kristoff@GENBANK.BIO.NET (Dave Kristofferson) (05/26/90)
COMMUNITY CLINICAL ONCOLOGY PROGRAM RFA AVAILABLE: CA-90-13 P.T. 34; K.W. 0403004, 0715035, 0755015, 0795003 National Cancer Institute Letter of Intent Receipt Date: June 15, 1990 Application Receipt Date: August 24, 1990 INTRODUCTION The Division of Cancer Prevention and Control (DCPC), National Cancer Institute (NCI), invites applications from domestic institutions for cooperative agreements to continue its Community Clinical Oncology Program (CCOP). New applicants and currently funded programs are invited to respond to this Request For Applications (RFA). Utilizing the national resource of highly trained oncologists in community practice, the CCOP: 1) provides support for expanding the clinical research effort in the community setting; 2) stimulates quality care in the community through participation in protocol studies; 3) fosters the growth and development of a scientifically viable community cancer network able to work closely with NCI-supported clinical cooperative groups and cancer centers, and public health departments; 4) supports development of and community participation in intervention cancer control research, including prevention, early detection, patient management, rehabilitation, and continuing care; 5) involves primary care providers and other specialists in cancer control studies; and 6) increases the involvement of minority and underserved populations in clinical research. Combining the expertise of community physicians and other health care professionals with NCI-approved treatment and cancer control clinical trials provides the opportunity for the transfer of the latest research findings to the community level. This issuance of the CCOP RFA seeks to build on the strength and demonstrated success of the CCOP over the past seven years by: 1) continuing the program as a vehicle for supporting community participation in treatment and cancer control clinical trials through research bases (clinical cooperative groups and cancer centers supported by NCI, and public health departments); 2) expanding and strengthening the cancer control research effort to equal that of cancer treatment; 3) utilizing the CCOP network for conducting NCI- assisted cancer control research; and 4) evaluating on a continuing basis CCOP performance and its impact in the community. BACKGROUND INFORMATION Over 80 percent of patients with cancer are treated in the community. The CCOP was initiated in 1983 to bring the benefits of clinical research to cancer patients in their own communities by providing support for physicians to enter patients onto treatment research protocols. In the first three years of the CCOP, 62 community programs in 34 states were funded. During this time, approximately 14,000 patients were entered onto NCI-approved treatment clinical trials through the CCOP. The data from CCOP participants met or exceeded all the quality control standards of the cooperative groups. The CCOP evaluation indicated that patients on protocol and patients treated by CCOP-participating physicians received more appropriate patterns of care than patients seen by physicians who never used protocols. The CCOPs also had an increase in the number of physicians using protocols, the number of protocols used, and the number of patient registrations. It was further documented that CCOPs with higher accruals were often associated with more appropriate patterns of care. All of these factors contribute to establishing a framework that is critical to the diffusion process and the widespread dissemination of state-of-the-art practices. The CCOPs clearly were very effective in accruing patients to treatment clinical trials. The second CCOP RFA, issued in 1986, expanded the focus to include cancer control research based on the rationale that the multi-institutional clinical trials model, essential for testing new treatment regimens, is also required for conducting large-scale cancer prevention and early detection trials. As a result of the second RFA, 52 community programs in 30 states received three-year awards in June 1987, with approximately 240 hospitals participating. To date, approximately 13,500 patients or 4500 patients per year have been entered onto treatment clinical trials through the CCOP; approximately 5700 patients/subjects per year have been enrolled in cancer control studies. The development of cancer control research in the CCOP network has been increasing steadily since funding was begun in 1987. Cancer control research in the CCOPs is aimed at reducing cancer incidence, morbidity, and mortality through the identification and testing of interventions in controlled clinical trials. Most research bases have formed active cancer control committees, DCPC has formed the Cancer Control Protocol Review Committee (CCPRC), and the structure and process for protocol development and review is in place. Protocols reviewed to date cover the full spectrum of cancer control research, including chemoprevention and marker studies for future prevention interventions, smoking cessation studies, screening and early detection, and pain control and other symptom management interventions. The CCOPs are a vital resource for conducting NCI cancer control research because they provide access to: 1) a national network for cancer control studies which require large sample sizes for completion; 2) geographic areas which include cross sections of the population, providing mixes of patients/subjects not always available in university or urban settings; 3) large clinics or health maintenance organizations (HMOs) which can provide the opportunity for population-based studies in screening and early detection; and 4) cancer patients' family members and others who may be at high risk of developing cancer and thus be candidates for prevention and detection studies. Participation in cancer control research by CCOPs also further expands the network of community physicians, increasing the potential for diffusion of state-of-the-art cancer control practices. Formal and informal input in the development of this RFA was provided to DCPC program staff by many sources, including the CCOP advisory group, CCOP principal investigators, cancer center directors, clinical cooperative group chairmen, the CCOP evaluation advisory group, and NCI Grants Administration and Grants Review Branches. Advice was also obtained during numerous presentations and discussions in conjunction with the meetings of professional organizations and clinical cooperative groups and from program staff site visits. RESEARCH GOALS AND SCOPE The CCOP initiative is designed to: o Bring the advantages of state-of-the-art treatment and cancer control research to individuals in their own communities by having practicing physicians and their patients/subjects participate in NCI-approved treatment and cancer control clinical trials; o Provide a basis for involving a wider segment of the community in cancer control research and investigate the impact of cancer therapy and control advances in community medical practices; o Increase the involvement of primary health care providers and other specialists (e.g., surgeons, urologists, gynecologists) with the CCOP investigators in treatment and cancer control research, providing an opportunity for education and exchange of information; o Facilitate wider community participation, including minorities, women, and other underserved populations, in treatment and cancer control research approved by NCI; and o Reduce cancer incidence, morbidity, and mortality by accelerating the transfer of newly developed cancer prevention, early detection, treatment, patient management, rehabilitation, and continuing care technology to widespread community application. Participating community programs (CCOPs) will be required to enter patients onto NCI-approved treatment and cancer control clinical trials through the research base(s) with which each CCOP is affiliated. Consideration will also be given for patients referred to cancer centers and entered onto NCI-approved treatment protocols. CCOPs may relate directly to NCI for assistance and participation in selected cancer control protocols. CCOP performance will be evaluated on a continuing basis by NCI program staff for its impact on community cancer treatment and control practices and the involvement of minorities, women, and other underserved populations in clinical research. Participating research bases