From owner-sci-resources@net.bio.net Tue Aug 05 23:00:00 1997 Path: biosci!biosci!not-for-mail From: BIOSCI Administrator Newsgroups: bionet.sci-resources Subject: NIH GUIDE - RFA HL-97-015 - V26(25) 08/01/97 Date: 5 Aug 1997 21:53:58 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 631 Sender: daemon@net.bio.net Approved: biosci-help@net.bio.net Distribution: world Message-ID: <5s9016$4v7@net.bio.net> NNTP-Posting-Host: net.bio.net SLEEP ACADEMIC AWARD NIH GUIDE, Volume 26, Number 25, August 1, 1997 RFA: HL-97-015 P.T. National Heart, Lung, and Blood Institute Letter of Intent Receipt Date: November 20, 1997 Application Receipt Date: December 23, 1997 THIS RFA USES "JUST-IN-TIME" PROCEDURES. THIS RFA INCLUDES DETAILED MODIFICATIONS TO STANDARD APPLICATION INSTRUCTIONS THAT MUST BE FOLLOWED WHEN PREPARING AN APPLICATION IN RESPONSE TO THIS RFA. PURPOSE The primary objective of this initiative is to encourage the development and/or improvement of the quality of medical curricula, physician/patient/nurse and community education, and clinical practice for the prevention, management, and control of sleep disorders. A secondary objective is to promote high quality clinical research in sleep. 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, Sleep Academic Award, is related to the priority areas of heart disease and stroke, diabetes, chronic disabling conditions, mental health and disorders, and clinical prevention services. 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 202-512-1800). ELIGIBILITY REQUIREMENTS Institutions Applications may be submitted by any domestic university or school of medicine or osteopathy. Institutions that have not yet developed a curriculum in sleep medicine are especially encouraged to apply. Eligible institutions may submit only one application in each competition. Institutions that are already receiving support from the Sleep Academic Award program may not apply for this competition. Institutions may sponsor a candidate experienced in both medical education and clinical sleep research or a candidate experienced in clinical sleep research if supported by faculty with expertise in medical education. Institutions should also be committed to implementing the curricula development and educational research programs proposed by candidates. In this competition, there is a special interest in receiving applications from minority institutions and institutions with eligible minority faculty members. Candidates A candidate for the Sleep Academic Award must have the following credentials: o knowledge and skills in sleep and sleep disorders medicine and a demonstrated commitment to one or more areas of medical education for students, physicians, patients, nurses, or the public; o sufficient post graduate training and experience in clinical sleep research, clinical practice, and/or medical education to develop and implement a high quality curriculum in sleep and sleep disorders and to provide leadership in clinical research on sleep; o established appointment on the faculty of an accredited school of medicine or osteopathy in the United States, its territories or its possessions; o unqualified support from the Dean and educational leadership of the institution and; o be a citizen or non-citizen national of the United States or have been lawfully admitted to the United States for permanent residence at the time of application. Individuals who have or have had another NIH career development award (K series) or a regular research grant (R01) are eligible for a Sleep Academic Award if the individual meets the requirements of the Sleep Academic Award program. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT This RFA is part of the Academic Award Program (K07) of the National Heart, Lung, and Blood Institute. Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. The total project period may not exceed five years and is non-renewable. Awards will be limited to a maximum of $50,000 for the salary of the Principal Investigator, plus applicable fringe benefits, and a maximum of $30,000 for technical support. Facilities and administrative (indirect) costs may not exceed 8 percent. It is anticipated that support for this program will begin September 1, 1998. Application instructions have been modified to reflect "just-in-time" streamlining efforts being considered by the NIH. The just-in-time concept requires applicants to submit certain materials only when there is the possibility of an award. It is anticipated that these changes will reduce the administrative burden for the applicants, reviewers, and NHLBI staff. For this RFA, only limited budgetary information is required in the application. However, the anticipated level of effort in all years and a brief description of responsibilities for the Principal Investigator and key personnel must be included in the research plan. Instructions for completing the Biographical Sketch have been modified. In addition, the Other Support information and application "Checklist" page are not required as part of the initial application. If the possibility of an award exists, the Budget, Other Support, and Checklist information will be requested by NHLBI staff following the initial review. The APPLICATION PROCEDURES section of this RFA provides specific details of these modifications to the standard PHS 398 application kit. FUNDS AVAILABLE It is anticipated that in fiscal year 1998, support will be available for total costs of approximately $300,000 and that approximately three to four grants will be awarded under this program. The actual number of awards each year, however, will depend upon the merit and scope of the applications received and the availability of funds. RESEARCH OBJECTIVES Background Recent estimates suggest that as many as 40 million people may suffer from chronic or intermittent disorders of sleep. Many remain undiagnosed and untreated, the consequences of which include reduced productivity, lowered cognitive performance, increased likelihood of accidents, higher risk of morbidity and mortality and decreased quality of life. It is now apparent that sleep disorders, disturbances of sleep, and sleep deprivation are major public health concerns. Sleep problems occur in both genders, in all races and socioeconomic groups, and increase with age. National attention has been directed to this problem. The National Commission on Sleep Disorders Research submitted their report entitled "Wake Up America: A National Sleep Alert" to the United States Congress in January 1993. The Commission's recommendations include encouraging broader awareness of sleep and training in sleep and sleep disorders, spanning the full range of health care professions, particularly at the primary care level. Several surveys have documented that physician training and knowledge about sleep and sleep disorders is minimal. For example, in 1978 the American Sleep Disorders Association (ASDA) conducted a survey of medical school teaching and found about one third of the medical schools provided between 1-4 hours of teaching in sleep. A more recent (1990) survey found that less than two hours were allocated to teaching about sleep at one third of the medical schools and one third reported no formal teaching about sleep. It was estimated that about 30% of medical students receive no instruction in sleep. These results would suggest that there actually has been a decrease in the amount of medical school training about sleep. The American Thoracic Society (ATS) surveyed pulmonary residency training programs and found that 70% had laboratories, but only 29% had formal training programs about sleep. Of greater concern was that 90% of the trainees diagnosed patients with sleep apnea, but only 33% of the trainees had formal training on how to conduct sleep studies. The major obstacles cited for increasing the attention to sleep in medical schools included low administrative priority, lack of qualified faculty, and limited curriculum time. Given the limited medical school training about sleep and sleep disorders, it is not surprising that several surveys have reported that health practitioners rarely diagnose sleep disorders. In fact, primary care physicians scored less than 50% correctly on factual items for diagnosis and management of sleep disorders. A 1991 Gallup survey showed that primary care physicians failed to correctly diagnose one in three adults with insomnia. Most narcoleptics contact as many as five physicians before a proper diagnosis is made. Clearly, physicians are not well trained or knowledgeable about sleep and sleep disorders. Sleep disorders cut across several medical specialties (e.g., neurology, psychiatry, internal medicine, pulmonary medicine, and otolaryngology etc.), which complicates the development of effective treatment guidelines and research. Although most sleep disorders can be controlled with medical treatment, many patients are not being diagnosed or receiving state-of-the-art medical care. This may be because many people believe that no effective treatments exist and therefore do not seek medical help. Multidimensional research is clearly necessary to improve clinical practice and patient education. Therefore, the aim of this program is to improve the quality of medical education and to stimulate the development of patient and community education, high quality clinical research programs, and clinical practice focused on the control of sleep disorders. Applicants are encouraged to submit program plans in sleep education and applied research that complement each other. Objectives The objectives of the Sleep Academic Award program include the following: o develop high quality curricula in schools of medicine that will significantly increase the knowledge and skills of students, house staff, practicing physicians, and others needed to apply state-of-the-art principles and practice to the prevention, management, and control of sleep disorders; o evaluate the impact of the proposed program and assemble curricular materials that can be adapted and used by other Institutions; o improve communication among specialists in primary care and other specialties to ensure appropriate strategies for the treatment of sleep disorders in patients of various ages and ethnic groups; o foster development of institutional environments facilitating the interchange of information on advances in sleep research and the implementation of improved interdepartmental programs with standardized diagnostic and therapeutic approaches to sleep medicine; o educate community health practitioners and the public about sleep and sleep disorders through the development of outreach programs, especially through the enhancement of sleep education programs in minority medical schools and the communities they serve; o develop the sleep medicine skills of faculty to provide high quality instruction in the diagnosis and management of sleep disorders, with special emphasis on minority faculties; o establish channels of communication between medical educators, institutions, sleep researchers, and community agencies to enhance the transfer of knowledge and ideas on educational requirements and optimal approaches to the prevention and management of sleep disorders; o contribute to public health efforts to address sleep disorders in the United States; o encourage the development of high quality clinical and applied research in the treatment and control of sleep disorders. In this competition, programs targeted to inner city populations and to rural areas needing education about sleep and sleep disorders and to community physicians, nurses, and other health care workers caring for medically undeserved populations are of particular interest. SPECIAL REQUIREMENTS Applicants should develop a comprehensive program that effectively addresses the needs in their area and the objectives of this RFA. The primary focus must be on plans to improve the quality of medical school education on sleep and sleep disorders for students and physicians. Plans and educational materials for curricular improvements must be of a design that facilitates replication at other sites. All applications must also include plans to evaluate the outcome of educational and research initiatives. The responsibilities of the Principal Investigator and key personnel must be specifically stated at the beginning of the research plan and placed in the context of other institutional and research commitments. Since the Sleep Academic Award primarily provides support for the salary of the Principal Investigator, applications that are contingent on receiving support from other agencies and institutions must specifically identify these resources in relationship to the program plan. For revised applications, the comments of the previous review committee should be specifically addressed in a preface to the program plan. INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of the NIH that women and members of minority groups and their subpopulations must be included in all NIH supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification is provided that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43) and supersedes and strengthens the previous policies (Concerning the Inclusion of Women in Study Populations, and Concerning the Inclusion of Minorities in Study Populations), which have been in effect since 1990. The policy contains some provisions that are substantially different from the 1990 policies. All investigators proposing research involving human subjects should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research," which have been published in the Federal Register of March 28, 1994, (F 59 14508-14513), and reprinted in the NIH GUIDE FOR GRANTS AND CONTRACTS of March 18, 1994, Volume 23, Number 11. Investigators may obtain copies of the policy from these sources or from the program staff listed under INQUIRIES. Program staff may also provide additional relevant information concerning the policy. Although the Sleep Academic Award is not primarily a mechanism to support research, it is likely that human subjects will be involved. Therefore, protection for human subjects must be addressed, and the approximate percent of women and each minority group that you expect in the total population must be included. LETTER OF INTENT Prospective applicants are asked to submit, by November 20, 1997, a letter of intent that includes a descriptive title of the proposed program plan, the name, address, and telephone number of the Principal Investigator, the identities of other key personnel, 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 faxed or sent to