INTERDISCIPLINARY STUDIES IN THE GENETIC EPIDEMIOLOGY OF CANCER Release Date: August 5, 1998 RFA: CA-98-018 P.T. National Cancer Institute National Institute on Aging Letter of Intent Receipt Date: October 20, 1998 Application Receipt Date: November 17, 1998 PURPOSE The Epidemiology and Genetics Program, Division of Cancer Control and Population Sciences, National Cancer Institute (NCI) and the National Institute on Aging (NIA) invite investigator-initiated cooperative agreement applications for collaborative and interdisciplinary genetic epidemiology investigations designed to identify and evaluate the interactions of genetic and epidemiologic risk factors leading to cancer susceptibility in individuals, families and populations, and factors influencing the rate of increase with age in cancer susceptibility. The special feature of this Request for Applications (RFA) is to solicit the submission of multi-site, cooperative research applications by multi- disciplinary teams of investigators wishing to collaborate within the common theme of the genetic epidemiology of cancer. Particular emphasis is placed on encouraging interdisciplinary, population-based research focusing on the etiologic mechanisms underlying the interaction of genetic and epidemiologic risk factors for cancer susceptibility. The effect on cancer susceptibility of age-related changes over the lifespan, and the genetic factors leading to older age at onset of cancer are also of interest. 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, Interdisciplinary Studies in the Genetic Epidemiology of Cancer, 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 for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Applications from minority and women investigators are encouraged. MECHANISM OF SUPPORT The administrative and funding instrument to be used for this program will be a cooperative agreement (U01), an "assistance" mechanism (rather than an "acquisition" mechanism), 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 purpose is to support and/or stimulate the recipient's activity by involvement in and otherwise working jointly with the award recipient in a partner role, but it is not to assume direction, prime responsibility, or a dominant role in the activity. Details of the responsibilities, relationships and governance of the study to be funded under cooperative agreement(s) are discussed later in this document under the section "Terms and Conditions of Award." The total project period for an application submitted in response to this present RFA may not exceed 5 years. The anticipated award date is July 1999. Because the nature and scope of the research proposed in response to this RFA may vary, it is anticipated that the sizes of awards will vary also. Awards and level of support depend on receipt of a sufficient number of applications of high scientific merit. Although this program is provided for in the financial plans of the NCI and NIA, awards pursuant to this RFA are contingent upon the availability of funds for this purpose. At this time, the NCI has not determined whether or how this solicitation will be continued beyond the present RFA. FUNDS AVAILABLE Approximately $5.0 million per year in total costs for five years will be committed by the NCI to specifically fund applications submitted in response to this RFA. The expected number of awards is three to four. The NIA will commit up to $500,000 per year for five years in total costs for the support of research on aging-relevant issues within funded projects. RESEARCH OBJECTIVES Background During the last decade, the progressive identification of human genes conferring susceptibility for complex diseases and the application of increasingly sophisticated molecular technologies to the study of human genetics have provided new ways to analyze the human genome and to look at the relationship between phenotype and genotype in complex diseases such as cancer. Investigators in the genetic epidemiology of cancer can now attempt to incorporate developments in molecular genetics into population studies, to greatly increase insights into the genetic and environmental determinants of this disease. In addition, traditional statistical methods used in genetics are yielding to new methodologies developed to encompass both genetic and epidemiologic risk factors. As genes are identified, mapped and cloned, the possibility of describing the polymorphic frequency of various genes in the general population, as well as the ways in which these genes and their polymorphisms interact with risk factors influencing their penetrance to determine cancer susceptibility, becomes feasible. For example, germline mutations at the BRCA1 and BRCA2 loci are thought to account for 5 to 10% of breast cancer incidence and 2 to 5% of ovarian cancer incidence. Genetic and epidemiologic studies suggest that other genes of markedly lower penetrance may also be important in determining breast cancer risk. These genes may modulate individual response to environmental factors and explain variability in risk associated with different exposures. This latter category of susceptibility genes may have very large attributable risks for cancer and may be very common in the general population. As a new cancer susceptibility genes are mapped and cloned, and the role of low-risk/high frequency candidate genes in cancer etiology is evaluated, it is extremely important to consider what new research approaches will be necessary to: (a) maintain the growth of scientific knowledge in this area; (b) effectively and efficiently translate this growing knowledge into benefits for affected