will be required to continue providing clinical research treatment and/or cancer control protocols as applicable and, as studies progress and findings indicate, to develop new protocols. Cancer control research should be intervention-oriented and may include areas such as cancer prevention, early detection, patient management, rehabilitation, and continuing care. Research bases will be expected to monitor the quality of protocol conduct, follow CCOP accrual, and participate in the continuing program evaluation. MECHANISM OF SUPPORT Support of this program will be through the Cooperative Agreement. The Cooperative Agreement is an assistance mechanism in which substantial NCI programmatic involvement with the recipient during performance of the planned activity is anticipated. The nature of NCI staff involvement is described in TERMS OF COOPERATION. Applicants will be responsible for the planning, direction, and execution of the proposed project. Except as otherwise stated in this RFA, awards will be administered under PHS grants policy as stated in the Public Health Service Grants Policy Statement, DHHS Publication No. (OASH) 82-50,000, revised January 1, 1987. NCI has determined that there is a continuing program need for community participation in cancer clinical research trials, both treatment and cancer control. It is expected that, if funds are available, an announcement of the annual receipt date for applications in response to this RFA will be published in the NIH Guide for Grants and Contracts. It is anticipated that up to $4.4 million in total costs per year for 5 years will be committed to specifically fund applications which are submitted in response to this RFA. Of the total, approximately $3.9 million will be committed to research bases and approximately $450,000 to CCOPs. It is anticipated that up to 17 research base awards and up to 5 CCOP awards will be made. This is dependent on the receipt of a sufficient number of applications of high scientific merit. NCI program staff will take into account demographic and geographic distribution of peer-reviewed and approved applicants in the final funding selection process to assure inclusion of minority and underserved populations. Multiple CCOP applicants approved for funding who are competing for the same patient population will be considered, but all may not be awarded unless warranted by the population density. The total project period for applications submitted in response to this RFA may not exceed 3 years for new applicants, and 5 years for applicants previously supported under this program. Previously supported applicants will be funded for 3, 4, or 5 years depending upon priority score/percentile, review committee recommendations, and programmatic considerations. The earliest feasible start date for the initial awards will be June 1, 1991. Although this program is provided for in the financial plans of NCI, the issuance of awards pursuant to this RFA is also contingent upon the continued availability of funds for this purpose. TERMS OF COOPERATION Under the cooperative agreement, a partnership will exist between the recipient of the award and NCI, with assistance from NCI in carrying out the planned activity. The following terms and conditions pertaining to the scope and nature of the interaction between NCI and the investigators will be incorporated in the Notice of Award. These terms will be in addition to the customary programmatic and financial negotiations which occur in the administration of grants. The "TERMS OF COOPERATION: Nature of NCI Staff Involvement" described in this section are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines; DHHS grant administration regulations 45 CFR 74; other DHHS, PHS, and NIH grant administration policy statements; and other NCI administrative terms of award. 1 Community (CCOP) Awardees Nature of NCI Staff Involvement Protocol Review All protocols utilized by the CCOPs must be reviewed and approved for CCOP use by the CCPRC, DCPC, and/or the Protocol Review Committee (PRC), Division of Cancer Treatment (DCT), NCI, prior to implementation. NCI will not provide investigational drugs, permit expenditure of NCI funds, or allow accrual credit for a protocol that has not been approved, or that has been closed (except for patients already on study). Monitoring There will be periodic on-site monitoring (auditing) of each CCOP by representatives of its research base(s), NCI, or an NCI-designee, such as DCT's current Clinical Trials Monitoring Service contractor. Such on-site visits may include monitoring the following: use of investigational drugs; compliance with regulations for Institutional Review Board (IRB) approval and informed consent (compliance with 45 CFR 46); compliance with protocol specifications; quality control and accuracy of data recording; completeness of reporting adverse drug reactions; protocol accrual; fiscal and administrative procedures. Reports of such site visits will be reviewed by the Quality Assurance and Compliance (QACS), Regulatory Affairs Branch (RAB), Cancer Therapy Evaluation Program (CTEP), DCT, and by the DCPC program director. Data Management The DCPC program director will have access to all data generated under this award and will periodically review the data management procedures of the CCOP. Data must also be available for external monitoring if required by NCI's agreement with other federal agencies, such as the Food and Drug Administration (FDA). Investigational Drug Management The Drug Management and Authorization Section, Investigational Drug Branch (IDB), CTEP, DCT/Chemoprevention Branch (CB), DCPC, staff will advise investigators of specific requirements and changes in requirements about investigational drug management that the FDA and NCI may mandate, either directly or through the research bases. Organizational Changes Certain CCOP organizational changes must have the prior written approval of the DCPC program director. These include the addition/deletion of a participating physician, affiliate, component, or research base. A change in the principal investigator, or in any key personnel identified on the "Notice of Award," must have the prior written approval of the NCI grants management specialist, with the advice of the DCPC program director. Program Review Annual progress reports must be submitted to DCPC. A suggested format developed by the DCPC program director for this purpose will be provided. The DCPC program director will review the progress of each CCOP through consideration of the CCOP annual report, program site visits, and reports from affiliated research bases. This review may include, but not be limited to, overall accrual credits, percent of available patients/subjects placed on study, eligibility and evaluability of individuals entered on study, and timeliness and quality of data reporting. The inability of a CCOP to meet the performance requirements set forth in the TERMS OF COOPERATION in the RFA, or significant changes in the level of performance, may result in an adjustment of funding, withholding of support, suspension or termination of the award. Strategy Sessions The DCPC program director will sponsor strategy sessions when indicated, attended by principal investigators from the CCOPs and appropriate DCPC/DCT representatives. At these meetings, information relevant to the CCOPs will be reviewed and discussed, including such issues as overall CCOP performance and the science of current or proposed studies. Data will be analyzed and the outstanding research questions established and prioritized into national research goals by CCOP investigators and the DCPC/DCT attendees. The DCPC program director will assist the CCOP investigators in exploring mutual interests in cancer control research. Federally Mandated Regulatory Requirements The DCPC program director/DCT representative will review mechanisms established by each CCOP to meet the Department of Health and Human Services (DHHS)/Public Health Service (PHS) regulations for the protection of human subjects and FDA requirements for the conduct of research using investigational agents. At a minimum, these include: o methods for assuring that each institution at which CCOP investigators are conducting clinical trials has a current, approved assurance on file with the Office for Protection from Research Risks (OPRR); that each protocol is reviewed by the responsible IRB prior to patient entry; and that each protocol is reviewed