Dr. C. James Scheirer, at the address listed under INQUIRIES. APPLICATION PROCEDURES Applications are to be submitted on the grant application form PHS 398 (rev. 5/95). These forms are available at most institutional offices of sponsored research and from the Grants Information Office, Office of Extramural Outreach and Information Resources, National Institutes of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone (301) 435-0714, Email: asknih@odrockm1.od.nih.gov. The RFA label available in the PHS 398 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" in item 2 of application page 1 and enter the title "Sleep Academic Award NIH HL-97-015". Use the following modifications in completing the standard PHS 398 application instructions: o BUDGET INFORMATION - No current/future year budgets or justifications (Form Pages 4 and 5) are required in the application. However, the anticipated level of effort in all years and a brief description of responsibilities for the Principal Investigator and all key personnel must be specifically stated at the beginning of the research plan. Necessary budget information will be requested by NHLBI staff if there is a possibility for an award. o BIOGRAPHICAL SKETCH - In addition to the standard information requested on Form Page 6, the applicant should provide the title and source of any sponsored support relevant to the proposed research. o OTHER SUPPORT - No other support information is required on the "Other Support" page (Form Page 7). Selected other support information relevant to the proposed research may be included in the Biographical Sketch as indicated above. Complete other support information will be requested by NHLBI staff if there is a possibility for an award. o CHECKLIST - No "Checklist" page is required as part of the initial application. A completed Checklist will be requested by NHLBI staff if there is a possibility for an award. o FACE PAGE - Currently, the Division of Research Grants requires that requested costs be reflected on the face page for computer system tracking purposes. Because no budgetary information is required as part of the "streamlined" application, we are requesting that the following amounts be entered on the face page: 7a. Direct Costs for Initial Budget Period - $80,000; 7b. Total Costs for Initial Budget Period - $86,400; 8a. Direct Costs for Proposed Period of Support - $400,000 and; 8b. Total Costs for Proposed Period of Support - $432,000. It is understood that these levels are strictly for administrative purposes and that actual award levels are subject to negotiation, prior to award. The applicant should provide the name, phone number, and facsimile phone number of the individual to contact concerning fiscal and administrative issues if additional information is necessary following the initial review. Applications not conforming to these guidelines will be considered unresponsive to this RFA and will be returned without further review. Submit a signed, typewritten original of the application and three signed, photocopies, in one package to: DIVISION OF RESEARCH GRANTS NATIONAL INSTITUTES OF HEALTH 6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710 BETHESDA, MD 20892-7710 BETHESDA, MD 20817 (for express courier service) At the time of submission, two additional copies of the application must be sent to Dr. C. James Scheirer, at the address listed under INQUIRIES. Applications must be received by December 23, 1997. 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 RFA that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. The DRG will also 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. o If an application is determined to be unresponsive to the RFA, the principal investigator will be notified and the application returned. The following sections are specific cost guidelines that will apply to those applications selected for award consideration. 1. Principal Investigator's Salary The salary for the Principal Investigator must not exceed the actual institutional salary rates for the effort being devoted to the Academic Award. In addition, salary rates must not exceed an annual salary level of $125,000 plus fringe benefits (a maximum of $50,000 plus fringe benefits for 40 percent effort). A candidate must devote at least 30 percent effort and no greater than 40 percent effort to this award. The combined efforts of any individual, Principal Investigator or key personnel, on the Sleep Academic Award and any other non-NIH or NIH-supported grant(s) or contract(s) must not exceed 100 percent. 2. Program Support Technical support will be provided up to a maximum of $30,000 per year for the following: o personnel, other than the Principal Investigator, if requested for the development, implementation, and evaluation of the program. Collaborations with consultants possessing medical, educational, or evaluative expertise complementary to that of the principal investigator are strongly encouraged. Salaries and the associated costs for any personnel other than the Principal Investigator are limited to the $30,000 per year allowed for technical support. o consumable supplies essential to the proposed program are allowable, but equipment costs are not allowable; o funds for educational development to enable the awardee to develop educational skills; o funds for the Principal Investigator to travel and meet with other investigators and NHLBI staff to exchange ideas, to develop collaborative projects, and to provide for some needed technical support. (Investigators may be requested to meet as a group up to two times a year; $2,000 should be allocated for this purpose.) 3. Facilities and Administrative Costs Facilities and administrative costs will be provided at eight percent of the total direct costs of each award excluding equipment. 4. Conditions of the Award Institutions must provide documentation that the applicant would have the necessary time and resources to implement the proposed plan. In some cases, it may be necessary for the applicant to be relieved of some responsibilities for the five years of the grant award in order to implement the proposed plan. An institution is expected to apply on behalf of a named individual meeting the criteria for this award. Only one application may be submitted from each eligible institution in each competition. Awards will be limited to one from each eligible school over the life of the award. After the first year, grants will be renewed for a maximum of four years on a noncompetitive basis depending upon progress in meeting the program's objectives and the availability of funds. An annual report that summarizes curriculum development at the institution, other elements of the program plan, and the outline of future plans will be required. This report will serve as the principal basis for renewal of the grant. Awards may not be transferred from one institution to another. If a principal investigator moves to another institution, the award will continue at the original institution only upon acceptance by the National Heart, Lung and Blood Institute of a suitable replacement proposed by the grantee institution. Such a replacement will not lengthen the overall term of the award. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by the DRG and responsiveness to this RFA by NHLBI. Incomplete or non-responsive applications will be returned to the applicant without further consideration. Applications will be evaluated for scientific and technical merit by an appropriate peer review group convened by the Division of Extramural Affairs, NHLBI. The roster of the review panel may be found on the NHLBI home page (gopher://fido.nhlbi.nih.gov:70/11/nhlbi/about/meet/sep/irsep) approximately one month prior to the review date. As part of the initial merit review, all applications will receive a written critique and undergo a review in which only those applications deemed to have the highest scientific merit of the applications under review (usually two to three times the number of applications that the NHLBI and participating Institutes anticipate funding under the program) will be discussed, assigned a priority score, and receive a second level review by the National Heart, Lung, and Blood Advisory Council. Review Criteria Applications for this Sleep Academic Award will be evaluated in terms of the following criteria: o qualifications and effort level of the candidate and key personnel, including pertinent experience in teaching, curriculum development, program evaluation, administration, and clinical research program planning and conduct; o plans to develop, improve, and integrate an interdepartmental curricula in sleep medicine with existing institutional training programs for medical students, graduates, and post-graduates; o plans to evaluate all proposed educational interventions, including strategies for both process and impact evaluation; o plans for communication and interdepartmental collaboration between medical specialists in appropriate disciplines to ensure the development, implementation, and evaluation of optimal treatment and educational programs; o plans and ability to work cooperatively with other investigators developing innovative and portable curricular materials in sleep medicine for replication at other sites; o the potential impact of the program on the degree of sleep medicine training and on the prevention, management, and control of sleep disorders within the population to be served; o plans for community outreach or collaborative projects with organizations having responsibility for or interest in sleep disorders, such as community centers, health departments, medical and nursing associations, voluntary health agencies, and home care agencies; o description of the need for this program and the magnitude of sleep disorders within the population to be served; o overall merit and feasibility of the proposed five year plan; o institutional commitment to implement the proposed curriculum and to maintain a program in education about sleep and sleep disorders after the termination of the award. AWARD CRITERIA The anticipated date of award is September 1, 1998. Factors that will be taken into consideration in making awards include the scientific merit of the proposed program as evidenced by the priority score and the availability of funds. Subject to the availability of necessary funds and consonant with the objectives of the Sleep Academic Award, the NHLBI will provide funds for a project period up to five years. INQUIRIES Inquiries concerning this RFA are encouraged. The opportunity to clarify issues or answer questions from potential applicants is also welcomed. Direct inquiries regarding programmatic issues to: Michael J. Twery, Ph.D. Division of Lung Diseases National Heart, Lung, Blood Institute 6701 Rockledge Drive, Suite 10018, MSC-7952 Bethesda, MD 20892-7952 Telephone: (301) 435-0202 FAX: (301) 480-3557 Email: TweryM@gwgate.nhlbi.nih.gov James P. Kiley, Ph.D. National Center on Sleep Disorders Research 6701 Rockledge Drive, Suite 7024, MSC-7920 Bethesda, MD 20892-7920 Telephone: (301) 435-0199 FAX: (301) 480-3451 Email: KileyJ@nih.gov Direct inquiries regarding review matters to: C. James Scheirer, Ph.D. Division of Extramural Affairs National Heart, Lung, and Blood Institute 6701 Rockledge Drive, Room 7220, MSC 7924 Bethesda, MD 20892-7924 Telephone: (301) 435-0266 FAX: (301) 480-3541 Email: ScheireJ@NIH.GOV Direct inquiries regarding fiscal matters to: Raymond L. Zimmerman Grants Operations Branch National Heart, Lung, and Blood Institute 6701 Rockledge Drive, Room 7154 Bethesda, MD 20892-7926 Telephone: (301) 435-0171 FAX: (301) 480-3310 Email: ZimmermR@NIH.GOV AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.838. Grants are made under the authorization of the Public Health Service Act, Title III, Section 301 (Public Law 78-410, as amended by Public Law 99-158, 42 US 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 to a review by a Health Systems Agency. The PHS strongly encourages all grant recipients to provide a smoke-free workplace and promote the non-use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people. From owner-sci-resources@net.bio.net Tue Aug 05 23:00:00 1997 Path: biosci!biosci!not-for-mail From: BIOSCI Administrator Newsgroups: bionet.sci-resources Subject: NIH GUIDE - RFA CA-97-022 - V26(25) 08/01/97 Date: 5 Aug 1997 21:53:24 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 803 Sender: daemon@net.bio.net Approved: biosci-help@net.bio.net Distribution: world Message-ID: <5s9004$4ul@net.bio.net> NNTP-Posting-Host: net.bio.net INFORMATICS SUPPORT FOR BREAST AND COLON CANCER COOPERATIVE FAMILY REGISTRIES NIH GUIDE, Volume 26, Number 25, August 1, 1997 RFA: CA-97-022 P.T. 34; K.W. 0710078, 0715035, 0715036, 0780030 National Cancer Institute Letter of Intent Receipt Date: September 3, 1997 Application Receipt Date: October 7, 1997 PURPOSE The Extramural Epidemiology and Genetics Program (EEGP), Division of Cancer Epidemiology and Genetics (DCEG), National Cancer Institute (NCI) invites applications from organizations with demonstrated excellence in information technology (informatics, software development), and operations management (coordination of participating centers, data management and quality assurance, biostatistics and study methodology) for a cooperative agreement (U01) for an Informatics Center (IC) for the NCI Cooperative Family Registries for Breast and Colon Cancer (see RFAs CA-95-003 and CA-96-011). Applicants are referred to the earlier RFAs for a full description of the purpose and organization of the Cooperative Family Registries for Breast and Colon Cancer Studies (CFRBCCS). Copies of the earlier RFAs can be obtained by request from the contact names listed in INQUIRIES, below. The purpose of the current solicitation is to provide technical assistance and resource support services for the Registries. The Registries represent an interdisciplinary consortium of participating centers of excellence in clinical and human genetics and epidemiology, funded as cooperative agreements. The Registries serve as a research infrastructure by linking the collective scientific expertise of the collaborating centers with study populations through a central registry of participating families, and providing access to scientific expertise beyond the scope of a single institution or organization. Technical skills and support services are required to: (1) assist the CFRBCCS investigators to assure the establishment, management and continuing quality of the CFRBCCS databases, including epidemiologic, clinical and repository-related information; (2) provide the technical expertise for the development of key information technologies, statistical methodology and study design that will be integral to the development of the next generation of cancer genetics studies; and (3) provide the technical expertise and training to the CFRBCCS necessary to develop, implement and maintain a central informatics system that facilitates the goals of the Registries and is secure and confidential. 