Full Text CA-94-010 CLINICAL/METABOLIC STUDIES IN NUTRITION AND BREAST CANCER PREVENTION NIH GUIDE, Volume 23, Number 10, March 11, 1994 RFA: CA-94-010 P.T. 34 Keywords: 0715036 Disease Prevention+ Nutrition/Dietetics Metabolism National Cancer Institute Letter of Intent Receipt Date: April 12, 1994 Application Receipt Date: June 9, 1994 PURPOSE The Division of Cancer Prevention and Control, National Cancer Institute (NCI), invites Interactive Research Project Grants (IRPGs) (see NIH Guide, Vol. 22, No. 16, April 23, 1994), to encourage and facilitate formal interdisciplinary collaborations through the coordinated submission of related research project applications that share a common research focus relevant to the development and conduct of clinical/metabolic studies for nutrition and breast cancer prevention research and do not require extensive shared physical resources or core functions. Complex questions in nutrition and breast cancer prevention research often require investigative efforts that extend beyond the level practicable in a single project or that require a variety of technical approaches beyond the means of a single investigator. The perceived merit of individual research project applications sometimes may be limited by the lack of a comprehensive, interdisciplinary, approach or by limitations in resident technical expertise. Many areas of nutrition and breast cancer investigations are under-represented in grant applications either because they cannot effectively be exploited without a collaborative effort or local opportunities for such interactions are not available. The objectives of this RFA for Interactive Research Project Grants (IRPGs) are to (1) increase the investigator-initiated pool of quality applications employing clinical/metabolic studies in human nutrition and breast cancer research and (2) stimulate an intermediate level of interdisciplinary collaborative efforts to build stronger research bridges between nutritional science and the disciplines that relate closely to basic and clinical research for the development, application and evaluation of new approaches to nutrition and breast cancer prevention research utilizing clinical/metabolic studies. A minimum of two independent investigators with related research objectives will be encouraged to submit concurrent, collaborative, cross-referenced individual research project grant applications that share a common research focus. The overall goals are to encourage and stimulate the integration of state-of-the-art approaches and skills to address the clinical relevance of findings suggested by epidemiologic and laboratory studies and provide more definitive data on the link between dietary intake or nutritional status and cellular/molecular mechanisms in the etiology, pathogenesis, and prevention of breast cancer. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This Request for Applications (RFA), Clinical/Metabolic Studies in Nutrition and Breast Cancer Prevention, is related to the priority area of cancer prevention. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-0043-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Domestic and foreign non-profit and for-profit organizations and institutions, governments, and their agencies are eligible to apply. Applications may be submitted from a single institution or may include arrangements with multiple institutions if appropriate. Applications from or involving minority institutions, individuals, and women are encouraged. MECHANISM OF SUPPORT Support of this program will be by the research project grant (R01). Applicants will be responsible for the planning, direction, and execution of the proposed projects. The total project period for each application submitted in response to the present RFA must not exceed four years. This is a one-time solicitation. Future unsolicited competing continuation applications will compete with all investigator-initiated applications and be reviewed according to customary peer review procedures. FUNDS AVAILABLE Approximately $2.5 million in total costs per year for up to four years will be committed to specifically fund applications that are submitted in response to this RFA. It is anticipated that six to nine awards will be made. This level of support is dependent on the receipt of a sufficient number of applications of high scientific merit. Although this program is provided for in the financial plans of the NCI, awards pursuant to this RFA are contingent upon the availability of funds for this purpose. RESEARCH OBJECTIVES Background Historically, the NCI has relied on multi-component awards, such as program projects (P01) and Cancer Center Support grants (P30), to encourage interdisciplinary collaborations in areas requiring integration and central direction of basic and clinical research components. A hallmark of such awards is the provision for extensive core facilities/resources to support the common research efforts of the program and appointment of a program director to manage the overall effort. For many investigations in nutrition and breast cancer research it may be more appropriate to consider an intermediate level of collaboration, less extensive than that described above, but beyond that practical for single projects. For such limited collaborative efforts, the exchange of research materials and ideas, rather than shared physical resources, is the primary requirement. The proposed concept of IRPGs aims to address and facilitate this class of research activities. Typically, the IRPG approach will be suited to many basic research questions, as well as research to develop and apply innovative technology or