annually by the IRB so long as the protocol is active; o methods for assuring or documenting that each patient (or patient's parent/legal guardian) gives fully informed consent to participation in a research protocol prior to the initiation of the experimental intervention; o a system for assuring timely reporting of all serious and unexpected toxicities to the IDB, CTEP, DCT, according to DCT guidelines and/or to DCPC according to DCPC guidelines; and o implementation of DCPC/DCT requirements for storage and accounting for investigational agents provided under DCPC/DCT sponsorship. Arbitration Process The TERMS OF COOPERATION require that the NCI program director make post-award administrative decisions related to program performance, adjustments in funding, etc. NCI will establish an arbitration process when a mutually acceptable agreement cannot be obtained between the awardee and NCI staff. An arbitration panel (with appropriate expertise) composed of one member of the recipient group, one NCI nominee, and a third member chosen by the other two will be formed to review the NCI decision and recommend a course of action to the Director, DCPC. These special arbitration procedures in no way affect the awardee's right to appeal an adverse action in accordance with PHS regulations 42 CFR Part 50, Subpart D, and DHHS regulations 45 CFR Part 16. 1 Community (CCOP) Awardees Responsibilities of Awardees Protocols All protocols utilized by the CCOPs must have been reviewed and approved for CCOP use by the CCPRC, DCPC, and/or the PRC, DCT, NCI, prior to implementation. The research base is responsible for the development and implementation of high quality treatment and cancer control clinical trials, and for evaluation of the results of such studies. To be eligible to receive credit for accrual to a research base protocol, the CCOP must have an affiliation agreement with the research base responsible to NCI for that protocol. Research Base Affiliation(s) Each CCOP may affiliate with up to five eligible research bases, only one of which may be a national multi-specialty cooperative group. Note: A list of currently eligible research bases may be obtained from the program official listed in LETTER OF INTENT. If participation in the protocols of one group competes with that of another group with which the CCOP is affiliated, the CCOP must prioritize the protocols in order to avoid bias in the allocation of patients to competing protocols. Initial affiliations should be maintained during the funding cycle. When circumstances require changes in research base affiliations, prior written approval from the DCPC program director is required. Accrual Each CCOP is required to accrue a minimum of 50 credits* per year to treatment clinical trials that have been approved by the PRC, DCT, NCI. (For applicants whose specialty is pediatrics, the 50 credit minimum requirement may be waived for those applicants who are able to place a majority of their eligible patients on protocols.) A CCOP will receive accrual credit for a patient that is referred to a cancer center for treatment and is placed on an NCI-approved protocol. As one measure of performance, it is expected that at least 10 percent of patients for whom protocols are available will be placed on studies by CCOP physicians. Each CCOP is required to accrue a minimum of 50 credits per year to cancer control studies that have been approved by the CCPRC, DCPC, and/or the PRC, DCT, NCI. * Credits will be based on the complexity of the intervention, the amount of data management required, and the duration of follow-up. For example, each patient accrued to an average Phase II or Phase III protocol will count 1 credit; an NCI-designated high-priority protocol 1.5 credits; and a childhood acute lymphocytic leukemia protocol 2 credits. Cancer control protocols will be assessed for credit using a similar approach. Credit will be assigned following final approval of the protocol (see Section TERMS OF COOPERATION, B Research Base Awardees). Quality Control The CCOP must follow the procedures required by each of its research bases and the QACS, RAB, CTEP, DCT/DCPC program director. Data Management The CCOP must provide the DCPC program director with access to all data generated under this award for periodic review of data management procedures of the CCOP. Data must also be available for external monitoring if required by NCI's agreement with other federal agencies, such as the FDA. Investigational Drug Management Investigators performing trials under cooperative agreements will be expected, in cooperation with NCI, to comply with all FDA monitoring and reporting requirements for investigational agents. Organizational Changes Certain CCOP organizational changes must have the prior written approval of the DCPC program director. These include the addition/deletion of a participating physician, affiliate, component, or research base. A change in the principal investigator, or in any key personnel identified on the "Notice of Award," must have the prior written approval of the NCI Grants Management specialist, with the advice of the DCPC program director. Radiotherapy Equipment Radiotherapy equipment must have its calibration verified according to standards set by the Radiologic Physics Center (RPC) in order for institutions to participate in protocols requiring radiation therapy, as required by the affiliated research base(s). Monitoring Each CCOP must agree to periodic on-site monitoring (auditing) by representatives of its research base(s), NCI, or an NCI-designee as described in TERMS OF COOPERATION, 1 Community (CCOP) Awardees, Nature of NCI Staff Involvement, Monitoring. Reporting Requirements Annual progress reports must be submitted to DCPC. A suggested format developed by the DCPC program director for this purpose will be provided. The DCPC program director will review the progress of each CCOP as described in TERMS OF COOPERATION, 1 Community (CCOP) Awardees, Nature of NCI Staff Involvement, Program Review. The inability of a CCOP to meet the performance requirements set forth in the TERMS OF COOPERATION in the RFA, or significant changes in the level of performance, may result in an adjustment of funding, withholding of support, suspension or termination of the award. Network Participation CCOPs are part of a national network for conducting treatment and cancer control clinical trials. As such, each CCOP may be asked to participate in strategy sessions or workshops and in the continuing evaluation of the program and its impact in the community. Patient Log Each CCOP may be asked periodically to maintain a new patient log or minimal registry to include age, sex, race, primary site of cancer, stage of disease, and treatment disposition for the potentially eligible patient pool seen by the CCOP investigators. Federally Mandated Regulatory Requirements Each CCOP must establish mechanisms to meet DHHS/PHS regulations for the protection of human subjects as described in TERMS OF COOPERATION, 1 Community (CCOP) Awardees, Nature of NCI Staff Involvement, Federally Mandated Regulatory Requirements. Publications Timely publication of major findings is encouraged. Publication or oral presentation of work done under this agreement requires acknowledgement of NCI support. 