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) 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 202-512-1800). ELIGIBILITY REQUIREMENTS Applications may be submitted by 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. Applicant institutions need not have a formal affiliation with an academic program in human genetics. However, experience in research related to genetic epidemiology and in the design and conduct of multi-site projects with data collection, management and quality assurance is highly desirable. Applications from centers of interdisciplinary research excellence, such as cancer centers, are encouraged. Applications from racial/ethnic minority individuals, women, and persons with disabilities as Principal Investigators are also encouraged. MECHANISM OF SUPPORT Support for this program will be through the cooperative agreement (U01). Substantial programmatic NCI involvement with the recipients is anticipated during development, implementation, and performance. Under the cooperative agreement, NCI will assist, support and/or stimulate the recipient's activities, working jointly with the participating centers and with the IC in a partnership role. Participating organizations will be responsible for planning and executing the proposed projects. Details of the responsibilities, relationship and governance of the project to be funded under cooperative agreements are discussed later in this document under the section "Terms and Conditions of Award." The total project period for applications submitted in response to the present RFA should not exceed five years. The anticipated award date is April 1, 1998. Although this program is provided for in the financial plans of the NCI, awards pursuant to this RFA are contingent upon the availability of funds for this purpose. This RFA is a one-time solicitation. At this time the NCI has not determined whether or how this solicitation will be continued beyond the present RFA. Except as otherwise stated in the RFA, awards will be administered under PHS grants policy as stated in the Public Health Service Grants Policy Statement, DHHS Publication No. (OASH) 94-50,000 (Rev.) April 1, 1994. FUNDS AVAILABLE Approximately $850,000 in total costs per year for five years will be committed to fund applications that are submitted in response to this RFA; the NCI anticipates making one award as a result of this RFA. Funding beyond the first and subsequent years of the cooperative agreement will be contingent upon satisfactory progress during the preceding years and availability of funds. RESEARCH OBJECTIVES Background The rapid identification of cancer susceptibility genes and the commercial availability of predictive genetic testing have created an urgent need for research to define the clinical implications of inherited mutations, including factors that modulate gene expression and potential preventive interventions, and to communicate up-to-date information about cancer genetics, genetic testing and cancer risk to health care providers and other interested individuals. To obtain answers to the next generation of questions in human cancer genetics, studies of unprecedented size and complexity will be required. By providing an infrastructure for interdisciplinary genetic epidemiology research, the CFRBCCS, in concert with other initiatives, will further our understanding of the genetics of cancer susceptibility, facilitate the translation of research findings into medical practice and address pressing public health issues. The strength of both the Breast and Colon Cancer Registries is based on the multicenter, multidisciplinary talents brought by the various teams and investigators, and on the collection of epidemiologic, clinical and family history data as well as biological specimens from participating families. The IC will provide the means to achieve cross-site analyses. The Cooperative Family Registry for Breast Cancer Studies is a network of investigators at seven sites who have had cooperative agreements since 1995 to collect pedigree information, epidemiologic and clinical data, and biological specimens from individuals and patients with a family history of breast cancer to provide a resource for basic, clinical, epidemiologic, and behavioral breast cancer genetics research, and to identify a population at high risk for breast cancer that could benefit from new preventive and therapeutic strategies. In the past two years, the Breast Cancer Registry has developed core protocols and questionnaires, as well as site-specific protocols reflecting the specific expertise and capability of each center. Participating Breast Cancer Registry institutions include: Northern California Cancer Center, Ontario Cancer Treatment and Research Foundation, Memorial Sloan-Kettering Cancer Center, University of Melbourne, Fox Chase Cancer Center, Huntsman Cancer Institute, University of California at Irvine. Recruitment of Breast Cancer Registry subjects is now actively underway; an estimated total of 8,000 families are projected to be enrolled during the coming two and one-half years. Similar to the Breast Cancer Registry, the Cooperative Family Registry for Epidemiologic Studies of Colon Cancer is envisioned to be a multi-center Registry which serves as a research resource to the scientific community. Plans for data collection are similar to the Breast Cancer Registry; in addition, genetic characterization is to be performed and population-based controls are to be accrued. The IC shall provide support to the Colon Cancer Registry as well as the Breast Cancer Registry. Six Colon Cancer Registry awards are pending. A total of 11,000 families are projected to be enrolled in the Colon Cancer Registry within five years. Illustrative of CFRBCCS projects that are envisioned but which require analysis of multi-site data to achieve adequate power include: Descriptive studies of the prevalence of carriers of specific mutations by ethnicity, religious affiliation, prior primary breast and colon cancer history, etc; assessment of the risk of breast and other cancers by mutation status and other demographic variables; and age-adjusted stage-specific survival from breast and colon cancer among mutation carriers; Pathology studies of the distribution of histologic types among breast and colon cancer cases with specific mutations; Etiologic studies of gene-gene and gene-environmental interactions including variables such as reproductive factors, alcohol consumption, body size, diet, physical activity, and radiation exposure; Psychosocial studies of the impact of registry participation on anxiety, family dynamics; the impact of genetic testing on psychological well-being; and the effectiveness of various interventions to increase understanding of genetic testing and to reduce anxiety; Pathology-based studies which compare histopathologic and molecular characteristics in carriers vs. non-carriers according to various demographic and epidemiologic characteristics. There is a need to provide for coordination of the central database that will permit ready access to cross-site core data from the Registries, conduct range and quality control checks, and ensure the confidentiality of the highly sensitive data. The central database will also include data collected in pilot studies approved by the Advisory and Steering Committees of the Registries (see Collaborative Responsibilities) and data generated from studies conducted by outside investigators who use Registry data for their investigations. Research Goals and Scope This RFA seeks to stimulate a cooperative effort to develop key information technologies and operational systems. Substantial effort should be directed towards design, implementation, maintenance, and technologic advancement of basic Registry activities. To facilitate these functions, this RFA will provide a broad base of support for technical services and developmental research, such as research on key information technologies, statistical methodology and study design integral to cancer genetics studies. Funds may be requested for personnel, for equipment, and for specific research projects relevant to development, implementation and support of the Registries. This RFA will support one group to develop the informatics infrastructure to support the CFRBCCS. Specifically, in collaboration with investigators from the Registry centers, the IC shall, at a minimum: Coordinate the activities of the operations units at the Registry centers, which are providing statistical and logistical support to the local centers as well as preparing data for the central databases; Provide information and software to support local entry of data that will go into the central databases; Provide training materials and conduct on-site training when needed to ensure consistency and quality control of data collection; Perform quality control checks of data collected and entered at local sites but submitted to the central databases, and provide timely feedback to sites to enhance quality control of data collection and entry; Provide service statistics to NCI program officials and to the Advisory and Steering Committees of the Registries concerning recruitment, retention, and protocol compliance; Conduct analyses of cross-site data at the request of Registry investigators or NCI program officials, as approved by the Steering Committees of the Registries; Develop and maintain anonymous databases for use as a research resource as approved by the Advisory Committees of the CFRBCCS; Promote information dissemination through newsletters and a WWW site. SPECIAL REQUIREMENTS Applicants must have existing programs of scientific excellence and technical expertise in areas relevant to the type of application submitted. All applications must address the following questions in a clear and organized manner: (1) How will existing (and proposed) resources and expertise support specific tasks in Registry development and implementation; contribute to support and maintenance of Registry functions; and present unique opportunities for Registry activities? (2) How does past technical experience and performance support the applicant's ability to provide the required technical services; demonstrate the scientific expertise and the ability to apply scientific considerations to technical functions; and show the applicant's ability and willingness to collaborate effectively as a member of a consortium? Study Organization and Function The NCI Cooperative Cancer Family Registries represent a consortium of participating centers of excellence in interdisciplinary genetic epidemiology research that will be linked in a dynamic and interactive fashion through the central informatics and operations functions of the IC into a research resource. To ensure close integration between the IC and the Registry participating centers, the Principal Investigator (PI) of the IC will serve as a full voting member of the Steering Committees of the Registries. The external Advisory Committees (ACs) of the Registries consist of senior scientists with multidisciplinary expertise in cancer genetics research and are responsible for reviewing, evaluating and prioritizing all research proposals involving the Registries. This will include proposals made by the IC. AC members are nominated by the members of the Steering Committees (SCs) and will be appointed by the NCI for a two-year tenure. Terms and Conditions of Award The Terms and Conditions of Award, below, will be included in any award issued as a result of this RFA. It is critical that each applicant include specific plans for responding to these terms. These special Terms of Award are in addition to and not in lieu of otherwise applicable OMB administrative guidelines, HHS grant administration regulations in 45 CFR Part 74 and 92, and other HHS, PHS and NIH grant administration policy statements. The administrative and funding instrument used for this program is a cooperative agreement (U01). This is an assistance mechanism for support of a research resource in which substantial NIH scientific and/or programmatic involvement with the awardee is anticipated during performance of the activity. Under the cooperative agreement, the NIH assist, supports and/or stimulates the recipient's activities, by facilitating performance of the program effort in a partner role. Consistent with this concept, the prime responsibility for the activity resides with the awardee for the project as a whole. I. Awardee Rights and Responsibilities The Informatics Center (IC) awardee will have primary rights and responsibilities to define projects and approaches and to plan and conduct the work of the IC. The IC will have engage in methodological and developmental investigations, and develop novel methodological approaches, using data from the CFRBCCS. The development of standardized instruments for data collection and management for this large multi-site project will provide an opportunity for methodological research that can be exported to other centers engaged in the informatics support of genetic studies. Responsibilities of the IC will include: A. Statistical and Research Design. The IC will provide intellectual input about statistical issues, study design and methodology for the Registries. The IC's responsibilities will include: 1. Providing expert statistical assistance to CFRBCCS investigators in developing design and analytic approaches, estimating sample size requirements for specific research questions, planning and performing interim and final analyses, and preparing reports that summarize the results of such analyses. Expertise in modeling, repeated methods, exploratory data analysis and robust methods will be important for the investigations supported by the CFRBCCS; and 2. Developing approaches to statistical modeling, analysis, and study design to maximize the efficiency of genetic epidemiology studies performed using Registry resources, especially the investigation of gene-gene and gene-environment interactions. B. Data Management and Quality Assurance. 