and at-risk individuals and populations; and (c) develop strategies for the resolution of ethical, social, and legal issues raised by the impact of these discoveries on our society. A current theory of carcinogenesis is that most forms of cancer result from the variable effects of epidemiologic risk factors, some of which may be modifiable (diet, physical activity, endogenous and exogenous hormones, addictive substances such as tobacco and alcohol, radiation exposure, etc.), on a broad range of genetic susceptibilities, in a multistage process that can be delineated and modified at each step by exogenous and host-determined factors. Supportive evidence for this theory has been provided in recent years by molecular, genetic and epidemiologic studies of specific cancers, such as colon, breast and lung. Because of the complex nature of these diseases, it is important that genetic epidemiology studies be performed by multi-disciplinary collaborative research groups capable of investigating both epidemiologic risk factors and genetic determinants of cancer and their complex interactions. A continuum of familial and population-based studies within a flexible research framework is necessary to identify high and low frequency cancer susceptibility genes and characterize their interaction with genetic and non-genetic effect modifiers. Because of the extreme public health relevance of such studies, the complexity of the scientific issues at stake, and the ethical and legal implications confronting the individuals and populations involved in such studies, such research is better conducted by multi-disciplinary teams combining cutting edge approaches to epidemiologic and genetics study design and analytical methodology, high throughput molecular genetics techniques, and clinical sciences expertise. Furthermore, the analytical power required to confer validity to these studies, especially for minority and underserved populations, will require collaborative studies among national and possibly international sites. Finally, cost-effectiveness requirements would suggest the utilization, where appropriate, of existing large cohorts, supported consortia or established research infrastructures. Recommendations from a panel on Research Priorities for the Study of Genetic Susceptibility to Cancer from the "Second International Conference Genetic Epidemiology of Cancer: From Gene Cloning to Populations" sponsored by the National Cancer Institute in 1996 suggest that there should be an increased effort in establishing multi-site, cooperative research efforts for an interdisciplinary approach to the type of genetic epidemiology studies addressing the issues outlined above. This effort would facilitate the pooling of data to increase power of needed analyses, the establishment of resources appropriate for multi-disciplinary and translational research efforts in this area, and the interdisciplinary training of genetic epidemiologists. Such cooperative efforts will be fostered and enhanced by the development of novel epidemiologic approaches into the study of the interaction between genetic susceptibility and epidemiologic risk factors in individuals and populations, and the expeditious transfer of molecular and biostatistical methods and technologies to population studies. Support of studies on genetic and other risk factors interplay leading to cancer susceptibility in understudied ethnic and racial groups was particularly recommended. Many genetic epidemiology studies are on Caucasian populations, and the information derived may not be applicable to ethnic and racial minorities. For example, few current studies will contribute information on the distribution of polymorphisms and mutations of the known cancer susceptibility genes in these populations. Genetic epidemiology studies of geographically isolated/inbred populations were also advocated. Another important research objective of this RFA is the understanding of genetic risk factors for cancer incidence in older populations, among whom the incidence of many malignancies reaches the highest rates, and the interactions between physiologic aging changes and genetic risk factors for cancer. This Request for Applications is the re-issuance of a previous NCI-funded initiative (RFA CA-93-020). Research supported under this initiative for the past four years has provided a fundamental contribution to the identification and characterization of breast, colon and ovarian cancer susceptibility genes and to the understanding of the interaction of these genes with known epidemiologic risk factors. The aim of the current RFA is to support multi- site, interdisciplinary studies of the complex interaction between genetic and other endogenous as well as exogenous risk factors in the etiology of cancer. Special consideration is given to population-based research on the unique aspects of cancer susceptibility genes (especially low relative risk, high attributable risk because of wide distribution in the population under study) in contrast to studies of major cancer susceptibility genes. Objectives and Scope The main goal of this initiative is to facilitate cross-disciplinary technological, methodological and conceptual transfer in order to advance research on the genetic epidemiology of cancer in families and populations. Inter- and Intra- institutional collaborations between epidemiologists, laboratory scientists, clinical oncologists, human geneticists, epidemiologists, biostatisticians, psychosocial and biobehavioral researchers, geriatricians and gerontologists and experts in related disciplines working on the same cancer site/syndrome are