evaluate intervention strategies in individuals and target subpopulations. The IRPG mechanism is well suited for clinical/metabolic studies to differentiate the biological activities of dietary patterns and dietary constituents with respect to their functions, actions, and associations and to quantitate the responses at the cellular and molecular level in the intact human host. Use of the IRPG mechanism will benefit applicants by establishing a larger framework of reference for the proposed work, facilitating formal collaborations tailored to achieving research objectives, providing a record of independently acquired awards credited to each funded investigator, and allowing retention of research autonomy by the named Principal Investigator on each of the interactive grants. Each grantee will have the ability to submit, on his/her own behalf, competing supplements as appropriate to incorporate promising new directions of research as they evolve. The freedom to establish collaborations at separate sites and the improved transferability of awards made to individual Principal Investigators also are significant benefits. In contrast, translational research programs that span a variety of disciplines and programs that require extensive ties to co-located core resources would continue to be served best by traditional multi-component program award mechanisms. The NCI encourages qualified investigators to develop and submit concurrently coordinated research project applications that address areas of relevance to nutrition and breast cancer where the interactive research project concept may be applied. Applications submitted as a package must be tightly focused and the interactions and benefits of the proposed linkages must be made explicit as explained in the section on "Special Instructions for IRPG Applications." Research Areas of Interest In U.S. women, breast cancer is the cancer with the highest incidence and, behind lung cancer, the second highest mortality. Approximately one of every eight women will develop breast cancer during her life. Epidemiological and animal studies provide evidence that dietary patterns or dietary constituents are associated with breast cancer incidence and mortality. Animal studies have demonstrated that mammary carcinogenesis can be influenced by dietary components. Further studies may permit the isolation of the active dietary constituents, define the underlying mechanisms for the effects of dietary components, and identify an optimal dietary pattern or dietary components that have potential for reducing breast cancer risk. Persistent interaction and research collaborations among the various disciplines of biomedical research are needed to fill the gaps and provide a more definitive understanding of how dietary, environmental and genetic factors interact to influence the risk of breast cancer. Representative areas of particular interest for this RFA include many basic issues of biological functions and modulating actions of dietary patterns and nutrients that need to be investigated directly in human studies. Another area of interest is the application of innovative research approaches to the development and evaluation of specific methodologies for use in human studies to elucidate the mechanisms of action and quantify the role of diet and dietary components in breast cancer prevention and control. Such human studies should contribute to an improved and more precise interpretation of the epidemiologic associations of diet with breast cancer risk; to the identification and evaluation of improved markers of dietary exposure and early indicators of breast cancer risk; and to broadening of the understanding of the role of diet and nutrition in women's health and breast cancer prevention. Although laboratory and animal studies provide valuable qualitative and mechanistic knowledge, it remains unknown whether the results of animals studies can be extrapolated to humans. Clinical/metabolic studies are a logical step in advancing our knowledge on the role of diet and nutrition in breast cancer cause and prevention and will provide a stronger scientific base for progression to randomized controlled clinical trials to determine the efficacy of optimal dietary intervention strategies for prevention of breast cancer. Several typical (non-exhaustive) examples of research areas relevant to the dietary intervention clinical/metabolic studies for nutrition and breast cancer prevention in which the IRPG concept may be applied are as follows: o Identification, evaluation, and validation of specific molecular, cellular, metabolic, and endocrine biomarkers that are associated with initiation and/or promotion of preneoplastic transformations that may be responsive to foods and nutrients o Determine the relation between dietary intake and gene expression in breast epithelial cells and breast cancer cells o Evaluate interactions such as nutrient-nutrient, nutrient-drug, and genetic-environment interactions o Define dose-response relationships for macronutrients, micronutrients, and non-nutrient dietary constituents on molecular and cellular events and alterations in metabolic pathways o Characterize individual variability in the biological response to specific dietary patterns or nutrients o Identification of biochemical markers as quantitative measures of food intake, digestion, absorption, metabolic breakdown of specific nutrients or nutritional status o Bioavailability of nutrients and non-nutrients at various intakes and from different food sources o Determine the relation between dietary intake of environmental carcinogens, i.e., pesticides and dioxins, and breast