1. The IC will establish an optimal computing environment for processing, storage and retrieval of data through a central data management facility or a distributed data system, including multiple sets of longitudinal data and creation of data files for specific analyses. The IC will maintain and update an information management system for tracking data from the study sites as well as maintain and update codebooks, active files and inventory files. Combined codebooks may need to be created to interface with other genetics and epidemiology databases, such as the Cancer Genetics Network. Archiving of data should be provided. Record-keeping and encrypting procedures should ensure confidentiality of data with personal identifiers. 2. A study-wide quality assurance system should be developed and implemented by the IC to allow for regular evaluation of reliability, validity and completeness of CFRBCCS databases. The IC should provide documentation of any changes in the quality assurance and data entry instruction manuals. The IC should site visit CFRBCCS centers during the first two years of funding, the schedule to be developed in consultation with the ACs and the NCI. The IC should bring any data suggesting quality assurance problems at study sites to the attention of the NCI and the SCs. The IC will play a central role in discussing such problems and suggesting solutions at the periodic AC meetings. 3. The data processing, storage and retrieval procedures and quality assurance systems of the IC will need to be approved by the SCs before implementation. 4. The IC will monitor adherence to the clinical and laboratory protocols, and will coordinate implementation of new or modified protocols approved by the SCs. IC activities related to new or modified protocols include new data collection form development, data management system modifications, operations and training manual updates, and study site staff training. C. Specimen Tracking System for the Storage and Retrieval of Biological Specimens. The IC should provide central coordination of stored specimens in collaboration with Registry site investigators. This includes updating and improving as needed a system for specimen tracking at each stage (collection, processing, transfer, storage and retrieval). The IC should also plan to maintain an electronic inventory updated biannually and integrated into the Registry databases. This inventory should list all specimens from each clinical site, describing the type and quantity of all specimens. To facilitate the evaluation of new studies by the AC, a repository status summary should be prepared and distributed to the AC members before their scheduled meetings. The IC should record requests for biological specimens and work with the repository and the SCs to account for the current amount and type of specimens available. D. Summary Data and Support and Coordination for Data Presentation. 1. The IC will be responsible for preparing and updating operations manuals and data collection forms and providing regular statistical summary reports to the CFRBCCS sites and the NCI, including summary data on descriptive statistics and response rates of the study participants. 2. The IC should coordinate with Registry investigators the process of generating scientific material for presentations at conferences and meetings. The IC should provide datasets for analysis by Registry investigators and outside collaborators, as requested by the SC. The IC will maintain and regularly distribute a list of all publications, manuscripts and presentations that use data from the CFRBCCS. E. Study-wide Communication, Coordination and Administrative Duties. The IC will have overall responsibility for the following activities: 1. Establishing electronic mail linkages among CFRBCCS sites and the NCI; 2. Developing milestones/time lines to identify major steps and anticipated accomplishments. Particular attention is suggested in setting milestones in the following areas: methods of data input; distribution of instruments/operation manuals; ongoing training of Registry site staff; and implementation of quality assurance protocols; 3. Providing regular data "freezes," based on a schedule established by the SCs; 4. Providing meeting-related support for SCs and ACs and working group meetings by distributing agendas and other materials and preparing highlights of meetings and conference calls; and 5. Developing and updating a CFRBCCS WWW site, and, in cooperation with the participating sites, developing a regular newsletter for distribution by the sites to participants. F. Communications with Registry Sites and NCI. Regular reporting of activities will help the Registry sites and the NCI to monitor progress and identify areas of potential interest for further investigation. G. Informatics and Information Technology Development. The IC will develop computer-based tools which will facilitate the data collection and distribution goals of the Registries. This responsibility will include development, implementation and maintenance of an information management system for core data. This management system will incorporate safeguards such as encryption technologies to ensure confidentiality and strictly limit access to databases. The information management system will be flexible enough to accommodate follow-up data collections and to integrate data generated through additional studies which use these resources. H. Software for Genetic Epidemiology Research. The IC will survey research needs for software and Internet-based applications to facilitate the collection, integration and analysis of genetic and pedigree data, evaluate existing software and develop new materials as needed, which will be made available to the genetic epidemiology community. I. Developmental Studies. The IC will provide technical expertise for the development of key information technologies, statistical methodology and study designs that will be integral to the development of the next generation of cancer genetics studies. II. The NCI Program Coordinator will: A. Serve as liaison from the NCI, specifically to coordinate activities among the IC, the Registry awardees, and the NCI program coordinator for the Registries (see INQUIRIES); B. Serve as scientific liaison between the awardees and other program staff at NCI with experience in informatics and multicenter studies; C. Serve as a full participant and voting member of the Registry SCs, and, as appropriate, their subcommittees; and attend AC meetings in a non-voting liaison member role; D. Assist the IC in the standardization of data collection methods across Registry participating centers for data that will go into the central databases; assist in developing operating guidelines, quality control procedures, and consistent policies for dealing with recurrent situations in data collection that require coordinated action; and assist in developing plans for information dissemination through newsletter and a WWW site. The NCI reserves the right to reduce the budget, to withhold support, and to suspend, terminate or curtail a study or an award in the event of delinquent data reporting, inadequate quality control of data collection, refusal to carry out the recommendations of the SCs or ACs, or substantial failure to comply with the terms of the award. Periodic external progress reviews of the program will be carried out as NCI deems appropriate. III. Collaborative Responsibilities The IC awardee will, in a dynamic and interactive fashion, link the NCI Cooperative Cancer Family Registries into a research resource. The PI of the IC will serve as a full voting member of the Steering Committees (SCs) of the Registries. The SCs for the Registries are responsible for development and implementation of CFRBCCS policies and procedures, integrating and coordinating activities of the participating centers and the IC. The SCs have responsibility for approving the procedures for data processing, storage, retrieval and quality assurance that are study-wide. The external Advisory Committees (ACs) of the Registries will evaluate all research proposals (those from Registry investigators as well as from the external research community) on a regular basis. This will include research proposals made by the IC. All reviews will be held according to rules pertaining to the conduct of reviews for NIH grants, contracts, and cooperative agreements, with special attention to issues of conflict of interest (whether real or apparent). The ACs will provide recommendations to the SCs as to the priority of the proposed research projects. The ACs will also provide advice to the SCs on scientific matters, as appropriate and as needed. The IC will provide data to the AC regarding recruitment and repository contents, and provide data for support of research approved by the SCs and ACs. IV. Arbitration Procedures Any disagreement that may arise on scientific/programmatic matters (within the scope of the award) between award recipients and the NCI may be brought to arbitration. An arbitration panel will be composed of three members -- one selected by the awardee, a second member selected by NCI, and the third member selected by the two previously selected members. These special arbitration procedures in no way affect the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations at 42 CFR Part 50, Subpart D, and HHS regulations at 45 CFR Part 16. INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of the NIH that women and members of minority groups and their subpopulations must be included in all NIH-supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification is provided that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This new policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing research involving human subjects should read the "NIH Guidelines on the Inclusion of Women and Minorities as Subjects in Clinical Research" which have been published in the Federal Register of March 28, 1994 (59 FR 14508-14513) and in the NIH GUIDE FOR GRANTS AND CONTRACTS, Volume 23, Number 11, March 18, 1994. LETTER OF INTENT Prospective applicants are asked to submit, by September 3, 1997, a letter of intent that includes a descriptive title of the proposed project, the name, address and a telephone number of the Principal Investigator, the names 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 is helpful in planning for the review of applications. It allows NCI staff to estimate the potential workload and to avoid conflicts of interest in the review. The letter of intent is to be sent to Amy Sheon, Ph.D., at the address listed under INQUIRIES below. APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 5/95) 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 Extramural Outreach and Information Resources, Division of Research Grants, National Institutes of Health, 6701 Rockledge Drive, Suite 6095, MSC 7910, Bethesda, MD 20892-7910, telephone 301-435-0714, e-mail asknih@odrockm1.od.nih.gov. The RFA label available in the application form PHS 398 (rev. 5/95) 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 number and title of the RFA must be typed on line 2 of the face page of the application and YES must be checked. Submit a signed, typewritten original of the application, including the Checklist, and three signed, exact photocopies in one package to the Division of Research Grants at the address below. The photocopies must be clear and single sided. DIVISION OF RESEARCH GRANTS NATIONAL INSTITUTES OF HEALTH 6701 ROCKLEDGE DRIVE, SUITE 1040 - MSC 7710 BETHESDA, MD 20892-7710 BETHESDA, MD 20817 (for express/courier service) At the time of submission, two additional copies of the application must by sent to: Ms. Toby Friedberg Referral Officer Division of Extramural Activities National Cancer Institute Executive Plaza North, Room 636 6130 Executive Blvd. Rockville, MD 20850 (if hand delivered or delivery service) Bethesda MD 20892-7399 (if using U.S. Postal Service) It is important to send these copies at the same time that the original and three copies are sent to DRG; otherwise, the NCI cannot guarantee that the application will be reviewed in competition with other applications received on or before the designated receipt date. Applications must be received by October 7, 1997. If an application is received after that date, it will be returned to the applicant without review. If the application submitted in response to this RFA is substantially similar to a research 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. REVIEW CONSIDERATIONS All applications will be judged on the basis of the scientific merit of the proposed project and the documented ability of the investigators to meet the OBJECTIVES of the RFA. Although the technical merit of the proposed protocol is important, it will not be the sole criterion of evaluation of a study. Review Method Upon receipt, applications will be reviewed for completeness by the DRG and for responsiveness to the RFA by the NCI. Incomplete applications will be returned to the applicant without further consideration. If NCI staff find that the application is not responsive to the RFA, it will be returned and receive no further consideration. Applications that are complete and responsive to the RFA will be evaluated for scientific and technical merit by an appropriate peer review group convened by the NCI in accordance with the review criteria stated below. As part of the initial merit review, all applications will receive a written critique and undergo a process by which only those applications deemed to have the highest scientific merit, generally the top half of applications under review, will be discussed, assigned a priority score, and receive a second level review by the National Cancer Advisory Board. Review Criteria Applications for IC awards will be judged on the basis of the scientific merit of the proposed project and the documented ability of the investigators to meet the OBJECTIVES of the RFA. Although the technical merit of the proposed protocol is important, it will not be the sole criterion of evaluation of an application. Applicants are expected to address all issues identified under SPECIAL REQUIREMENTS of the RFA. In addition, applicants will be evaluated based on the additional criteria listed below. Applications for the IC will be reviewed on the basis of the following criteria: 1. Scientific excellence of the application and the extent to which it addresses the special scientific and technical program requirements presented in the RFA; 2. The adequacy of the applicant's plan for safeguarding confidentiality of the central Registry database and providing technical advice to Registry participating centers in developing protocols to ensure local data security; 3. Demonstrated ability and willingness to provide