis of criteria intended to assess the following overall questions: (1) How will the proposed change in the research environment facilitate the applicant's ability to conduct or support biomedical/behavioral research? (2) How will the proposed project meet national needs for biomedical/behavioral research and/or research support facilities? Thus, the reviewers will consider the following factors: o Appropriateness and suitability of the proposed facilities for the research to be conducted and/or research support to be provided. o The overall scope and quality of the ongoing biomedical/behavioral research or research support programs of the applicant institution, as well as the expanded or proposed future biomedical/behavioral research and/or research support activities. o The applicant's consideration of safety and biohazard issues in planning the construction and administering the facilities. o Specific deficiencies in the existing research facilities that would be remedied. o The proposed physical location and layout of the new facility. o Reasonableness of the proposed time-course and sequence for the construction. o Adequacy of the proposed administrative arrangements with respect to: --Institutional commitment to use the space for biomedical/behavioral research and/or research support. --Safety and biohazard issues. --Capabilities of the Principal Investigator and staff for scientific and fiscal administration of the facility. AWARD CRITERIA Conditions Advertisement for construction bids and construction can be initiated only after receipt of the construction grant award and subsequent approval of the working drawings and specifications by NIH staff. Therefore, consistent with Public Health Service policy, no requests to initiate construction will be entertained prior to receipt of a construction grant award from the NIH and subsequent approval of working drawings and specifications by NIH staff. The Principal Investigator should be a highly placed institutional official, at the level of Dean or equivalent, who has the responsibility for allocation of space for the program(s) of biomedical/behavioral research, and/or research support addressed in the submitted application. The facility must be utilized for the specific biomedical/behavioral research and/or research support purposes for which it was constructed for at least 20 years beginning 90 days following completion of the construction project. The NIH staff will evaluate use of the facility periodically to assure its continued use for the approved purposes. INQUIRIES For additional application information and application Standard Form 424 materials, contact: Mr. Kenneth Brow Chief, Research Facilities Branch Division of Cancer Biology, Diagnosis, and Centers National Cancer Institute Executive Plaza North, Room 300 Bethesda, MD 20892 Telephone: (301) 496-8534 For information concerning programmatic issues related to the construction program of the National Cancer Institute (NCI) contact Mr. Kenneth Brow at the address above. For information concerning fiscal matters related to NCI construction programs contact: Mrs. Kathy Hancock Grants Administration Branch Office of Administrative Management National Cancer Institute Executive Plaza South, Room 242 Bethesda, MD 20892 Telephone: (30l) 496-7800, Ext. 23 For information concerning programmatic issues related to the construction program of the National Heart, Lung and Blood Institute (NHLBI) contact: Dr. Ronald G. Geller Director, Division of Extramural Affairs National Heart, Lung and Blood Institute Westwood Building, Room 7A17 Bethesda, MD 20892 Telephone: (301) 496-7416 For information concerning fiscal matters related to the NHLBI construction program contact: Ms. Marie Willett Deputy Chief, Grants Operations Branch National Heart, Lung and Blood Institute Westwood Building, Room 4A12B Bethesda, MD 20892 Telephone: (301) 496-7255 For information concerning programmatic issues related to the construction program of the National Eye Institute (NEI) contact: Dr. Jack A. McLaughlin Associate Director, Extramural and Collaborative Program National Eye Institute Building 31, Room 6A04 Bethesda, MD 20892 Telephone: (301) 496-9110 For information concerning fiscal matters related to the NEI construction program contact: Ms. Gaye Lynch Chief, Grants Management Section Extramural Services Branch National Eye Institute Building 31, Room 6A52 Bethesda, MD 20892 Telephone: (301) 496-5884 For information concerning programmatic issues related to the AIDS Infrastructure Construction Program that will be administered by the National Center for Research Resources (NCRR) contact: Dr. Charles L. Coulter Director, Research Facilities Improvement Program National Center for Research Resources Westwood Building, Room 8A15 Bethesda, MD 20892 Telephone: (301) 496-8482 For information concerning fiscal matters related to the AIDS Infrastructure Construction Program contact: Ms. Katherine A. Springman Office of Grants and Contracts Management National Center for Research Resources Westwood Building, Room 849 Bethesda, MD 20892 Telephone: (301) 496-9840 For information concerning programmatic issues related to the drug abuse, pharmacotherapeutics research program of the National Institute on Drug Abuse contact: Ms. Eleanor Friedenberg Director, Office of Extramural Program Review National Institute on Drug Abuse 5600 Fishers Lane, Room 10-42 Rockville, MD 20857 Telephone: (301) 443-2755 For information concerning fiscal matters related to the NIDA construction program contact: Ms. Shirley A. Denney Chief, Grants Management Branch National Institute on Drug Abuse 5600 Fishers Lane, Room 8A-54 Rockville, MD 20857 Telephone: (301) 443-6710 AUTHORITY AND REGULATIONS All awards will be made under the authority of the Public Health Service Act, Title IV, Sections 413(b)(6)(B), 421(b)(2)(B), 455, 464P(b) (3) and Title XXIII, Section 2351(a)(7)(B) administered under PHS grants policies and Federal Regulations 45 CFR Part 74 and for cancer construction only, 42 CFR Part 52b. This program is described in the Catalog of Federal Domestic Assistance, Number 93.392, Cancer-Construction. REFERENCES A. PHS Policy. The project shall meet the PHS policies as described in the "Public Health Service Grants Policy Statement," current edition. B. The design of facilities to be constructed or altered with PHS grant funds will be evaluated for compliance with design requirements contained in the most recent edition of Technical andbook 2.1, "Information for Project applicants and State Agencies on Design and Construction Related Activities." The and book is part of the Department's Facilities Engineering and Construction Manual and is available from the Office of Engineering Services. Applicants from Regions I, II, III, and V should write to: Director of the Regional Office of Engineering Services Office of the Regional Health Administration, PHS Jacob K. Javits Federal Building 26 Federal Plaza New York, NY 10278 Applicants from Regions IV, VI, and IX should write to: Director of the Regional Office of Engineering Services Office of the Regional Health Administration, PHS 1200 Main Tower Dallas, TX 75202 Applicants from Regions VII, VIII, and X should write to: Director of the Regional Office of Engineering Services Office of the Regional Health Administration, PHS Blanchard Plaza Building 2201 6th Avenue Seattle, WA 98121 Where State and local codes or requirements exceed the design requirements set forth in Technical Handbook 2.1 or standards incorporated in it, the more stringent requirement will be applied. State or local codes may be used as a basis for facility design in lieu of the design requirements in Technical Handbook 2.1 but a prior determination must be made by HHS that the specific State or local code is equivalent to, or exceeds, HHS requirements. $$XID RFA CA9301 CA-93-01 P1O1 ***************************************** RADIOLOGIC DIAGNOSTIC ONCOLOGY GROUP V: STEREOTACTIC BIOPSY FOR NON-PALPABLE BREAST LESION CHARACTERIZATION NIH GUIDE, Volume 21, Number 44, December 11, 1992 RFA: CA-93-01 P.T. 34; K.W. 0715035, 0706030, 0745020 National Cancer Institute Letter of Intent Receipt Date: January 12, 1993 Application Receipt Date: March 12, 1993 PURPOSE The Radiation Research Program (RRP), Division of Cancer Treatment (DCT) of the National Cancer Institute (NCI), invites applications for cooperative agreements to establish a multi-institutional scientific group to optimize a clinical algorithm for subclinical, non-palpable breast lesion characterization. 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 Request for Application (RFA), Radiologic Diagnostic Oncology Group V: Stereotactic Breast Biopsy for Non-Palpable Lesion Characterization, is related to the priority area of cancer. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Non-profit and for-profit organizations and institutions, governments and their agencies, and foreign and domestic institutions are eligible to apply. Applications from minority individuals and women are encouraged. Applications may be submitted from institutions that desire to be a participating Clinical Institution in a consortium and/or as a headquarters institution. The same institution may serve in both capacities within this cooperative agreement. MECHANISM OF SUPPORT Support of this program will be through the cooperative agreement (U01), an assistance mechanism in which substantial NCI programmatic involvement with the recipient during performance of the planned activity is anticipated. The nature of NCI staff involvement is described in the Terms of Cooperation section. Applicants will be responsible for the planning, direction, and execution of the proposed project. Except as otherwise stated in this RFA, awards will be administered under PHS grants policy as stated in the PHS Grants Policy Statement, DHHS Publication No. (OASH) 90-50,000, revised October 1, 1990. This RFA is a one-time solicitation. Future unsolicited competitive continuation applications will compete as research project applications with all other investigator-initiated applications and be reviewed by the Division of Research Grants (DRG). If the NCI determine that there is a sufficient continuing program need, the NCI will invite recipients of awards under this RFA to submit competitive continuation cooperative agreement applications for review according to the procedures described in REVIEW CONSIDERATIONS below. FUNDS AVAILABLE Approximately $1,500,000 in total costs per year for four years will be committed to fund applications that are submitted in response to this RFA. It is anticipated that a consortium of about ten clinical institutions and the headquarters component will be funded to establish the RDOG V. It is anticipated that approximately one-fourth of the total funds expended each year will be devoted to the headquarters function, and approximately three-quarters will be awarded to the participating Clinical Institutions. This funding level is dependent on the receipt of a sufficient number of applications of high scientific merit. The total project period for applications submitted in response to the present RFA may not exceed four years. RESEARCH OBJECTIVES Background The Radiologic Diagnostic Oncology Group (RDOG) was formed in September 1987, in response to an RFA. The RDOG objective is timely evaluation of current and emerging imaging modalities in the management of patients with cancer. The development of multi-institutional clinical trial groups allows for rapid patient accrual within a short period of time. This in turn assures rapid evaluation and optimization of imaging techniques for diagnosis, staging and serial monitoring of cancer, with early dissemination to the public of proven new methods. Since the time of its establishment, RDOG clinical research has been important for the development of optimal imaging algorithms for prostate and lung cancer (RDOG I), pancreatic and colon cancer (RDOG II), and musculoskeletal and head and neck cancer (RDOG III). Five protocols are currently underway in fourteen academic centers in this country. Recently, a new RFA (RDOG IV) has been issued to study ovarian and pediatric solid tumor imaging, and six to eight new institutions are expected to be funded. RDOG has had significant impact on clinical research in radiology. This is the first time that multi-institutional clinical trials in diagnostic imaging have been conducted in a centrally coordinated fashion with strict quality control and analysis of cost-effectiveness. Ultimately, RDOG study findings would be useful for design of therapeutic protocols, in formulating clinical and reimbursement policy. The specific focus of this RFA is to expand RDOG in order to study imaging-guided stereotactic breast lesion biopsy as a minimally invasive alternative to an open surgical biopsy. This RFA is based on the recommendations of the NCI workshop organized by the Diagnostic Imaging Research Branch of the Division of Cancer Treatment in collaboration with the Early Detection Branch of the Division of Cancer Prevention and Control. The majority of patients (about 80 percent) undergoing open surgical biopsy of the breast lesions do not have cancer. Recently, imaging-guided stereotactic breast biopsy has emerged as a minimally invasive novel tool with the potential to replace open surgical biopsy in a significant fraction of patients. There are two potential advantages of stereotactic breast biopsies compared to surgery: (1) minimization of tissue damage (and thus improvement in cosmetic results) and (2) cost effectiveness. In addition, recent reports indicate that stereotactic technique, which allows for precise, quantitative, pinpoint localization of breast lesions, improves diagnostic yield of conventional free-handed approaches to imaging-guided biopsy of breast lesions; indeed, stereotactic methodology may decrease the insufficient sample rate when fine needle biopsy is performed (Schmidt R., University of Chicago, Presented at the NCI Workshop, September 5, 1991). Two approaches to imaging-guided stereotactic breast tissue diagnosis are employed: (1) Stereotactic Fine Needle Aspiration (SFNA) and (2) Stereotactic Core Needle Biopsy (SCNB). SFNA produces aspiration cytology, and SCNB produces tissue samples comparable to open surgery. The sensitivity of SFNA compared to open surgery ranges from 79 to 100 percent (depending on the clinical center), while the insufficient sample rate ranges from zero to 25 percent (Schmidt R., University of Chicago, Presented at the NCI Workshop, September 5, 1991). The sensitivity for SCNB, on the other hand, was reported at 95 percent of the sensitivity of open surgical biopsy---with no insufficient samples (Parker et al. Radiology 1991; 180:403-407; Parker et al. Radiology 1990; 176:741-747). SCNB and in particular SFNA are less traumatic than open surgery, and the cost of stereotactic tissue diagnosis is about 28 percent of that for surgical procedures. In summary, these preliminary clinical data indicate patient benefit and cost-effectiveness of imaging-guided stereotactic breast biopsy compared to open surgical biopsy. However, indications for stereotactic (SFNA or SCNB) compared to open surgical biopsy have not been defined, and a number of questions remain to be addressed (e.g., false negative rate--missed lesions, the quality of samples). Research Goals The goal of this RFA is to stimulate multi-center evaluation of imaging- guided stereotactic breast lesion biopsy and its impact on patient management and cost-effectiveness compared to open surgical biopsy. Major clinical questions can be answered by such a study: o what specific stereotactic technique is most appropriate? o can stereotactic breast biopsy replace open surgery? o in what specific clinical situations? o in what percentage of patients? o what gain in patient management and health care cost management can be achieved? In order to address these questions, a centrally-coordinated, cooperative, multi-institutional study, with consensus-based experimental design development and data analysis should be performed. SPECIAL REQUIREMENTS Terms of Cooperation A. Nature of Participation by NCI Staff All RRP staff assistance, advice, and support, as described throughout these Terms of Cooperation, will be communicated to awardees by the Associate Director, RRP (ADRRP), or the designated Program Coordinator (from RRP staff), who will act as deputy for the ADRRP in his absence or when directed. In all cases, the role of the NCI is to assist and facilitate but not to direct research activities. Thus the ADRRP and Program Coordinator, even in cases where review of protocols or other decisions are undertaken, will be serving as facilitators to aid the awardees in arriving at optimal protocols, mutually suitable methods of operation and communication, efficient use of NCI-referred assistance when needed, compliance with established NIH and/or FDA regulations, and achievement of the research goals of this cooperative agreement. If objective differences of opinion should arise, the arbitration panel described below will be available to assist in their resolution. 1. RRP as a Scientific Resource for NCI-supported Clinical Investigations The ADRRP, or designee, will serve as a resource available to awardees for specific scientific information with respect to clinical trial design. The staff will assist the RDOG V institutions as appropriate in developing information concerning the scientific basis for specific research protocols and also will be responsible for advising the group of the nature and results of relevant studies being carried out nationally or internationally. The ADRRP, or designee, will participate in planning and strategy meetings of the RDOG V institutions. At these meetings, RDOG V institutions, assisted by the ADRRP, or designee, will review relevant information and establish and prioritize the outstanding research questions. 2. RRP Assistance in Protocol Development The protocol must be a study document mutually acceptable to the RDOG V and to the ADRRP. Communication at the various stages of protocol development is encouraged. The ADRRP, or designee, will be available to assist the group in developing a mutually acceptable protocol, consistent with the research interests, abilities, and strategic plans of the group and of the NCI. The ADRRP will assist the RDOG V institutions in protocol design as may be appropriate by providing information regarding: (a) the existence and nature of concurrent clinical trials in the area of RDOG V research, pointing out possible duplication of effort, and (b) relevant data concerning imaging research. The ADRRP, or designee, will also comment on the scientific rationale and value of the proposed study, the design, the statistical requirements, and the implementation of the study, if indicated. All protocols for submission to the NCI must be preceded by a letter from the RDOG V Chairperson to the ADRRP describing the hypothesis investigated, the general design of the contemplated trial, and relevant information on accrual capabilities to document feasibility. The ADRRP will then formally review and provide a program response to these concepts, commenting on study originality and programmatic interest. This preliminary review will expedite protocol development and implementation and facilitate agreement on study priority and design. 