encouraged. Although this research will ultimately lead to more targeted prevention efforts and novel therapeutic designs, the latter are beyond the scope of this RFA. Collaborative proposals could include, but should not be limited to: Identification and characterization of novel cancer susceptibility through interdisciplinary genetic epidemiology studies; Studies of complex genetic interactions in cancer etiology (gene modifiers, gene-gene interaction); Characterization of the interactions of cancer susceptibility genes with known and suspected epidemiologic risk factors; Development and validation of novel statistical models to evaluate gene/environment interactions, genetic heterogeneity and alternative modes of inheritance (e.g., gene imprinting) within existing cohort or family datasets; Feasibility and validation studies to test the applicability of experimental laboratory techniques to genetic epidemiology investigations; Genetic epidemiology studies of precancerous lesions in familial clusters, including the analysis of heritable and environmental factors affecting the progression of the precursor state to malignancy; Exploration of possible differences among age groups in the contributions of specific genetic risk factors for incidence of cancers, and genetic factors contributing to age-associated differences in aggressiveness and other clinical properties of malignancies. Studies of genetic factors affecting the rate of progression of precancerous lesions in older populations and age of onset of malignancies; and Studies to evaluate the potential benefits, risks, and psychosocial impact of testing and counseling for individuals at increased risk of developing cancer and their families. SPECIAL REQUIREMENTS Each multi-site application must state clearly, in section 7 of the application form PHS 398, how the sites plan to collaborate. Applicants who already have ongoing collaborations must indicate how their response to this RFA will augment their current collaboration. Applicants are encouraged to establish collaborations that will enable them to use established resources and facilities (e.g., familial cancer registries, SEER, SPORES, Cancer Centers, Cancer Genetics Network, etc.) to facilitate the collection of patients and pedigrees and to increase cost effectiveness. Applicant institutions must demonstrate existing programs of scientific excellence in areas related with the genetic and epidemiology of cancer. All applications must address the following questions in a clear and organized manner, as described below: What existing resources, capabilities, and expertise does the applicant bring to the cooperative agreement? How will the support requested for this cooperative agreement enhance the applicant's ability to establish an interdisciplinary program to investigate the mechanisms and nature of gene-gene and gene-epidemiologic risk factor interactions in cancer susceptibility? Will the proposed project utilize an existing resource or constitute a new one? Applications should include, at a minimum, descriptions of the following: The source of recruitment (catchment area) for the population/families studied and their expected age-ranges; Capability and facilities to collect, process, and manage epidemiologic and clinical data (data coordination unit); Capability for establishing or previous existence of a biospecimen bank related to the population studied and to the scientific aims of the cooperative agreement; Availability of laboratory and/or high throughput genotyping/sequencing facilities, where needed; Methods for assuring privacy and maintaining confidentiality of participant records, including specific protections for Internet-based data systems. Timetable: a detailed timetable for the proposed study must be included in the application. Unique Capabilities Applicants should highlight unique expertise and/or unusual opportunities as related to the purpose of this RFA. Examples include, but are not limited to: Expertise in specialized areas with potential applications to the issues/questions considered in this RFA, such as molecular technology applicable to large scale genetic epidemiology studies, or the development of novel study design and analytical approaches in the genetic epidemiology of complex diseases or cancer; Access to special participant populations, such as ethnically diverse groups, older age cohorts, populations that could be followed-up for long-term longitudinal studies, cohorts with unique mutations or specific exposure to known or potential risk factors for cancer; Expertise in diagnosing and phenotyping of cancers highly prevalent in old age, and in detection and characterization of premalignant changes predisposing to such cancers; and /or in clinical and epidemiologic studies of older people, or Experience and/or expertise in state-of-the-art informatics technology. Study Organization and Function Successful grant awardees under this RFA should include in their budget support for the participation of the Principal Investigator (P.I.) and at least one Co-Principal Investigator in an annual program meeting of all awardees with the Advisory Committee. The meeting will be of one or two days duration and may be held in Bethesda, Maryland, or in other convenient locations. The Project Scientist from NCI will coordinate the annual meetings to review and assess overall progress and provide the opportunity for investigators to exchange information and discuss research issues. To demonstrate the feasibility of a successful multi-site collaboration, a number of issues need to be addressed in the applications as discussed below. Applicants