technical assistance for the development of informatics structures for collaborative multi-center research; 4. Qualifications and research experience of the Principal Investigator and staff with regard to development and implementation of complex informatics structures; previous experience with design and administration and analysis of data from multi-institutional clinical trials and relevant epidemiologic or laboratory studies; competence with regard to the mechanisms for administration, experimental design, quality control, study monitoring, data management and reporting, statistical analysis, and compliance with regulatory requirements; 5. The adequacy of existing physical facilities and resources of the applicants' institution(s); how effectively any proposed resource expansion will enhance the applicant's participation in Registry functions; and the unique resources and capabilities the applicant will bring to the Registries; 6. Adequacy of plans for effective communication and coordination between the participating centers, IC, and NCI; 7. Appropriateness and adequacy of proposed developmental and methodological studies; and 8. Scientific and technical merit of the proposed project as determined by peer review. The review group will also examine the proposed budget and will recommend an appropriate budget and period of support for each application that is recommended for further consideration. The second level of review by the National Cancer Advisory Board considers the special needs of the Institute and the priorities of the National Cancer Program. AWARD CRITERIA Applications recommended by the National Cancer Advisory Board will be considered for award based upon technical merit of the application as reflected in the priority score, availability of resources, and availability of funds. Furthermore, the applicant organization must indicate a commitment to accept provisions outlined under the SPECIAL REQUIREMENTS section, Terms and Conditions of Award. The earliest anticipated date of award is April 1, 1998. INQUIRIES Written and telephone inquiries concerning the RFA and the opportunity to clarify any issues or questions from potential applications are welcome. Direct inquiries regarding RFA-related programmatic and scientific issues to: Amy Sheon, Ph.D. Division of Cancer Epidemiology and Genetics National Cancer Institute 6130 Executive Boulevard, Suite 535 - MSC 7395 Bethesda, MD 20892-7395 Telephone: (301) 496-9600 Email: as31r@nih.gov Direct inquiries regarding the CFRBCCS to: Daniela Seminara, Ph.D., M.P.H. Division of Cancer Epidemiology and Genetics National Cancer Institute 6130 Executive Boulevard, Suite 535 - MSC 7395 Bethesda, MD 20892-7395 Telephone: (301) 496-9600 Direct inquiries regarding fiscal matters to: Ms. Crystal Wolfrey Grants Management Specialist National Cancer Institute 6120 Executive Boulevard, Suite 243 Bethesda, MD 20892 Telephone: (301) 496-7800, ext. 282 Email: wolfreyc@gab.nci.nih.gov AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No.93.393, Cancer Cause and Prevention 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 and 92. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. Unless otherwise noted all PHS grants policies apply. The Public Health Service strongly encourages all grant recipients to provide a smoke-free workplace and promote the non-use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases any portion of a facility) in which regular or routine education, library, day care, health care, or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people. From owner-sci-resources@net.bio.net Tue Aug 05 23:00:00 1997 Path: biosci!biosci!not-for-mail From: BIOSCI Administrator Newsgroups: bionet.sci-resources Subject: NIH GUIDE - RFA HG-97-003 - V26(25) 08/01/97 Date: 5 Aug 1997 21:52:15 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 475 Sender: daemon@net.bio.net Approved: biosci-help@net.bio.net Distribution: world Message-ID: <5s8vtv$4u0@net.bio.net> NNTP-Posting-Host: net.bio.net MOUSE GENE MAP NIH GUIDE, Volume 26, Number 25, August 1, 1997 RFA: HG-97-003 P.T. National Human Genome Research Institute National Institute of Alcohol Abuse and Alcoholism National Cancer Institute National Institute of Drug Abuse National Institute of Mental Health Letter of Intent Receipt Date: August 18, 1997 Application Receipt Date: September 16, 1997 PURPOSE The purpose of this Request for Applications (RFA) is to solicit applications for research projects to construct a gene-based physical map of the mouse genome consisting of an ordered set of EST-derived markers integrated with the genetic and other physical maps of the mouse genome. 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, A Mouse Gene Map, is related to several priority areas. 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 202-512-1800). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic for-profit and non-profit organizations, public and private, such as universities, colleges, companies, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal Government. Applications from social/ethnic minority individuals, women, and persons with disabilities are encouraged. Applications from foreign institutions will not be accepted. However, subcontracts to foreign institutions are allowable, with sufficient justification. MECHANISM OF SUPPORT This RFA will use the National Institutes of Health (NIH) individual research grant (R01) mechanism. If more than one grant is funded under this initiative, the investigators will be expected to work cooperatively, and with any other project(s) with similar goals, so that the resources developed will be of maximum usefulness to the community. The total project period for applications submitted in response to the present RFA may not exceed 2 years. The anticipated award date is March 2, 1998. This RFA is a one-time solicitation. This RFA is an initiative of the Institutes listed above. However, the awards will be made by the National Human Genome Research Institute (NHGRI) and will be managed by the NHGRI and the other participating institutes. FUNDS AVAILABLE At least $2 million (including direct and indirect costs) per year will be available. It is anticipated that one to three awards may be made. Proposed funding levels are subject to change due to budgetary, administrative, and/or scientific considerations. RESEARCH OBJECTIVES Background The mouse is an important model for the study of many aspects of mammalian biology, including many human diseases. Among its other advantages, the mouse is the most well developed system for mammalian genetic analysis. In the past few years, genomics has become an increasingly important approach to the development of the resources necessary for molecular genetic analysis of biological questions. In recognition of the important role played by the mouse in modern biomedical research, the development of resources to support study of the mouse genome has been an integral goal of the Human Genome Project (HGP) since its inception. Through HGP funding, a high resolution genetic map of the mouse based on microsatellite markers has been completed, and a physical map including both genetic and random STS markers is currently under development. Although the genomic resources currently being developed will be extremely useful, identifying and isolating mouse genes of interest is still not routine, and investigators involved in such efforts would benefit from additional resources. In particular, a catalogue and map of mouse genes would greatly increase the usefulness of the mouse in studying human disease, health, and behavior. A successful approach to constructing such a gene map has recently been demonstrated for the human. Schuler et al. [Science 274:540 (1996)] used a catalog of human genes to construct a map containing more than 16,000 gene-based markers. STS markers were developed from expressed sequence tags (ESTs) which were derived, in turn, from human cDNA clones. At present, a large number of mouse ESTs is being generated at the Washington University (St. Louis) Sequencing Center, with support from the Howard Hughes Medical Institute (HHMI). To date, approximately 180,000 mouse ESTs have been produced and submitted to the public database and the Washington University-HHMI effort is scheduled to produce a total of 400,000 ESTs within the next two years. Analysis of the existing mouse ESTs has already shown that there are many overlaps and a number of contigs (or clusters), which are comparable to the UniGene clusters that were used to generate STS-based gene markers for the Human Gene Map. The HHMI has recently increased its investment in the mouse EST project to include full insert sequencing of clones representing all of the unique clusters. This will generate sequences covering the 3' ends of the cDNA inserts, thereby increasing the usefulness of the EST information for mapping. Finally, a project to construct a mouse gene map has begun in Europe with plans to incorporate about 15,000 mouse ESTs in the next three years. The European project is financed by the European Commission and will be carried out at the Mouse Genome Centre in the United Kingdom and Genethon in France. This effort plans to anchor the RH panel described below using genetically mapped microsatellite markers and then to put about 15,000 EST-based markers on the commercially available RH panel. Most of the ESTs to be used will be derived from the Washington University-HHMI collection, but a fraction will be obtained from European production efforts on specialized libraries. The European project will focus on ESTs that do not have a human homologue, although approximately 20% will be human homologues in order to relate the gene maps of the two organisms. The availability of a gene map will enhance the value of the mouse as a model for studying human biology. The map will be useful for isolating and cloning mouse genes by the positional cloning and positional candidate cloning methods. Comparison of detailed mouse and human gene maps will increase the efficiency with which investigators can define and take advantage of the syntenic relationships between chromosomes of the two organisms. Adding additional value to this approach will be a rat gene map which is currently being developed under support from the National Heart, Lung, and Blood Institute. Once identified, many genes will be better studied in the mouse (and/or the rat); the information obtained in such studies can then be applied to human studies. Objectives and Scope The purpose of this RFA is to support the development of a gene-based physical map of the mouse genome in the most efficient, timely and cost-effective manner. The resulting map should be cross-referenced to the existing STS-based mouse genetic map and integrated with the mouse gene map being generated by the European effort. There are several reagents that are available to facilitate generation of the mouse gene map. Mapping Reagents. Investigators at the University of Cambridge have developed a mouse radiation hybrid panel, T31. The retention rate is 27.3 percent and preliminary characterization of the panel indicates that it has between 1,000 and 1,500 bins. Investigators at the Whitehead Institute have generated two mouse YAC libraries consisting of approximately 40,000 YACs with an average insert size of 829 kb (approximately 10 genome equivalents). Investigators at the California Institute of Technology have produced a mouse BAC library consists of approximately 200,000 clones with average insert size of 130 kb (approximately 9 genome equivalents). Currently, a non- redundant overlapping set of YAC or BAC clones is not available. The radiation hybrid panel and the clone libraries are available commercially. It is anticipated that applicants may want to utilize one or more of these existing resources for mapping, but NHGRI and the collaborating NIH institutes would be willing to support the cost of developing a new mapping resource, if the applicant presents convincing evidence that the resulting map would be substantially better than one produced using existing mapping resources. Unique Clusters of ESTs. The Washington University Sequencing Center, through support from Howard Hughes Medical Institute, is in the process of sequencing a significant number of ESTs. These ESTs will be reduced to a unique set of clustered ESTs by the National Center for Biotechnology Information, National Library of Medicine, NIH, as has been done for the human gene mapping project. Within the next two years, Washington University plans to have sequenced over 400,000 ESTs. Based on the experience with the human ESTs, it is estimated that there should be about 50,000 unique clusters of ESTs available for mapping. There are already 2,500 unique mouse EST clusters available for mapping. Cross Reference and Integration with Other Mouse Maps. A mouse genetic map has already been constructed (http:\\www- genome.wi.mit.edu). In order for the genetic map and the gene maps being generated by the U.S. and European efforts to be maximally useful to the scientific community, it is essential that the resulting gene map be cross-referenced to the genetic map and integrated with the European gene map. This RFA does not specify the desired resolution or other properties of the gene map to be generated. However, it is expected that most, if not all, of the unique gene clusters emanating from the Washington University-HHMI mouse EST project will be mapped. Each applicant must propose the most cost efficient strategy for producing a mouse gene map and should justify why a map of the proposed resolution would be the most useful resource for studies using the mouse and related studies of human. DATA AND RESOURCE SHARING The sharing of materials and data in a timely manner has been an essential element in the rapid progress made in construction and use of the human and mouse genetic maps. Public Health Service policy requires that investigators make the results and accomplishments of funded activities publicly available. The advisors to the NIH and the DOE genome programs have developed a set of "NIH-DOE Guidelines for Access to Mapping and Sequencing Data and Material Resources" that address the special needs of genome research. These guidelines call for material and information from genome research to be made available within six months of the time the data or materials are generated; more rapid sharing is encouraged and has become the norm in the genome community. Applications submitted in response to this RFA should include detailed plans for sharing data and materials generated through the grant. Where appropriate, grantees may work with the private sector in making unique resources available to the larger biomedical research community at a reasonable cost. The plans proposed for sharing and data release will be reviewed for adequacy by NIH staff prior to award of the grant and the proposed sharing plan will be made a condition of the award. Investigators may request funds to defray the costs of sharing materials or submitting data in their application. Such requests must be adequately justified. POST-AWARD MANAGEMENT During the course of the grant period, technologies will improve, genomic technologies will evolve, and the rate of progress and focus of work supported by the grant(s) may change. It is expected that the Principal Investigator(s) will make any necessary adjustment in scientific direction to accommodate the changing environment. In order to ensure that the project(s) remain(s) focused on appropriate goals, maintain(s) excellent coordination with the other projects funded under this RFA, incorporate(s) new technological advances and make(s) sufficient progress, scientific and programmatic visits to the grantee(s) may be conducted at a frequency to be negotiated with the awardee(s). In addition, applications should include travel funds for the Principal Investigators and the other investigators on the grant to meet annually with NIH staff in the metropolitan Washington D.C. area, should such meetings be advisable. LETTER OF INTENT Prospective applicants are asked to submit, by August 18,1997, 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. Any applicant planning to submit an application for more than $500,000 direct cost in any one year must contact the NHGRI staff listed under INQUIRIES in order for the application to be accepted by NIH. 