2 Research Base Awardees Nature of NCI Staff Involvement Scientific Resource The DCPC/ DCT, NCI, staff will serve as a resource for specific scientific information on treatment regimens, cancer control studies, and clinical trial design. NCI staff will assist the research base as appropriate in developing information concerning the scientific basis for specific trials and will also be responsible for advising the research base of the nature and results of relevant trials being carried out nationally or internationally. The DCPC program director will sponsor strategy sessions when indicated, attended by leading investigators from the research bases and appropriate DCPC/DCT representatives. At these meetings relevant information will be reviewed and the outstanding research questions established and prioritized into national research goals by investigators and the DCPC/DCT attendees. The IDB, CTEP, DCT/ CB, DCPC staff will provide updated information on the efficacy, toxicity and availability of all Investigational New Drugs (INDs) supplied by NCI to the research base. Protocol Development The protocol should be a document mutually acceptable to the research base and to DCPC/DCT. Communication at the various stages of development is encouraged. DCPC/DCT will assist the research base in protocol design as appropriate by providing information regarding: a) the existence and nature of concurrent clinical trials in the area of research with an emphasis on preventing duplication of effort; b) relevant pharmacokinetic and pharmacodynamic data on investigational agents; c) availability of investigational agents, including biologic response modifiers; d) feasibility and appropriateness of the research for use by the CCOPs and/or in a community setting; and e) basic research in cancer centers and other NCI-funded programs which may be ready for clinical trials. When indicated, DCPC/DCT will also comment on the scientific rationale, value, priority, design, statistical requirements, and implementation of the proposed study. All protocols proposed for use by the CCOPs must be preceded by a concept/Letter of Intent review by DCPC/DCT. All concepts and protocols should be submitted to the Protocol Information Office (PIO), CTEP, DCT, for review by the appropriate committee. Protocol Review All research base protocols utilized by the CCOPs must be reviewed and approved for CCOP use by the CCPRC, DCPC, and/or the Protocol PRC, DCT, NCI, prior to implementation. Ad hoc reviewers, external to NCI, will be utilized when deemed appropriate by the CCPRC chairperson and/or the PRC chairperson. The major considerations in protocol review by DCPC/DCT include: a) strength of the scientific rationale supporting the study; b) importance of the question being posed; c) avoidance of undesirable duplication with ongoing studies; d) appropriateness of study design; e) satisfactory projected accrual rate and follow-up period; f) patient/subject safety; g) compliance with NIH and other federal regulatory requirements; h) adequacy of data management; and i) appropriateness of patient/subject selection, evaluation, assessment of toxicity, response to intervention, and follow- up. The DCPC/DCT review committee chairperson will provide the research base with a consensus review that describes recommended modifications and other suggestions as appropriate. If a protocol is disapproved, the specific reasons for lack of approval will be communicated to the research base principal investigator as a consensus review within a reasonable time. DCPC/DCT will work with the research base to develop a mutually acceptable protocol compatible with the research interests, abilities, and needs of the base, its affiliates, and NCI. Credit will be assigned following final approval of the protocol. NCI will not provide investigational drugs, permit expenditure of NCI funds, or allow accrual credit for a protocol that has not been approved. Data Management and Analysis Data generated is the property of the awardee; however, DCPC/DCT will have access to all data generated under this award. The DCPC program director/DCT representative may review data management and analysis procedures of the research base, under mutually agreeable circumstances, for consistency with policies and procedures established by DCPC/DCT for awardees conducting treatment and cancer control clinical trials. Data must also be available for external monitoring if required by NCI's agreement with other federal agencies, such as the FDA. Quality Control and Monitoring The QACS, RAB, CTEP, DCT/DCPC program director may review quality control and monitoring procedures of the research base for consistency with policies and procedures established by DCT/DCPC for awardees conducting treatment and cancer control clinical trials. Investigational Drug Management NCI will have the option to cross file or independently file an IND on investigational drugs evaluated in trials supported under cooperative agreements. This would apply to drugs not developed in the NCI drug development program. The Drug Management and Authorization Section, IDB, CTEP, DCT/CB, DCPC, staff will advise investigators of specific requirements and changes in requirements concerning investigational drug management that the FDA may mandate. Organizational Changes A change in the research base principal investigator, or in any key personnel identified in the "Notice of Award," must have the prior written approval of the NCI grants management specialist, with the advice of the DCPC program director. Program Review Annual progress reports, including an annual performance report on each affiliated CCOP, must be submitted to DCPC. A suggested format developed by the DCPC program director for this purpose will be provided. The DCPC program director will review the progress of each research base through consideration of the research base annual report and program site visits. The annual report will include, as a minimum, information on: overall case accrual credits; cancer control research, existing or planned; eligibility and evaluability of patients/subjects entered on study; timeliness and quality of data reporting; and results of quality control review and audits if performed during that year. Research base funding is contingent on accrual from affiliated CCOPs/Minority- Based CCOPs and annual adjustments in funding may be made. The inability of a research base to meet the performance requirements set forth in the TERMS OF COOPERATION in the RFA, or significant changes in the level of performance, may result in an adjustment of funding, withholding of support, suspension or termination of the award. Protocol Closure DCPC/DCT will review research base mechanisms for interim monitoring of results and will monitor protocol progress. DCPC/DCT may request that a protocol study be closed for reasons including: a) insufficient accrual rate; b) accrual goal met; c) poor protocol performance; d) patient/subject safety; e) already conclusive study results; and f) emergence of new information which diminishes the scientific importance of the study question. NCI will not provide investigational drugs, permit expenditure of NCI funds, or allow accrual credit for a study after requesting closure (except for patients already on study). If a research base wishes to close accrual to a study prior to meeting the initially established accrual goal, the interim results and other documentation should be made available to NCI for review and concurrence prior to implementation of the decision by the research base. It is recommended that statistical guidelines for early closure be presented as explicitly as possible in the protocol in order to facilitate these decisions. Federally Mandated Regulatory Requirements The DCPC program director/DCT representative will review mechanisms established by each research base to meet Department of Health and Human Services (DHHS)/Public Health Service (PHS) regulations for the protection of human subjects and FDA requirements for the conduct of research using investigational agents. At a minimum, these include: o an on-site audit program for periodic data verification and review of regulatory responsibilities at each CCOP, cooperative group member, and Cooperative Group Outreach/cancer center affiliate institution; and o a method of providing, upon DCPC/DCT request, summary efficacy and toxicity data to be included in DCPC/DCT's annual reports to the FDA for each investigational agent. CCOPs/Minority-Based CCOPs The DCPC program director will notify research bases when CCOPs/Minority-Based CCOPs are funded. Arbitration Process The TERMS OF COOPERATION require that the NCI program director make post-award decisions related to protocol review, program performance, adjustments in funding, etc. NCI will establish an arbitration process when a mutually acceptable agreement cannot be obtained between the awardee and NCI staff. An arbitration panel (with appropriate expertise) composed of one member of the recipient group, one NCI nominee, and a third member chosen by the other two will be formed to review the NCI decision and recommend an appropriate course of action to the Director, DCPC. These special arbitration procedures in no way affect the awardee's right to appeal an adverse action in accordance with PHS regulations 42 CFR Part 50, Subpart D, and DHHS regulations 45 CFR Part 16. 