should document their ability to recruit a sufficient number of study participants as related to the collaborative study aims, should discuss their capability and willingness to participate in a collaborative, multi-site study and discuss in detail the coordination and interaction among the groups involved in the application groups. Steering Committee An single project Steering Committees (SC) will serve as the main governing boards of each of the awarded multi-site cooperative agreements. Each SC will be responsible for the coordination and execution of the cooperative agreement's proposed research in all its aspects. SC membership will include the Principal Investigator, the NCI Project Scientist, an NIA representative, and a Co-Principal Investigator for each of the collaborating institutions. Additional members may be appointed by mutual agreement of the SC membership. Advisory Committee A single External Advisory Committee (EAC) will be composed of senior scientists (not affiliated with the awarded Institutions) with multi- disciplinary expertise in cancer genetics and epidemiology research, and other areas relevant to the research supported. The EAC will be responsible for advising NCI, NIA and all the awardees on scientific matters related to the overall initiative and to each single research project, and to review as appropriate and consult with the NCI representative on the awardees' scientific progress. EAC members may be nominated by the Principal Investigator of each awarded U01, and will be appointed by the NCI and NIA for a two-year tenure. The following terms and conditions will be incorporated into the award statement and provided to the Principal Investigator(s) as well as the institutional official at the time of award. Terms and Conditions of Award The Terms and Conditions of Award, below, will be incorporated in all awards 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 at 45 CFR Parts 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), an "assistance" mechanism (rather than an "acquisition" mechanism) 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 purpose is to support and/or stimulate the recipient's activity by involvement in and otherwise working jointly with the award recipient in a partner role, but it is not to assume direction, prime responsibility, or a dominant role in the activity. Consistent with this concept, the dominant role and prime responsibility for the activity resides with the awardee(s) for the project as a whole, although specific tasks and activities in carrying out the studies will be shared among the awardees and the NCI Project Scientist and/or the NIA representative where appropriate, including the following. 1. Awardee Responsibility a. The Awardee is responsible for enrollment and follow-up of the study participants, and for the establishment and maintenance of mechanisms to ensure that data collection and management procedures have necessary quality control and assure confidentiality of data. b. The Principal Investigator and the Co-Principal Investigator (s) will serve as permanent members of their SC. The SC will determine the policy and procedures pertinent to the study and meet yearly with the overall EAC and with the other awardees. c. The Awardee must provide a semi-annual progress report to the NCI Project Scientist. This report should include progress during the reporting period (including accrual and follow-up), staffing changes, a summary of project expenditures, manuscripts prepared during the reporting period, and priorities for the coming reporting period. Additional reports may be required by the NCI Project Scientist as needed. d. The Awardee will cooperate in the scientific reporting of findings. The NCI will have access to and may periodically review all data generated under an award. Plans for joint publication with NCI extramural program staff of pooled data will be reviewed and approved by the Steering Committee. NIH policies governing co-authorship of publications with NCI extramural program staff will apply in all cases. e. The Awardee(s) will retain custody of and have primary rights to the data developed under these awards, subject to Government rights of access consistent with current HHS, PHS and NIH policies. However, publication or oral presentation of results obtained under this Cooperative Agreement will require appropriate acknowledgment of NCI support. Awardees will have primary and lead responsibilities for the project as a whole, including research design and protocol development and implementation, participant recruitment and follow-up, data collection, quality control, interim data and safety monitoring, final data analysis and interpretation and preparation of publications, as well as collaboration with other awardees were needed, and with assistance from and in collaboration with the NCI Project Scientist. 2. NCI Staff Responsibilities The NCI Project Scientist will have substantial scientific-programmatic involvement during conduct of this activity, through technical assistance, advice and coordination above and beyond normal program stewardship for grants. The NCI Project Scientist will: a. Serve as liaison from the NCI, helping to coordinate activities among the Awardees; b. Serve as scientific liaison between the Awardees and other program staff at NCI with experience in multi-center studies, cancer genetics and epidemiology; c. Provide expert consultation in the area of genetic epidemiology; d. Serve as a full participant and voting member of the SC, and, as appropriate, SC subcommittee(s); serve as liaison between the SC and the EAC, attending EAC meetings in a non-voting liaison member role; and e. Assist in the monitoring of field data collection, and assist in developing operating guidelines, quality control procedures, and consistent policies for dealing with recurrent situations that require coordinated action. f. Participate in the joint description of study findings for both the scientific and public policy arena. The NIA staff representative will review progress of the studies with particular regard to aging-relevant issues, participating in Steering Committee meetings, and consult with the NCI Program Coordinator on pertinent issues. 