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 IC 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: Bettie J. Graham, Ph.D. Division of Extramural Research National Human Genome Research Institute Building 38A, Room 614 38 Library Drive, MSC 6050 Bethesda, MD 20892-6050 Tel: (301) 496-7531 Fax: (301) 480-2770 e-mail: bettie_graham@nih.gov APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 5/95) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research; from the Office of Extramural Outreach and Information Resources, National Institutes of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone (301) 435-0714; e-mail: ASKNIH@odrockm1.od.nih.gov and from the program director listed under INQUIRIES.. The RFA label available in the PHS 398 (rev. 5/95) 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 2 of the face page of the application form and the YES box must be marked. Submit a signed, typewritten original of the application, including the Checklist, and three signed, photocopies, in one package to: DIVISION OF RESEARCH GRANTS NATIONAL INSTITUTES OF HEALTH 6701 ROCKLEDGE DRIVE, ROOM 1040-MSC7710 BETHESDA, MD 20892-7710 BETHESDA, MD 20817 (for express/courier service) At the time of submission, two additional copies of the application must also be sent to Ken Nakamura, Ph.D. Office of Scientific Review National Human Genome Research Institute Building 38A, Room 613, MSC 6050 38 Library Drive Bethesda, MD 20892-6050 Applications must be received by September 16, 1997. If an application is received after that 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 RFA 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 DRG and for responsiveness to the RFA by NHGRI program staff. Incomplete applications will be returned to the applicant without further consideration. If the application is not responsive to the RFA, NHGRI 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. 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 NHGRI. As part of the initial merit review, a process may be used by the initial review group in which applications will be determined to be competitive or non-competitive based on their scientific merit relative to other applications received in response to the RFA. Applications judged to be competitive will be discussed and be assigned a priority score. All applicants will receive a summary statement consisting of the reviewer's written comments essentially unedited. Summary Statements for competitive applications will also contain a summary of the review committee's discussion. The second level of review will be provided by the appropriate national advisory council or board. Review criteria will include the following: * scientific and technical merit of the research proposed to meet the objectives of this RFA; * the value of the proposed gene map to the scientific community; * appropriateness and adequacy of the experimental approach and methodology proposed to carry out the research; * qualifications and research experience of the Principal Investigator and staff, particularly, but not exclusively, in the area of the proposed research; * adequacy of plans to integrate the resulting gene map with the European gene map; * adequacy of plans to make resources/data available to the community in a timely manner; * availability of the resources and technology necessary to perform the research; * adequacy of facilities and resources and the level of institutional commitment; and * appropriateness of the proposed budget and duration in relation to the proposed research. AWARD CRITERIA The anticipated date of award is March 1, 1998. Factors that will be used to make award decisions are as follows: * Quality of the proposed project as determined by peer review; * Promise of the proposed program to accomplish the goals of this RFA; * Cost effectiveness of the proposed strategy; * Quality of the plans to cooperate with other projects that may be funded under this RFA and with the European effort; * Nature and extent of the plans for sharing and distributing data and resources in a timely manner ; and * Availability of funds. INQUIRIES 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: Bettie J. Graham, Ph.D. Division of Extramural Research National Human Genome Research Institute Building 38A, Room 610, MSC 6050 Bethesda, MD 20892-6050 Phone: (301) 496-7531 FAX: (301) 480-2770 Email: bettie_graham@nih.gov Robert Karp, Ph.D. Division of Basic Research National Institute on Alcohol Abuse and Alcoholism 6000 Executive Boulevard, Suite 402, MSC 7003 Bethesda, MD 20892-7003 Telephone: (301) 443-2239 Fax: (301) 594-0673 Email: rkarp@willco.niaaa.nih.gov Grace L. Shen, Ph.D. Cancer Genetics Branch Division of Cancer Biology National Cancer Institute 6130 Executive Boulevard, Room 501, MSC 7381 Rockville, MD 20892-7381 Telephone: (301) 435-5226 Fax: (301) 496-8656 Email: gs35r@nih.gov Theresa Lee, Ph.D. Division of Basic Research National Institute of Drug Abuse 5600 Fishers Lane, Room 10A-19 Rockville, MD 20857 Telephone: (301) 443-6300 Fax: (301) 594-6043 Email: tl37h@nih.gov Stephen H. Koslow, Ph.D. Division of Neuroscience and Behavioral Science National Institute of Mental Health 5600 Fishers Lane, Rockville, MD 20857 Telephone: (301) 443-3942 Fax: (301) 443-3563 Email: koz@helix.nih.gov Direct inquiries regarding fiscal matters to: Ms. Jean Cahill Grants Management Officer Division of Extramural Research National Human Genome Research Institute Building 38A, Room 613, MSC 6050 Bethesda, MD 20892-6050 Telephone: (301) 402-0733 Fax: (301) 402-1951 e-mail: jean_cahill@nih.gov AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.172. 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. The Public Health Service (PHS) strongly encourages all grant recipients to provide a smoke-free workplace and promote the non-use of all tobacco products. In addition, Public Law 103-227, the Pro- Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people. From owner-sci-resources@net.bio.net Tue Aug 05 23:00:00 1997 Path: biosci!biosci!not-for-mail From: BIOSCI Administrator Newsgroups: bionet.sci-resources Subject: NIH GUIDE - RFA HL-97-013 - V26(25) 08/01/97 Date: 5 Aug 1997 21:54:15 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 584 Sender: daemon@net.bio.net Approved: biosci-help@net.bio.net Distribution: world Message-ID: <5s901n$4vs@net.bio.net> NNTP-Posting-Host: net.bio.net CLINICAL RESEARCH ON COOLEY'S ANEMIA NIH GUIDE, Volume 26, Number 25, August 1, 1997 RFA NUMBER: HL-97-013 P.T. National Heart, Lung, and Blood Institute National Institute of Diabetes and Digestive and Kidney Diseases Letter of Intent Receipt Date: October 15, 1997 Application Receipt Date: January 8, 1998 PURPOSE The Blood Diseases Program of the Division of Blood Diseases and Resources, National Heart, Lung, and Blood Institute (NHLBI), and the Hematology Program of the Division of Kidney, Urologic and Hematologic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), invite grant applications for support of research efforts to improve the clinical management of patients with Cooley's anemia (beta-thalassemia). The focus of this initiative is to support clinically-related or translational research. Areas of particular importance include studies on improved methods for the non-invasive measurement of tissue iron burden, alternative approaches to iron chelation therapy, and pharmacologic enhancement of fetal hemoglobin. 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), Clinical Research on Cooley's Anemia, is related to the priority area of maternal and infant health, and diabetes and chronic disabling diseases. 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 202-512-1800). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign, for-profit and nonprofit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State or local governments, and eligible agencies of the Federal government. Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as Principal Investigators. Domestic applications may include foreign components. FOREIGN INSTITUTIONS: Awards under this announcement may be made to foreign institutions provided the application (1) is of high scientific merit and (2) offers a special opportunity for furthering research programs through the use of unusual talents, resources, populations, or conditions in other countries which are not readily available in the United States or which augment existing U.S. resources. All current policies and requirements that govern the research grant programs of the NIH will apply to grants awarded under this RFA. MECHANISM OF SUPPORT This RFA will use the NIH Research Project grant (R01) mechanism of support. Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. Applicants, including those from foreign institutions, may request up to five years of support. It is anticipated that support for this program will begin in July 1998. Administrative adjustments in project period and/or amount may be required at the time of the award. This RFA is a one-time solicitation. Successful applicants, upon completion of their entire project period (up to five years) may submit an unsolicited competing renewal application which will compete with all investigator-initiated applications and be reviewed according to the customary peer review procedures. FUNDS AVAILABLE Awarding of grants pursuant to this RFA is contingent upon receipt of funds for this purpose. Approximately seven awards will be made. The NHLBI is planning for five grants at a total cost of $2,000,000 for the first year of support for this initiative. The NIDDK will award approximately two grants and has budgeted $800,000 for the first year of support. The specific number of grants to be funded will depend on the merit and scope of the applications received and on the availability of funds. Applicants may request up to a 3 percent inflationary increase per year. Increases above this amount must be specifically justified. CONSORTIUM ARRANGEMENTS If a grant application includes research activities that involve institutions other than the grantee institution, the program is considered a consortium effort. A consortium application should be prepared so that the scientific, fiscal, and administrative considerations are explained fully. The published policy governing consortia is available in the business offices of institutions that are eligible for Federal grants-in-aid. Consult the latest published policy governing consortia before developing the application. If clarification of the policy is needed, please contact Ms. Jane R. Davis (see below). RESEARCH OBJECTIVES Background Cooley's anemia (also called beta-thalassemia major or thalassemia major) and its clinical management has been the subject of an extensive review (1). Cooley's anemia is a genetic blood disease that results in an inadequate production of hemoglobin, the essential oxygen-carrying substance in blood. This causes severe anemia that begins shortly after birth. As a group, thalassemic disorders are one of the most common single-gene genetic diseases worldwide. In the United States, thalassemia mainly affects specific ethnic groups, including people of Mediterranean, Middle Eastern, African, Southeast Asian, Chinese, and Asiatic Indian origin. Individuals affected with Cooley's anemia require frequent and lifelong blood transfusions to sustain life. Because there are no natural means for the body to eliminate iron, the iron contained in the transfused red blood cells builds up over many years and eventually becomes toxic to tissues and organ systems. This excess iron must be removed from Cooley's anemia patients or they may not survive beyond the second decade of life. To accomplish this, patients must use the iron-binding or chelating drug, deferoxamine, that is administered for about 10 hours every day by pumping it through a needle inserted either under the skin or intravenously. Before the introduction of transfusion and chelation therapy, life expectancy for patients with Cooley's anemia was two or three years. Today, the picture is considerably brighter with some patients living into their thirties and beyond. Survival and quality of life depend upon the absence or control of transfusion complications such as infectious diseases (mainly hepatitis and AIDS) and the adequate removal of excess iron. In spite of the increased survival and quality of life, the current treatment modalities are inadequate. Iron-chelation therapy is extremely demanding, and many patients experience considerable discomfort from administration of the drug. In fact, the therapy is so burdensome that many adolescents and teenagers have refused to continue. The prognosis for these noncompliant patients is quite poor. In addition to the physical and psychological burden of therapy, the financial burden on the family is