3. RRP Review of Proposed Protocols All the RDOG V scientific protocols will be reviewed by the ADRRP. For all protocols, the ADRRP, or designee, will provide the RDOG V Chairperson with a written consensus review that describes recommended modifications and other suggestions as appropriate. The major considerations relevant to protocol review by the NCI include: (a) the strength of the scientific rationale supporting the study, (b) the medical importance of the question being posed, (c) the avoidance of undesirable duplication with other ongoing studies, (d) the appropriateness of study design, (e) a satisfactory projected accrual rate and follow-up period, (f) patient safety, (g) compliance with federal regulatory requirements, (h) adequacy of data management, and (i) appropriateness of patient selection and follow-up, evaluation, and assessment of complications/toxicity. If a proposed protocol is disapproved by the NCI, the specific reasons for lack of approval will be communicated by the ADRRP to the RDOG V Chairperson as a consensus review within 45 days of receipt of the proposed protocol. Disagreements arising pursuant to protocol disapproval may be submitted to an arbitration panel. An arbitration panel composed of one RDOG V nominee, one ADRRP nominee, and a third member with clinical trials expertise chosen by the other two will be formed to review the NCI decision and recommend an appropriate course of action to the ADRRP. These special arbitration procedures in no way affect the awardee's right to appeal an adverse determination in accordance with PHS regulations at 42 CFR Part 50, subpart D, and HHS regulations at 45 CFR Part 16. The RDOG V will not expend NCI funds to conduct any study not approved by the NCI unless the disapproval has been modified by the arbitration process outlined above. 4. RRP Study Monitoring The ADRRP, or designee, will review RDOG V mechanisms for study monitoring (see Responsibilities of Awardees, RDOG V Headquarters). 5. RRP Review of Data Management and Analysis The ADRRP, or designee, will review RDOG V mechanisms established by the RDOG V Headquarters for data management and analysis (see Responsibilities of Awardees, RDOG V Headquarters). The ADRRP, or designee will make recommendations to the RDOG V Group Chairperson for assuring that data collection and management procedures are adequate for quality control and analysis and sufficiently uniform across the RDOG V participating institutions. Any disagreements between NCI and RDOG V members relating to data management and analysis that cannot be resolved by bilateral discussions will be submitted to the same arbitration process previously outlined. 6. Access to Data The NCI will have access to all data generated under this cooperative agreement and may periodically review the data. Data must also be available for external monitoring as required by agreement between the NCI and the Food and Drug Administration (FDA) with respect to the responsibility of the NCI as a study sponsor. The awardee will retain custody and primary rights to the data consistent with current HHS, PHS, and NIH policies. 7. RRP Involvement in Protocol Closure The ADRRP, or designee, will review RDOG V mechanisms for interim monitoring of results and will monitor protocol progress. The ADRRP may request that a protocol study be closed to accrual for reasons including: (a) insufficient accrual rate; (b) achievement of the original accrual goal; (c) poor protocol performance; (d) patient safety; (e) conclusive study results; and (f) emergence of new information that diminishes the scientific importance of the study. The NCI will not permit expenditures of NCI funds for a study after requesting closure (except for patients already on-study). For any study closure, the NCI will establish an arbitration process for institutions that wish to appeal protocol closure. This process will be identical to that described above for protocol disapproval. If the RDOG V wishes to close accrual to a study prior to meeting the initially established accrual goal, the RDOG V Chairperson must submit the interim results and written justification to NCI staff for review and approval. Unresolved disagreements between NCI staff and the RDOG V institutions regarding the appropriateness of early study closure will be arbitrated by the process outlined above. 8. RRP Involvement in Investigational Device and Agent Management a. If applicable, RRP staff will advise the RDOG V institutions of specific requirements and changes in requirements concerning investigational device and/or agent management that the FDA may mandate. Investigators performing trials under RDOG V cooperative agreements will be expected, with RRP assistance, to comply with all FDA monitoring and reporting requirements for investigational devices, if applicable. b. Investigators performing NCI funded clinical trials will be advised by NCI staff of potential studies that will be relevant to new avenues of cancer diagnosis. When this involves an investigational device and/or agent, the clinical information must be acceptable to the FDA. With ADRRP assistance, the RDOG V institutions will develop protocols to obtain such information needed, if applicable, for the projects. 9. RRP Review of Procedures for Compliance with Federally Mandated Regulations RRP staff will review procedures established by the RDOG V headquarters for monitoring of compliance and assurance to meet FDA regulatory requirements for studies involving investigational devices/agents, if applicable, and Office for Protection from Research Risks (OPRR) requirements for the protection of human subjects by all RDOG V institutions (see Responsibilities of Awardees, RDOG V headquarters). 10. RRP Review of Progress Performance of each RDOG V member and affiliate will be reviewed annually by the ADRRP, or designee, on the basis of the information provided at the progress review meetings, annual and semi-annual reports. Each RDOG V institution must submit an annual progress report. Annual and semi-annual reports submitted to the NCI will contain highlights of progress made during that period and will include, at a minimum, summary data on protocol performance by each RDOG V member and affiliate and other relevant data. In addition, periodic accrual information may be requested by the NCI for all active studies whenever deemed appropriate. A system for providing such information in a timely manner must be in place. Support recommended for the remainder of the project will be contingent upon favorable review by the ADRRP, or designee, of the progress of the project and sufficient patient accrual. Insufficient patient accrual, or noncompliance with the terms of award, including these Terms of Cooperation, may result in a reduction of budget, withholding of support, or termination of the award. B. Responsibilities of Awardees It is the responsibility of the awardee to develop the details of the research design including definition of objectives and approaches, planning, implementation, analysis, and publication of results, interpretations and conclusions of studies. The awardee, with ADRRP or designee assistance, shall develop RDOG V research goals, develop protocols for clinical cancer research in accord with the awardee's research interests, abilities and goals, and submit to the NCI for review and approval prior to implementation. 1. RDOG V Headquarters The Principal Investigator of the headquarters institution will serve as the RDOG V Chairperson. The RDOG V Headquarters, under the leadership of the RDOG V Chairperson, will be responsible for the coordination of protocol development, quality control and study monitoring, data management and analysis, adherence to requirements regarding investigational device management (when applicable) and federally mandated regulations, protocol and performance reporting, and recommendations for resource adjustments. All the scientific and administrative decisions related to the RDOG V-funded activities and made by the RDOG V institutions or affiliates will be communicated to the ADRRP or designee by the RDOG V Chairperson. The RDOG V Chairperson will communicate the results of the NCI protocol reviews to the RDOG V institutions. a. Study Monitoring The RDOG V Headquarters, under the leadership of the RDOG V Chairperson, is responsible for establishing a mechanism for study monitoring to ensure accurate and timely knowledge of the progress of each study through: o tracking and reporting of patient accrual and adherence to defined accrual goals; o ongoing assessment of case eligibility and evaluability; o timely review and assessment of patient data; o if applicable, rapid reporting of procedure-related morbidity and measures to ensure communication of this information to all parties; o if applicable, interim evaluation and consideration of measures of outcome, as consistent with patient safety and good clinical trials practice; o timely communication of results of studies; and o a method of providing, upon NCI request, summary of the imaging methodology sensitivity/specificity and, when appropriate, morbidity data. b. Data Management and Analysis The RDOG V Headquarters, under the leadership of the RDOG V Chairperson, will develop procedures to ensure that data collection and management are: (a) adequate for quality control and analysis; (b) as simple as appropriate in order to encourage maximum participation of physicians entering patients and to avoid unnecessary expense; and (c) standardized among the RDOG V participating institutions. Any disagreements between RRP and RDOG V members relating to data management and analysis that cannot be resolved by bilateral discussions will be submitted to the same arbitration process previously outlined. c. RDOG V Compliance with Federally Mandated Regulations The RDOG V Headquarters, under the leadership of the RDOG V Chairperson, is responsible for establishing procedures for all RDOG V institutions to comply with DHHS and FDA regulatory requirements for studies involving investigational devices/agents, if applicable, and the OPRR requirements for the protection of human subjects. These procedures include: o methods for ensuring that each protocol is reviewed by the responsible Institutional Review Board (IRB) prior to patient entry, and that each protocol is reviewed at least annually by the IRB while the protocol is active in accordance with 45 CFR 46, Protection of Human Subjects. o a system for ensuring timely reporting of all serious and unexpected complications to the ADRRP, or designee. d. Progress Review The RDOG V Headquarters, under the leadership of the RDOG V Chairperson, will have a mechanism in place for assessing performance of its members, with particular attention to accrual of an adequate number of eligible patients onto group trials, timely submission of required data, conscientious observance of protocol requirements, authorship, and participation in group leadership. This mechanism will include a procedure for the RDOG V Chairperson to recommend to the NCI an adjustment of funds within the group as appropriate for the level of participation in group activities including, but not limited to, accrual. Financial adjustments may be made by NCI at the time a non-competing continuation [Type 5] award is negotiated. The RDOG V Chairperson, Principal Investigator from each RDOG V institution, and the ADRRP, or designee, shall meet jointly twice a year to review RDOG V progress, establish priorities, and plan future activities. The frequency of such meetings may be increased if it is deemed necessary. 2. Membership in RDOG V NCI funding is contingent upon the institution remaining a member of the RDOG V. 3. Planning Procedures It is anticipated that decisions on all RDOG V activities will be reached by consensus of the group under the leadership of the RDOG V Chairperson who will be responsible for communication with the ADRRP or designee. 4. Attendance Requirements It is required that a Principal Investigator, or designee, from all RDOG V members participate at all meetings and workshops relevant to their protocol(s). 5. Protocol Development All RDOG V institutions are expected to participate in the development of new and revised protocols under the leadership of the RDOG V Chairperson. The RDOG V Chairperson will submit such protocols in a timely fashion for review and approval by NCI. 6. Conduct of Research and Patient Accrual Awardees are expected to conduct pertinent clinical imaging studies consistent with approved applications and post-award procedures. Awardees also are expected to provide timely results from sufficient numbers of patients. All new and revised protocols must be submitted by the RDOG V investigators to the appropriate IRB within 30 days of the date of the written approval from the RDOG V Chairperson. Patients may not be entered into new or revised protocols until the protocol has been reviewed and approved by the IRB in accordance with 45 CFR 46, Protection of Human Subjects. 7. Progress Review The RDOG V Chairperson, the Principal Investigator from each RDOG V institution and the ADRRP, or designee, shall meet twice a year to review RDOG V progress, establish priorities, and plan future activities. The frequency of such meetings may be increased if it is deemed necessary. 8. Reporting Requirements Annual and semi-annual progress reports will be submitted to the NCI and will include at a minimum summary data on protocol performance by each awardee. Interim reports of each activated and ongoing study shall appear in the minutes of each RDOG V meeting and shall include specific data on patient accrual and, whenever appropriate, detailed reports of device/agent-associated morbidity. Awardees should have a system in place for providing semi-annual accrual information, if requested by the ADRRP, or designee, for all active studies. 9. Publication of Data Timely publication of major findings is encouraged. Publication and oral presentation of work done under this agreement will require appropriate acknowledgement of NCI support. The NCI will have access to all data generated under this cooperative agreement and may periodically review the data. The awardee will retain custody of and primary rights to the data consistent with current DHHS, PHS, and NIH policies. C. These Terms of Cooperation are in addition to and not in lieu of otherwise applicable OMB administrative guidelines, HHS grant administration regulations at 45 CFR Part 74, and DHHS, PHS, and NIH grants administration policies. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements will be required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis must be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale should be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group, together with a rationale for its choice. In addition, gender and racial/ethnic issues should be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information should be included in the form PHS 398 (rev. 9/91) in the Research Plan, 1-4, AND summarized in 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., Native Americans [including American Indians or Alaskan Natives], Asian/Pacific Islanders, Blacks, Hispanics). The rationale for studies on single minority population groups should be provided. For the purpose of this policy, clinical research includes human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including but not limited to clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded. However, every effort should be made to include human tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. For foreign awards, the policy on inclusion of women applies fully; since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. If the required information is not contained within the application, the application will be returned. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and will be reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. LETTER OF INTENT Prospective applicants are asked to submit, by January 12, 1993, a letter of intent that includes a descriptive title of the proposed research, the name and address of the Principal Investigator, the names of other key personnel, the 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 is requested in order to provide an indication of the number and scope of applications to be reviewed. The letter of intent is to be sent to: Dr. Faina Shtern Chief, Diagnostic Imaging Research Branch Radiation Research Program National Cancer Institute Executive Plaza North, Suite 800 Bethesda, MD 20892 Telephone: (301) 496-9531 APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 9/91) is to be used in applying for cooperative agreements. These forms are available at most institutional offices of sponsored research; from the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone (301) 496-7441; and from the NCI program director named below. The RFA label available in the application form PHS 398 must be affixed to the bottom of the face page. 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 number and title must be typed on line 2a of the face page of the application form. Submit a signed, typewritten original of the application, including the Checklist, and three signed, exact photocopies, in one package to the address below. The photocopies must be clear and single sided. Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** At the time of submission, send two additional copies of the application to: Referral Officer Division of Extramural Activities National Cancer Institute Westwood Building, Room 838 5333 Westbard Avenue Bethesda, MD 20892 Applications must be received by March 12, 1993. If an application is received after that date, it will be returned without review. If the application submitted in response to this RFA is substantially similar to a grant application already submitted to the NIH for review, but has not yet been reviewed, the applicant will be asked to withdraw either the pending application or the new one. Simultaneous submission of identical applications will not be allowed, nor will essentially identical applications be reviewed by different review committees. Therefore, an application cannot be submitted in response to this RFA that is essentially identical to one that has already been 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. Special Instructions for Preparation of Cooperative Agreement Applications General instructions for the preparation of the cooperative agreement application are contained in the grant application form PHS 398 (rev. 9/91). Because the Terms of Cooperation, discussed above, will be included in all awards issued as a result of this RFA, it is critical that each applicant include specific plans for responding to these terms. Plans must describe how the applicant will comply with the program staff involvement and how all the Responsibilities of Awardees will be fulfilled. Principal Technical Requirements for Membership: A. Requirements for a Consortium of Clinical Institutions 1. A commitment to participate in multi-institutional protocols and documentation of the facilities and professional personnel available to conduct cooperative imaging trials. This includes assignment of appropriate specialists required by each protocol including, but not limited to, radiologists, surgeons, and pathologists, in order to ensure complete patient evaluation. 2. Individual applicant institutions in a consortium must demonstrate the availability of state-of-the-art instrumentation and the capacity to perform stereotactic and surgical breast biopsy. Each member institution must have the instruments, facilities, and capabilities for the proposed experimental protocol. Applicant institutions must be able to correlate mammographic imaging-guided stereotactic and surgical biopsies as designed by the protocol. 3. The presence of expertise for review and evaluation of the quality of mammographic images, the existing procedures for quality control of imaging equipment, imaging technique, and image interpretation must be demonstrated. 4. The availability of qualified support personnel to ensure timely and accurate data retrieval and reporting is necessary. 5. The availability of sufficient expertise and the potential for adequate patient accrual (no less than 50 patients per year per individual institution) must be demonstrated by a Consortium. Applicants must show the ability to organize, conduct, and monitor clinical trials in radiology. 6. The organizational plan must be presented for personnel and facilities capable of performing and supporting the administrative functions of a cooperative group member conducting imaging trials in cancer. 