2 Research Base Awardees Responsibilities of Awardees Protocol Development The research base is responsible for the development and implementation of high quality treatment and cancer control clinical trials, and for evaluation of the results of such studies. Protocol Review All research base protocols utilized by the CCOPs must have been reviewed and approved for CCOP use by the CCPRC, DCPC, and/or the PRC, DCT, NCI, prior to implementation. Treatment and cancer control protocols must be submitted to the PIO, CTEP, DCT, for review by the appropriate committee. All protocols must be preceded by a concept/Letter of Intent review by DCPC/DCT. Accrual A research base for treatment research is required to accrue a minimum of 50 credits (see TERMS OF COOPERATION, 1 Community (CCOP) Awardees, Responsibilities of Awardees, Accrual) per year from affiliated CCOPs to treatment clinical trials that have been approved by the PRC, DCT, NCI. (An exemption may be approved by the DCPC program director for an unusual situation such as a well-established relationship between a cancer center and a CCOP.) A research base for cancer control research is required to accrue a minimum of 50 credits (see TERMS OF COOPERATION, 1 Community (CCOP) Awardees, Responsibilities of Awardees, Accrual) per year from affiliated CCOPs to cancer control studies that have been approved by the CCPRC, DCPC, and/or the PRC, DCT, NCI. Data Management and Analysis Data generated is the property of the awardee; however, the research base must provide DCPC/DCT with access to all data generated under this award. The DCPC program director/DCT representative may review data management and analysis procedures of the research base under mutually agreeable circumstances. Data must also be available for external monitoring if required by NCI's agreement with other Federal agencies, such as the FDA. Quality Control A DCT-funded research base must follow all the policies and procedures for quality control established by DCT. Similar policies and procedures for quality control will be expected from cancer centers and public health departments. Investigational Drug Management Investigators performing trials under cooperative agreements will be expected, in cooperation with DCPC/DCT to comply with all FDA distribution, monitoring, and reporting requirements for investigational agents. Organizational Changes A change in the research base principal investigator, or in any key personnel identified in the "Notice of Award," must have the prior written approval of the NCI Grants Management specialist, with the advice of the DCPC program director. Audits Each research base will be responsible for auditing its affiliated CCOPs. Cooperative group research bases will be responsible for site visit monitoring (auditing) affiliated CCOPs according to the established guidelines for monitoring its other members and/or affiliates. Cancer center research bases may initiate their own audit programs following guidelines established by the RAB, CTEP, DCT. As an alternative, they may choose to include CCOP records in the audits of center studies conducted by CTEP. If this latter option is chosen, the center must prospectively assure that medical charts and other records from the affiliated CCOPs will be brought to the center for audit when they are requested. Results of CCOP audits will be reported to the QACS, RAB, CTEP, DCT, and the DCPC program director. Public health departments and cancer centers approved as research bases for only cancer control research must have audit procedures for affiliated CCOPs. Results of these CCOP audits will be reported to the DCPC program director. Reporting Requirements Annual progress reports, including an annual performance report on each affiliated CCOP, must be submitted to DCPC. A suggested format developed by the DCPC program director for this purpose will be provided. The DCPC program director will review the performance of each research base as described in TERMS OF COOPERATION, 2 Research Base Awardees, Nature of NCI Staff Involvement, Program Review. Research base funding is contingent on accrual from affiliated CCOPs/Minority-Based CCOPs and annual adjustments may be made. The inability of a research base to meet the performance requirements set forth in the TERMS OF COOPERATION in the RFA, or significant changes in the level of performance, may result in an adjustment of funding, withholding of support, suspension or termination of the award. Network Participation Research bases are part of a national network for conducting treatment and cancer control clinical trials. As such, each research base may be asked to participate in strategy sessions or workshops and the continuing evaluation of the program and its impact in the community. Federally Mandated Regulatory Requirements Each research base must establish mechanisms to meet FDA regulatory requirements for studies involving DCPC/DCT- sponsored investigational agents and DHHS/PHS regulations for the protection of human subjects as described in TERMS OF COOPERATION, 2 Research Base Awardees, Nature of NCI Staff Involvement, Federally Mandated Regulatory Requirements. CCOPS/Minority-Based CCOPs Research bases must agree to affiliate with CCOPs/Minority- Based CCOPs when they are funded, according to guidelines established by each research base for its affiliates, and as appropriate. Publications Timely publication of major findings is encouraged. Publication or oral presentation of work done under this agreement requires acknowledgement of NCI support. ELIGIBILITY REQUIREMENTS 1 CCOP Applicants o An applicant may be a hospital, a clinic, a group of practicing physicians, a health maintenance organization (HMO), or a consortium of hospitals and/or clinics and/or physicians and/or HMOs that agree to work together with a principal investigator and a single administrative focus. o A university, military, or Veterans Administration hospital may be included in an application as a non-dominant member of a consortium led by a community institution, but may not be the applicant organization or the major contributor to accrual. An unfunded, nonuniversity clinical trials cooperative group member is eligible to apply. o Funded Cooperative Group Outreach Program (CGOP) participants are eligible to apply, but should state in the application that CGOP support will be relinquished if a CCOP award is received. Institutions not eligible to apply as a CCOP include: o A comprehensive, consortial, or clinical cancer center holding an NCI Cancer Center Support (CORE) grant; o A university hospital that is the major teaching institution for that university; or o A university hospital clinical trials cooperative group member funded by DCT, NCI. 2 Research Base Applicants An applicant may be: o An NCI-funded clinical trials cooperative group; o An NCI-funded clinical, consortial, or comprehensive cancer center; or o A public health department with cancer control expertise. Cooperative groups must participate in both treatment and cancer control clinical trials; cancer centers may participate in treatment and cancer control studies or cancer control research only; and public health departments may participate only in cancer control research. PREPARATION OF APPLICATIONS General instructions for the preparation of the cooperative agreement application are contained in the Grant Application Form PHS-398 (revised 10/88). Responses to the instructions concerning "Human Subjects" verification should be provided when the application is initially submitted. 