substantial. The cost of transfusions and iron-chelation therapy amounts to about $30,000 per year per patient, and it has been estimated that the total annual Cooley's anemia-related costs may be as much as $100,000 per year per patient. The search for an improved chelator continues. A variety of compounds have been produced and examined as potential oral iron- chelating agents. One of these, deferiprone (1,2-dimethyl-3- hydroxypyridin-4-one, also known as L1, CP20, and DMHP) has been administered to patients in other countries, but some patients have developed neutropenia or agranulocytosis. The magnitude of the risk of agranulocytosis is being evaluated in a multicenter clinical trial in the U.S. and other countries. No published data, however, are available on the long-term efficacy of deferiprone. A recent prospective evaluation of this orally active chelator (2) has suggested that deferiprone may induce decreases in hepatic iron, but continued use does not result in sufficiently diminished levels of hepatic iron, despite the continued urinary excretion of iron in these patients. This implies that deferiprone may be chelating a pool of iron that may not be readily accessible to deferoxamine and that perhaps therapy utilizing a combination of these two chelators may be clinically superior to a single agent. Experts would still argue that deferiprone alone may be quite efficacious in the prevention, rather than the reversal, of iron overload in young children. There is an urgent need to undertake further studies to firmly establish whether this promising oral iron chelator has a role in the management of iron overload in transfusion-dependent anemias. Other iron chelators are being investigated. A single bolus injection of a long-acting form of deferoxamine linked to a polymeric backbone of hydroxyethyl starch has been reported to induce a urinary iron excretion equal to that excreted after several days of deferoxamine infusions. This approach should be investigated further. Results of animal studies have shown that a new, water soluble, synthetic hexadentate chelator (IRC11) having a higher affinity for iron(III) than deferoxamine, but much less toxic, may be useful in the treatment of transfusional iron overload (4). Progress in our ability to reverse the ontogenic switch from fetal to adult hemoglobin, thereby reactivating the expression of the dormant gamma-globin gene, has increased in the past decade. This holds promise that a new, effective form of therapy for thalassemic patients may soon be available. Three classes of drugs, (a) cytotoxic drugs, (b) hematopoietic growth factors and cytokines, and (c) fatty acids, have been shown to enhance fetal hemoglobin production, but their effects have been minimal. However, there are encouraging suggestions that the effects of these drugs may be additive (5). Clinical studies are needed to test the effectiveness and safety of combinations of these drugs and other new hemoglobin switching agents as they are identified. The importance of the accurate assessment of body iron in patients with thalassemia major has been emphasized by advances in understanding the quantitative relationship between iron burden and clinical outcome. The current gold standard for quantifying tissue iron burden still relies on the chemical analysis of liver biopsy specimens. None of the less invasive clinically available methods of evaluating body iron (serum ferritin concentration, transferrin saturation, or urinary iron excretion after administration of a chelating agent) is sufficiently accurate to permit optimal management of iron-chelation therapy. Magnetic susceptometry measurement of hepatic iron using the Superconducting Quantum Interference Device (SQUID) can provide accurate measurements. However, perhaps due to the liquid helium operating temperature and the large size, only two such instruments are available worldwide. Potential approaches to improving the measurement of body iron include refinements in the assay of serum ferritin (such as the measurement of ferritin iron, glycosylated ferritin, H- or L- subunits, and other methods), advances in the quantitative use of magnetic resonance imaging (MRI), and improvement in the availability of magnetic susceptibility by development of instruments utilizing "high-temperature" (liquid nitrogen) superconducting materials. Approaches that would be useful for measuring cardiac iron levels are of particular importance. Transfusion therapy continues to be the centerpiece of the management of thalassemia. The advantages of regular transfusion of red cells are well established and include improved growth and development, decreased enlargement of the liver and spleen, increased longevity and a vastly improved overall well-being. At the same time, transfusions continue to be the source of toxic iron deposits in vital organs. In addition, patients with thalassemia major are at a particularly high risk of contracting transfusion-transmitted diseases because of their lifelong dependence on blood transfusions. The optimal hemoglobin level at which to maintain patients with thalassemia remains uncertain, and new methods for determining the relationship between hemoglobin level and suppression of bone marrow erythropoietic activity may help clinicians adjust the hemoglobin level to achieve the desired results of transfusion therapy while limiting the number of donor exposures and the amount of newly accumulated iron. Alternative approaches to conventional transfusion therapy, including erythrocytapheresis, have been suggested as methods for decreasing the amount of transfusional iron accumulation but currently remain unproven. Clinical studies are needed to improve the safety and effectiveness of transfusion therapy and to develop alternative methods of blood transfusion to reduce the degree of iron loading. This initiative is intended to stimulate the submission of grant applications which address important clinical issues in the management of Cooley's anemia. GRANT APPLICATIONS MUST INCLUDE STUDIES DIRECTLY INVOLVING PATIENTS, either for an intervention protocol or for the development and testing of diagnostic technologies such as noninvasive measurement of tissue iron concentration. Areas of particular importance include, but are not limited to, the following: 1) Clinical studies of more effective iron chelators, new modes of administration of existing chelators, and combinations of chelators. Such studies must include measurement of patient compliance with drug therapy and accurate assessment of changes in body iron stores. 2) Research on improved technology for the non-invasive measurement of tissue iron deposits. 3) Clinical studies of fetal hemoglobin enhancing drugs and combinations of these agents. 4) Clinical studies to improve the safety and effectiveness of transfusion therapy and to develop alternative methods of blood transfusion to reduce the degree of iron loading. The demographics of beta-thalassemia in the United States have been changing because of the large increases in the Asian population in the last ten years. Therefore, applicants are encouraged to include patients with hemoglobin E beta-thalassemia, hemoglobin H, and hemoglobin H-Constant Spring genotypes if their inclusion would not diminish the scientific merit of the proposed clinical study. References (1) "Thalassemia Management I," Seminars in Hematology, P Beris, Ed., Vol 32, No 4 (October), 1995 and "Thalassemia Management II," Seminars in Hematology, P Beris, Ed., Vol 33, No 1 (January), 1996. (2) Olivieri NF, Long-term follow-up of body iron in patients with thalassemia major during therapy with the orally active iron chelator deferiprone (L1). BLOOD 88 (Suppl. 1):1229a, 1996. (3) Olivieri NF, Nisbet-Brown E, Srichairatanakool S, Dragsten P, Hallaway P, Hedlund B, Porter JB. Studies of iron excretion and non- transferrin-bound plasma iron (NTBPI) following a single infusion of hydroxyethyl starch-deferoxamine (HES-DFO): A new approach to iron chelation therapy. BLOOD 88 (Suppl. 1):1228a, 1996). (4) Hershko C, Rivkin G, Link G, Simhon E, Cyjon RL, Klein JY. IRC11, a new synthetic chelator with selective interaction with catabolic red blood cell iron. BLOOD 88 (Suppl. 1):1951a, 1996. (5) Olivieri NF, Rees DC, Ginder GD, Thein SL, Waye JS, Chang L, Brittenham GM, Dover GJ, Weatherall DJ. First report of long-term elimination of red cell transfusions in thalassemia major through augmentation of fetal hemoglobin with sodium phenylbutyrate (SPB) and hydroxyurea (HU). BLOOD 88 (Suppl. 1):1227a, 1996. SPECIAL REQUIREMENTS Upon initiation of the program, the NHLBI and the NIDDK 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 1-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. INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of the NIH that women and members of minority groups and their subpopulations must be included in all NIH-supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification is provided that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This new policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing research involving human subjects should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research", which have been published in the Federal Register of March 28, 1994 (FR 59 14508-14513) and in the NIH Guide to Grants and Contracts, Volume 23, Number 11, March 18, 1994. Investigators also may obtain copies of the policy from the program staff listed under INQUIRIES. Program staff may also provide additional relevant information concerning the policy. LETTER OF INTENT Prospective applicants are asked to submit, by October 15, 1997, 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 a subsequent application, the information that it contains allows staff to estimate the potential review workload and to avoid conflict of interest in the review. The letter of intent may also be helpful to the applicant since it may alert NHLBI staff to the possibility of an application being unresponsive to the goals of the RFA. In such an instance, the applicant would be notified before preparing the application. The letter of intent is to be mailed, or faxed, to: Dr. C. James Scheirer Chief, Review Branch Division of Extramural Affairs National Heart, Lung, and Blood Institute 6701 Rockledge Drive, Room 7220, MSC 7924 Bethesda, MD 20892-7924 Telephone: (301) 435-0266 FAX: (301) 480-3541 E-mail: James_Scheirer@NIH.GOV APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 5/95) is to be used in applying for these grants. Application kits are available at most institutional offices of sponsored research and may be obtained from the Office of Extramural Outreach and Information Resources, National Institutes of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone: 301-435-0714, E-mail: ASKNIH@odrockm1.od.nih.gov; and from the program staff listed under INQUIRIES. The RFA label found in the PHS 398 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 and three signed, photocopies, in one package to: DIVISION OF RESEARCH GRANTS NATIONAL INSTITUTES OF HEALTH 6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710 BETHESDA, MD 20892-7710 BETHESDA, MD 20817 (for express/courier service) At the time of submission, two additional copies of the application must be sent to Dr. C. James Scheirer, at the address given above in the section on LETTER OF INTENT. Applications must be received by January 8, 1998. If an application is received after that 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 RFA that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. 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 DRG and for responsiveness by the NHLBI. Incomplete applications will be returned to the applicant without further consideration. If NHLBI staff find that the application is not responsive to the RFA, it will be returned without further consideration. Applications that are complete and responsive to the RFA will be evaluated for scientific and technical merit by an appropriate peer review group convened in accordance with NIH peer review procedures. As part of the initial merit review, all applications will undergo a peer review streamlining process in which only those applications deemed to have the highest scientific merit, generally the top half of applications under review, will be discussed, assigned a priority score, and receive a second level review by the National Advisory Councils of the NHLBI and the NIDDK. A written critique will be provided for all applications, including those that are not discussed and not scored. The NIH will withdraw from further competition those applications that were unscored and the applicant Principal Investigator and institutional official will be notified. The personnel category will be reviewed for appropriate staffing based on the requested percent effort and any changes requested in future years. The total budget request will be reviewed for consistency with the proposed methods and specific aims. The duration of support will be reviewed to determine if it is appropriate to ensure successful completion of the recommended scope of the project. 