7. Each proposed Consortium of Individual Clinical Institutions must describe procedures by which they would perform their functions, including protocols for accomplishing the clinical work and data accrual. The application should include a sample protocol for correlation of image-guided stereotactic and surgical biopsies of non-palpable breast lesions. B. Requirements for the Headquarters 1. Expertise in the design and coordination of multi-institutional cooperative clinical trials including interactions with participating institutions. 2. Capability to provide educational workshops and ongoing training for group participants in order to ensure the development of scientifically valid results in the most efficient manner. 3. Capacity to develop and implement an administrative and management structure for the RDOG V including criteria for membership, an Executive Committee, a Quality Assurance Committee, a Protocol and a Research Strategy Committee that will assume responsibility for randomized studies and set the priorities for protocol development. 4. Capacity for monitoring performance of studies and producing timely reports on the quality of data, including, but not limited to, image interpretation and related information, sensitivity and specificity of various stereotactic and surgical approaches to minimal breast lesions characterization. 5. Expertise in the development of experimental design for statistically valid multi-institutional imaging trials. 6. Availability of facilities and professional personnel with expertise in data management and analysis and the ability to participate in cooperative clinical trials to provide centralized statistical services. 7. Headquarters applicants must describe procedures by which they would perform their functions, including data management and analyses. REVIEW CONSIDERATIONS A. Review Procedure Upon receipt, applications will be reviewed by the DRG for completeness. Incomplete applications will be returned to the applicant without further consideration. Evaluation for responsiveness to the program requirements and criteria stated in the RFA is an NCI program staff function. Applications that are judged non-responsive will be returned by the NCI, but may be submitted as investigator-initiated research grants at the next receipt date. Questions concerning the responsiveness of proposed research to the RFA may be directed to program staff listed under INQUIRIES. If the number of applications is large compared to the number of awards to be made, the NCI may conduct a preliminary scientific peer review to eliminate those that are clearly not competitive. The NCI will remove from competition those applications judged to be noncompetitive for award and notify the applicant and institutional business official. Those applications judged to be both competitive and responsive will be further evaluated according to the review criteria stated below for scientific and technical merit by an appropriate peer review group convened by the Division of Extramural Activities, NCI. The second level of review will be by the National Cancer Advisory Board. B. Review Criteria 1. Applications for the Headquarters will be reviewed on the basis of the following criteria: a. Scientific merit and resources, appropriateness and adequacy of the proposed approach to experimental protocol development and biostatistical data processing. The proposed methodology must exhibit scientific soundness showing how the trials will be conducted to attain the objectives. b. Qualifications and research experience of the Principal Investigator and staff including, but not limited to, previous experience with administration of multi-institutional clinical trials in imaging science. These should include the experience of the proposed personnel (statisticians, programmers, and data management staff) in the design, monitoring, analysis, and reporting of cooperative multi-center clinical trials. c. Feasibility and merit of the proposed structure for RDOG V administration and data management including, but not limited to, interactions with the RDOG V participating institutions. 2. Applications for a Consortium of Clinical Institutions will be reviewed on the basis of the following criteria: a. The overall qualifications of applicant institutions in accordance with the "Principal Technical Requirements for Membership" in the collaborative group as stated above. b. Adequacy of professional and support personnel. Record or evidence of willingness to work as a team with other group members and to participate in group-generated and program-monitored protocols according to their capacity. c. Evidence of the ability to develop clinical trials in radiology. Relevance and merit of sample typical protocols submitted with the application will be considered. Such suggested protocols may be considered as logical bases for budget presentations and justifications d. Evidence of the ability of the applicant to complete imaging trials of substantial scientific merit. It is anticipated that different institutions will have varying patterns of patient referral and accession. Applicants must show that they have the potential to accomplish multi-center imaging trials of sound scientific quality in a reasonable period of time. e. Evidence of the ability to accrue an adequate number of patients. f. Availability of appropriate facilities, equipment, instrumentation, and other resources to ensure that each institution is capable of performing innovative cooperative trials in cancer diagnosis. g. Appropriateness of the proposed budget and duration in relation to the proposed research. AWARD CRITERIA The earliest feasible start date for the initial awards will be September 30, 1993. In making funding recommendations, the National Cancer Advisory Board considers the special needs of the NCI and the priorities of the National Cancer Program. Although this program is provided for in the financial plans of the NCI, the award of cooperative agreements pursuant to this RFA is also contingent upon the availability of funds for this purpose. INQUIRIES Written and telephone inquiries concerning the objectives and scope of this RFA and inquiries about whether or not specific proposed research would be responsive are encouraged and may be directed to Dr. Shtern at the address below. Dr. Shtern welcomes the opportunity to clarify any issues or questions from potential applicants. Direct inquiries regarding programmatic issues to: Dr. Faina Shtern Chief, Diagnostic Imaging Research Branch Radiation Research Program National Cancer Institute Executive Plaza North, Suite 800 Bethesda, MD 20892 Telephone: (301) 496-9531 Direct inquiries regarding fiscal matters to: Ms. Barbara Fisher Grants Administration Branch National Cancer Institute Executive Plaza South, Suite 242 Bethesda, MD 20892 Telephone: (301) 496-7800, Extension 29 FAX: (301) 496-8601 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.395, Cancer Treatment Research. Awards are 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 Part 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. From owner-sci-resources@net.bio.net Sun Dec 13 22:00:00 1992 Path: biosci!NET.BIO.NET!kristoff From: kristoff@NET.BIO.NET (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NSF - Summary of new documents on STIS - 13 Dec 1992 Message-ID: Date: 14 Dec 92 18:04:23 GMT Sender: kristoff@net.bio.net Distribution: bionet Lines: 85 ** NEW DOCUMENTS ON STIS ** Document Type: Form Title: NSF Form 1295 - Division of Undergraduate Education Project Data and Summary Form (Sample) File size (bytes): 1432 STIS Filename: fm1295 Title: NSF Form 1295 - Division of Undergraduate Education Project Data and Summary Form (Sample) File size (bytes): 1433 STIS Filename: fm1295s Document Type: Program Guideline Title: NSF 92-126 - Instrument Development For Biological Research Multi-User Biological Equipment and Instrumentation Resources File size (bytes): 22973 STIS Filename: nsf92126 Title: Undergraduate Education Program Announcement File size (bytes): 150243 STIS Filename: nsf92135 Document Type: SRS Data Brief Title: Federal R&D Obligations to Reach About $70 Billion in FY 1992 File size (bytes): 4164 STIS Filename: db92320 Title: Federal Academic R&D Support Increased by 6 Percent Between FYs 1989 and 1990 File size (bytes): 6053 STIS Filename: db92328 Title: U.S. Universities and Colleges Report a 9-Percent Net Increase in Research Space Since 1988, the Majority of It Within Doctorate- granting Institutions File size (bytes): 7505 STIS Filename: db92333 ------------------------------------------------------------------------ ** FOR YOUR REFERENCE ** ------------------------------------------------------------------------ HOW TO OBTAIN DOCUMENTS The above files can be retrieved in electronic form using the STIS system. If you don't know how to use STIS, send an E-mail message to stisinfo@nsf.gov (Internet) or stisinfo@NSF (BITNET). You will receive a copy of the STIS flyer via E-mail. If you are already using STIS, you can use the information above to retrieve these files: Documents via E-mail: Send a message to stisserv@nsf.gov (Internet) or stisserv@NSF (BITNET). Use the "STIS Filename" shown above in the "get" command. For example, to retrieve db92333, the text of your message should be as follows: get db92333 Anonymous FTP: FTP to stis.nsf.gov. Use the "STIS Filename" shown above to retrieve a file. For example, to retrieve db92333, you would enter: ftp> get db92333 WAIS or Gopher: Do a word search on the filename as shown in the summary. If you want a *printed* copy of a document: Send your name and postal mailing address, and the document title and number to "pubs@nsf.gov" (Internet) or "pubs@nsf" (BITNET). If you have problems with the above procedures: Send a message to "stis@nsf.gov" (Internet) or "stis@NSF" (BITNET). From owner-sci-resources@net.bio.net Sun Dec 13 22:00:00 1992 Path: biosci!TIGGER.STCLOUD.MSUS.EDU!q00023 From: q00023@TIGGER.STCLOUD.MSUS.EDU Newsgroups: bionet.sci-resources Subject: HOW TO START INSECT CELL CULTURE Message-ID: <00965137.0DCA20C0.7521@TIGGER.STCLOUD.MSUS.EDU> Date: 14 Dec 92 18:52:20 GMT Sender: daemon@net.bio.net Distribution: bionet Lines: 10 DEAR HELPER, I AM STUDENT IN ST.CLOUD STATE UNIVERSITY WHO IS LOOKING FOR WAYS TO START INSECT CELL CULTURE. THAT WILL BE ONE OF OUR CLASSES IF THE CELL LINE DEVELOPES WELL. I HAVE LOOKED AT A LOT OF ARTICLES AND CATALOGES, BUT I STILL HAVEN'T FOUND ANY USEFULL INFORMATION TO START. THEREFORE I HOPE SOMEBODY OUT THERE WILL HELP ME WITH THAT. THANKS IN ADVANCE. GABRIEL CHEUNG From owner-sci-resources@net.bio.net Wed Dec 16 22:00:00 1992 Path: biosci!NET.BIO.NET!kristoff From: kristoff@NET.BIO.NET (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 21, no. 45, pt. 5, 18 December 1992 Message-ID: Date: 17 Dec 92 02:47:36 GMT Sender: kristoff@net.bio.net Distribution: bionet Lines: 1383 $$XID RFA AI9302 AI-93-02 P1O1 ***************************************** TUBERCULOSIS VACCINE DEVELOPMENT NIH GUIDE, Volume 21, Number 45, December 18, 1992 RFA: AI-93-02 P.T. 34; K.W. 0745020, 0715125, 0710070, 0785035, 0710030, 0755010 National Institute of Allergy and Infectious Diseases Letter of Intent Receipt Date: January 19, 1993 Application Receipt Date: March 18, 1993 PURPOSE The Respiratory Diseases Branch of the Division of Microbiology and Infectious Diseases of the National Institute of Allergy and Infectious Diseases (NIAID) invites applications for basic research that will lead to the development of effective new vaccines for the prevention and control of tuberculosis. At present, a live attenuated strain of Mycobacterium bovis, Bacillus Calmette Guerin (BCG), is the only vaccine available for protecting humans from tuberculosis. Protection elicited by BCG in controlled clinical trials has been variable Applications that feature improvements to BCG will not be considered responsive to this Request for Applications (RFA). However, applications that use BCG components in the development of a novel vaccine(s) are encouraged. 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 RFA, Tuberculosis Vaccine Development, is related to the priority areas immunization and infectious diseases. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Domestic and foreign non-profit and for-profit organizations and institutions, governments and their agencies, are eligible to apply. Foreign institutions are not eligible for First Independent Research Support and Transition (FIRST) (R29) awards. Minorities and women are encouraged to apply. Applications from, or involving, minority institutions or women's institutions are encouraged. MECHANISM OF SUPPORT This RFA will use the National Institutes of Health (NIH) individual research project grant (R01), and the FIRST (R29) award. Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. The total project period for applications submitted in response to this RFA may not exceed five years. This RFA is a one-time solicitation. Future recompeting applications will compete with unsolicited applications and will be reviewed according to customary review procedures. FUNDS AVAILABLE The estimated total funds (direct and indirect costs) available for the first year of this program will be $1,000,000. In fiscal year 1993, the NIAID plans to fund at least four R01s and/or R29s. This level of support is dependent on the receipt of a sufficient number of applications of high scientific merit and the availability of funds. RESEARCH OBJECTIVES Background A century ago, tuberculosis (TB) was a leading cause of death in the United States. Through the efforts of researchers, physicians, and public health officials, as well as through improvements in living conditions and the introduction of effective drug therapy, the number of TB cases and deaths in the United States had declined steadily for 40 years. This trend stopped in 1985. The new cases of TB in the U.S. reported to the Centers for Disease Control were 22,517 in 1987, 23,495 in 1989 and 26,283 in 1991. This resurgence of TB is a matter of grave concern. In the United States TB is responsible for an estimated 2000 deaths annually. Approximately 10 million persons in the United States are presently infected with the TB organism and have the potential to develop clinical TB (active disease) at some time in their lives. Globally, TB is an even more serious threat. An estimated 8 million new TB cases and 2.9 million TB deaths occur each year . (Science, Vol. 21, p1055-1064, Aug. 21, 1992). The recent rise in tuberculosis cases reported in the United States and elsewhere is attributed, at least in part, to the heightened susceptibility to TB infections of HIV-positive persons. Other factors, including intravenous drug abuse, the increased influx of immigrants from less developed nations, and poor socio-economic status also contributed to this rise. The concern of health officials about the number of cases is intensified by the recent growth in the number of isolates of multi-drug-resistant M. tuberculosis (MDRTB). The background to these developments is documented in publications of the Centers for Disease Control (see, for instance, Morbidity and Mortality Weekly Reports, March 1, 1991, Vol. 40, No. 8 and June 19, 1992, Vol. 41, No. RR-11). The case fatality rate for TB resistant to two or more drugs (MRDTB) is 40 to 60 percent, and the overall costs for treatment of these cases is five times higher than for drug-susceptible TB patients. While treatment of drug-responsive tuberculosis infections is generally effective, the treatment regimen is lengthy, and many patients do not complete therapy. This interruption in treatment not only increases the likelihood of relapse but also is believed to promote the emergence of drug-resistant Mycobacterium tuberculosis strains. These problems continue, mainly because of the lack of a safe and efficacious vaccine to control tuberculosis. An effective vaccine will likely induce responses in the host similar to those induced by natural infection. Ordinarily, persons are infected after exposure to an infected patient. Tuberculosis is transmitted through airborne droplets containing the bacillus. The transmission is difficult to control through behavior modification for the principal risk factor is breathing. Inhaled bacilli are typically ingested by phagocytes in the lung where they may either be killed or grow to a limited extent. Usually, cell-mediated immunity develops with a few weeks and the infection is controlled. A clear understanding of this immunity and of other aspects of the host response to natural infection could serve as the basis for the development of a safe, effective vaccine. Identification of protective antigens and epitopes could provide insight into both pathogenic mechanisms and the immunologic responses evoked in the infected host. At present, a live attenuated strain of Mycobacterium bovis, Bacillus Calmette-Guerin [BCG], is the only vaccine available for protection of humans from tuberculosis. Protection elicited by BCG in controlled clinical trials has been variable; therefore, the efficacy of this vaccine has been seriously questioned. Moreover, there is no single BCG vaccine. It is produced at dozens of sites located throughout the world, each site maintaining its individual seed strain. This potential for diversity is a cause for concern among some health care personnel. Because BCG is a live vaccine, it may be unsuitable for HIV-positive individuals; it is contraindicated for AIDS patients. A new, more effective vaccine that prevents primary and/or reactivation tuberculosis would be of great benefit. Research Objectives The long term goal of this initiative is to promote efforts to develop new, more effective vaccines, not based on BCG, to prevent and control tuberculosis. This will require innovative research approaches to develop candidate vaccine preparations that will elicit appropriate and protective functional responses. In order to achieve this objective, a focused effort on the basic biology of the mycobacterium and an understanding of the host response to natural infection is needed. Consistent with this, applicants are encouraged to develop innovative projects that address any of, though not be limited to, the following areas: o Identification and characterization of components of M. tuberculosis that are immunogenic. o Identification and characterization of immunogens that elicit responses by the host during natural infection. o Isolation and characterization of relevant immunogen-coding sequences and their products. o Characterization of the host response to natural infection and definition of the correlates of protective immunity. Should an applicant have access to, or have already identified and prepared a novel candidate vaccine, this RFA would also encourage research in the area of: o Enhancement of the immunogenicity of candidate vaccine immunogens. o Development of animal model(s) for testing candidate vaccine immunogens. The areas outlined are not intended to be all-inclusive nor are they all required. SPECIAL REQUIREMENTS NIAID program staff will organize annual meetings that Principal Investigators and other key members (as designated by the Principal Investigators) of the projects are encouraged to attend to discuss progress. This will facilitate overall program planning and development, evaluation of the feasibility of planned approaches, and will promote productive interactions among the awardees. Funds for travel to these meetings may be included in the budget. NIAID program staff will also ensure and arrange for the participation in these meetings of investigators from other relevant NIAID-supported tuberculosis research projects, if appropriate, in order to further promote fruitful interactions. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements will be required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis should be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale should be provided. The composition of the proposed study populations must be described in terms of gender and racial/ethnic group, together with a rationale for its choice. In addition, gender and racial/ethnic issues should be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information should be included in the form PHS 398 (rev. 9/91) in Sections 1-4 of the Research Plan AND summarized in Section 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., Native Americans including American Indians or Alaskan Natives, Asian/Pacific Islanders, Blacks, Hispanics). The rationale for studies on single minority population groups should be provided. For the purpose of this policy, clinical research includes human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including but not limited to clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded. However, every effort should be made to include human tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. For foreign awards, the policy on inclusion of women applies fully; since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign populations groups to the United States' populations, including minorities. If the required information is not contained within the application, the application will be returned. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and will be reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not support applications that do not comply. LETTER OF INTENT Prospective applicants are asked to submit, by January 19, 1993, a letter of intent that includes a descriptive title of the proposed research, the name, address and telephone number of the Principal Investigator, the identities of other key personnel and the participating institution, and the number and title of the RFA. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information it contains allows NIAID staff to estimate the potential review workload and avoid conflict of interest in the review. The letter of intent is to be sent to Dr. Olivia Preble at the address listed under INQUIRIES. APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 9/91) is to be used in applying for these grants. These forms are available at most institutional offices for sponsored research or business offices and from the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone (301) 496-7441. The deadline for receipt of applications in response to this RFA is March 18, 1993. Applications for FIRST (R29) awards must include at least three sealed letters of reference attached to the face page of the original application. FIRST award applications submitted without the required number of reference letters will be considered incomplete and will be returned without review. Applicants from institutions that have a General Clinical Research Center (GCRC) funded by the NIH National Center of Research Resources may wish to identify the Center as a resource for conducting the proposed research. If so, a letter of agreement from the GCRC Program Director must be included in the application material. The RFA label available in the application form must be affixed to the bottom of the face page. 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 "Tuberculosis Vaccine Development" and number (AI-93-02) must be typed on line 2a of the face page of the application and the "Yes" box marked. Submit a signed, typewritten original of the application including the Checklist, and three signed, exact single-sided photocopies, in one package, to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** At the time of submission to the Division of Research Grants (DRG), two additional exact copies must be sent to Dr. Olivia Preble at the address listed under INQUIRIES. Applications received after the deadline will be returned without review. Alternatively, the late applicant will be contacted and given the choice of having the application returned or of having it submitted for review in competitition with unsolicited applications at the next DRG review cycle. The DRG will not accept any application in response to this announcement that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. The DRG will not accept any application that is essentially the same as one already reviewed. This does not exclude the submission of substantial revisions of application already reviewed. These applications must, however, include an introduction addressing the previous critique. REVIEW CONSIDERATIONS Upon receipt, applications and supporting material will be reviewed by the DRG for completeness and by NIAID staff for responsiveness to the RFA. Incomplete applications will be returned without further consideration. If the application is complete but not responsive to the RFA, NIAID staff will contact the applicant and present the same options for handling the application as in late applications, above. Applications may be triaged by an NIAID peer review group on the basis of relative competitiveness among the applications responsive to the RFA. The NIH will withdraw from further competition those applications judged to be non-competitive for award and notify the applicant Principal Investigator and institutional official. Those applications that are complete and responsive will be evaluated in accordance with the criteria stated below for scientific/technical merit by an appropriate review committee convened by the NIAID. The second level of review will be provided by the National Advisory Allergy and Infectious Diseases Council. Review criteria for applications received in response to an RFA are generally the same as those for unsolicited applications, namely: o Scientific, technical, or medical significance and originality of the proposed research. o Appropriateness and adequacy of the experimental approach and methodology proposed to accomplish the research. o Qualification and research experience of the Principal investigator and staff, particularly, but not exclusively, in the area of the proposed research. o Availability of resources to carry out the proposed research. o Appropriateness of the proposed budget and duration of the project in relation to the proposed research. AWARD CRITERIA The anticipated date of award is September 30, 1993. The primary criterion for award is the scientific and technical merit of the application as judged by peer reviewers and reflected in the priority score. Additional award criteria are the availability of funds and the receipt of a sufficient number of scientifically meritorious applications that are responsive to the RFA. INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. The opportunity to clarify issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Dr. John Foulds Tuberculosis Program Officer Respiratory Diseases Branch Division of Microbiology and Infectious Diseases National Institute of Allergy and Infectious Diseases Solar Building, Room 3A31 Bethesda, MD 20892 Telephone: (301) 496-5305 FAX: (301) 496-8030 Direct inquiries regarding the review of applications to: Dr. Olivia Preble Chief, Microbiology and Immunology Review Section Scientific Review Branch Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4C20 Bethesda, MD 20892 Telephone: (301) 496-8208 FAX: (301) 402-2638 Direct inquiries regarding fiscal matters to: Mr. Todd Ball Chief, Microbiology and Infectious Diseases Grants Management Section Grants Management Branch Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Bldg., Room 4B35 Bethesda, MD 20892 Telephone: (301) 496-7075 The mailing address for sending applications, letters of intent, or other correspondence to NIAID staff in the solar building is the central mailing address for the NIH. Applicants who use express mail or a courier service are advised to follow the carrier's requirements for showing a street address. The address for the solar building is: 6003 Executive Boulevard Rockville, MD 20852 SCHEDULE Letter of intent date: January 19, 1993 Application receipt date: March 18, 1993 Scientific review date: July 1993 Advisory Council date: September 1993 Award date: September 30, 1993 AUTHORITY AND REGULATIONS This program is supported under authorization of the Public Health Service Act, Sec. 301 (c), Public Law 78-410, as amended. The Catalogue of Federal Domestic Assistance Citation is Sec. 93.856, Microbiology and Infectious Diseases Research. Awards will be administered under PHS grants policies and Federal Regulations 42 CFR Part 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems review. $$XID RFA HL9311 HL-93-11 P1O1 ***************************************** ASTHMA CLINICAL RESEARCH NETWORK NIH GUIDE, Volume 21, Number 45, December 18, 1992 RFA: HL-93-11-L P.T. 34; K.W. 0715013, 0745070, 0755018 National Heart, Lung, and Blood Institute Letter of Intent Receipt Date: March 1, 1993 Application Receipt Date: May 6, 1993 PURPOSE The Division of Lung Diseases invites applications for four Clinical Groups and one Data Coordinating Center to participate, with the assistance of the National Heart, Lung, and Blood Institute (NHLBI), in the establishment of a network of interactive asthma clinical research groups designed to facilitate evaluation of novel treatment methods and management strategies for asthma; and to rapidly disseminate the findings from these clinical studies to the health care community. This request for applications (RFA) is to: (1) provide a mechanism to establish and maintain the infrastructure required to perform multiple therapeutic trials of novel treatments and management strategies for asthma using common protocols with the requisite numbers of patients. Support would be provided to maintain the infrastructure with additional funds provided on a cost per patient basis for conducting clinical protocols. (2) Establish a Data Coordinating Center for the network. It is envisioned that the Clinical Groups would have significant experience and a strong history of basic and clinical research on the pathogenesis and treatment of asthma, since the program infrastructure should be built around existing research projects. 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 RFA, Asthma Clinical Research Network, is related to the priority areas of chronic disabling conditions and clinical prevention services. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic, for-profit, and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of state and local governments, and eligible agencies of the Federal government. Foreign organizations are not eligible to apply and domestic applications may not include international components. Applications from minority individuals and women are encouraged. Awards for a Clinical Group and a Data Coordinating Center under this RFA will not be made to the same Principal Investigator (PI) to ensure that data analysis is done independently of data acquisition. The same institution may apply for both a Clinical Group and the Data Coordinating Center award, but the applications for each must be from different individuals. MECHANISM OF SUPPORT The administrative and funding mechanism to be used to undertake this program will be a cooperative agreement (U01), an assistance mechanism. Under the cooperative agreement, the NIH assists, supports, and/or stimulates and is substantially involved with recipients in conducting a study by facilitating performance of the effort in a "partner" role. Details of the responsibilities, relationships, and governance of a study funded under a cooperative agreement are discussed later in this document under the section Terms and Conditions of Award. FUNDS AVAILABLE An estimated four awards for Clinical Groups and one award for a Data Coordinating Center will be made under this RFA. A maximum of about $17.4 million (including direct and indirect costs) over a five-year period will be awarded for the Clinical Groups and the Data Coordinating Center. Approximately $2.5 million will be available for the first year, $3.5 million for the second year, $3.6 million for the third year, $3.8 million the fourth year and $3.9 million for the last year. It is anticipated that the award for each Clinical Group will be about $475,000 total costs for the first year and the award for the Data Coordinating Center will be about $600,000 total costs for the first year. Because the nature and scope of the research proposed in response to this RFA may vary, it is anticipated that the size of an award will also vary in all years. Future year costs will be redistributed based on the recommended protocols. Awards and level of support are dependent on the receipt of a sufficient number of applications of high scientific merit. Although this program is provided for in the financial plans of the NHLBI, awards pursuant to this RFA are contingent upon the availability of funds for this purpose. The total project period for applications submitted in response to the present RFA may not exceed five years. The anticipated award date is September 30, 1993. At this time the NHLBI anticipates that there will be a renewed competition after five years. However, the final decision will depend upon experience with the network during the first five years as well as financial considerations. RESEARCH OBJECTIVES Background Asthma is an increasingly serious cause of morbidity and mortality in the United States. There are approximately 12 million asthmatics in this country. The disease affects both sexes and impacts all racial/ethnic groups. It is now recognized that asthma is a complex disease of varied etiology triggered by a number of factors such as allergens, drugs, chemicals, exercise, cold dry air, infections and emotions, making asthma therapy difficult and sometimes complicated. Multiple drugs are often required, including medications to treat and control symptoms (bronchodilator agents such as beta-2 adrenergic agonists, theophylline, and anticholinergics), as well as drugs thought to control the underlying process (anti-inflammatory agents such as inhaled and systemic corticosteroids, cromolyn sodium and nedocromil). Despite major advances in understanding the etiology and pathophysiology of asthma and the development of new therapeutic modalities, the prevalence, severity, and mortality from asthma have increased over the past decade in all age groups. In addition to the rise in morbidity and mortality, hospitalizations for asthma have doubled in adults and increased fivefold for children over the past 20 years. Mortality rates appear to be particularly high in urban and rural minority populations. Asthma continues to place a heavy burden on patients and their families, the health care system, and society as a whole. Therefore, new approaches are needed to help alleviate this growing problem. One important need is to establish a mechanism to allow rapid evaluation of new and existing therapeutic approaches for asthma, and for dissemination of laboratory and clinical findings to the health care community. This program seeks to accomplish this through a network of interactive asthma Clinical Groups that conduct clinical research in a coordinated and multidisciplinary setting. There are several key reasons why establishment of an asthma network would greatly accelerate clinical research: (1) The sometimes complicated clinical picture often makes it difficult to accumulate a large number of comparable patients in any one center. (2) The distribution of underlying disease processes may vary between populations and influence outcome independent of experimental treatment. (3) Uniformity in treatment protocols would decrease the variability of data and decrease the numbers of patients needed for each clinical study. (4) Results from the basic and clinical research laboratories can be rapidly disseminated to health care professionals for optimal care of the asthmatic patient. Availability of a coordinated asthma network would ensure appropriate patient categorization and bring together the necessary clinical expertise and administrative resources to conduct multiple therapeutic trials. Centralized protocols will promote high quality design, decrease the variability in supportive modalities, and reduce unnecessary or redundant support for conducting multiple independent clinical studies. A separate Data Coordinating Center will support protocol development, sample size calculations, common questionnaires, complete data analysis and overall study coordination. Objectives and Scope The objective of this program is to establish a network of interactive asthma clinical research groups to rapidly assess novel treatment methods and to ensure that these findings on optimal management of asthmatic patients are rapidly disseminated to practitioners and health care professionals. This program is intended to provide a mechanism to establish and maintain the required infrastructure to perform multiple therapeutic trials in asthmatic patients. The therapeutic trials may involve investigational drugs, approved agents not currently used, or drugs currently used in treatment of asthma. It will be advantageous for groups to have had substantial previous basic and/or clinical research experience in asthma and asthma related fields, since it is anticipated that the program infrastructure will be built around existing research projects. Although some of the characteristics of the network and experimental protocols are specified, the specific selection, prioritization and design of the various protocols remain in the hands of the investigators. A number of possible examples are listed purely for illustrative purposes. In order to rapidly conduct multiple clinical protocols to test novel therapeutic approaches for asthma, a collaborative effort will be required by approximately four Clinical Groups and one Data Coordinating Center. Participating institutions will develop and then follow uniform study protocols and use standardized data collection procedures. The collaborative protocols will be developed by a Steering Committee, composed of the Principal Investigators and the NHLBI Project Scientist. The various protocols will be subject to peer review by an uninvolved expert group. The clinical trials will proceed into their second (or implementation) phase only with the concurrence of both the awardees and the NHLBI. Study Design and Population It is envisioned that over the five year period several multicenter clinical trials will be developed and implemented by the Principal Investigators. The individual Clinical Groups within the network should emphasize clinical research that can be conducted under mutually agreed upon protocols. The study population is envisioned to be asthmatic patients encompassing a broad range of age groups and consisting of appropriate gender and minority representation with clearly defined and documented asthma. At a minimum, one third of the patient population at each clinic should be minority individuals and one half women. It is expected that each Clinical Group would have the ability to access at least 400 patients for various protocols over the five year period, but it is not envisioned that all 400 patients would necessarily be enrolled in research protocols at any one time, and it is possible that an individual patient may be involved in more than one study. Patient access may be accomplished by establishing strong links with community health groups such as HMOs, asthma clinics, or private practice physicians to ensure adequate numbers of patients for initiation of the clinical trials. Of the total patients accessible, investigators should include substantial numbers from a broad age range, as well as a description of the age distribution and characteristics of the population that they might recruit into potential clinical trials. Also, it is expected that Clinical Groups will develop plans to establish partnerships with the practicing physicians responsible for primary patient care. Applicants should propose two examples (conducted either concurrently or sequentially) of clinical protocols requiring multicenter participation that they consider important. For each example applicants