1 CCOP Applicants Because the TERMS OF COOPERATION above will be included in all awards issued as a result of this RFA, it is critical that each applicant include specific plans for responding to these terms. Plans should describe how the applicant will comply with NCI staff involvement as well as how all the responsibilities of awardees will be fulfilled. An application from a currently funded program will be a competitive continuation and must include a progress report, which at a minimum consists of: 1) a summary of prior CCOP activities/accomplishments, including a clear presentation of yearly accrual over the funding period, and evaluation of CCOP performance by affiliated research base(s); and 2) a complete description of how the applicant has met the special cooperative agreement terms and conditions of the award. o Each applicant must delineate its patient catchment area. A map of the service area, designating counties or zipcodes from which approximately 80 percent of the patients will be drawn, should be provided. A description of other cancer care resources in the catchment area (i.e., hospitals, clinics, physicians, cancer centers) which are not part of the application should be included. o Each applicant must demonstrate the potential and stated commitment to accrue a minimum of 50 credits per year (see TERMS OF COOPERATION, 1 Community (CCOP) Awardees, Responsibilities of Awardees, Accrual) to treatment clinical trials (except if waived for applicants whose specialty is pediatrics, as stated in TERMS OF COOPERATION, 1 Community (CCOP) Awardees, Responsibilities of Awardees, Accrual. Documentation should include any prior participation in treatment research clinical trials. A list of the treatment protocols in which the applicant expects to participate and projected accrual to each should be provided. o Each applicant must demonstrate the potential and stated commitment to accrue a minimum of 50 credits per year (see TERMS OF COOPERATION, 1 Community (CCOP) Awardees, Responsibilities of Awardees, Accrual) to cancer control studies. The CCOP applicant should document experience in cancer control activities and research, ability to access the appropriate physicians and patient/subject populations, and adequate facilities to participate in the proposed studies. The ability of CCOPs and research bases to collaborate in cancer control research must be demonstrated by each applicant. Working with affiliated research bases, the applicant should provide at least two examples of intervention cancer control protocols, existing or planned, appropriate for the CCOP's participation, and should describe their implementation, including specifics on how eligible patients will be identified. o A designated principal investigator is required. An associate principal investigator should also be named to assure continuity in the event of resignation of the principal investigator. The qualifications and experience of both, in terms of ability to organize and manage a community oncology program that includes treatment and cancer control research and related activities, should be described. o Each applicant is expected to have a committed multidisciplinary professional group appropriate for its expected protocol participation. This team may include medical oncologists, surgeons, radiation oncologists, pathologists, oncology nurses, data managers, health educators, and other disciplines (e.g., gynecology, pediatrics, internal medicine, family practice) as appropriate. The training and experience of participating physicians should be provided, along with a description of working relationships. Any experience working together as a group, particularly in implementing clinical treatment and cancer control research and related activities, should be included. An organizational chart showing how the group will function should also be included. o Each applicant should provide the qualifications and experience of all proposed support personnel as well as a description of the proposed duties for each position. o Through formal affiliations with a maximum of five research bases, only one of which may be a national multi- specialty cooperative group, each applicant must demonstrate access to both treatment and cancer control research protocols. Evidence must be provided that an affiliation has been established with at least one NCI-funded research base which has the capacity to provide both clinical treatment and cancer control protocols. In addition, affiliations with research bases offering only cancer control protocols (e.g., cancer centers, public health departments) are appropriate. The conditions of affiliation must be provided in the CCOP- research base affiliation agreement(s). Initial affiliations should be maintained during the funding cycle. Multiple research base affiliations are permitted provided they are not conflicting (see TERMS OF COOPERATION, 1 Community (CCOP) Awardees, Responsibilities of Awardees, Research Base Affiliation(s)). The affiliation agreements must state specifically how the problem of competing protocols will be resolved. Note: A list of currently eligible research bases may be obtained from the program official listed in LETTER OF INTENT. o Quality control procedures should be described in detail. Assurance of quality is the joint responsibility of the CCOP and its research base(s). Quality control procedures of the research base will be applied to the CCOPs and should be specified in the CCOP-research base affiliation agreement. Procedures for investigational drug monitoring and data management should also be described. o The availability of facilities, including laboratories, inpatient and outpatient resources, cancer registries, etc., should be described. A statement of commitment from each participating institution or organization and/or documentation of consortium arrangements should be provided. Evidence of involvement with community-based voluntary organizations may be submitted. In addition, each applicant must have a defined space for administrative activities and administrative personnel which will serve as a focus for data management, quality control, and communication. Allocation of funds to support community costs for receipt, handling, and quality control of patient data should be specified. Allowable items in the budget are requests for full or part-time administrative personnel, data managers, and study assistants; supplies and services directly related to study activities (e.g., processing and sending material for pathology review, processing and sending port films for radiation therapy quality control); and appropriate travel to meetings directly related to study activities (e.g., research base meetings, NCI-sponsored strategy sessions/workshops, local travel). Funding is not allowed for clinical care provided to patients (e.g., patient care reimbursement, transportation costs). Physician compensation is only an allowable cost for the Principal Investigator (PI) and Co-PI, specifically for time spent on CCOP organizational/ administrative tasks. Justification must be provided for personnel time and effort and funds requested. 2 Research Base Applicants Because the TERMS OF COOPERATION above will be included in all awards issued as a result of this RFA, it is critical that each applicant include specific plans for responding to these terms. Plans should describe how the applicant will comply with NCI staff involvement as well as how all the responsibilities of awardees will be fulfilled. An application from a currently funded program will be a competitive continuation and must include a progress report, which at a minimum consists of: 1) a summary of prior research base activities/accomplishments, including a clear presentation of yearly accrual from affiliated CCOPs over the funding period; 2) and a description of how the applicant has met the special cooperative agreement terms and conditions of the award. Cooperative groups must participate in both treatment and cancer control clinical trials; cancer centers may participate in treatment and cancer control studies or cancer control research only; and public health departments may participate only in cancer control research. o Each applicant must demonstrate the ability to design and implement multi-institutional treatment clinical trials, if applicable as stated above. A list of treatment protocols available for CCOP participation should be provided. o Each applicant must demonstrate the ability to design and implement multi-institutional cancer control clinical trials. A list of cancer control protocols available for CCOP participation should be provided. The research base applicant should also provide at least two examples of cancer control protocols, existing or planned, and describe plans for study design and intervention(s); access to potential patients/subjects to be studied; and procedures for data management, quality control, and follow- up. The availability of appropriate expertise to design, implement, and analyze the results of the proposed studies should be documented. o Each applicant must have an organizational structure for involving appropriate personnel in the design and implementation of treatment and/or cancer control research. The stability of the functional unit within the organizational structure should be described, as well as the relationship and integration of the functional unit with other functional units in the research base. An organizational chart showing the relationship(s) between the scientific and administrative functional units of the research base, vis-a-vis the