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 the GCRC program director could be included with the application. Peer Review Criteria The goals of NIH-supported research are to advance our understanding of biological systems, improve the control of disease, and enhance health. In judging the likelihood that the proposed research will have a substantial impact on the pursuit of these goals and those of the RFA, the reviewers will address each of the listed criteria, and consider them in assigning the overall priority score, weighting them as they feel appropriate for each application. Please note that your grant application may not need to be strong in all categories to be judged likely to have a major scientific impact and thus deserve a high priority score. For example, an investigator may propose to carry out important work, that by its nature is not innovative but is essential to move a field forward. (1) Significance Does the study address an important problem? If the aims of the application are achieved, how will scientific knowledge be advanced? What will be the effect of these studies on the concepts or methods that drive this field? (2) Approach Are the conceptual framework, design, methods, and analyses adequately developed, well integrated, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics? (3) Innovation Does the project employ novel concepts, approaches or methods? Are the aims original and innovative? Does the project challenge existing paradigms or develop new methodologies or technologies? (4) Investigator Is the investigator appropriately trained and well suited to carry out this work? Is the proposed study appropriate to the experience level of the principal investigator and other researchers (if any)? (5) Environment Does the scientific environment in which the work will be performed contribute to the probability of success? Do the proposed experiments take advantage of unique features of the scientific environment or employ useful collaborative arrangements? Is there evidence of applicant institutional support? The initial review group will also examine the provisions for the protection of human and animal subjects and the safety of the research environment. AWARD CRITERIA Applications will compete for available funds with all other applications submitted in response to this RFA. The following will be considered in making funding decisions: quality of the proposed project as determined by peer review, availability of funds, and program priority. Schedule Letter of Intent Receipt Date: October 15, 1997 Application Receipt Date: January 8, 1998 Initial Review: March 1998 Review by NHLBI and NIDDK Advisory Councils: May 1998 Anticipated Award Date: July 1, 1998 INQUIRIES Inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding scientific and programmatic issues to either of the Program staff below. However, for specific questions regarding the responsiveness of the planned research grant application to the goals of this RFA, please contact the NHLBI Program Administrator. Dr. Helena O. Mishoe Blood Diseases Program Division of Blood Diseases and Resources, NHLBI 6701 Rockledge Drive, Room 10156 Bethesda, MD 20892-7950 Telephone: (301) 435-0050 FAX: (301) 480-0868 E-mail: helena.mishoe@nih.gov or Dr. David G. Badman Division of Kidney, Urologic and Hematologic Diseases National Institute of Diabetes and Digestive and Kidney Diseases 45 Center Drive, Room 6AS-13C MSC 6600 Bethesda, MD 20892-6600 Telephone: (301) 594-7717 FAX: (301) 480-3510 E-mail: David_Badman@nih.gov Direct inquiries regarding fiscal matters to: Ms. Jane R. Davis Grants Management Office National Heart, Lung, and Blood Institute 6701 Rockledge Drive, MSC 7926 Bethesda, MD 20892-7926 Telephone: (301) 435-0166 FAX: (301) 480-3310 E-mail: jane_davis@nih.gov or Aretina Perry-Jones Division of Extramural Activities, NIDDK 45 Center Drive, Room 6AN-38B, MSC 6600 Bethesda, MD 20892-6600 Telephone: (301) 594-8862 FAX: (301) 480-3504 E-mail: PerryA@extra.niddk.nih.gov AUTHORITY AND REGULATIONS The programs of the Division of Blood Diseases and Resources, NHLBI, and the Division of Kidney, Urologic and Hematologic Diseases, NIDDK are described in the Catalog of Federal Domestic Assistance Nos. 93.839 and 93.849, respectively. Awards are made under the authority of the Public Health Service (PHS) Act, Section 301 (42 USC 241) and administered under PHS grant 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. The PHS strongly encourages all grant and contract recipients to provide a smoke-free workplace and promote the non-use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people. From owner-sci-resources@net.bio.net Tue Aug 05 23:00:00 1997 Path: biosci!biosci!not-for-mail From: BIOSCI Administrator Newsgroups: bionet.sci-resources Subject: NIH GUIDE - RFA DE-97-002 - V26(25) 08/01/97 Date: 5 Aug 1997 21:55:48 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 361 Sender: daemon@net.bio.net Approved: biosci-help@net.bio.net Distribution: world Message-ID: <5s904k$527@net.bio.net> NNTP-Posting-Host: net.bio.net COMPREHENSIVE ORAL HEALTH RESEARCH CENTERS OF DISCOVERY NIH GUIDE, Volume 26, Number 25, August 1, 1997 RFA: DE-97-002 P.T. 04; K.W. 0715048, 0710030 National Institute of Dental Research Letter of Intent Receipt Date: March 1, 1998 Application Receipt Date: May 8, 1998 THIS REQUEST FOR APPLICATIONS (RFA) IS A REVISION OF THE RFA APPEARING IN THE MAY 30 ISSUE OF THE NIH GUIDE. THIS REVISION CORRECTS THE RESEARCH OBJECTIVES SECTION IN THE FULL TEXT OF THE RFA. PURPOSE The National Institute of Dental Research (NIDR) invites applications for Comprehensive Oral Health Research Centers of Discovery (COHRCD). Each COHRCD will be organized around an unifying scientific theme related to dental, oral and craniofacial diseases and disorders. Individual COHRCDs will encompass a full range of outstanding multidisciplinary research pertinent to these diseases and disorders and will be expected to: include basic, translational and applied research projects with behavioral, health services and clinical research components; accelerate transfer of research findings to application by health professionals and the public as well as to facilitate the development of marketable products and other effective health promoting interventions; support research concerning demonstration and outreach programs; and enhance the training of health professionals and the public concerning health promotion and the prevention, improved diagnosis and treatment of the dental, oral or craniofacial diseases and disorders relating to the chosen theme. 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), Comprehensive Oral Health Research Centers of Discovery, is related to the priority area of Oral Health. 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: 202-512-1800). ELIGIBILITY REQUIREMENTS Applications may be submitted by all domestic for-profit and non- profit organizations, public and private, including universities, colleges, hospitals, laboratories, units of State and local governments and eligible agencies of the Federal government. Applicants need not have submitted proposals or been awarded funds for the developmental grants for these centers (RFA: DE-96-004) nor are applicants required to use the same central theme as the one that may have been supported through the developmental grants. Foreign organizations are not eligible to apply; however, domestic applications may include international components. The NIDR encourages applications that include investigators who are racial/ethnic minority individuals, women and persons with disabilities. Although an application must be submitted from a single institution, collaborative arrangements with other institutions are strongly encouraged. Also, applications are not restricted to traditional dental, oral and craniofacial research settings. MECHANISM OF SUPPORT The mechanism for the support of applications in response to this RFA is the Comprehensive Center (P60). Choice of an appropriate theme and the direction and execution of the proposed activities are solely the responsibility of the applicant. This RFA is a one-time solicitation by NIDR and applicants may apply for and receive up to five years of support. The earliest possible award date will be May, 1999. FUNDS AVAILABLE It is anticipated that the NIDR will allocate approximately $16.5 million to support seven COHRCDs provided that sufficient applications of high scientific merit are received. The direct costs requested for the initial year of these applications may not exceed $1.5 million. The $1.5 million direct cost limit includes any indirect costs associated with subcontracts listed as part of the application. Requested increases in direct costs for subsequent years may not exceed 3 percent. Although support for this program is provided for in the financial plans of the NIDR, the award of grants pursuant to this RFA is contingent upon the availability of appropriated funds. Policies that govern research grant programs of the National Institutes of Health (NIH) will prevail. RESEARCH OBJECTIVES Background The NIDR has very effectively utilized the center concept to advance research in oral biology, periodontology, cariology, craniofacial anomalies, aging and materials science. Specialized research centers were designed to intensify research in these areas and have been and continue to be successful in accomplishing this aim. However, it is becoming increasingly apparent that future meaningful insights concerning the mechanisms involved in the induction and progression as well as in the prevention, diagnosis and treatment of dental, oral and craniofacial diseases and disorders must consider not only basic research but also extensive integration of basic, clinical and behavioral sciences; health services and epidemiologic research as well as demonstration, education and outreach activities. The establishment of the COHRCDs addresses this need to accommodate all aspects of certain dental, oral and craniofacial disease processes by stimulating increased collaborations, partnerships and leveraged funding. It is an opportune time to implement this expansive approach to optimally utilize the current rapid advances being made in biomedical and behavioral sciences. To redirect efforts towards the far-reaching aims described in this RFA, a previous RFA (DE-96- 004, Developmental Grants: Comprehensive Oral Research Centers) announcing support to develop plans for these centers was issued. Goals and Objectives It is the intent of the current RFA to provide support for COHRCDs. These comprehensive centers will broaden the expertise available and approaches taken in addressing major research themes within the mission of the NIDR. Choice of the theme is the responsibility of the applicant. The objectives of the COHRCDs are to: (1) foster integrated biomedical, behavioral, social science and health services research and development at the fundamental, clinical and applied levels and to facilitate transfer of the acquired findings to marketable products and other effective health promoting interventions; (2) initiate and expand research on community education, screening, counseling and related services programs; and (3) promote research related to education of health professionals and the public concerning the etiology, prevention, diagnosis and treatment of dental, oral and craniofacial diseases and disorders. Five organizational components are required for each COHRCD: (1) a biomedical, behavioral, social science and health services research base; (2) a demonstration research component that will, among other things, provide a means for developing effective and efficient outreach and community liaison functions; (3) a component that facilitates and manages research concerning education of health professionals and future scientists as well as the immediate and extended communities within which the center resides; (4) a technology transfer component that would support developmental activities to move fundamental and clinical research products and processes from the laboratory to the marketplace; and (5) administrative and research support cores, including biostatistics, appropriate to the focus of the research. While a strong base of biomedical or behavioral research is an essential prerequisite, all components indicated above need not be developed to the same degree, acknowledging the variety of strengths present within a given group of researchers. Details of the various components of the COHRCDs including all collaborating units as well as acquisition of complementary funding to expand the potential scientific yield of each center must be addressed. Shared resources will be used to enhance productivity, stimulate collaborative efforts and increase cost effectiveness. Award of a COHRCD indicates that the applicant group and the research they propose is at a level of excellence unparalleled in a field. A COHRCD might be located within a single institution but, preferably, would involve consortia with other institutions such as universities, research institutes, hospitals, computer facilities, regional centers, health departments, industry and primate centers. These comprehensive centers may include free-standing specialized centers, program projects, and investigator-initiated research projects as integral components and could typically include research cores, newly proposed research projects, support for feasibility studies and support for demonstration and outreach research. Support will not be provided for routine patient care costs or training expenses. The strength of the COHRCDs lies in the fact that, as thematically-based organizations, they will be capable of incorporating the full range of expertise needed to accomplish the desired objectives. Each COHRCD must be a clearly defined organizational entity with a Director responsible for management of the center. Evidence of his/her strong and effective scientific leadership must be provided. The Director will be responsible for the organization and operation of the center, for communication within the center and with the NIDR on scientific and administrative matters, for maintaining high quality research efforts and for ensuring effective collaboration and communication among scientists and cooperating institutions. INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of the NIH that women and members of minority groups and their subpopulations must be included in all NIH supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification is provided that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing research involving human subjects should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research," which have been published in the Federal Register of March 28, 1994 (FR 59 14508-14513) and in the NIH Guide for Grants and Contracts, Vol. 23, No. 11, March 18, 1994. LETTER OF INTENT Prospective applicants are asked to submit, by March 1, 1998, a letter of intent that includes the number and title of this RFA and a descriptive title for the COHRCD grant. Potential applicants also are asked to provide the name, mailing address, FAX, email address and telephone number of the Center Director and the identities of other key personnel and participating institutions and departments. Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains is helpful in estimating the potential review workload and avoiding conflict of interest in the review. The letter of intent is to be sent to Dr. Ann L. Sandberg at the address listed under INQUIRIES. APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 5/95) 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 Division of Extramural Outreach and Information Resources, National Institutes of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone 301/435-0714, email: ASKNIH@odrockm1.od.nih.gov. The RFA label available in the PHS 398 application form kit must be affixed to the bottom of the face page of the original and the original must be placed on top of the entire package. Failure to use this label could result in delayed processing of the applic