should submit concept documents not more than four pages long, that briefly outline the rationale and background of the proposed clinical trials, study design, type of patients to be included in the protocols, eligibility criteria, and baseline and outcome measures. These examples should represent clinical trials that the investigators are interested in conducting, keeping in mind that the network mechanism allows using specific non-approved investigational drugs. For each of the clinical protocols, applicants should discuss the characteristics and numbers of potential patients that would be available from their own geographic area. Examples of clinical protocols appropriate to the program may include, but are not limited to: o long term evaluation of safety, efficacy, and side effects of high dose inhaled steroids in the treatment of moderate to severe asthma, including the effects on airways responsiveness, growth, bone density, pituitary and adrenal axis function; o efficacy of alternative anti-inflammatory therapies (e.g., methotrexate, gold) in the treatment of chronic asthma; the role of 5-lipoxygenase inhibitors and other new agents that inhibit the final pathways in the treatment of asthma; o comparison of leukotriene antagonists and 5-lipoxygenase inhibitors with inhaled steroids; o efficacy of long acting beta-2 agonists and their interaction with inhaled steroids. The topics for the network protocols will be proposed and prioritized by the steering committee, but the actual number of clinical trials conducted will be dependent upon availability of funds. It is anticipated that many of the initial network protocols will be selected from among those proposed by the successful applicants. Timetable The timetable for the study may be roughly subdivided into three phases over a five year period. There may be some overlap of functions within each of the phases, and the time estimates are only approximations. The purpose of the phases is to provide broad guidelines of the total scope of work to be accomplished for this RFA. Phase I: Planning and development of the network infrastructure, protocol development 0-12 months Phase II: Patient recruitment, protocol implementation, further protocol development 12-60 months Phase III: Data analysis, report preparation, protocol development and recruitment for next studies 24-60 months The first twelve months of the study may be devoted to planning and development of the network infrastructure and committee structure. Possible objectives for the planning and development stage are to select a steering committee chairperson; determine patient eligibility criteria for initial clinical trials; train staff in diagnostic procedures; help set up data acquisition and consent forms; define terms and outcome measures; develop a manual of operations, questionnaires, procedures for quality control, determine priorities for protocol development and begin to develop specific protocols. The Principal Investigators, through the Steering Committee, will lead the planning effort, with the assistance of the Project Scientist at NHLBI. Key Clinical Group staff may also be involved in the planning. Subcommittees of the Steering Committee may be formed to help in this effort. The Data Coordinating Center will also play a key role in the planning and development stage. Possible objectives for the planning and development stage for the Data Coordinating Center, in addition to assisting Clinical Groups in their planning and organization of the network, are to help develop study protocols, randomization and analytic plans; select a data acquisition, transfer, and management system; plan for any subcontracts for chemical analysis; develop procedures for quality control, training, and certification; print the protocols and data forms; develop and produce a Manual of Operations, and take the lead for the orderly accumulation and transmission of data for the network. In Phase II, the Clinical Groups will select and prioritize common protocols for the network, proceed with subject recruitment and protocol implementation for the first studies and concurrent development of additional protocols. Possible objectives for Phase II for the Data Coordinating Center are to assist the Clinical Groups with respect to completing protocol development, patient recruitment, randomization, data acquisition, and ongoing quality control. In Phase III, after the last patients in the first study have completed their follow-up measurements, Clinical Groups will review their data and assist the Data Coordinating Center in the closeout of the initial study. Initiation of patient accrual will begin for the next studies and protocol development continues for subsequent trials. The Data Coordinating Center will continue with its activities in data management, editing, data analysis and protocol development. It will also support manuscript preparation through data analysis, statistical consultation, editorial tasks, and coordination of meetings. It is anticipated that the main results paper for each network clinical trial will be collaboratively prepared by the investigators and submitted for publication. SPECIAL REQUIREMENTS Additional Material to Include in the Application To promote the development of a collaborative program among the award recipients, a number of issues discussed below need to be addressed in each application for a Clinical Group. Each application should discuss the qualifications and experience of the investigators. It is envisioned that the Principal Investigator will be an established investigator with experience in conducting multicenter trials that include patients, physicians, and the community. It is anticipated that the program infrastructure will be built around existing research projects. Therefore, applicants should have a substantial base of funded research in asthma or asthma related fields. The level of this current research support (direct costs per year) and past record of achievement in research related to the pathogenesis and treatment of asthma should be discussed as well as the laboratory/clinical facilities available at their institutions, and the facilities at any proposed participating subcontracting organizations. For any subcontracts, especially for access to asthma patients, there should be a description of the organization of that facility including the means of assuring quality control of patient care as well as data entry, plans for coordination, and a process for filing patient assurances. Also, plans for accessing at least 400 asthmatic patients encompassing a broad range of age groups, and consisting of appropriate gender and minority representation with clearly defined and documented asthma for use over the five year period should be detailed in the application. These plans should outline links between individual Clinical Groups and community health groups. In addition, applicants should provide a brief description of the patient characteristics, age distribution, and any other relevant baseline information of the patient population. It is anticipated that the patient population will consist of about one third minority groups and one half women. The patient population available to investigators should be recruited primarily from within a clinic's immediate geographic area, and include a substantial number of patients covering a broad age range. As part of these community based contacts, clinics should discuss potential approaches to disseminate new knowledge gained from these clinical studies to various health care groups. Applicants should also discuss their willingness, and that of the institutions involved, to pursue capitation of operational costs for each protocol, and general support of collaborative research through this network concept. Clinical Group applicants must be able to interact effectively with the Data Coordinating Center to transmit and edit data and should discuss their capability to participate in a distributed data entry system if this approach is selected. Clinical Group applicants should also state their willingness to participate in a cooperative and interactive manner with other Clinical Groups, the NHLBI and the Data Coordinating Center within the context of the network. Applicants from institutions that 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. If so, a letter of agreement from either the GCRC Program Director or Principal Investigator should be included with the application. Data Coordinating Center applicants should discuss various aspects of study design that would be important in developing asthma clinical protocols; their familiarity with asthma and other pulmonary diseases, eligibility criteria, methods of randomization, important considerations for making sample size and power calculations, baseline and outcome measures, other relevant measures including objective outcome measures of asthma, methods and frequency of data collection and entry, monitoring accuracy of data collection, methods of data acquisition and transfer, quality control procedures including training and certification, chemical analysis of blood samples, and plans for statistical analysis of results. Budget and Related Issues The underlying concept of this network is that a core effort is essential to maintain the infrastructure required to perform multiple therapeutic trials in asthma. Based on this approach we estimate that the individual Clinical Groups will require a minimum level of effort to sustain the organizational aspects of the network. Therefore, individual Clinical Groups should submit requests for a BASE BUDGET, not to exceed $125,000 total costs per year, for the organizational aspects of the network over five years. The suggested level of commitment to maintain the infrastructure for each year may be in the order of 10 percent for the Principal Investigator, five percent for the co-investigator, 25 percent for a secretary, 100 percent for a clinical coordinator, and travel costs for approximately four trips to Bethesda for two people. Additional support (in the range of $350,000 total costs for the first year per clinic) will be provided on a per patient basis for conducting the actual clinical protocols. Applications for the Clinical Groups and Data Coordinating Center should present five budget periods of 12 months each. For the Clinical Groups, budgets for the first twelve months should include the base costs and a budget for only one of the proposed clinical trials that is outlined in the application for the duration of the proposed trial. The budget for the clinical protocol should be developed on a cost per patient basis and include all direct and any applicable indirect costs. Capitation costs should not include funds for investigational drugs. However, any approved drugs or laboratory tests should be part of the per patient cost of conducting a protocol. Applicants should identify the potential source(s) for any drugs or substances that are being considered for clinical protocols that are currently unavailable commercially. Investigators should only prepare budgets for their own Clinical Group and not for the entire network. Applicants should also indicate whether the capitation costs for the second protocol included in the application will be similar or markedly different (if so by how much) from the sample budget. Only the base budget should be escalated four percent for the remaining future years. It is not the intent of this network to provide support for only a single protocol that runs for the entire five years. Ongoing annual budgets of the Clinical Groups within the asthma network will be based on individual recommended protocols that will be funded through a capitation funding mechanism. Each Clinical Group will be given base costs as defined above and in addition, a flat fee per patient successfully enrolled and completed as defined. Future year costs will be redistributed based on the recommended protocols. The individual clinics will be expected to project patient enrollment for a specific protocol during a specified time frame; continuation and level of funding will be based on actual recruitment and overall performance. Applicants for the Data Coordinating Center should prepare budgets that roughly correspond with the standard coordinating center responsibilities related to the above mentioned network phases. These awards will be subject to administrative review annually. It should be recognized that not all clinical protocols proposed or recommended may be done, and it is possible that not all clinics would be participating equally in all protocols. Given the current resources and range of anticipated costs, it is possible that the network may be able to simultaneously conduct between two and four simple protocols per year. However, availability of funds and ability to recruit the required patients will determine the actual numbers of protocols that can ultimately be accomplished through the network. The protocols of successful applicants will be submitted to the Steering Committee for further consideration once the cooperative agreements have been awarded. It is anticipated that many of the initial network protocols will be selected from among those highly meritorious studies proposed by the successful applicants. However, a decision to fund a particular Clinical Group will not commit the network to develop that group's clinical protocol. Study Organization Steering Committee The Steering Committee will be the main governing body of the network and, at a minimum, will be composed of the PIs of each Clinical Group, the Principal Investigator of the Data Coordinating Center, and the NHLBI Project Scientist (Branch Chief, Airways Diseases Branch, Division of Lung Diseases). Each Clinical Group, the Data Coordinating Center and the NHLBI will have one vote. The Committee may meet as often as four to six times in the first 12 months of the study and two to four times per year thereafter. All major scientific decisions will be determined by majority vote of the Steering Committee. The Chairperson, who will be someone other than an NHLBI staff member, should be selected by the end of the second meeting of the Steering Committee. The first meeting of the Steering Committee will be convened by the NHLBI Project Scientist. The Steering Committee will have primary responsibility for developing common clinical protocols, facilitating the conduct and monitoring of the studies, and reporting the study results. Topics for the protocols will be proposed and prioritized by the Steering Committee. In certain instances, FDA cooperation may be sought in protocol development, especially if unconventional interventions are being considered. Subcommittees of the Steering Committee will be established as necessary. The NHLBI will have one voting representative on each subcommittee. The collaborative protocols will be developed by the Steering Committee. With data submitted centrally to the Data Coordinating Center, the protocols will define rules regarding access to data and publications. An independent Data and Safety Monitoring Board, to be appointed by NHLBI, will review progress at least annually and report to NHLBI. Terms and Conditions of Award The administrative and funding mechanism to be used to undertake this project will be cooperative agreements (U01), an assistance mechanism. Under the cooperative agreement, the NIH assists, supports and/or stimulates, and is involved substantially with recipients in conducting a study by facilitating performance of the effort in a "partner" role. Consistent with this concept, the tasks and activities in carrying out the studies will be shared among the awardees and the NHLBI Project Scientist. The tasks or activities in which awardees have substantial responsibilities include protocol development, participant recruitment and follow-up, data collection, quality control, interim data and safety monitoring, final data analysis and interpretation, preparation of publications, collaboration with other awardees, and collaboration with the NHLBI Project Scientist. The NHLBI Project Scientist will have substantial responsibilities in protocol development, quality control, interim data and safety monitoring, final data analysis and interpretation, preparation of publications, collaboration with awardees, and coordination and performance monitoring. It is anticipated that awardees will have lead responsibilities in study design, protocol development, final data analysis and interpretation, and the preparation of most publications. It is anticipated that the NHLBI Project Scientist will have lead responsibilities in quality control and catalyzing interim monitoring of data and safety and may, consistent with publication policy to be adopted by the Steering Committee, have lead responsibilities in the preparation of some publications. The NHLBI Project Scientist will have voting membership on the Steering Committee, and as appropriate, its subcommittees. Awards resulting in response to this RFA are for five years for the Clinical Groups and Data Coordinating Center. Awardees will retain custody of and have primary rights to their data developed under these awards, subject to Government, e.g., NHLBI, NIH, or PHS, rights of access consistent with current HHS, PHS, and NIH policies. The NHLBI reserves the right to terminate or curtail the study (or an individual award) in the event of (a) substantial shortfall in participant recruitment, follow-up, data reporting, quality control, or other major breech of the protocol, (b) substantive changes in the agreed-upon protocol to which the NHLBI does not agree, (c) reaching a major study endpoint substantially before schedule with persuasive statistical significance, or (d) human subject ethical issues that may dictate a premature termination. Any disagreement that may arise in scientific matters between award recipients and the NHLBI may be brought to arbitration. An arbitration panel will be composed of three members--one selected by the Steering Committee (with the NHLBI member not voting) or by the individual awardee in the event of an individual disagreement, a second member selected by NHLBI, and the third member selected by the two prior members. This special arbitration procedure in no way affects the awardee's right to appeal an adverse action that is otherwise appealable in accordance with the PHS regulations at 42 CFR part 50, subpart D and HHS regulation at 45 CFR part 16. These special Terms of Award are in addition to and not in lieu of otherwise applicable OMB administrative guidelines, HHS Grant Administration Regulations at 45 CFR part 74, and other HHS, PHS, and NIH Grant Administration policy statements. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements are required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of disease, disorder, or condition under study; special emphasis must be placed on the need for inclusion of minorities and women in studies of diseases, disorders, and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale must be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues must be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information must be included in the form PHS 398 (rev. 9/91) in Sections 1-4 of the Research Plan, and summarized in Section 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., Native Americans [including American Indians or Alaskan Natives], Asian/Pacific Islanders, Blacks, Hispanics). The rationale for studies on single minority population groups should be provided. For the purpose of this policy, clinical research includes human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including but not limited to clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are not subject to these policies. However, every effort should be made to include human tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. If the required information is not contained within the application, the application will be returned. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women in a study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and will be reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. LETTER OF INTENT Prospective applicants are asked to submit, by March 1, 1993, a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, the identities of other key personnel and participating institutions, and the number and title of 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, the information that it contains is helpful in planning for the review of applications. It allows 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: C. James Scheirer, Ph.D. Review Branch, Division of Extramural Affairs National Heart, Lung, and Blood Institute Westwood Building, Room 648 Bethesda, MD 20892 Telephone: (301) 496-7363 FAX: (301) 402-1660 APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 9/91) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research; from the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone (301) 496-7441; and from the NIH Project Scientist named below. The RFA label available in the application form 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 and number must be typed in line 2a of the face page of the application form and the YES box must be marked. Send or deliver the original, signed application and three legible complete photocopies to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** Send two additional copies of the application to: C. James Scheirer, Ph.D. Review Branch, Division of Extramural Affairs National Heart, Lung, and Blood Institute Westwood Building, Room 648 Bethesda, MD 20892 Telephone: (301) 496-7363 It is important to send these two copies at the same time as the original and that three copies are sent to the Division of Research Grants. Otherwise, the NHLBI cannot guarantee that the application will be reviewed in competition for this RFA. Applications must be received by May 6, 1993. If an application is received after this date it will be returned to the applicant without review. The Division of Research Grants (DRG) will not accept any application in response to this announcement that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. The DRG 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 reviewed, but such applications must include an introduction addressing the previous critique. REVIEW CONSIDERATIONS General Considerations All applicants will be judged on the basis of the scientific merit of their proposed protocols and their documented ability to conduct the essential study components as broadly outlined in the RESEARCH OBJECTIVES of this RFA. Although the technical merit of the protocol is important, it will not be the sole criterion for selection of a Clinical Group. Other considerations such as the importance and timeliness of the proposed clinical trials, access to patients, and multidisciplinary nature of the studies will be part of the evaluation criteria. Review Method Upon receipt, applications will be reviewed by the DRG for completeness and by NHLBI staff for responsiveness to this RFA. Incomplete applications will be returned to the applicant without further consideration. If the application is judged unresponsive, the applicant will be contacted and given an opportunity to withdraw the application or to have it considered for the regular, investigator-initiated grant program of the NIH. If the application submitted in response to this RFA is substantially similar to a grant application already submitted to the NIH for review, but has not yet been reviewed, the applicant will be asked to withdraw either the pending application or the new one. Simultaneous submission of identical applications will not be allowed, nor will essentially identical applications be reviewed by different review committees. Therefore, an application cannot be submitted in response to this RFA that is essentially identical to one that has already been 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. Applications judged to be responsive by NHLBI staff will be reviewed for scientific and technical merit by an initial peer review group, which will be convened by the Division of Extramural Affairs, NHLBI, solely to review these applications. The initial review will include a preliminary evaluation to determine scientific merit relative to the other applications received in response to this RFA (triage); the NIH will remove from further consideration applications judged to be noncompetitive and promptly notify the Principal Investigator and the official signing for the applicant organization. Those applications judged to be competitive will be further evaluated for scientific/technical merit by the usual peer review procedures, including, if deemed appropriate, an applicant interview in or near Bethesda at the applicant's expense. Subsequently, they will be reviewed by the National Heart, Lung, and Blood Advisory Council. Review Criteria Applicants are encouraged to submit and describe their own ideas on how best to meet the goals of the network and their specific protocols, but they are expected to address issues identified under SPECIAL REQUIREMENTS of this Request for Applications. Applications will be judged primarily on the scientific quality of the application, the appropriateness, importance and timeliness of the proposed clinical trials, facilities and access to patients, multidisciplinary nature of the study, approach to cost containment, the discussion of considerations relevant to this RFA, expertise of the investigators, their capability to perform the work proposed, and a demonstrated willingness to work as part of the network and with the NHLBI Project Scientist. The review group will assess the scientific merit of the protocols and related factors, including: Clinical Groups o Importance and scientific merit of the proposed protocols, including adequacy of the methodology to carry out the research and utilization of the multicenter nature of the network. o Adequacy of the patient population and numbers of patients, including appropriate representation of minorities and women. o Availability of adequate facilities and other resources including a plan for the administrative structure within the Clinical Group. o Rationale and cost-effectiveness of the research approach proposed. o Adequacy of data collection, preliminary analysis, and reporting procedures, including adequacy to process the volume of data expected within their Clinical Group and manage the individual study databases. Plans to ensure quality control of data. o Expertise, training, and experience of the investigators and staff, including the scientific and administrative abilities of the PI and co-investigators; their potential to accomplish the proposed research goals; the time they plan to devote to the program for the effective conduct of the study; their previous experience conducting clinical research in asthma; their ability and experience to participate in multicenter clinical trials; and willingness to work collaboratively with other Clinical Groups, the Data Coordinating Center, and the NHLBI in the manner summarized in the RFA, including implementation of common protocols within the network framework. o Facilities, equipment, and organizational structure to effectively implement the proposed research. Data Coordinating Center o Understanding of the scientific, statistical, logistical, and technical issues underlying multicenter studies, including issues related to treatment and management of asthma, and taking a leadership role in the area of study design, statistics, logistics, data acquisition and management, quality control, data analysis, and network coordination. o Adequacy of the proposed plans for acquisition, transfer, management, and analysis of data, quality control of data collection and monitoring, and overall coordination of network activities. o The expertise, training, and experience of the investigators and staff, including the administrative abilities of the Principal Investigator and co-investigators, and the time they plan to devote to the program for the effective coordination of the network. o The administrative, supervisory, and collaborative arrangements for achieving the goals of the program, including willingness to cooperate with the participating Clinical Groups and the NHLBI. o Facilities, equipment, and organizational structure to effectively assist Clinical Groups in implementing the network protocols and in data collection procedures and in overall coordination of network activities. o Appropriateness of the budget for the work proposed. AWARD CRITERIA Applications recommended by the National Heart, Lung, and Blood Advisory Council will be considered for award based upon (a) scientific and technical merit, importance of the proposed clinical trial, timeliness, multidisciplinary nature of the study, and the requirements explicitly stated in this RFA; (b) program balance, including in this instance, sufficient compatibility of features to make a successful collaborative program a reasonable likelihood; and (c) availability of funds. Letter of Intent: March 1, 1993 Application Receipt Date: May 6, 1993 Review by NHLBAC: September 2-3, 1993 Anticipated Award Date: September 30, 1993 INQUIRIES Written and telephone inquiries are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Inquiries regarding this announcement may be directed to: James P. Kiley, Ph.D. Chief, Airways Diseases Branch Division of Lung Diseases National Heart, Lung, and Blood Institute Westwood Building, Room 6A15 Bethesda, MD 20892 Telephone: (301) 496-7332 FAX: (301) 496-9886 Inquiries regarding review and application procedures may be directed to: C. James Scheirer, Ph.D. Review Branch, Division of Extramural Affairs National Heart, Lung, and Blood Institute Westwood Building, Room 648 Bethesda, MD 20892 Telephone: (301) 496-7363 FAX: (301) 402-1660 Inquiries regarding fiscal and administrative matters may be directed to: Mr. Raymond Zimmerman Grants Management Officer, Lung Section Grants Operations Branch Division of Extramural Affairs National Heart, Lung, and Blood Institute Westwood Building, Room 4A11C Bethesda, MD 20892 Telephone: (301) 496-4970 FAX: (301) 402-1200 AUTHORITY AND REGULATIONS This project is described in the Catalog of Federal Domestic Assistance No. 93.837. Awards are made under 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 74. This project is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. From owner-sci-resources@net.bio.net Wed Dec 16 22:00:00 1992 Path: biosci!NET.BIO.NET!kristoff From: kristoff@NET.BIO.NET (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 21, no. 45, pt. 2, 18 December 1992 Message-ID: Date: 17 Dec 92 02:44:05 GMT Sender: kristoff@net.bio.net Distribution: bionet Lines: 1194 $$XID NIHGUIDE 19921218 V21N45 P2O2 ************************************ Ms. Helen Ling Grants Management Specialist Division of Extramural Activities National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 649 Bethesda, MD 20892 Telephone: (301) 496-7467 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.849. Awards are made under 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 requirements of Executive Order 12372 or Health Systems Agency review. $$R7 END ************************************************************ $$R8 BEGIN DK-93-21 FULL-TEXT *************************************** UROLOGY RESEARCH CENTERS NIH GUIDE, Volume 21, Number 45, December 18, 1992 RFA AVAILABLE: DK-93-21 P.T. 04; K.W. 0785220, 1002004, 1002008, 0710070, 1002019, 0710030 National Institute of Diabetes and Digestive and Kidney Diseases The National Cancer Institute Letter of Intent Receipt Date: March 8, 1993 Application Receipt Date: April 9, 1993 THE REQUEST FOR APPLICATIONS (RFA) ANNOUNCED IN THIS NOTICE CONTAINS ESSENTIAL INFORMATION FOR THE PREPARATION OF AN APPLICATION. POTENTIAL APPLICANTS MAY OBTAIN THE RFA FROM THE CONTACT NAMED IN INQUIRES, BELOW. PURPOSE This RFA invites investigators to submit research applications for the George M. O'Brien Research Centers Program. The emphases for this program are threefold: (1) to attract new scientific expertise into the study of the basic mechanisms of urological diseases and disorders; (2) to encourage multidisciplinary research focused on the causes of these diseases and disorders; and (3) to extend the development of innovative clinical and epidemiologic studies of the causes, therapy and possible prevention of urological diseases and disorders. In approaching the study of these disease processes, it is anticipated that extensive collaboration will be required between individuals in the clinical and basic sciences, including for example investigators with training and expertise in cell biology, molecular biology, immunology, genetics, epidemiology, biochemistry, physiology, and pathology. It is the express intent of the announcement to attract new investigators not currently active in this field and to explore new basic areas that may have clinical research applications. Individual institutions with both basic and clinical research capabilities are invited to apply. Interinstitutional collaborative research arrangements are also appropriate and encouraged. Coordination for such arrangements must be evident and clearly meaningful and appropriate for the research proposed. The National Cancer Institute (NCI) plans to provide support for this program in the area of prostate cancer. 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 RFA, Urology Research Centers, is related to the area of diabetes and other chronic disabling conditions. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Foreign institutions are not eligible to apply. Minority individuals and women are encouraged to submit as principal investigators. MECHANISM OF SUPPORT Support of this program will be through the National Institutes of Health (NIH) specialized center (P50) award. Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. Except as otherwise stated in this announcement, awards will be administered under PHS grants policy as stated in the PHS Grants Policy Statement. FUNDS AVAILABLE The NCI and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) expect to jointly award up to two center grants (P50) in fiscal year 1993 for research into urologic disorders. The anticipated awards are for five years and are contingent upon the availability of appropriated funds. The total amount of available funds to support this program is anticipated to be no more than $1.5 million per year. No applicant may request more than $750,000 (including both direct and indirect costs) in total costs in the initial budget period. A standard escalation factor may be used for subsequent budget periods. The award date for these grants will be September 30, 1993. SPECIAL REQUIREMENTS Successful applicants are expected to attend a yearly meeting of Center Directors convened by the NIDDK. Funds to support travel to this meeting may be requested in the budget proposed for the center. STUDY POPULATIONS It is NIH policy that women and minorities must be included in clinical study populations unless there is a good reason to exclude them. The study design must seek to identify any pertinent gender or minority population differences. SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS For projects involving clinical research, NIH requires applicants to give special attention to the inclusion of women and minorities in study populations. If women or minorities are not included in the study populations, a specific justification for his exclusion must be provided. Applications without such documentation will not be accepted for review. LETTER OF INTENT Prospective applicants are asked to submit, by March 8, 1993, a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, the identities of other key personnel and participating institutions, and the number and title of the RFA in response to which the application may be submitted. A letter of intent is not required, is not binding, and does not enter into the review of subsequent applications. The letter of intent is to be sent to: Chief, Review Branch Division of Extramural Activities National Institutes of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 605 Bethesda, MD 20892 Telephone: (301) 496-7083 FAX: (301) 402-1277 APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 9/91) is to be used in applying for these grants. The form is available from most institutional offices of sponsored research and from the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, Maryland 20892, telephone (301) 496-7441. The RFA label available in the application form must be affixed to the bottom of the face page. Detailed instructions on submission procedures are described in the RFA. REVIEW CONSIDERATIONS Upon receipt, applications will be initially reviewed for completeness and responsiveness. Incomplete applications or non-responsive applications will be returned to the applicant without further consideration. Those applications that are complete and responsive will be evaluated in accordance with the usual NIH peer review procedures. Following this review, the applications will be given a secondary review by the National Diabetes and Digestive and Kidney Diseases Advisory Council and the National Cancer Advisory Board unless not recommended for further consideration by the initial review group. INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. Inquiries regarding non-cancer programmatic issues and requests for copies of the RFA may be directed to: Ralph L. Bain, Ph.D. Director, Centers Program Division of Kidney, Urologic, and Hematologic Diseases National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 3A-05 Bethesda, MD 20892 Telephone: (301) 496-7574 Inquiries regarding cancer related programmatic issues and requests for the RFA may be directed to: Andrew Chiarodo, Ph.D. Chief, Organ Systems Coordinating Branch Centers, Training, and Resources Program Division of Cancer Biology, Diagnosis and Centers National Cancer Institute Executive Plaza North, Suite 316 Bethesda, MD 20892 Telephone: (301) 496-8528 Inquiries regarding fiscal matters may be directed to: Ms. Helen Ling Grants Management Specialist Division of Extramural Activities National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 649 Bethesda, MD 20892 Telephone: (301) 496-7467 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.849. Awards are made under 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 requirements of Executive Order 12372 or Health Systems Agency review. $$R8 END ************************************************************ $$R9 BEGIN HL-93-11 FULL-TEXT *************************************** ASTHMA CLINICAL RESEARCH NETWORK NIH GUIDE, Volume 21, Number 45, December 18, 1992 RFA AVAILABLE: HL-93-11-L P.T. 34; K.W. 0715013, 0745070, 0755018 National Heart, Lung, and Blood Institute Letter of Intent Receipt Date: March 1, 1993 Application Receipt Date: May 6, 1993 THE REQUEST FOR APPLICATIONS (RFA) ANNOUNCED IN THIS NOTICE CONTAINS ESSENTIAL INFORMATION FOR THE PREPARATION OF AN APPLICATION. POTENTIAL APPLICANTS MAY OBTAIN THE RFA FROM THE CONTACT NAMED IN INQUIRIES BELOW. PURPOSE The Division of Lung Diseases invites applications for four Clinical Groups and one Data Coordinating Center to participate, with the assistance of the National Heart, Lung, and Blood Institute (NHLBI), in the establishment of a network of interactive asthma clinical research groups designed to facilitate evaluation of novel treatment methods and management strategies for asthma; and to rapidly disseminate the findings from these clinical studies to the health care community. This RFA is to: (1) provide a mechanism to establish and maintain the infrastructure required to perform multiple therapeutic trials of novel treatments and management strategies for asthma using common protocols with the requisite numbers of patients. Support would be provided to maintain the infrastructure with additional funds provided on a cost per patient basis for conducting clinical protocols. (2) Establish a Data Coordinating Center for the network. The solicitation is for five years. 