conduct of treatment and/or cancer control clinical trials, should be provided. The organizational focus within the research base for cancer control research should be described, including the composition and activities of the research base cancer control committee, if applicable, and its relationship to clinical trial activities. o Collaboration with affiliated CCOPs in treatment and/or cancer control research, as applicable, is required. CCOP- research base affiliation agreements should be included in the application. For treatment research, each applicant must demonstrate the ability to accrue a minimum of 50 credits (see TERMS OF COOPERATION, 1 Community (CCOP) Awardees, Responsibilities of Awardees, Accrual) per year from affiliated CCOPs to treatment clinical trials. For cancer control research, each applicant must demonstrate the ability to accrue a minimum of 50 credits (see TERMS OF COOPERATION, 1 Community (CCOP) Awardees, Responsibilities of Awardees, Accrual) per year from affiliated CCOPs to cancer control studies. It is expected that selected cooperative group members and/or Cooperative Group Outreach/cancer center affiliates other than the CCOPs may wish to participate in cancer control research. If it is anticipated that these research base affiliates will be participating, the applicant should indicate the participants and their expected level of participation, and describe their ability to participate. o A designated principal investigator is required and his/her qualifications and experience should be described. Each applicant must also demonstrate the ability to access professionals with the appropriate expertise to design and implement the proposed treatment and/or cancer control clinical trials. Basic scientists, medical, surgical, radiation and other oncology specialists, nurse oncologists, epidemiologists, health educators and/or other public health professionals may be included. o Each applicant's ability to manage the data from multi- institutional treatment and/or cancer control clinical trials should be described. Data management includes development of data collection forms, procedures for data transmittal, procedures for data entry, data editing, compilation, and analysis, as well as procedures for quality control and verification of submitted data. Standards should exist for determining eligibility and evaluability of patients entered on protocols. Statistical capability must exist to develop protocol statistical parameters, analyze the data, and report results. o Each applicant must demonstrate the ability to initiate procedures for training and maintaining the proficiency of personnel from affiliated CCOPs on techniques for successful management of treatment and/or cancer control clinical trials research. Depending on the studies initiated and the interventions involved, this will include training for data managers/nurses and any other individuals responsible for data collection, monitoring, or carrying out the intervention(s). o Each applicant's ability to provide mechanisms for periodic review of the performance of affiliated CCOPs, including on-site monitoring (auditing) and written procedures and criteria for continued affiliations, should be described. Requests for funds should reflect headquarters operational, quality control and data management add-on costs for CCOP participation in protocols, based on the expected accrual credits of affiliated CCOPs/Minority-Based CCOPs and for member/affiliate accrual credits in cancer control. CCOP- research base affiliation agreements should be included. Minimal funding may be requested for development and pilot testing of new cancer control research initiatives (such as a cancer control committee for the research base), and for appropriate travel to meetings directly related to study activities (such as NCI-sponsored strategy sessions/workshops). Specific justification must be provided. REVIEW PROCEDURES AND CRITERIA 1 Procedure Upon receipt, applications will be reviewed (initially) by the Division of Research Grants (DRG) for completeness. Incomplete applications will be returned to the applicant without further consideration. Evaluation for responsiveness to the program requirements and criteria stated in the RFA is an NCI program staff function. Applications which are judged non-responsive will be returned to the applicant. In cases where the number of applications is large compared to the number of awards to be made, NCI may conduct a preliminary scientific peer review to eliminate those which are clearly not competitive for award. NCI will remove from competition those applications judged to be noncompetitive and notify the applicant and institutional business official. Those applications judged to be both competitive and responsive will be further evaluated according to the review criteria stated below for scientific and technical merit by an appropriate peer review group convened by the Division of Extramural Activities (DEA), NCI. 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. 2 Review Criteria CCOP Applicants o Ability to accrue a minimum of 50 credits (see TERMS OF COOPERATION, 1 Community (CCOP) Awardees, Responsibilities of Awardees, Accrual) per year to treatment clinical trials (may be waived for applicants whose specialty is pediatrics, as stated in TERMS OF COOPERATION, 1 Community (CCOP) Awardees, Responsibilities of Awardees, Accrual. Any prior participation in treatment research clinical trials will be considered. o Ability to accrue a minimum of 50 credits (see TERMS OF COOPERATION, 1 Community (CCOP) Awardees, Responsibilities of Awardees, Accrual) per year to cancer control studies. Each applicant's ability to access the appropriate populations, professional disciplines, and facilities to participate with affiliated research bases in at least two cancer control studies (see PREPARATION OF APPLICATIONS, 1 CCOP Applicants, bullet three) will be appraised. Any prior participation in cancer control research will be considered. o Qualifications and experience of the principal investigator/associate principal investigator, in terms of ability to organize and manage a community oncology program that includes both treatment and cancer control research and related activities. o Training, experience, and commitment of participating physicians for accruing individuals to protocols in which the applicant has agreed to participate. The experience of proposed investigators in the entry and treatment of cancer patients on research trials (gained from residency, fellowships, postdoctoral training and/or subsequent practice) will be appraised. For multidisciplinary studies, evidence of the availability of appropriate professional resources (e.g., radiotherapy, pediatrics, surgery, gynecology, urology, pathology, internal medicine, family practice, nursing, and nutrition) will be required. Experience or special skills in cancer control research and related activities will be considered, together with availability of other community resources and personnel for such studies. o The stability of the functional unit or group applying to become a CCOP. Preexisting organizational affiliations of at least a core of the group applying, and evidence of stable working relationships, will be appraised. Examples of established consortium arrangements, and committee structure which demonstrates the participation of appropriate physicians and administrators, may be submitted. Evidence of previous success as a group in implementing clinical treatment and cancer control research and related activities will be considered. o Qualifications and experience of all proposed support personnel relative to their position descriptions. The relevant credentials and expected contributions to the program of personnel resources not fiscally supported by the award will be considered. o Adequacy of quality assurance mechanisms for both treatment and cancer control interventions, and adequacy of procedures for investigational drug monitoring and data management. o Adequacy of available facilities, including laboratories, in-patient and outpatient resources, cancer registries, etc., and adequacy of space for administrative activities and personnel. o Appropriateness of research base affiliations and of the treatment and cancer control research protocols chosen. Affiliation agreements must be provided in the application. o For competitive continuations, adequacy of progress during the funding period, including ability to meet the minimum accrual credits, progress made as a CCOP, and evaluation of CCOP performance by affiliated research bases(s). The research base evaluation report(s) must be provided in the application. The review group will critically examine the submitted budget and will recommend an appropriate budget and period of support for each approved application. Allowable items in the budget are requests for full or part- time administrative personnel, data managers, and study assistants; supplies and services directly related to study activities (e.g., processing and sending material for pathology review, processing and sending port films for radiation therapy quality control); and appropriate travel to meetings directly related to study activities (e.g., research base meetings, NCI-sponsored strategy sessions/workshops, local travel). Funding is not allowed for clinical care provided to patients (e.g., patient care reimbursement, transportation costs). Physician compensation is only an allowable cost for the Principal Investigator (PI) and Co-PI, specifically for time spent on CCOP organizational/ administrative tasks. Justification must be provided for personnel time and effort and funds requested. 