cancer, including potential effects of contaminants in the food and water supply Prospective applicants are encouraged to explore other areas of potential for the IRPG mechanism with the NCI Program Director. The overall goal is to provide more definitive data for developing quantitative dietary guidance and translation into optimal and desirable eating patterns and food choices that have the potential for a substantial reduction in the risk of diet-related cancers in the general population. Special Instructions for IRPG Applications One Principal Investigator from the IRPG group must be identified as the "Program Coordinator," and should be cited in all applications on Page 2 of form PHS 398 (rev. 9/91). Individual investigators may request funds for the time and effort contributed toward the coordination of the overall research and for collaborative resource activities. To facilitate referral, all applications submitted under the IRPG mechanism MUST be as a single package. Each application must be complete in itself, with all appropriate approvals, budgets and signatures. A cover letter must accompany the package identifying all principal investigators and project titles that are a part of the combined submission. The letter should be firmly attached to the face page of the top application. Each application must be identified by checking "YES" on line 2a of the PHS 398 face page and citing this RFA, "Clinical/Metabolic Studies in Nutrition and Breast Cancer Prevention." The use of the IRPG mechanism must be mentioned briefly in form PHS 398 (rev. 9/91), Sections 1-4 of the Research Plan. The goal of the collaborative efforts MUST be identified in the specific aims of each application, with the major rationale and explanation for the use of the IRPG mechanism to be given in Section 7, Consultants/Collaborators. A complete list of applications in the IRPG must be provided in Section 7, as well as an indication of the specific collaborations to be established for the individual application under consideration. Requests for limited shared resources, if any, should be proportionally budgeted in each application based on anticipated use, with a full explanation given in the budget. Personnel Time and Effort requests for management of shared resources are allowable. Where consortium arrangements between independent institutions are proposed that would make transfer of funds for required new equipment impractical, the entire equipment request may be budgeted by the responsible laboratory. This must be clearly justified. All PHS and NIH grants policies will apply to applications received in response to this RFA. STUDY POPULATIONS SPECIAL INSTRUCTION TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements will be required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis should be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale should be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues should be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information should be included in the form PHS 398 in Sections 1-4 of the Research Plan AND summarized in Section 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., Native Americans (including American Indians or Alaskan Natives), Asian/Pacific Islanders, Blacks, Hispanics). The rationale for studies on single minority population groups should be provided. For the purpose of this policy, clinical research includes human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including but not limited to clinical trials. The usual policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded. However, every effort should be made to include human tissue from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. For foreign awards, the policy on inclusion of women applies fully; since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. If the required information is not contained within the application, the application may be returned, or may be deferred until additional information can be provided. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and will be reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants that do not comply with these policies. LETTER OF INTENT Prospective applicants are asked to submit, by April 12, 1994, a letter of intent that includes a descriptive title of the proposed research, the name and address of the Principal Investigator, the names of other key personnel, the participating institutions, and the number and title of the RFA in response to which the application may be submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, it is requested in order to provide an indication of the number and scope of applications to be reviewed. The letter of intent is to be sent to: Ms. Toby Friedberg Division of Extramural Activities National Cancer Institute 6130 Executive Boulevard Executive Plaza North, Room 636 Rockville, MD 20852 Telephone: (301) 496-3428 FAX: (301) 402-0275 APPLICATION PROCEDURES The regular research grant application form PHS 398 (rev. 9/91) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research; from the Office of Grants Information, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone 301/710-0267; and from the NCI Program Director listed under INQUIRIES. The RFA label available in the application form PHS 398 must be affixed to the bottom of the face page. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the title of the application, "Clinical/Metabolic Studies in Nutrition and Breast Cancer Prevention," and the RFA number, CA-94-010, must be typed on line 2a of the face page of the application form. Submit a signed, typewritten original of the application, including the Checklist, and three signed, exact, clear, and single-sided photocopies, in one package to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** At time of submission, two additional copies of the application must be sent to: Ms. Toby Friedberg Division of Extramural Activities National Cancer Institute 6130 Executive Boulevard Executive Plaza North, Room 636 Bethesda, MD 20852 Applications must be received by June 9, 1994. If an application is received after that date, it will be returned. Also, the Division of Research Grants (DRG) will not accept any application in response to this RFA that is the same as one currently being considered by any other NIH review group or awarding unit. Each application will be considered on its own merit as an individual research project. Therefore, applicants for IRPGs may not concurrently submit R01 applications that represent significant duplication of the efforts described in the applicant's IRPG. In this regard, it should be noted that the NCI will consider funding meritorious individual IRPG applications if it is not possible to fund the IRPG package as a whole. Concurrent submission of program project (P01) applications that request support for essentially similar work is prohibited. Applicants from institutions that have a General Clinical Research Center (GCRC) funded by the NIH National Center for Research Resources may wish to identify the GCRC as a resource for conducting the proposed research. If so, a letter of agreement from either the GCRC program director or Principal Investigator could be included with the application. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed (initially) by the DRG for completeness. Incomplete applications will be returned to the applicant without further consideration. Evaluation for responsiveness to the program requirements and criteria stated in the RFA is an NCI program staff function. Questions concerning the responsiveness of proposed research to the RFA may be directed to the Program Director listed under INQUIRIES. Applications may receive a preliminary scientific peer review by an NCI peer review group on the basis of relative competitiveness. The NCI will withdraw from further competition those applications judged to be noncompetitive for award and notify the applicant Principal Investigator and institutional business official. Those applications judged to be both competitive and responsive will be further evaluated according to the review criteria stated below for scientific and technical merit by an appropriate peer review group convened by the Division of Extramural Activities, NCI. The second level of review by the National Cancer Advisory Board considers the special needs of the Institute and the priorities of National Cancer Program. The following factors will be considered in evaluating the scientific merit of each response to this RFA: o Scientific, technical, or medical significance and originality of the proposed research; o Appropriateness and adequacy of the experimental approach and methodology proposed to carry out the research; o Qualifications and research experience of the Principal Investigator and staff particularly, but not exclusively, in the area of the proposed studies; o Adequacy of plans for coordination of the overall research and for collaborative resource activities; o Availability of resources necessary to perform the research; o Appropriateness of the proposed budget and duration in relation to the proposed research; o Qualifications and experience of Principal Investigator identified as the "Program Coordinator" in the context of having an oversight role in the IRPG research effort. For each application that is given a priority score, the review group will assign an adjectival descriptor that reflects the extent and effectiveness of its collaboration(s) with other applications included in the IRPG. This assessment will be documented in a brief administrative note in the summary statement to assist the NCI in making final decisions on each application in the context of the overall IRPG. AWARD CRITERIA The anticipated date of award is March 1, 1995. Although this program is provided for in the financial plans of the National Cancer Institute (NCI), awards made pursuant to this RFA are contingent upon the availability of funds for this purpose. In addition to the scientific merit; priority score, availability of funds, and programmatic priorities will be considered in making awards. INQUIRIES Written and telephone inquiries concerning the objectives and scope of this RFA and inquiries about whether or not specific proposed research would be responsive are encouraged. The program staff welcomes the opportunity to clarify any issues or questions from potential applicants. Direct inquiries regarding programmatic issues to: Carolyn K. Clifford, Ph.D. Division of Cancer Prevention and Control National Cancer Institute Executive Plaza North, Suite 212 Bethesda, MD 20892-6130 Telephone: (301) 496-8573 FAX: (301) 402-0553 Direct inquiries regarding fiscal matters to: Kathleen Shino Grants Administration Branch National Cancer Institute 6120 Executive Boulevard Executive Plaza South, Room 243 Rockville, MD 20852 Telephone: (301) 496-7800 Ext. 48 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.399, Cancer Control. Awards will be made under the authority of the Public Health Services Act, Title IV, Section 301 (Public Law 78-410,;42 U.S.C. 241 and Section 412, as amended by Public Law 99-518, 42 U.S.C 258a-1); 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 12732 or Health Systems Agency review. .
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