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 RFA, Asthma Clinical Research Network, is related to the priority areas of chronic disabling conditions and clinical prevention services. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic, for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Foreign organizations are not eligible to apply and domestic applications may not include international components. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT The administrative and funding mechanism to be used to undertake this program will be a cooperative agreement (U01), an assistance mechanism. Under the cooperative agreement, the NIH assists, supports, and/or stimulates and is substantially involved with recipients in conducting a study by facilitating performance of the effort in a "partner" role. The anticipated award date is September 30, 1993. FUNDS AVAILABLE An estimated four awards for Clinical Groups and one award for a Data Coordinating Center will be made under this RFA. A maximum of about $17.4 million (including direct and indirect costs) over a five-year period will be awarded for the Clinical Groups and the Data Coordinating Center. Approximately $2.50 million will be available for the first year, $3.5 million for the second year, $3.6 million for the third year, $3.8 million the fourth year and $3.9 million for the last year. It is anticipated that the award for each Clinical Group will be about $475,000 total costs for the first year and the award for the Data Coordinating Center will be about $600,000 total costs for the first year. Because the nature and scope of the research proposed in response to this RFA may vary, it is anticipated that the size of an award will also vary in all years. Future year costs will be distributed based on the recommended protocols. At this time the NHLBI anticipates that there will be a renewed competition after five years. However, the final decision will depend upon experience with the network during the first five years as well as financial considerations. RESEARCH OBJECTIVES Asthma is an increasingly serious cause of morbidity and mortality in the United States. There are approximately 12 million asthmatics in this country. The disease affects both sexes and impacts all racial/ethnic groups. Despite major advances in understanding the etiology and pathophysiology of asthma and the development of new therapeutic modalities, the prevalence, severity, and mortality from asthma have increased over the past decade in all age groups. In addition to the rise in morbidity and mortality, hospitalizations for asthma have doubled in adults and increased fivefold for children over the past 20 years. Mortality rates appear to be particularly high in urban and rural minority populations. Asthma continues to place a heavy burden on patients and their families, the health care system, and society as a whole. Therefore, new approaches are needed to help alleviate this growing problem. One important need is to establish a mechanism to allow rapid evaluation of new and existing therapeutic approaches for asthma, and for dissemination of laboratory and clinical findings to the health care community. This program seeks to accomplish this through a network of interactive asthma clinical groups that conduct clinical research in a coordinated and multidisciplinary setting. The objective of this initiative is to establish a network of interactive asthma clinical research groups to rapidly assess novel treatment methods, and to ensure that these findings on optimal management of asthmatic patients are rapidly disseminated to practitioners and health care professionals. This program is intended to provide a mechanism to establish and maintain the required infrastructure to perform multiple therapeutic trials in asthmatic patients. It is envisioned that the Clinical Groups would have significant experience and a strong history of basic and clinical research on the pathogenesis and treatment of asthma, since the program infrastructure should be built around existing research projects. Therefore, it will be advantageous for groups to have had substantial previous basic and/or clinical research experience in asthma and asthma related fields. The study population is envisioned to be asthmatic patients encompassing a broad range of age groups and consisting of appropriate gender and minority representation with clearly defined and documented asthma. At a minimum, one third of the patient population at each clinic should be minority individuals and one half women. It is expected that each Clinical Group will have the ability to access at least 400 patients for various protocols over the five year period, but it is not envisioned that all 400 patients would necessarily be enrolled in research protocols at any one time, and it is possible that an individual patient may be involved in more than one study. Of the total patients accessible, investigators should include substantial numbers from a broad age range, as well as a description of the age distribution, and characteristics of the population that they might recruit into potential clinical trials. The overall population to be studied should provide data that are broadly applicable to diverse minority groups as well as whites; thus, the composition of the study population in this RFA program must reflect this diversity. The timetable for the network may be roughly subdivided into three phases over a five year period. Phase I consists of the first twelve months and may be devoted to planning, development of the network infrastructure, and protocol development. In Phase II, protocol development continues, patient recruitment and protocol implementation are estimated to proceed over a 48-month period. Phase III will consist of data analysis, report preparation, closeout of the initial studies, further protocol development, continued recruitment for the next studies, which may proceed over approximately a 36-month period. STUDY POPULATIONS SPECIAL INSTRUCTIONS FOR INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDIES For projects involving clinical research, the NIH requires applicants to give special attention to the inclusion of women and minorities in study populations. If women or minorities are not included in the study populations for clinical studies, a specific justification for this exclusion must be provided. Applications without such documentation will not be accepted for review. LETTER OF INTENT Prospective applicants are asked to submit, by March 1, 1993, a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, the identities of other key personnel and participating institutions, and the number and title of 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, the information that it contains is helpful in planning for the review of applications. It allows 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 at the address listed under INQUIRIES. APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 9/91) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research; from the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone (301) 496-7441; and from the NIH Project Scientist named below. Applications must be received by May 6, 1993. If an application is received after this date it will be returned to the applicant without review. REVIEW CONSIDERATIONS Applicants are encouraged to submit and describe their own ideas on how best to meet the goals of the study, but they are expected to address issues identified under SPECIAL REQUIREMENTS of the RFA. Note that this document is not the RFA. Applications will be judged primarily on the scientific quality of the application. Although the technical merit of the protocol is important, it will not be the sole criterion for selection of a Clinical Group. Other considerations such as the importance and timeliness of the proposed clinical trials, access to patients, multidisciplinary nature of the study, the discussion of considerations relevant to this RFA, expertise of the investigators, their capability to perform the work proposed, and a demonstrated willingness to work as part of the network and with the NHLBI Project Scientist will be part of the evaluation criteria. The review group will assess (as further detailed in the RFA): Clinical Groups o Scientific merit of the proposed clinical trials. o Qualifications, experience, and commitment of key personnel, including their previous experience conducting clinical research in asthma. o Plans to recruit an adequate number of patients, including appropriate representation of minorities and women. o Facilities, equipment and organizational structure to effectively implement protocols through the network. o Rationale and cost-effectiveness of the research approach proposed. Data Coordinating Center o Scientific merit of the proposed clinical trials. o Organizational, administrative, and supervisory ability and statistical expertise to serve as a Data Coordinating Center for multiple multicenter randomized controlled clinical trials in asthma. o Qualifications, experience, and commitment of key personnel. o Facilities and equipment to function as a Data Coordinating Center for a multicenter network. o Appropriateness of the budget for the work proposed. AWARD CRITERIA Applications recommended by the National Heart, Lung, and Blood Advisory Council will be considered for award based upon (a) scientific and technical merit, importance of the proposed clinical trials, timeliness, multidisciplinary nature of the study, and the requirements explicitly stated in this RFA; (b) program balance, including in this instance, sufficient compatibility of features to make a successful collaborative program a reasonable likelihood; and (c) availability of funds. Letter of Intent: March 1, 1993 Application Receipt Date: May 6, 1993 Review by NHLBAC: September 1993 Anticipated Award Date: September 30, 1993 INQUIRIES Written and telephone inquiries are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Inquiries regarding this announcement and requests for the RFA may be directed to: James P. Kiley, Ph.D. Division of Lung Diseases National Heart, Lung, and Blood Institute Westwood Building, Room 6A15 Bethesda, MD 20892 Telephone: (301) 496-7332 FAX: (301) 496-9886 Inquiries regarding review and application procedures may be directed to: C. James Scheirer, Ph.D. Review Branch, Division of Extramural Affairs National Heart, Lung, and Blood Institute Westwood Building, Room 648 Bethesda, MD 20892 Telephone: (301) 496-7363 FAX: (301) 402-1660 Inquiries regarding fiscal and administrative matters may be directed to: Mr. Raymond L. Zimmerman Grants Operations Branch Division of Extramural Affairs National Heart, Lung, and Blood Institute Westwood Building, Room 4A11C Bethesda, MD 20892 Telephone: (301) 496-4970 FAX: (301) 402-1200 AUTHORITY AND REGULATIONS This project is described in the Catalog of Federal Domestic Assistance No. 93.837. Awards are made under 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 74. This project is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$R9 END ************************************************************ ONGOING PROGRAM ANNOUNCEMENTS $$P1 BEGIN PAR-93-33 ************************************************ NATIONAL CANCER INSTITUTE/MINORITY ACCESS TO RESEARCH CAREERS SUMMER TRAINING SUPPLEMENT NIH GUIDE, Volume 21, Number 45, December 18, 1992 PAR NUMBER: PAR-93-33 P.T. 34, FF; K.W. 0715035, 0720005 National Cancer Institute Application Receipt Date: February 1, 1993 PURPOSE The Comprehensive Minority Biomedical Program (CMBP) of the Division of the Extramural Activities (DEA), National Cancer Institute (NCI), invites interested grantee institutions that have Minority Access to Research Careers (MARC) grants to apply for CMBP support of MARC scholars interested in obtaining laboratory research experience at the NCI. This program announcement will be reissued on an annual basis. The NCI, through a co-funding arrangement with the MARC program of the National Institute of General Medical Sciences (NIGMS), provides support for research training to minority individuals and institutions and conference grant support to further address and enhance the mission of the National Cancer Program. The NCI/MARC Summer Training Program is an extension of the co-funding process. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Health People 2000," a PHS-led national activity for setting priority areas. This program announcement, NCI/MARC Summer Training Supplement, is related to the priority area of cancer research. Potential applicants may obtain a copy of "Health People 2000" (Full Report: Stock No. 017-001-00474-0) or (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY CRITERIA All domestic institutions with active MARC research training grants are eligible to apply. MECHANISM OF SUPPORT A MARC honors training grant (T34) to the academic institution requesting support for a student will be administratively supplemented. Unless otherwise noted, all PHS and NIH grants policies apply to applications received in response to this announcement. The supplement will provide the following: (1) A subsistence of $300 per week ($3,000 for a maximum ten-week period), and (2) round-trip transportation (from MARC student's academic institution to the National Institutes of Health, Bethesda, Maryland, and return to student's academic institution). Indirect costs may be awarded to the institution for up to a maximum of eight percent of the direct costs. RESEARCH OBJECTIVES The purpose of this award is to increase research training opportunities in the NCI for underrepresented minority scholars and to increase the number of minority scholars entering cancer-related research careers through the influence of short-term laboratory training at the NCI. APPLICATION PROCEDURES The Principal Investigator must submit a letter, countersigned by an authorizing official of the grantee institution, requesting support of a student for short-term laboratory training at the NCI. This letter will constitute an application and must include the following: o A statement from the student that describes his/her research interests and career objectives and a brief resume; o Two letters of recommendation; o A current official college/university transcript; o The student's selection of three NCI laboratory choices prioritized by level of interest; o The title of the announcement; o A copy of the face page of the active MARC grant including the grant number and period of award; and o A description of the personnel to which the student will report his/her NCI laboratory experience. A list of NCI laboratory choices will be available to all applicants through the CMBP office. Application packages must be received by the CMBP no later than February 1, 1993. The 10-week training period may be between May 1993 and August 1993, inclusive. Under this announcement funding is available for this period only. More than one supplemental application may be submitted by each grantee institution. Supplemental applications to active MARC undergraduate training grants must be submitted directly to the CMBP, with a copy to the MARC program, at the address listed below. REVIEW CONSIDERATIONS Applications in response to this announcement will be considered by NCI Staff; final selection for laboratory experience will be made by the relevant laboratory directors. Selection will be made on the following criteria: o The strength of the interest in pursuing a laboratory experience in the biomedical sciences based on the statement from the student; o The strength of the letters of recommendation; o Cumulative grade point average (2.75 or more based on 4.0 maximum). Applications found to be responsive to the announcement will be considered; those found to be unresponsive will not be considered. A letter from the CMBP Director will be sent to the grantee institution stating the reason for the outcome of the evaluation. INQUIRIES Direct inquiries regarding programmatic issues to: Program Director Comprehensive Minority Biomedical Program Division of Extramural Activities National Cancer Institute Building 31, Room 10A04 Bethesda, MD 20892 Telephone: (301) 496-7344 Program Director Minority Access to Research Careers National Institute of General Medical Sciences Westwood Building, Room 9A18 Bethesda, MD 20892 Telephone: (301) 496-7941 Direct inquiries regarding fiscal matters to: Ms. Carolyn Mason Grants Management Specialist Grants Administration Branch National Cancer Institute Executive Plaza South, Room 243 Bethesda, MD 20892 Telephone: (301) 496-7800, Extension 59 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance, No. 93.398 Cancer Research Manpower. National Institutes of Health, Public Health Service, Department of Health and Human Services Authorization: Public Health Service Act, Service 413, as amended by Public Law 99-158, 42 U.S.C. 288. Federal Agency: National Institutes of Health, Public Health Service, Department of Health and Human Service Authorization: Public Health Service Act, Section 301, Public Law 78- 410, 42 U.S.C. 241, and Section 412, as amended by Public Law 99.158, 42 U.S.C. 285a-1. Executive Order 12372 applicable. $$P1 END ************************************************************ ERRATUM $$E1 BEGIN P2 19921120 APPEND PA-93-22 BOTH **************************** "FAILURE TO THRIVE" SYNDROME AMONG OLDER PERSONS NIH GUIDE, Volume 21, Number 45, December 18, 1992 PA NUMBER: PA-93-22 P.T. 34; K.W. 0710010, 0710095, 0715072, 0710070, 0765035 National Institute on Aging National Institute of Mental Health This erratum is issued for Program Announcement PA-93-22, published in the NIH Guide for Grants and Contracts, Vol. 21, No. 42, November 20, 1992. There are two staff changes under the section INQUIRIES. INQUIRIES James K. Cooper, M.D., Geriatrics Program, Suite 3E327 Telephone: (301) 496-6761 Pamela Starke-Reed, Ph.D., Biology of Aging Program, Suite 2C231 Telephone: (301) 496-6402 $$E1 END ************************************************************ $$XID RFA DK9309 DK-93-09 P1O1 ***************************************** KIDNEY RESEARCH CENTERS NIH GUIDE, Volume 21, Number 44, December 11, 1992 RFA: DK-93-09 P.T. 04; K.W. 0785095, 1002004, 1002008, 0710070, 1002019, 0710030 National Institute of Diabetes and Digestive and Kidney Diseases Letter of Intent Receipt Date: March 8, 1993 Application Receipt Date: April 9, 1993 PURPOSE This Reques for Applications (RFA) invites investigators to submit research applications for the George M. O'Brien Research Centers Program. The emphases for this program are threefold: (1) to attract new scientific expertise into the study of the basic mechanisms of kidney diseases and disorders; (2) to encourage multidisciplinary research focused on the causes of these diseases; and (3) to extend the development of innovative clinical and epidemiologic studies of the causes, therapy, and possible prevention of kidney diseases and disorders. In approaching the study of these disease processes, it is anticipated that extensive collaboration will be required between individuals in the clinical and basic sciences, including, for example, investigators with training and expertise in cell biology, molecular biology, immunology, genetics, epidemiology, biochemistry, physiology, and pathology. It is the express intent of this announcement to attract new investigators not currently active in this field and to explore new basic areas that may have clinical research applications. Individual institutions with both basic and clinical research capabilities are invited to apply. Interinstitutional collaborative research arrangements are also appropriate and encouraged. Coordination for such arrangements must be evident and clearly meaningful and appropriate for the research proposed. 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 RFA, Kidney Research Centers, is related to the area of diabetes and other chronic disabling conditions. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Foreign institutions are not eligible to apply. Minority individuals and women are encouraged to submit as Principal Investigators. MECHANISM OF SUPPORT Support of this program will be through the National Institutes of Health (NIH) specialized center (P50) award. Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. Except as otherwise stated in this announcement, awards will be administered under PHS grants policy as stated in the PHS Grants Policy Statement. FUNDS AVAILABLE The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) expects to award up to two center grants (P50) in FY 1993 for research into kidney disorders. The anticipated awards will be for five years and will be contingent upon the availability of appropriated funds. The total amount of available funds to support this program is anticipated to be no more than $1.5 million per year. No applicant may request more than $750,000 in total costs (including both direct and indirect costs) in the initial budget period. A standard escalation factor may be used for subsequent budget periods. The award date for these grants will be September 30, 1993. RESEARCH OBJECTIVES Kidney diseases and disorders place a substantial burden on individuals and on society in the United States. They threaten the health, well-being, and longevity of millions of Americans. Chronic renal failure, for example, accounted for an estimated $3.7 billion of direct hospital and physican costs in 1990. Although considerable progress has been made in understanding the basic physiology and pathophysiology of the normal renal systems, there has been only limited progress in unraveling the mechanisms of those processes that lead to progressive deterioration in the function of these systems. Nevertheless, major progress has been made in the management of their clinical consequences. For example, renal dialysis and transplantation are life saving procedures. Unfortunately, these scientific and medical advances have not led to the means to prevent or reverse the consequences of these diseases and disorders; moreover their incidence is steadily increasing. The proposed multidisciplinary research centers should help to provide an environment for investigators to apply the necessary and appropriate expertise to topical areas of research related to the pathogenesis of kidney diseases such as: immunologically mediated diseases; diabetes mellitus and other endocrine and metabolic disorders; primary renal hypertension; genetic abnormalities; and nephrotoxins and toxic cell injury. Applicants from institutions that 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. If so, a letter of agreement from either the GCRC program director or Principal Investigator may be included with the application. SPECIAL REQUIREMENTS Successful applicants are expected to attend a yearly meeting of Center Directors convened by the NIDDK. Funds to support travel to this meeting may be requested in the budget proposed for the center. STUDY POPULATIONS It is NIH policy that women and minorities must be included in clinical study populations unless there is a good reason to exclude them. The study design must seek to identify any pertinent gender or minority population differences. SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements are required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis must be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale must be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues must be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information must be included in the form PHS 398 (rev. 9/91) in Item 4 (Research Design and Methods) of the Research Plan AND summarized in Item 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations; i.e., Native Americans [including American Indians or Alaskan Natives], Asian/Pacific Islanders, Blacks, Hispanics. The rationale for studies on single minority population groups should be provided. For the purpose of this policy, clinical research is defined as human biomedical and behavioral studies of etiology, epidemiology, prevention [and preventive strategies], diagnosis, or treatment of diseases, disorders or conditions, including but not limited to clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded. However, every effort should be made to include human tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. If the required information is not contained within the application, the application will be returned without review. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. LETTER OF INTENT Prospective applicants are asked to submit, by March 8, 1993, a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, the identities of other key personnel and participating institutions, and the number and title of 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, the information that it contains is helpful in planning for the review of applications. It allows NIDDK staff to estimate the potential review workload and to avoid possible conflict of interest in the review. The letter of intent is to be sent to: Chief, Review Branch, Division of Extramural Activities National Institute of Daibetes and Digestive and Kidney Diseases Westwood Building, Room 605 5333 Westbard Avenue Bethesda, MD 20892 Telephone: (301) 496-7083 FAX: (301) 402-1277 APPLICATION PROCEDURES The research grant application form PHS-398 (rev. 9/91) is to be used in applying for these grants. The form is available from most institutional offices of sponsored research and from the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone (301) 496-7441. The RFA label available in the application form must be affixed to the bottom of the face page. 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 2a of the face page of the application form and check the YES box. Applications must include the following items: o A Table of Contents; o A Rationale for the proposed Center and a Statement of Objectives; o Institutional Environment and Resources; o Organization and Administrative Structure of the Center; o Specific Managerial Responsibilities for the Center; o Travel funds in the proposed budget for an annual meeting of Center Directors; o A description of the method for the replacement of the Center Director (should the need arise); o A description of the proposed research projects; o A description of the proposed cores; o A description of the procedure to be used for the addition/deletion of cores and projects during the proposed period of operation; o A description of the administrative relationship of the Center to the applicant institution. Submit a signed, typewritten original of the application, including the Checklist, and three signed, exact photocopies, in one package to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** At time of submission, two additional copies of the application must also be sent under separate cover to: Chief, Review Branch, Division of Extramural Activities National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 605 5333 Westbard Avenue Bethesda, MD 20892 Applications must be received by April 9, 1993. If an application is received after that date, it will be returned to the applicant. REVIEW CONSIDERATIONS Upon receipt, applications will be initially reviewed for completeness and responsiveness. Incomplete applications or non-responsive applications will be returned to the applicant without further consideration. Evaluation for responsiveness to the program requirements and criteria stated in the RFA is an NIDDK staff function. Those applications that are complete and responsive will be evaluated in accordance with the criteria stated below for scientific/technical merit by an appropriate peer review group convened by the NIDDK. If the number of applications is large compared to the number of awards to be made, a preliminary scientific peer review may be conducted and applications withdrawn from further competition when they are not competitive for the award. The NIDDK will notify the applicant and institutional official of this action. Those applications judged to be competitive will be reviewed for scientific and technical merit in accordance with the usual NIH peer review procedures by an initial review group specifically convened for this RFA. Following this review, the applications will be given a secondary review by the NIDDK Advisory Council unless not recommended for further consideration by the initial review group. The review criteria for individual research projects include: o The scientific, technical or medical significance and originality of the proposed research; o The feasibility and adequacy of the experimental design(s); o The qualifications and research experience of the proposed personnel; o The availability of resources necessary for the research; o The appropriateness of the budget and timetable in relation to the scope of the proposed research; The review criteria for scientific cores include: o The appropriateness and utility of the core to the proposed Center; o Each core unit must provide facilities or services to at least two research projects recommended for approval; o The quality of the proposed facilities or services including administrative arrangements for utilizing the core; o The qualifications, experience, and commitment of the personnel involved in the core; o The appropriateness of the budget. The review criteria for the overall Center program include: o The scientific merit of the program as a whole; o The significance of the overall goals of the Center; o The cohesiveness and multidisciplinary scope of the Center and the coordination and interrelationship of the projects and cores to the common theme of the Center; o The leadership, scientific expertise, and commitment of the proposed Center Director. Administrative Considerations: o The institutional environment for and resources available to Center investigators; o The institutional commitment to the proposed Center; o The administrative leadership necessary to provide for the quality control of supported projects in the Center, the allocation of funds, and the ability to foster communication and cooperation among Center investigators; o The appropriateness of the budget in relation to the proposed activities of the Center; o The adequacy of addressing the protection of human subjects, animal welfare, and biohazard issues. AWARD CRITERIA The anticipated date of award is September 30, 1993. Factors that will be taken into consideration in making awards include the scientific merit of the proposed Center as determined by peer review and the availability of funds. Schedule Letter of Intent: March 8, 1993 Application Receipt: April 9, 1993 Initial Review: July 1993 Second Level Review: September 13-14, 1993 Anticipated Award: September 30, 1993 INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. Inquiries regarding programmatic issues may be directed to: Ralph L. Bain, Ph.D. Director, Centers Program Division of Kidney, Urologic, and Hematologic Diseases National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 3A-05 Bethesda, MD 20892 Telephone: (301) 496-7574 Inquiries regarding fiscal matters should be directed to: Ms. Helen Ling Division of Extramural Activities National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 649 5333 Westbard Avenue Bethesda, MD 20892 Telephone: (301) 496-7467 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.849. Awards are made under 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 requirements of Executive Order 12372 or Health Systems Agency review. From owner-sci-resources@net.bio.net Wed Dec 16 22:00:00 1992 Path: biosci!NET.BIO.NET!kristoff From: kristoff@NET.BIO.NET (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 21, no. 45, pt. 3, 18 December 1992 Message-ID: Date: 17 Dec 92 02:45:42 GMT Sender: kristoff@net.bio.net Distribution: bionet Lines: 1022 $$XID RFA CA9307 CA-93-07 P1O1 ***************************************** PHASE I TRIALS OF NEW ANTI-CANCER AGENTS NIH GUIDE, Volume 21, Number 45, December 18, 1992 RFA: CA-93-07 P.T. 34; K.W. 0755015, 0715035, 0740020, 0710100 National Cancer Institute Letter of Intent Receipt Date: January 22, 1993 Application Receipt Date: March 23, 1993 PURPOSE The Division of Cancer Treatment (DCT), National Cancer Institute (NCI) invites cooperative agreement (U01) applications from single institutions wishing to perform Phase I trials of promising anti-cancer agents in patients with cancer refractory to currently available therapy and to conduct laboratory studies in support of the clinical trials such that their conduct leads to a greater understanding of the relationship between drug administration and biological changes in patients. Patients should be treated only at the applicant institution, although support for laboratory studies may be conducted by collaborators at other institutions. The increasing numbers of promising new agents with novel mechanisms of action and the large number of institutions both capable of and interested in conducting Phase I clinical trials of cancer therapies makes it desirable to expand NCI grant support in this area. The need for increased resources for clinical development of a wide range of novel anti-cancer agents has led to this request for cooperative agreement applications to establish the pharmacological and initial clinical characteristics of these agents. Institutions responding to this Request for Applications (RFA) should be able to perform Phase I trials and establish the pharmacological characteristics, in parallel with biochemical and other appropriate biological studies, of the effects of these agents on cancer cells and normal tissues. It is expected that the application from any one institution will focus on studies of one or more classes of agents, reflecting the interest, expertise, and experience of the applicant investigators. 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 RFA, Phase I Trials of New Anti-Cancer Agents, is related to the priority area of cancer. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202/783-3238). ELIGIBILITY REQUIREMENTS Domestic for-profit and non-profit organizations such as universities, colleges and hospitals and governments and their agencies are eligible to apply. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT Support of this program will be through the cooperative agreement (U01), an assistance mechanism in which substantial NCI programmatic involvement with the recipient during performance of the planned activity is anticipated. The nature of NCI staff involvement is described in the section SPECIAL REQUIREMENTS, Terms of Cooperation, Nature of Participation by NCI Staff. Applicants will be responsible for the planning, direction, and execution of the proposed project. There is no intent, real or implied, for NCI staff to direct awardee activities or to limit the freedom of investigators. Under the cooperative agreement, a relationship exits between the recipient of the award and the NCI, in which the recipient is responsive to the requirements and conditions set forth in the RFA. Specifically, the Principal Investigator defines the details for the project within the quidelines of the RFA, retains primary responsibility for the performance of the activity, and agrees to accept close coordination, cooperation and assistance of the NCI extramural staff (through the NCI Program Director - see INQUIRIES) in all aspects of scientific and technical management of the project in accordance with the Terms of Cooperation. Except as otherwise stated in this RFA, awards will be administered under PHS grants policy as stated in the Public Health Service Grants Policy Statement, DHHS Publication No. (OASH) 90-50,000, revised October 1, 1990. This RFA is a one-time solicitation. However, if it is determined that there is a sufficient continuing program need, the NCI will invite recipients of awards under this RFA to submit competitive continuation cooperative agreement applications for review according to the procedures described in Review Considerations, Part A. FUNDS AVAILABLE Approximately $2,000,000 in total costs per year for four years will be committed to specifically fund applications submitted in response to this RFA. This funding level is dependent on the receipt of a sufficient number of applications of high scientific merit. It is anticipated that six to eight awards will be made. The total project period for applications submitted in response to the present RFA may not exceed four years. The earliest feasible start date for the initial awards will be December 1, 1994. Although this program is provided for in the financial plans of the NCI, the award of cooperative agreements pursuant to this RFA is contingent upon the availability of funds for this purpose. RESEARCH OBJECTIVES A. Background The purpose of this RFA is to provide support for single institution Phase I clinical trials with investigational anti-cancer agents. Phase I clinical trials have as their objectives the characterization of drug toxicity, maximally tolerated dose, pharmacokinetics, and biological effects (pharmacodynamics) of drugs. These anti-cancer agents have traditionally been obtained either from the NCI drug development program or through collaborative drug development agreements with the pharmaceutical industry. Recent advances in understanding of the pathobiology of malignancy are leading to the development of a wide range of novel anti-cancer therapeutic agents that require Phase I testing. These agents include, but are not limited to, new classes of cytotoxic agents derived from natural products, as well as rationally designed anti-cancer agents targeted specifically to novel cancer cell targets, including surface receptors, signal transduction molecules, transcriptional factors, and particular DNA and RNA sequences. Furthermore, mechanisms of action of these new anti-cancer agents available for clinical study include not only the mediation of anti-cancer effects through cytotoxic mechanisms, but also through growth inhibition by interruption of specific oncogene-associated biochemical functions, inhibition of protein synthesis through targeted toxins, induction of differentiation and/or programmed cell death (apoptosis), and through anti-tumor angiogenesis. In addition, new strategies to overcome resistance to conventional cancer therapeutic approaches are also of interest. In an attempt to reduce the time period between new drug discovery and the general introduction of an effective new therapy to patients, the NCI offers assistance at many levels to investigators attempting to develop active new cancer therapies. In addition to the funding assistance offered to the investigator(s) by this RFA, NCI may sponsor (in the Food and Drug Administration sense) or co-sponsor the agents under development. An organization or individual who assumes legal responsibilities for supervising or overseeing clinical trials with investigational agents is termed a sponsor. As sponsor of an investigational drug, DCT and specifically, CTEP, is responsible for ensuring that clinical trials proceed safely and rationally from the initial dose-finding studies to a definitive evaluation of the role of the new drug in the treatment of one or more specific cancer(s). Fulfillment of this goal obviously requires the active participation of CTEP staff throughout the entire process. NCI sponsorship of investigational agents increases the likelihood that agents will be further developed so that they will ultimately be broadly available for use in cancer treatment and will accelerate the time frame in which this process would occur. B. Research Goals and Scope The aims of this initiative are: (1) to provide support for Phase I trials of promising new anti-cancer agents in cancer patients; and (2) to provide support for complete pharmacokinetic, pharmacodynamic, and other importan