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 substantial shortfall in accrual, data reporting, inadequate quality control of data collection, refusal to carry out the recommendations of the SC and EAC, 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. 3. Collaborative Responsibilities Steering Committees Steering Committees will serve as the main governing boards for each of the awarded multi-site cooperative agreement. It will be responsible for the coordination and execution of the proposed research in all its aspects, e.g., implementing the research designs, developing protocols and manuals as needed, and reporting study results. Its membership will include the Principal Investigator (as Chairperson), the NCI Project Scientist, and the Co-Principal Investigator for each of the collaborating institutions within a cooperative agreement. Additional members may be appointed by mutual agreement of the SC membership. Subcommittees will be established by the Steering Committee, as it deems appropriate; the NCI Project Scientist will serve on or chair subcommittees as deemed appropriate. It is anticipated that awardees will have lead responsibilities in all tasks and activities, except it is anticipated that the NCI Project Scientist will have lead responsibilities in providing programmatic guidance and in functioning as liaison between the awardees of different cooperative agreements and the multi-disciplinary EAC. The NCI Project Scientist will have voting membership on the Steering Committee and, as appropriate, its subcommittees. 4. Arbitration 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 Steering Committee (with the NCI member not voting) or by the individual awardee in the event of an individual disagreement, a second member selected by NCI, and the third member selected by the two prior selected members. This special arbitration procedure in no way affects the awardee's right to appeal an adverse action that is otherwise appealable in accordance with the PHS regulations at 42 CFR Part 50, Subpart D and HHS regulation at 45 CFR Part 16. INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of 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 s 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 or 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, Volume 23, Number 11, March 18, 1994. NIH POLICY AND GUIDELINES ON THE INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of NIH that children (i.e., individuals under the age of 21) must be included in all human subjects research, conducted or supported by the NIH, unless there are clear and compelling reasons not to include them. This policy applies to all initial (Type 1) applications submitted for receipt dates after October 1, 1998. All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines on the Inclusion of Children as Participants in Research Involving Human Subjects" that was published in the NIH Guide for Grants and Contracts, March 6, 1998, and is available at the following URL address: https://grants.nih.gov/grants/guide/notice-files/not98-024.html Investigators may also 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 20, 1998, a letter of intent that includes a descriptive title of the proposed research, name, address, and telephone number of the Principal Investigator, identities of other key personnel and participating institutions, and 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 allows NCI 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: Daniela Seminara, Ph.D., M.P.H. Division of Cancer Control and Population Sciences National Cancer Institute 6130 Executive Boulevard, Room 535, MSC 7395 Bethesda, MD 20892-7395 Telephone: (301) 496-9600 FAX: (301) 402-4279 Email: [email protected] APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 5/95) is to be used in applying for these cooperative agreements. Applications kits 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 301/710-0267, E-mail: [email protected]. Applications are also available on the web at https://grants.nih.gov/grants/funding/phs398/forms_toc.html. 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. A detailed timetable for the proposed study must be included in the application. Submit a signed, typewritten original of the application, including the Checklist, and three signed photocopies, in one package to: CENTER FOR SCIENTIFIC REVIEW NATIONAL INSTITUTES OF HEALTH 6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710 BETHESDA, MD 20892-7710 BETHESDA, MD 20817 (for express/courier service) At the time of submission, two additional copies of the application must also be sent to: Referral Officer Division of Extramural Activities National Cancer Institute 6130 Executive Boulevard, Room 636 Bethesda, MD 20892 Rockville, MD 20850 (for express/courier service) Applications must be received by November 17, 1998. If an application is received after that date, it will be returned to the applicant without review. The Center for Scientific Review (CSR) will not accept any application in response to this RFA that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. The CSR will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of a substantial revision of an application already reviewed, but such an application must follow the guidance in the PHS Form 398 application instructions for the preparation of revised applications, including an introduction addressing the previous critique. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by the CSR and responsiveness by the NCI. Incomplete and/or non-responsive applications will be returned to the applicant without further consideration. Those applications that are complete and responsive, and judged to be competitive, will undergo further scientific merit review in accordance with the criteria stated below for scientific/technical merit by an appropriate peer review group convened by the NCI. The second level of review will be provided by the National Cancer Advisory Board and the National Aging Advisory Council. 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 RESEARCH OBJECTIVES of the RFA. Although the technical merit of the proposed protocol is important, it will not be the sole criterion for evaluation of a study. Other considerations, such as the importance and timeliness of the proposed study, access to the study population, and the interdisciplinary nature of the studies, will be part of the evaluation criteria. As part of the initial merit review, all applications will receive a written critique and undergo a process in which only those applications deemed to have the highest scientific merit, generally the top half of the applications under review, will be discussed, assigned a priority score, and receive a second level review by the appropriate national advisory council. Review Criteria Applicants are encouraged to submit and describe their own ideas about how best to meet the goals of the cooperative study and their specific protocols, and are expected to address issues identified under SPECIAL REQUIREMENTS of the RFA. The review group will assess the scientific merit of the protocols and related factors as follows: Significance: Does this study address an important problem in the genetic epidemiology of cancer? If the aims of the applications 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? 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? 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? Investigators: Are the Principal Investigator, Co-Principal Investigators and their teams appropriately trained and have adequate experience to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and his/her collaborators? Environment: Does the scientific environment in which the work will be done significantly 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 institutional support? Is a suitable population(s) available for this study? In addition to the above criteria, in accordance with NIH policy, all applications will also be reviewed with respect to the following: The reasonableness of the proposed budget and duration in relation to the proposed research. The adequacy of plans to include both genders, minorities and their subgroups, and children as appropriate for the scientific goals of the research. Plans for the recruitment and retention of subjects will also be evaluated. The adequacy of the proposed protection for humans, animals or the environment, to the extent they may be adversely affected by the project proposed in the application. Availability of special opportunities for furthering research programs through the use of unusual talent resources, populations, or environmental conditions in other countries which are not readily available in the United States, or which provide augmentation of existing U.S. resources. The application of creative and innovative (high risk/high impact) experimental approaches and the development of interactive strategies and collaborative teams are integral to the research goals of this RFA and are encouraged. AWARD CRITERIA Applications recommended by the NCI Advisory Board and the NIA Advisory Council will be considered for award based upon (a) scientific and technical merit; (b) program balance, including in this instance, sufficient compatibility of features to make a successful collaborative program a reasonable likelihood; and (c) availability of funds. Schedule Letter of Intent Receipt Date: October 20, 1998 Application Receipt Date: November 17, 1998 Review by NCAB Advisory Board: May 1999 Anticipated Award Date: July 1999 INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Daniela Seminara, Ph.D., M.P.H. Division of Cancer Control and Population Sciences National Cancer Institute 6130 Executive Boulevard, Room 535, MSC 7395 Bethesda, MD 20892-7395 Telephone: (301) 496-9600 FAX: (301) 402-4279 Email: [email protected] Direct inquiries regarding aging-related topics to: Rosemary Yancik, Ph.D. Cancer Section National Institute on Aging Gateway Building, Suite 3E-327 Bethesda, MD 20892-9205 Telephone: (301) 496-5278 FAX: (301) 402-1784 Email: [email protected] Direct inquiries regarding fiscal matters to: Catherine E. Blount Grants Administration Branch National Cancer Institute Executive Plaza South, Room 243 Bethesda, MD 20892 Telephone: (301) 496-7800 Ext. 262 FAX: (301) 496-8601 Email: [email protected] AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No.93.393. 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 Parts 52 and 45 CFR Part 74 [and Part 92 when applicable for State and Local governments]. 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.
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