2 Review Criteria Research Base Applicants o Experience in conducting multi-institutional clinical trials; demonstrated ability to develop such studies and act as a coordinating and statistical center; and adequate facilities to conduct the studies. o Quality and availability of treatment and/or cancer control protocols, as applicable (see ELIGIBILITY REQUIREMENTS, 2 Research Base Applicants), which are appropriate for CCOP participation, or the potential for developing such studies. Description of existing or planned cancer control protocols, including a detailed description of at least two examples of such protocols, will be evaluated as part of the application along with professional expertise to assure the quality of the proposed intervention studies. o For treatment research, ability to accrue a minimum of 50 credits (see TERMS OF COOPERATION, 1 Community (CCOP) Awardees, Responsibilities of Awardees, Accrual) per year from affiliated CCOPs to treatment clinical trials. For cancer control research, ability to accrue a minimum of 50 credits (see TERMS OF COOPERATION, 1 Community (CCOP) Awardees, Responsibilities of Awardees, Accrual) per year from affiliated CCOPs to cancer control studies. Experience as well as the potential for developing future studies will be considered. Documentation should include CCOP-research base affiliation agreements. o Organizational structure for involving appropriate personnel in the design and implementation of treatment and/or cancer control research. The stability of the functional unit within the organizational structure will be considered, as well as the relationship and integration of the functional unit with other functional units in the research base. In addition, the organizational focus within the research base for cancer control research, including the composition and activities of the cancer control committee, and its relationship to clinical trial activities, will be assessed. o Qualifications and experience of the principal investigator and/or the individual responsible for directly relating to the CCOPs. The availability and experience of multidisciplinary health professionals and allied professionals with skills needed to develop, utilize, and analyze treatment and/or cancer control clinical trials will also be evaluated. o Experience in working with community oncologists, orienting community data personnel to protocol requirements, organizing scientific and educational meetings for those participating in the clinical trials, and participating in intergroup studies. o Ability to establish quality control, quality assurance, and data management procedures. Experience in data management and analysis of multi-institutional studies and adequacy of data management staff will be appraised. The availability of mechanisms for periodic review of quality control, quality assurance, and data management procedures will be assessed. o For competitive continuations, adequacy of progress during the funding period, including ability to meet minimum accrual credits from affiliated CCOPs, and progress in meeting the requirements of a research base for CCOP. The review group will critically examine the submitted budget and will recommend an appropriate budget and period of support for each approved application. Requests for funds should reflect headquarters operational, quality control and data management add-on costs for CCOP participation in protocols, based on the expected accrual credits of affiliated CCOPs/Minority-Based CCOPs and for member/affiliate accrual credits in cancer control. Minimal funding may be requested for development and pilot testing of new cancer control research initiatives (such as a cancer control committee for the research base), or for appropriate travel to meetings directly related to study activities (such as NCI-sponsored strategy sessions/workshops). Specific justification must be provided. LETTER OF INTENT Prospective applicants are asked to submit by June 15, 1990, 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 is being 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 should be sent to: Leslie G. Ford, M.D. Community Oncology and Rehabilitation Branch Division of Cancer Prevention and Control, NCI Executive Plaza North - Room 300-D Bethesda, Maryland 20892 Telephone: (301) 496-8541 METHOD OF APPLYING The regular research grant application form PHS-398 (revised 10/88) must be used in applying for cooperative agreements. These forms are available at most institutional business offices; from the Office of Grants Inquiries, Division of Research Grants, Westwood Building - Room 449, 5333 Westbard Avenue, Bethesda, Maryland 20892; or from the NCI program official named in LETTER OF INTENT. It is requested that some of the information be submitted in a tabular format. The suggested format will be sent to applicants submitting a letter of intent or may be obtained from the program official named in LETTER OF INTENT. The RFA label available in the 10/88 revision of PHS-398 must be affixed to the bottom of the face page. Failure to use this label could result in delayed processing of your application such that it may not reach the review committee in time for review. The RFA number and title should be typed in bold letters on line 2 of the face page of the application form. Submit a signed, typewritten original of the application, including the Checklist, and four (4) signed, exact photocopies, in one package to DRG at the address below. The photocopies must be clear and single sided. Grant Application Receipt Office Division of Research Grants National Institutes of Health Westwood Building - Room 240 Bethesda, Maryland 20892** At time of submission, send two (2) additional copies of the application to: Referral Officer National Cancer Institute National Institutes of Health Westwood Building - Room 838 5333 Westbard Avenue Bethesda, Maryland 20892 Applications must be received by August 24, 1990. If an application is received after that date, it will be returned. Also, DRG will not accept any application in response to this announcement that is the same as one currently being considered by any other review group or NIH awarding unit. INQUIRIES Written or telephone inquiries concerning the objectives and scope of this RFA or inquiries about whether or not specific proposed research would be responsive are encouraged and should be directed to Leslie G. Ford, M.D., at the address provided in LETTER OF INTENT. The program official welcomes the opportunity to clarify any issues or questions from potential applicants. Inquiries pertaining to business matters should be directed to: Ms. Eileen Natoli Grants Administration Branch Office of the Director, NCI Executive Plaza South - Room 243 Bethesda, Maryland 20892 Telephone: (301) 496-7800 This program is described in the Catalog of Federal Domestic Assistance No. 13.399, Cancer Control. Awards are under authorization of the Public Health Service Act, Title IV, Part A (Section 301, Public Law 78-410, 42 USC 241, and Section 412, as amended by Public Law 99-158, 42 USC 285a-1) and administered under PHS grant policies and Federal Regulations 42 CFR Part 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements