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COMMUNITY CLINICAL ONCOLOGY PROGRAM RELEASE DATE: April 23, 2004 RFA NUMBER: RFA-CA-05-014 EXPIRATION DATE: July 15, 2004 Department of Health and Human Services (DHHS) PARTICIPATING ORGANIZATION: National Institutes of Health (NIH) (http://www.nih.gov) COMPONENT OF PARTICIPATING ORGANIZATION: National Cancer Institute (NCI) (http://www.nci.nih.gov/) CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S): 93.399 LETTER OF INTENT RECEIPT DATE: June 14, 2004 APPLICATION RECEIPT DATE: July 14, 2004 This RFA is a reissuance of RFA-CA-04-008, which was published in the NIH Guide on May 19, 2003. THIS RFA CONTAINS THE FOLLOWING INFORMATION o Purpose of this RFA o Research Objectives o Mechanism of Support o Funds Available o Eligible Institutions o Individuals Eligible to Become Principal Investigators o Special Requirements o Where to Send Inquiries o Letter of Intent o Submitting an Application o Supplementary Instructions o Peer Review Process o Review Criteria o Receipt and Review Schedule o Award Criteria o Required Federal Citations PURPOSE The Division of Cancer Prevention (DCP), National Cancer Institute (NCI), invites domestic institutions to apply for cooperative agreements in response to this Community Clinical Oncology Program (CCOP) Request for Applications (RFA). Applicants for new and currently funded Community Clinical Oncology Programs (CCOP) and research bases (cooperative groups and cancer centers that design the protocols for clinical trials, collect and analyze study data, and monitor the data quality and patient accrual performance of CCOPs and other institutional members) are invited to respond to this RFA. Using 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; 4) supports development of and community participation in cancer prevention and control intervention research, which includes chemoprevention, biomarkers, early detection, symptom management, quality of life, rehabilitation, and continuing care research; 5) involves primary care providers and other specialists in cancer prevention and control clinical trials; and 6) increases the involvement of minority and underserved populations in clinical research. Combining the efforts and expertise of community physicians and other health care professionals with those of the NCI-funded cancer treatment and prevention and control clinical trials groups provides opportunities for transfers of the latest research findings to the community level. The NCI-supported clinical cooperative groups and/or cancer centers serve as research bases for the CCOPs. These research bases design the protocols for the clinical trials in cancer treatment, prevention, and early detection as well as evaluating interventions affecting quality of life, rehabilitation, and symptom management associated with cancer and its treatment. In addition, research bases manage and analyze all data collected and monitor data quality and subject accrual. The research bases seek to define the key unanswered questions in cancer and then conduct clinical trials to answer these questions. This reissuance of the CCOP RFA seeks to build on the strength and demonstrated success of the CCOP network over the past 20 years by: 1) continuing the program as a vehicle for supporting community participation in cancer treatment and prevention and control clinical trials through research bases (clinical cooperative groups and cancer centers supported by NCI); 2) expanding and strengthening the cancer prevention and control research effort; 3) utilizing the CCOP network for conducting NCI-assisted cancer prevention and control research; and 4) evaluating on a continuing basis CCOP performance and its impact in the community. RESEARCH OBJECTIVES Background The CCOP network (CCOPs and research bases) 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 3 years, 62 community programs in 34 states were funded and accrued 14,000 patients to NCI-funded treatment clinical trials. The CCOPs were clearly effective in accruing patients to treatment clinical trials. The second CCOP RFA, issued in 1986, expanded the focus to include cancer prevention and control research based on the rationale that the multi- institutional clinical trials model essential for testing new treatment regimens is also central for conducting large-scale cancer prevention and control trials. In 2003, there were 50 programs in states involving over 375 hospitals and over 3,075 physicians. Approximately 5,700 patients were entered onto treatment trials and 7,000 participants on cancer prevention and control trials in 2003. Cancer prevention and control research in the CCOPs is aimed at reducing cancer incidence, morbidity, and mortality through the identification, testing, and evaluation of interventions in controlled clinical trials. The development of cancer prevention and control research in the CCOP network has been increasing steadily since funding started in 1987. Protocols cover the full spectrum of cancer prevention and control research, from chemoprevention and the validation of biomarkers, screening and early detection, pain control, symptom management and quality of life, and other rehabilitation and continuing care interventions. Several large chemoprevention trials have been implemented through the CCOP network, including the prostate cancer prevention trial with finasteride (PCPT), the study of tamoxifen and raloxifene in the prevention of breast cancer (STAR) and the selenium and vitamin E trial (SELECT) in the prevention of prostate cancer. The CCOP network is a vital resource for conducting NCI cancer prevention and control research because this consortium provides access to: 1) a national network for cancer prevention and control trials which require large sample sizes for completion; 2) large populations of cancer patients for symptom management, supportive care, quality of life, and rehabilitation interventions 3) large populations of cancer patients free of disease and survivors which provide a unique resource for chemoprevention clinical trials; 4) cancer patients' family members and others who may be at increased risk of developing cancer and thus be candidates for prevention and detection studies; and 5) geographic areas which include cross sections of the population, providing mixes of patients/participants not always available in university or urban settings. Participation in cancer prevention and control research by CCOPs, in particular, further expands the network of community physicians, increasing the potential for diffusion of state-of-the-art cancer prevention and control practices. Objectives and Scope The CCOP Network is designed to: (1) bring the advantages of state-of-the-art cancer treatment and prevention and control research to individuals in their own communities by having practicing physicians and their participants enter onto NCI-approved cancer treatment and prevention and control clinical trials; (2) provide a basis for involving a wider segment of the community in cancer prevention and control research and investigate the impact of cancer therapy and control advances in community medical practices; (3) increase the involvement of primary health care providers and other specialists (e.g., surgeons, family practitioners, gastroenterologists, urologists, gynecologists) with the CCOP investigators in cancer treatment and prevention and control research, providing an opportunity for education and exchange of information; (4) facilitate wider community participation, including minorities, women and, other underserved populations, in cancer treatment and prevention and control research approved by NCI; and (5) 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 CCOPs are required to enter patients onto NCI-approved cancer treatment and prevention and control clinical trials through the research base(s) with which each CCOP is affiliated. CCOPs may have direct access to selected protocols through specific NCI-sponsored programs. Participating research bases are required to develop clinical treatment and/or cancer prevention and control research protocols, and provide them to the CCOPs as well as to the research bases’ member/affiliate institutions. Cancer prevention and control research should be intervention-oriented and may include such areas as cancer prevention, early detection, symptom management, rehabilitation, quality of life, and continuing care. Research bases will monitor the quality of protocol conduct, follow accrual, and participate on a continuing basis in program evaluation. MECHANISM OF SUPPORT This RFA will use the NIH U10 award mechanism. The NIH U10 is a cooperative agreement award mechanism in which the Principal Investigator retains the primary responsibility and dominant role for planning, directing, and executing the proposed project, with NIH staff being substantially involved as a partner with the Principal Investigator, as described under the section "Cooperative Agreement Terms and Conditions of Award.” This RFA uses just-in-time concepts. It uses the non-modular budgeting formats so follow the instructions for non-modular research grant applications. This program does not require cost sharing as defined in the current NIH Grants Policy Statement at http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part2.htm. The total project period for applications submitted in response to this RFA may not exceed 3 years for new applicants, and no more than 5 years for applicants currently supported under this program. Currently supported applicants will be funded for 3, 4, or 5 years depending upon priority score, review committee recommendations, and programmatic considerations. The anticipated award date is June 1, 2005. NCI has determined that there is a continuing program need for community participation in cancer clinical research trials, both cancer treatment and prevention and control. While this RFA is a one-time issuance, it is expected that a CCOP RFA will be published in the NIH Guide for Grants and Contracts on an annual basis, provided that funds are available. FUNDS AVAILABLE The NCI intends to commit approximately $18.5 million in total costs FY 2005 to fund seventeen to twenty-one new and/or competitive continuation grants in response to this RFA. The $18.5 million in total costs per year for 5 years is to specifically fund applications that are submitted in response to this RFA. Approximately four research base awards and seventeen CCOP awards will be made. Because the nature and scope of the research proposed in response to this RFA may vary, it is anticipated that the size of awards will also vary. Awards and level of support is dependent on the receipt of a sufficient number of applications of high scientific merit. Although this program is provided for in the financial plans of NCI, awards pursuant to this RFA are contingent upon the availability of funds for this purpose. ELIGIBLE INSTITUTIONS You may submit (an) application(s) if your institution meets any of the following characteristics: o For-profit or non-profit organizations o Public or private institutions, such as universities, hospitals and health maintenance organizations o Domestic institutions/organizations o Foreign institutions are not eligible to apply o Faith-based or community organizations A. For CCOP applicants, the following provisos apply. 1. 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. 2. A university, Veterans Administration hospital, or military treatment facility (MTF) may be included in an application as a member of a consortium led by a community institution, but may not be the applicant organization or the major contributor to patient accrual. An unfunded, non-university clinical trials cooperative group member is eligible to apply. 3. Funded cooperative group affiliate programs are eligible to apply, but should state in the application that support through this mechanism will be relinquished if a CCOP award is received. 4. Institutions not eligible to apply as the CCOP applicant organization include: a. A comprehensive, consortial, or clinical cancer center holding an NCI Cancer Center Support (Core) grant; b. A university hospital that is the major teaching institution for that university; or c. A university hospital clinical trials cooperative group member funded by the Division of Cancer Treatment and Diagnosis (DCTD), NCI. B. For research base applicants, the following provisos apply. An applicant may be: 1. An NCI-funded Clinical Trials Cooperative Oncology Group (Cooperative Group); 2. An NCI-funded clinical center, consortium, or comprehensive cancer center. Cooperative Groups as CCOP research bases must participate in both cancer treatment and prevention and control clinical trials. Cancer Centers as CCOP research bases may participate in both cancer treatment and prevention and control studies or only cancer prevention and control research. INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with their institution to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH programs. SPECIAL REQUIREMENTS Cooperative Agreement Terms and Conditions of Award The administrative and funding instrument used for this program is a cooperative agreement (U10), which involves anticipated assistance to awardees from the NCI Program Staff. 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 partnership 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 Program Staff, as described below. 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 that occur in the administration of grants. The terms and conditions described in this section are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines; HHS Grant Administration Regulations at 45 CFR part 74; other HHS, PHS, and NIH Grant Administration policy statements; and other NCI administrative terms of award. A. TERMS AND CONDITIONS OF AWARD FOR CCOP AWARDEES 1. CCOP – AWARDEES’ RESPONSIBILITIES The awardee's programmatic responsibilities for the conduct of the research supported by this cooperative agreement are described in the following documents: the INVESTIGATOR'S HANDBOOK, a Manual for Participants in Clinical Trials of Investigational Agents Sponsored by the Division of Cancer Treatment and Diagnosis, (DCTD), National Cancer Institute (http://ctep.cancer.gov/handbook/); GUIDELINES FOR ON-SITE MONITORING OF CLINICAL TRIALS FOR COOPERATIVE GROUPS AND CCOP RESEARCH BASES (http://ctep.cancer.gov/monitoring/guidelines.html); and the Intellectual Property Option to Collaborator (http://ctep.cancer.gov/industry/ipo.html). These documents (and any subsequent modifications of them) are hereby incorporated by reference as terms of award and are available at the URLs cited above or from the program staff listed under “INQUIRIES.” a. PROTOCOLS All protocols originating from and/or coordinated by the research bases for CCOP use must be reviewed and approved by the Cancer Prevention and Control Protocol Review Committee (CPCPRC), Division of Cancer Prevention (DCP), and/or the Protocol Review Committee (PRC), Division of Cancer Treatment and Diagnosis (DCTD), NCI, prior to implementation. Protocols will be assigned credit upon approval by the review committee. Each research base protocol approved for CCOP use will be assigned a credit value. 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 treatment protocol will count 1 credit. Cancer prevention and control protocols will be assessed for credit using a similar approach. For example, a randomized Phase III chemoprevention protocol will be assigned a value of 1 credit per participant entered. Cancer control protocols involving limited interventions will receive credit that is commensurate with the amount of data management effort required. Follow-up credit for chemoprevention protocols may also be assigned. To receive credit for accruals the CCOP must access NCI-approved treatment and/or prevention and control protocols through the research bases with which it has affiliation agreements. The research base is responsible for the development and implementation of high quality cancer treatment and prevention and control clinical trials, and for evaluation of the results of such studies. The CCOP also may access treatment trials from research bases with which it is not affiliated through the NCI’s Cancer Trials Support Unit (CTSU). CCOP accruals to CTSU protocols will receive credits and not per case reimbursement. The purpose of the CTSU is to broaden access to clinical trials and to streamline and centralize administrative, financial and data collection tasks associated with conducting NCI-approved treatment trials. CCOPs are encouraged to participate in cancer prevention and control research that is supported through other federally funded mechanisms such as investigator-initiated awards. Collaborations between CCOPs and independent investigators may facilitate the implementation of a wide variety of nonintervention research in cancer control such as descriptive, qualitative, survey, methods development or epidemiology that will contribute to improving public health outcomes. Participation in such research will be considered in the evaluation of the CCOP’s productivity. b. RESEARCH BASE AFFILIATIONS Each CCOP must affiliate with one national multi-specialty cooperative group having a spectrum of cancer treatment and prevention and control clinical trials. Exceptions to affiliation with more than one multi-specialty group may be granted in conjunction with participation in NCI-sponsored “pilot” projects. In addition, each CCOP may affiliate with as many other research bases, exclusive of the multi-specialty groups, as the CCOP deems appropriate. In deciding on the optimum number of other research bases to affiliate with, the CCOP should consider the administrative burden and the membership requirements that will result from increased numbers of research base affiliations. The resources of the CCOP should also be factored into this decision. The CCOP must justify the reasons for multiple other research base affiliations, either existing or planned in terms of the scope and breadth of research that the CCOP anticipates undertaking in its new or competing continuation application. 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 to avoid bias in the allocation of patients to competing protocols. NOTE: A list of eligible research bases may be obtained from the URL address: http://www3.nci.nih.gov/prevention/ccop/rbccop.html or by contacting the Community Oncology and Prevention Trials Research Group, DCP, NCI at (301) 496-8541. Initial affiliations should be maintained for the duration of the funding cycle. When circumstances require changes in research base affiliations, prior written approval from the DCP Program Director is required. The Guidelines for Obtaining Approval of CCOP Organizational Changes is available at http://cancer.gov/prevention/ccop/guidelines.html. c. 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, DCTD, NCI. An additional measure of performance is that at least 10 percent of patients for whom protocols are available will be placed on clinical trials by CCOP physicians. The 50 credit minimum to treatment requirement may be waived for: 1) those applicants whose specialty is pediatrics and are able to place a majority of their eligible patients on protocols; and 2) for those applicants with an outstanding record in accrual to cancer prevention and control protocols. Each CCOP is required to accrue a minimum of 50 credits per year to cancer prevention and control clinical trials that have been approved by the CPCPRC, DCP. The 50 credit minimum to cancer prevention and control requirement may be waived for those applicants whose specialty is pediatrics and are able to place a majority of their eligible patients on protocols. In addition, CCOPs are encouraged to participate in cancer prevention and control research that is supported through other federally funded mechanisms, such as investigator-initiated awards. Participation in such research will be considered in the evaluation of CCOP productivity. d. QUALITY CONTROL In accordance with research base guidelines and NCI policies, the CCOP must establish and follow procedures for the assurance of data quality and for the prevention and/or identification of false or otherwise unreliable data. The CCOP must follow policies developed by the research bases with which they are affiliated and approved by the NCI for auditing the accuracy of scientific data submitted to them by the CCOP participants. A list of the research bases is available at the URL address: http://www3.nci.nih.gov/prevention/ccop/rbccop.html. e. DATA MANAGEMENT The CCOP must provide the DCP 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, and with NCI's agreements with pharmaceutical companies for the co-development of investigational agents. The awardees will retain custody of and primary rights to their data. f. 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. Specifically, all CCOP investigators accruing patients must have an active FDA Form 1572 on file with the Pharmaceutical Management Branch, CTEP, DCTD, NCI. g. MONITORING Each CCOP must agree to periodic on-site audits by representatives of its research base(s), NCI, or an NCI-designee. Such on-site audits may include review of 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; and completeness of reporting adverse drug reactions. Reports of such on-site audits will be reviewed by the Clinical Trials Monitoring Branch (CTMB), Cancer Therapy Evaluation Program (CTEP), DCTD, and by the DCP Program Director. In addition, NCI program and grants management staff will review protocol accrual, and fiscal and administrative procedures. CCOP member/affiliate performance sites and/or individual investigators participating or collaborating on NCI-supported multi-institutional clinical trials must be in compliance with the monitoring standards established by the research base. The sites should include the following standards: (1) Medical records submitted in support of NCI multi-institutional trials must conform to usual standards for the maintenance of clear, accurate, and unambiguous medical records. White-outs on medical records are unacceptable; (2) If it is the usual and customary practice of a department, laboratory, clinic or office to prepare or issue official reports, then only that department, laboratory, clinic, or office can change the report, and alterations of the medical record must be initialed and dated by the person making such alterations. For clinical progress notes, the change must be dated and initialed by the person making the change. Only one line should be placed through the initial entry, so that both the original entry and the change are legible; (3) The improper modification of important patient records will result in additional investigations by the NCI Clinical Trials Monitoring Branch (CTMB) and may lead to suspension of accrual and funding. h. 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). i. ORGANIZATIONAL CHANGES Certain CCOP organizational changes must have the prior written approval of the DCP Program Director. These include the addition/deletion of a participating physician, a health professional other than a physician (who actively enters patients to cancer prevention and control trials), an affiliate, a component, or a research base. The Guidelines for Obtaining Approval of CCOP Organizational Changes is available at the URL address: http://cancer.gov/prevention/ccop/guidelines.html. j. REPORTING REQUIREMENTS Annual progress reports must be submitted to DCP. A suggested format will be provided for this purpose. The format is available at the URL address: http://cancer.gov/prevention/ccop/. The inability of a CCOP to meet the performance requirements set forth in the Terms and Conditions of Award 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. k. NETWORK PARTICIPATION CCOPs are part of a national network for conducting cancer treatment and prevention and 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. l. PATIENT/PARTICIPANT LOG Each CCOP may be asked to periodically maintain a new patient/participant log or minimal registry to include as applicable age, sex, race, insurance status, risk factors, primary site of cancer, stage of disease, and disposition for the potentially eligible patient/participant pool seen by the CCOP investigators. m. FEDERALLY MANDATED REQUIREMENTS Each CCOP must establish mechanisms to meet DHHS/PHS regulations for the protection of human subjects. At a minimum, these include: (1) methods for assuring that each facility at which CCOP investigators are conducting clinical trials has a current, approved assurance on file with the Office of Human Research Protection (OHRP); 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; (2) methods for assuring or documenting that each patient (or patient's parent/legal guardian) gives fully informed written consent to participation in a research protocol prior to the initiation of the experimental intervention; (3) a system for assuring timely reporting of all serious and unexpected toxicities to the Investigational Drug Branch, CTEP, DCTD, according to DCTD guidelines and/or to DCP according to DCP guidelines; (4) implementation of DCP/DCTD requirements for storage and accounting for investigational agents provided under DCP/DCTD sponsorship; and (5) education on the protection of human research participants for all investigators involved in the design or conduct of research involving human subjects. NIH requires that CCOP studies meet the NIH policy requirements for inclusion of women and minorities in clinical research and inclusion of children as participants in research involving human subjects. The NIH expects investigators supported by NIH funding to make their research data available to the scientific community for subsequent analysis based on a data sharing plan approved as part of the award; see the NIH Data Sharing Policy website at http://grants.nih.gov/grants/policy/data_sharing/ and CCOP guidance at http://cancer.gov/prevention/ccop. This requirement on data sharing is an extension to NIH policy regarding sharing research resources, which expects that recipients of NIH support will provide prompt and effective access to research tools. n. PUBLICATIONS Timely publication of major findings is encouraged. Publication or oral presentation of work done under this cooperative agreement requires acknowledgment of NCI support. 2. NCI STAFF INVOLVEMENT a. PROTOCOL REVIEW To be eligible for credit assignment protocols must be reviewed and approved by the CPCPRC, DCP, and/or the PRC, DCTD, NCI, prior to implementation. Credit will be assigned after the protocol is approved. 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). b. MONITORING There will be periodic on-site audits of each CCOP by representatives of its research base(s), NCI, or an NCI-designee, such as DCTD's current Clinical Trials Monitoring Service contractor. The DCP and CTMB/CTEP will review and provide advice regarding mechanisms established for study monitoring including the on-site auditing program. DCP/CTEP and/or its contractor staff may attend the on-site audits conducted by the research base or its NCI designee as observers. c. DATA MANAGEMENT The DCP 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). d. INVESTIGATIONAL DRUG MANAGEMENT The Regulatory Affairs Branch (RAB), Pharmaceutical Management Branch (PMB), CTEP, DCTD and the Chemopreventive Agent Development Research Group (CADRG), DCP will advise investigators of specific requirements and changes in requirements about investigational drug management that the FDA and NCI may mandate. e. ORGANIZATIONAL CHANGES The DCP program director will review requests for certain organizational changes and provide written approval. These include the addition/deletion of a participating physician, a health professional other than a physician (who actively enters patients to cancer prevention and control trials), an affiliate, component, or research base. The Guidelines for Obtaining Approval of CCOP Organizational Changes is available at: http://cancer.gov/prevention/ccop/guidelines.html f. PROGRAM REVIEW The DCP program director will provide a suggested format for the CCOP’s annual report. The DCP 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/ participants 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 and Conditions of Award 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. g. STRATEGY SESSIONS The DCP Program Director or designee will sponsor strategy sessions when indicated, attended by principal investigators from the CCOPs and appropriate DCP/DCTD staff. 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 clinical trials. Data will be analyzed and the outstanding research questions established and prioritized into national research goals by CCOP investigators and the DCP/DCTD attendees. The principal investigators will have the primary responsibility for analyzing and prioritizing the research questions to be developed into clinical trials. The DCP Program Director will also assist the CCOP investigators in exploring mutual interests in cancer prevention and control research. h. FEDERALLY MANDATED REQUIREMENTS The DCP Program Director or designee and DCTD staff 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. 3. ARBITRATION PROCESS The Terms and Conditions of Award require that the DCP Program Director make post-award administrative decisions related to program performance, programmatic decisions on scientific-technical matters, and funding adjustments. NCI will establish an arbitration process when a mutually acceptable agreement cannot be obtained between the awardee and the DCP Program Director. 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, DCP. 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 at 45 CFR Part 16. B. TERMS AND CONDITIONS OF AWARD FOR RESEARCH BASE AWARDEES 1. RESEARCH BASE AWARDEES’ RESPONSIBILITIES It is the responsibility of the Research Base in accordance with its constitution, bylaws, policies, and procedures to develop the details of the research design, including definition of objectives and approaches, planning, implementation, analysis, and publication of results, interpretations and conclusions of studies. The research base shall designate research base investigators to serve as Protocol Chairpersons for each proposed study. Protocols will be developed in accordance with the instructions in the INVESTIGATOR'S HANDBOOK available at the following URL address: http://ctep.cancer.gov/handbook/ from the program staff listed under INQUIRIES. a. PROTOCOL DEVELOPMENT The research base is responsible for the development and implementation of high quality cancer treatment and prevention and control clinical trials, and for evaluation of the results of such clinical trials. The protocol should be a document mutually acceptable to the research base and to DCP/DCTD. Communication at the various stages of development is encouraged. b. CONCEPT/PROTOCOL SUBMISSION All research base protocols utilized by the CCOPs and/or research base member/affiliate institutions must be reviewed and approved by the Cancer Prevention and Control Protocol Review Committee, (CPCPRC) DCP, and/or the Protocol Review Committee (PRC), DCTD, NCI, prior to implementation. All research base cancer prevention and control protocols must be preceded by the submission of a concept proposal for review by the DCP Cancer Prevention and Control Concept Review Committee (CPCCRC). The CPCCRC considers scientific merit and the feasibility of implementing prospective cancer control protocols in the CCOP research network. All documents for cancer prevention and control concepts and/or protocols should be submitted to the DCP Protocol Information Office (PIO), NCI, http://www3.cancer.gov/prevention/pio Similarly, concept proposals for research base cancer treatment protocols may precede protocol development. The CTEP Protocol Review Committee (PRC) in the DCTD, NCI is responsible for review of all cancer treatment concepts and protocols. All documents for treatment concepts and/or protocols should be submitted to the CTEP Protocol Information Office (PIO), DCTD, NCI (http://ctep.cancer.gov/about/pio.html). DCTD may also require a letter of intent for new cancer treatment trials. c. ACCRUAL Each research base protocol approved for CCOP and/or research base member/affiliate institution use will be assigned a credit value. 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 treatment protocol will count 1 credit. Cancer prevention and control protocols will be assessed for credit using a similar approach. For example, a randomized Phase III chemoprevention protocol will be assigned a value of 1 credit per participant entered. Follow-up credit for chemoprevention protocols also may be assigned. Cancer control protocols involving limited interventions will receive credit that is commensurate with the amount of data management effort required. A research base involved in the design of treatment protocols is required to accrue a minimum of 50 credits per year from affiliated CCOPs to treatment clinical trials designed by the research base applicant and approved by the PRC, DCTD, NCI. During its initial competitive segment (project period), a new research base applicant is expected to develop a menu of treatment protocols that will allow the research base to meet the credit minimums per year in its subsequent competing segments. A research base for cancer prevention and control research is required to accrue a minimum of 50 credits per year from CCOPs, and other research base member/affiliate institutions to cancer prevention and control clinical trials led by the research base applicant and approved by the CPCPRC, DCP. A new research base applicant is expected, during its initial competitive segment (project period), to develop a menu of cancer prevention and control protocols that will allow the research base to meet the credit minimums per year in its subsequent competing segments. Research bases are encouraged to participate in and/or facilitate CCOP participation in cancer prevention and control research that is supported through other federally funded mechanisms. This activity is encouraged because the cooperative agreements awarded under this RFA primarily support development and conduct of studies evaluating an intervention. Research supported through these other mechanisms might include nonintervention research in cancer control (e.g., epidemiology, methods development, population-based surveys, etc.). Research base participation and/or facilitation of CCOP participation in these studies will be considered in the evaluation of the research bases’ productivity. d. DATA MANAGEMENT AND ANALYSIS The research base shall establish and implement mechanisms for data management and analysis that ensure that data collection and management procedures are: (a) adequate for quality control and analysis; (b) as simple as is appropriate to encourage maximum participation of physicians entering patients and to avoid unnecessary expense; and (c) sufficiently uniform across research bases. CCOP member/affiliate performance sites are required to follow procedures for data management and analysis. Data generated are the property of the awardee; however, the research base must provide DCP/DCTD with access to all data generated under this award. In addition, the research bases must have a data-sharing plan as required by the extension of NIH policy regarding sharing research resources (See NIH Grants Policy, Part II Subpart A, Availability of Research Results). See also the “Suggestions for Organizing Information for a CCOP Research Base Application,” for guidance on the application of this policy to research base cooperative agreements at http://cancer.gov/prevention/ccop. Data must also be available for external monitoring if required by NCI's agreement with other Federal agencies, such as the FDA and by NCI's agreements with pharmaceutical companies for the co-development of investigational agents The research bases may contract with independent investigators to perform data management and analysis for research supported by other federally funded mechanisms. e. QUALITY CONTROL A DCP-funded research base must follow all the policies and procedures for quality control established by NCI. The research bases shall establish mechanisms for quality control of all procedures and modalities employed in its trials. CCOP and research base members/affiliates are required to follow research base procedures for quality control. The research base shall establish mechanisms for study monitoring. CCOP and research base members/affiliates are required to follow the awardee procedures for study monitoring. The research base is responsible for monitoring the progress of each study following good clinical practices through: (1) tracking and reporting of patient accrual and adherence to defined accrual goals; (2) ongoing assessment of case eligibility and evaluability; (3) timely medical review and assessment of patient data; (4) medical records used in support of NCI multi- institutional trials must conform to usual standard for the maintenance of clear, accurate, and unambiguous medical records. Quality control procedures must be in place for incoming data for quality control and quality assurance. (5) rapid reporting of treatment-related morbidity and measures to ensure communication of this information to all parties; (6) interim evaluation and consideration of measures of outcome as consistent with patient safety and good clinical trials practice; (7) timely communication of results of studies; and (8) an on-site monitoring program. The research base is responsible for ensuring that all performance sites have routine audits that are reported to the NCI in accordance with the NCI/CTMB GUIDELINES FOR ON-SITE MONITORING OF CLINICAL TRIALS FOR COOPERATIVE GROUPS AND CCOP RESEARCH BASES. Guidelines are available at http://ctep.cancer.gov/monitoring/guidelines.html In the event that the NCI determines that the awardee failed to comply with these guidelines, the accrual of new patients/participants to the research base's protocols at the affected performance site shall be suspended immediately upon notice of the NCI determination. The suspension will remain in effect until the awardee conducts the required audit and the audit report is accepted by the NCI. The research base will be responsible for notifying any affected performance site of the suspension. During the suspension period, no funds from this award may be provided to the performance site for new accruals, and no changes to the award for new accruals will be permitted. The NCI will also notify an institution that is the direct recipient of a cooperative agreement from the NCI if it is necessary to suspend accrual at that institution. f. QUALITY ASSURANCE OF DATA The research base must develop and follow procedures for the assurance of data quality in accordance with research base guidelines and NCI policies. The research base must follow NCI-approved procedures for the prevention and/or identification of false or otherwise unreliable data and for quality assurance of data collected. The research base must develop and implement NCI-approved policies for auditing the accuracy of scientific data submitted to them. In the event that there is a finding through the quality assurance and/or quality control programs of any indication of a pattern of non-compliance with protocol or regulatory requirements or a finding of possible alteration of data, these findings must be reported in accordance with the NCI-CTMB GUIDELINES FOR ON-SITE MONITORING OF CLINICAL TRIALS FOR COOPERATIVE GROUPS AND CCOP RESEARCH BASES. Guidelines are available at http://ctep.cancer.gov/monitoring/guidelines.html. g. MONITORING PLAN AND DATA SAFETY AND MONITORING BOARDS NIH policy requires that all clinical trials require data and safety monitoring, with the method and degree of monitoring being commensurate with the risks (NIH Policy for Data Safety and Monitoring, NIH Guide for Grants and Contracts, June 12, 1998 (http://grants.nih.gov/grants/guide/notice-files/not98-084.html). The research base must establish and maintain Data and Safety Monitoring Committees (DSMCs) for allPhase III clinical trials in accordance with the NCI’s policy for Data Safety and Monitoring of Clinical Trials at http://deainfo.nci.nih.gov/grantspolicies/datasafety.htm. The research base must comply with the approved policies and procedures of the DSMB. Further, the research base must establish data safety and monitoring plans for all phase I and II clinical trials in accordance with NIH policies at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-038.html. A research base may develop standard monitoring plans for Phase I and II trials however; these plans should be evaluated for appropriateness to each particular clinical trial. Information concerning essential elements of data safety monitoring plans for clinical trials funded by the NCI is available at http://www.cancer.gov/clinical_trials. These monitoring activities are distinct from the requirement for study review and approval by an Institutional Review Board (IRB). h. PROTOCOL CLOSURE The research base shall establish a mechanism for interim monitoring of results and monitoring protocol progress. If the 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 staff for review and concurrence prior to closure. It is recommended that statistical guidelines for early closure be presented as explicitly as possible in the protocol in order to facilitate these decisions. In the event that the DSMC has recommended early closure, DSMC procedures regarding notification of DCP must be followed. i. PROTOCOL REPORTING REQUIREMENTS Reporting requirements will be in agreement with FDA regulations and NCI procedures. Interim reports of each activated and ongoing study shall appear in the minutes of each research base meeting and shall include specific data on patient/participant accrual as well as, when appropriate, detailed reports of treatment-associated morbidity. Quarterly accrual reports must be provided as appropriate to CTEP for all active studies through the NCI’s Clinical Data Update System (CDUS). Instructions and Guidelines for CDUS are at http://ctep.cancer.gov/reporting/cdus.html. j. ANNUAL PROGRESS REPORT Annual progress reports, including an annual performance report on each affiliated CCOP must be submitted to DCP. A suggested format will be provided for this purpose. The DCP Program Director will review the performance of each research base. The annual report will include, at a minimum, information on: overall case accrual credits; cancer prevention and control research, existing or planned; eligibility and evaluability of patients/participants entered on study; timeliness and quality of data reporting; and results of quality control review and audits if performed during that year. A research base must submit a list of the participating sites as defined by the Clinical Trials Monitoring Branch, CTEP, DCTD, along with the audit schedule of these sites in the annual progress report. Research base funding is contingent upon: 1) accrual from affiliated CCOPs/Minority-Based CCOPs and members/affiliate institutions, and 2) development and implementation of prevention and control clinical trials. The inability of a research base to meet the performance requirements set forth in the Terms and Conditions of Award 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. k. ADVERSE EVENT REPORTING PROCEDURES To be in compliance with FDA regulations, all recipients of NCI support for clinical trials, including research bases responsible for coordinating and monitoring such trials, must promptly report adverse events (including adverse drug reactions) to the NCI and any other trial sponsor(s) according to NCI Guidelines. For treatment trials utilizing CTEP investigational agents guidelines are listed at http://ctep.cancer.gov/reporting/adeers.html. For cancer prevention and control trials utilizing DCP investigational agents guidelines are listed at http://www3.cancer.gov/prevention/pio/index.html. The awardee will notify all institutions/investigators participating in this project, funded or unfunded, about the above requirement and about the institutions'/investigators' responsibility to report adverse events as specified in the protocol. l. PERFORMANCE REVIEW The research base shall establish policies and procedures for credentialing participating CCOPs and conducting periodic review of the performance and membership status of each performance site conducting prevention and control clinical trials. This review should examine scientific contributions, patient accrual, data accuracy and timeliness, protocol compliance, and audit results. m. DATA FILES AVAILABLE TO NCI UPON REQUEST Upon the request of the Grants Management Officer, NCI, copies of data files and supporting documentation for all NCI-supported protocols that have a major impact on patterns of care, as determined by the NCI, shall be made available to the NCI in a timely manner. n. INVESTIGATIONAL DRUG MANAGEMENT Investigators performing trials under cooperative agreements will be expected, in cooperation with DCP/DCTD to comply with all FDA distribution, monitoring, and reporting requirements for investigational agents. o. NETWORK PARTICIPATION Research bases are part of a national network for conducting cancer treatment and prevention and 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. p. FEDERALLY MANDATED REQUIREMENTS Each research base must establish mechanisms to meet FDA regulatory requirements for clinical trials involving DCP/DCTD-sponsored investigational agents and DHHS/PHS regulations for the protection of human subjects. These regulations include, but are not limited to, Title 21 CFR 50, 56 and 312 and Title 45 CFR 46. At a minimum the research base must be able to: (1) demonstrate that each participant has a current approved assurance on file with the Office of Human Research Protections (OHRP); (2) demonstrate that each protocol and informed consent is approved by the responsible Institutional Review Board (IRB) prior to patient entry, that each investigator has a current FDA Form 1572 and curriculum vitae on file with the Pharmaceutical Management Branch, (PMB), CTEP, DCTD; (3) demonstrate that each patient (or legal representative) gives written informed consent prior to entry on study; (4) implement the CTEP requirement for storage and accounting for investigational agents provided under DCP/DCTD sponsorship; (5) establish an on-site audit program for periodic data verification and review of regulatory responsibilities at each CCOP, cooperative group member, cooperative group affiliate program, and cancer center affiliate institution; (6) provide a method, upon DCP/DCTD request, of summarizing efficacy and toxicity data to be included in DCP/DCTD's annual reports to the FDA for each investigational agent; (7) establish a method for the timely reporting of all serious and unexpected toxicities; (8) verify completion of education on the protection of human research participants for all investigators involved in the design or conduct of research involving human subjects; and (9) institute data and safety monitoring plans for all phase I and II clinical trials and establish and maintain Data and Safety Monitoring Committees (DSMCs) for all Phase III clinical trials in accordance with the NCI’s policy for Data Safety and Monitoring of Clinical Trials. NIH requires that research base studies meet the NIH policy requirements for inclusion of women and minorities in clinical research and inclusion of children as participants in research involving human subjects. The NIH expects investigators supported by NIH funding to make their research data available to the scientific community for subsequent analysis based on a data sharing plan approved as part of the award; see the NIH Data Sharing Policy website at http://grants.nih.gov/grants/policy/data_sharing/ and CCOP guidance at http://cancer.gov/prevention/ccop. This requirement on data sharing is an extension to NIH policy regarding sharing research resources, which expects that recipients of NIH support will provide prompt and effective access to research tools. q. 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. r. PREVENTION MEMBERS Cooperative group members, affiliate programs and/or cancer center affiliates other than CCOPs may be included in a research base application as “prevention members.” Such non-CCOP member institutions would contribute to the research base applicant’s cancer prevention research agenda. Specific activities of “prevention members” should include, but are not limited to, one or more of the following: 1) significant accrual to chemoprevention studies led by the research base applicant; 2) development of chemoprevention protocols; 3) membership in the research base applicant’s cancer prevention committees; 4) conduct of pre-clinical studies necessary for development of chemoprevention trials; and 5) conduct of ancillary research, such as that related to mechanisms of action, recruitment strategies, etc. s. PUBLICATIONS Timely publication of major findings is encouraged. Publication or oral presentation of work done under this agreement requires acknowledgment of NCI support. t. PROCEDURES IN THE EVENT OF SCIENTIFIC MISCONDUCT If a duly authorized governmental or institutional body issues a final determination that scientific misconduct has occurred or if the awardee determines that other events have occurred which have significantly affected the quality or integrity of the Group data or patient safety, the awardee is responsible for notifying the Group Data and Safety Monitoring Committee (DSMC), the CTMB, the collaborating investigators, the appropriate Institutional Review Boards (IRBs), and other sponsors of the affected work. The awardee is also responsible, if the events described above have occurred, for ensuring that submitted but unpublished abstracts and manuscripts are corrected, if possible. If publication deadlines have passed or if abstracts and/or manuscripts containing the affected data have already been published, the awardee is responsible, within 90 days after learning of the event(s) significantly affecting the quality of the Group data or patient safety, for submitting to NCI a re-analysis of the results deleting the false or otherwise unreliable data, and disclosing within the text the reason(s) for the re- analysis. The awardee must submit the re-analysis for publication. The NCI may disseminate information about the re-analysis as broadly as it deems necessary. The awardee must use its best efforts to notify all scientists, research laboratories, and other organizations to which the awardee has sent research materials affected by false or otherwise unreliable data. True copies of data files and other supporting documentation from studies affected by scientific misconduct or other findings affecting the quality or integrity of data or patient safety shall be made available to the NCI in a timely manner upon the request of the Grants Management Officer, NCI. The NCI reserves the right to re-analyze, to publish, or to distribute its analyses of these data when it is in the interest of public health. Prior to release, publication or distribution of such analyses, the NCI will provide such analyses to the awardee. u. NOTIFICATION OF PATIENTS BY THE AWARDEE DURING PATIENT’S LIFETIME In order for there to be an appropriate response in the event the NCI determines, either while a protocol is active or (if relevant) during the lifetime of the participants following protocol closure, that a medically important toxicity or side effect is associated with protocol-directed treatment or that the medical care of one or more participants may have been compromised by scientific misconduct or other finding affecting the integrity of the data or patient safety at the awardee institution or at a third-party institution, funded or unfunded, the awardee shall assure that the institution(s) responsible for these participant(s') accrual, whether funded or unfunded, will have procedures in place to: (a) contact each participant individually at his or her last known address on file with the institution and give each participant contacted appropriate information and the right to communicate with an appropriate institutional representative and, in the event of misconduct, to meet with a physician not connected with the clinical trial or study in which the participant has participated; and (b) encourage participants to notify the institution of any changes of address. The procedure must provide for informing the participants fully of the consequences of the toxicity or misconduct for their care and well-being, if any, and the availability of follow-up; and their opportunity to examine any portion of their medical records relevant to the potential effect of the toxicity or side effect upon them or that may be affected by scientific misconduct or other findings affecting the quality or integrity of the data or patient safety. It is understood that under regulations at 45 CFR Section 74.53, NCI has a right of access to research records pertinent to the NCI funding. In exceptional circumstances, such as a public health emergency, the institutions will be required to provide participant names and treatments to the NCI in a format that allows direct notification of the patient by the NCI. 2. NCI STAFF INVOLVEMENT a. SCIENTIFIC RESOURCE The Division of Cancer Prevention (DCP) and Division of Cancer Treatment and Diagnosis (DCTD) staff will serve as a resource for specific scientific information on cancer prevention and control clinical trials, treatment regimens, and clinical trial design. The DCP Program Director 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 DCP Program Director will sponsor strategy sessions when indicated, attended by leading investigators from the research bases, other extramural scientists, and appropriate experts to discuss specific research initiatives. The Investigational Drug Branch (IDB), Cancer Therapy Evaluation Program (CTEP), DCTD, and the Chemopreventive Agent Development Research Group (CADRG), DCP, through the DCP Program Director, will provide updated information on the efficacy, toxicity and availability of all Investigational New Drugs (INDs) supplied by NCI to the research base. b. PROTOCOL DEVELOPMENT The protocol is a document mutually acceptable to the research base and to DCP/DCTD. Communication at the various stages of development is encouraged. DCP/DCTD staff 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. DCP/DCTD will also comment on the scientific rationale, programmatic relevance, priority, design, statistical requirements, and implementation of the proposed study. c. CONCEPT/PROTOCOL REVIEW All research base protocols utilized by the CCOPs and research base member/affiliate institutions must be reviewed and approved by the Cancer Prevention and Control Protocol Review Committee, (CPCPRC) DCP, NCI and/or the Protocol Review Committee (PRC), DCTD, NCI, prior to implementation. The major considerations in protocol review by DCP or DCTD include; a) strength of the scientific rationale supporting the study; b) importance of the question being proposed; c) avoidance of undesirable duplication with ongoing clinical trials; d) appropriateness and feasibility of study design; e) satisfactory projected accrual rate and follow-up period; f) patient/participant safety; g) compliance with NIH and the federal regulatory requirements; h) adequacy of data management; and i) appropriateness of patient/participant selection, evaluation, assessment of toxicity, response to intervention, and follow-up. The DCP/DCTD 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, reasons will be communicated to the research base principal investigator as a consensus review within a reasonable time. The DCP Program Director will work with the research base, where appropriate, to develop a mutually acceptable protocol compatible with the research interests, abilities, and needs of the research 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. d. DATA MANAGEMENT AND ANALYSIS The awardees will retain custody of and primary rights to their data; however, DCP/DCTD will have access to all data generated under this award. The DCP Program Director or a DCTD representative may review data management and analysis procedures of the research base, under mutually agreeable circumstances, for consistency with policies and procedures established by DCP/DCTD for awardees conducting cancer treatment and prevention and control clinical trials. 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) and by NCI's agreements with pharmaceutical companies for the co-development of investigational agents. e. QUALITY CONTROL AND MONITORING The Clinical Trials Monitoring Branch (CTMB), CTEP, DCTD/DCP Program Director may review quality control and monitoring procedures of the research base including the on-site auditing program for consistency with policies and procedures established by DCTD/DCP for awardees conducting cancer treatment and prevention and control clinical trials. f. REVIEW OF QUALITY CONTROL AND STUDY MONITORING The DCP and CTMB, CTEP will review and provide advice regarding mechanisms established for study monitoring including the on-site auditing program. DCP/CTEP and/or its contractor staff may attend as observers, the on-site audits conducted by the Research Base or its NCI designee. The frequency of participation by an NCI representative as observer will be determined by the NCI. g. DATA SAFETY AND MONITORING COMMITTEE The NCI Staff will assess the research base compliance with NCI established policies on Data and Safety Monitoring Plans for Phase I and II trials and Data and Safety Monitoring Committees for Phase III trials. One or more DCP/CTEP staff will serve as non-voting members on the DSMC. h. INVESTIGATIONAL DRUG MANAGEMENT The Regulatory Affairs Branch, CTEP, DCTD, and the Chemopreventive Agent Development Research Group (CADRG), DCP, staff will advise investigators of specific requirements and changes in requirements concerning investigational drug management that the FDA may mandate. i. PROGRAM REVIEW Annual progress reports, including an annual performance report on each affiliated CCOP, must be submitted to DCP. DCP staff will provide a suggested format for this purpose. The DCP Program Director will review the progress of each research base through consideration of the research base quarterly accrual reports, annual progress report and program site visits. The DCP program director will make funding recommendations based on accrual from affiliated CCOPs/Minority-Based CCOPs, and other members and affiliates as well as the development and implementation of cancer prevention and control protocols in the CCOP network. The inability of a research base to meet the performance requirements set forth in the Terms and Conditions of Award 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. j. PROTOCOL CLOSURE DCP/DCTD will review research base mechanisms for interim monitoring of results and will monitor protocol progress. DCP/DCTD 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/participant 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). k. FEDERALLY MANDATED REQUIREMENTS The DCP Program Director and a DCTD 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. l. CCOPs/MINORITY-BASED CCOPs The DCP Program Director will notify research bases when CCOPs/Minority-Based CCOPs are funded. 3. ARBITRATION PROCESS The Terms and Conditions of Award require that the DCP Program Director make post-award decisions related to protocol review, program performance and adjustments in funding. 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, DCP. 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. WHERE TO SEND INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Inquiries may fall into three areas: scientific/programmatic, peer review, and financial or grants management issues: o Direct your questions about programmatic issues to: Lori Minasian, MD, FACP Chief, Community Oncology and Prevention Trials Research Group Division of Cancer Prevention, NCI 6130 Executive Boulevard, EPN Room 2017, MSC-7340 Bethesda, MD 20892-7340 Rockville, MD 20852 (for courier/express service) Telephone: (301) 496-8541 Fax: (301) 496-8667 E-mail address: lm145a@nih.gov o Direct your questions about peer review issues to: Referral Officer National Cancer Institute Division of Extramural Activities 6116 Executive Boulevard, Room 8041, MSC 8329 Bethesda, MD 20892-8329 Rockville, MD 20852 (for courier/express service) Telephone: (301) 496-3428 FAX: (301) 402-0275 Email: ncirefof@dea.nci.nih.gov o Direct your questions about financial or grants management matters to: Ms. Jane Paull Grants Administration Branch Office of the Director, NCI 6120 Executive Boulevard. EPS Room 243 Bethesda, MD 20892 Rockville, MD 20852 (for courier/express service) Telephone: (301) 496-2182 Fax: (301) 496-8601 E-mail: jp97x@nih.gov LETTER OF INTENT Prospective applicants are asked to submit a letter of intent that includes the following information: o Descriptive title of the proposed research o Name, address, and telephone number of the Principal Investigator o Names of other key personnel o Participating institutions o Number and title of this RFA Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows NCI staff to estimate the potential review workload and plan the review. The letter of intent is to be sent by the date listed at the beginning of this document. The letter of intent should be sent to: Lori Minasian, MD, FACP Chief, Community Oncology and Prevention Trials Research Group Division of Cancer Prevention, NCI 6130 Executive Boulevard, EPN Room 2017, MSC-7340 Bethesda, MD 20892-7340 Rockville, MD 20852 (for courier/express service) Telephone: (301) 496-8541 Fax: (301) 496-8667 E-mail address: lm145a@nih.gov SUBMITTING AN APPLICATION Applications must be prepared using the PHS 398 research grant application instructions and forms (rev. 5/2001). Applications must have a Dun and Bradstreet (D&B;) Data Universal Numbering System (DUNS) number as the Universal Identifier when applying for Federal grants or cooperative agreements. The DUNS number can be obtained by calling (866) 705-5711 or through the web site at http://www.dunandbradstreet.com/. The DUNS number should be entered on line 11 of the face page of the PHS 398 form. The PHS 398 document is available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. For further assistance, contact GrantsInfo, Telephone: (301) 435-0714, Email: GrantsInfo@nih.gov. SUPPLEMENTARY INSTRUCTIONS A suggested format (“Suggestions for Organizing Information for a CCOP or CCOP Research Base Application,”) is available at http://cancer.gov/prevention/ccop/. All applicants are encouraged to obtain and use the suggested format instructions for organizing the specific information concerning the RFA programmatic requirements in the PHS 398. If tables from the suggested format are included, those tables should be part of the body of the application, and NOT included in the appendix. These tables should be included in the application as part of the Resources, Progress Report and/or Human Subjects Research sections, as appropriate. Also, responses to the instructions concerning "Human Subjects" verification must be included in the application at the time of submission. Applications submitted in response to this RFA may use up to 75 pages to describe the research plan, sections a through d. Applicants are encouraged to use the minimum number of pages necessary to clearly and succinctly describe the research plan. The 75 page limit may be increased for those applications that include supplements for support of large-scale prevention trials and/or with a substantial number of proposed “prevention members.” These applicants should contact the Community Oncology and Prevention Trials Research Group, DCP, NCI at (301) 496-8541. 1.CCOP APPLICANTS Because the Terms and Conditions of Award (discussed in the SPECIAL REQUIREMENTS Section above) will be included in all awards issued as a result of this RFA, it is critical that each applicant include specific plans for responding to these terms. Plans must describe how the applicant will comply with 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 competing 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 annual accrual over the funding period. Accrual tables from previous annual progress reports should be included. A summary of accrual to all cancer treatment and a summary of accrual to all cancer prevention and control protocols by gender and ethnicity must be provided; progress in meeting DCP's established accrual goals must be presented; (2) a plan for continuing to meet prevention and control accrual requirements including plans for follow-up of participants from the large prevention trials as well as plans for implementation of additional cancer control protocols; (3) tables of the current budget and FTEs with a justification for any request for additional resources; (4) an evaluation of CCOP performance by affiliated research base(s); and (5) a complete description of how the applicant has met the special cooperative agreement terms and conditions of the award. Both new and currently funded applicants should address the following: a. Each applicant must delineate its catchment area. A map of the service area, designating counties or zip codes 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) that are not part of the application should be included. In describing the study population, a breakdown by percentage of the gender and minority composition of the study population should be provided. This information may be based on the institutional records and/or prior experience. b. Each applicant must demonstrate the potential and stated commitment to accrue a minimum of 50 credits per year to treatment clinical trials (except if waived for applicants whose specialty is pediatrics and are able to place a majority of their eligible patients on protocols or those applicants with an outstanding record in cancer prevention and control accrual). Documentation must include any prior participation in treatment research clinical trials with a clear presentation of the total number of patients and credits accrued to NCI-approved treatment clinical trials. A list of the NCI approved treatment protocols in which the applicant expects to participate and the projected accrual to each must be provided. Plans for recruiting women and minority participants must be included. c. Each applicant must demonstrate the potential and plans for accrual of a minimum of 50 credits per year to cancer prevention and control protocols (except if waived for applicants whose specialty is pediatrics and are able to place a majority of their eligible patients on protocols). Documentation must include any prior participation in cancer prevention and control research clinical trials with a clear presentation of the total number of patients and credits accrued to NCI approved cancer prevention and control clinical trials. A list of the NCI approved prevention and control protocols in which the applicant expects to participate and the projected accrual must be provided. Plans for recruiting women and minority participants must be included. If applicable, CCOP applicants should describe their participation in cancer prevention and control research supported by other federally funded mechanisms (e.g., research projects grants (R01s), contracts). Participation in such research will be considered in the evaluation of CCOP productivity. NEW Applicants must provide implementation plans for at least two examples of NCI-approved cancer prevention and control protocols that utilize an intervention. The applicant should describe their plan for implementation, including specifics on patient/participant recruitment, compliance and follow- up. These studies must come from research bases with which they propose to affiliate. The CCOP applicant must document the ability to access the appropriate physicians and patient/participant populations, and adequate facilities to participate in the proposed clinical trials. d. A designated Principal Investigator is required. An associate principal investigator also should 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 cancer treatment and prevention and control research and related activities, as well as experience in accruing patients/participants to treatment and cancer prevention and control clinical trials must be described. e. 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, urology, gastroenterology, pediatrics, internal medicine, family practice) as appropriate. The training and experience of participating physicians must be provided, along with a description of working relationships. Any experience working together as a group, particularly in implementing clinical cancer treatment and prevention and control research and related activities, should be included. An organizational chart showing how the group will function must also be included. f. Each applicant must provide the qualifications and experience of all proposed support personnel as well as a description of the proposed duties for each position. g. Through formal affiliations with only one multi-specialty cooperative group (exceptions may be granted in conjunction with participation in an NCI sponsored “pilot” project) and with as many other research bases (excluding the multi-specialty groups) as the CCOP deems appropriate, each applicant must demonstrate access to both cancer treatment and prevention and control research protocols. The CCOP must justify the reasons for multiple other research base affiliations, either existing or planned, in terms of the scope and breadth of research that the CCOP anticipates undertaking in its new or competing continuation application. Evidence must be provided that an affiliation has been established with one NCI-approved multi-specialty cooperative group. 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, as described above, provided they are not conflicting. 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 at: http://cancer.gov/prevention/ccop or from the Community Oncology and Prevention Trials Research Group, DCP, NCI at (301) 496-8541. h. Quality control procedures must 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 must also be described. i. The CCOP must describe how it plans to share data. The procedures to be used and a timeline for making the data available should be included in the description of the plan. The CCOP also should discuss how the rights and confidentiality of participants are protected. j. The availability of facilities, including laboratories, inpatient and outpatient resources, cancer registries, etc., must be described. A statement of commitment from each participating institution or organization and/or documentation of consortium arrangements must 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 that will serve as a focus for data management, quality control, and communication. k. Allocation of funds to support community costs for receipt, handling, and quality control of patient data must be specified. Allowable items in the budget are requests for full or part-time administrative personnel, clinical research associates, 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., reimbursement of patient care expenses; transportation costs). Funding is not allowed for clinical support personnel (e.g. pharmacist, physicist, clinical psychologist, dosimetrist). 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, effort and funds requested. 2. RESEARCH BASE APPLICANTS Because the Terms and Conditions of Award (discussed in the Special Requirements Section above) will be included in all awards issued as a result of this RFA, it is critical that each applicant include specific plans for responding to these terms. Plans must describe how the applicant will comply with NCI staff involvement as well as how all the responsibilities of awardees will be fulfilled. An application from a currently funded research base will be a competing 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 annual accrual to cancer treatment protocols (if applicable) (gender and racial/ethnic minority composition) from affiliated CCOPs; annual accrual to cancer prevention and control protocols (gender and racial/ethnic minority composition) from affiliated CCOPs and research base member and affiliates over the funding period; (NOTE: An applicant submitting the first competing continuation application must demonstrate that the research base has generated a sufficient number of NCI approved protocols to meet the credit minimums during the ensuing project period. The research base’s menu of NCI-approved concepts or concepts in development is another measure of the applicant’s viability as a research base.) (2) progress in developing and implementing a cancer prevention and control research program. Include the process and organizational structure for protocol development and implementation, selection and evaluation (auditing) of performance sites, data management, quality control, statistical analysis, and study safety monitoring; (3) a clear presentation of annual accrual to each NCI-approved prevention and control clinical trial for CCOPs, and research base members and affiliates; (4) status of concepts and protocols under development; (5) a description of how the applicant has met the special cooperative agreement terms and conditions of the award. Cooperative Groups as research bases must participate in both cancer treatment and prevention and control clinical trials. Cancer Centers as research bases may participate in both cancer treatment and prevention and control clinical trials or only cancer prevention and control research. Research bases are encouraged to participate in and/or facilitate CCOP participation in cancer prevention and control research that is supported through other federally funded mechanisms. Research supported through these other mechanisms might include nonintervention research in cancer control (epidemiology, methods development, population-based surveys, etc.). Expanding access to and involvement of the CCOP network in investigator- initiated research will be considered in the evaluation of the research bases’ productivity. In describing the study population, it is required that a description of the gender and minority population and subpopulation served be provided, as well as an outreach plan. This information may be based on the institutional records and/or prior experience. a. Each applicant must demonstrate the ability to design and implement multi- institutional treatment clinical trials (if applicable). A list of treatment protocols available for CCOP participation must be provided. b. Each applicant must demonstrate the ability to design and implement multi- institutional cancer prevention and control clinical trials. A list of cancer prevention and control protocols available for CCOP and research base member/affiliate institution participation must be provided. New research base applicants must also provide at least two examples of active or proposed cancer prevention and control intervention clinical trials and describe plans for study design, intervention(s), and statistical considerations; access to potential patients/participants 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 clinical trials must be documented. c. Each applicant must have an organizational structure for involving appropriate personnel in the design and implementation of treatment and/or cancer prevention and control research. An organizational chart and a description of the research base operations 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 prevention and control clinical trials, must be provided. The organizational focus within the research base for cancer prevention and control research must be described, including the composition and activities of the research base cancer prevention and control committee, or equivalent, and its relationship to other clinical trial committees and activities. d. Collaboration with affiliated CCOPs/Minority-Based CCOPs in treatment and/or cancer prevention and control research, as applicable, is required. CCOP-research base affiliation agreements must be included in the application. For treatment research, each applicant must demonstrate the ability to accrue a minimum of 50 credits per year from affiliated CCOPs/Minority-Based CCOPs to treatment clinical trials developed by the research base applicant. A new research base applicant is expected, during its initial competitive segment (project period), to develop a menu of treatment protocols that will allow the research base to meet the credit minimums per year in its subsequent competing segments. For cancer prevention and control research, each applicant must demonstrate the ability to accrue a minimum of 50 credits per year from affiliated CCOPs/Minority-Based CCOPs, members and other affiliates to cancer prevention and control clinical trials led by the research base applicant. A new research base applicant is expected, during its initial competitive segment (project period), to develop a menu of cancer prevention and control protocols that will allow the research base to meet the credit minimums per year in its subsequent competing segments. If applicable, CCOP research base applicants should describe their participation in and/or facilitation of CCOP participation in cancer prevention and control research studies supported by other federally funded mechanisms such as research project grants (R01s) and contracts. It is expected that selected cooperative group members, affiliate programs and/or cancer center affiliates other than the CCOPs will participate in cancer prevention and control research. Research base applications may include requests for these non-CCOP member institutions to become "prevention members". Such non-CCOP member institutions would contribute to the goals of its base’s cancer prevention research agenda. Specific activities of “prevention members” should include, but are not limited to, one or more of the following: 1) significant accrual to chemoprevention studies developed by the research base applicant; 2) development of chemoprevention protocols; 3) membership in the research base applicant’s cancer prevention committees; 4) conduct of pre-clinical studies necessary for development of chemoprevention trials; and 5) conducting ancillary research, such as that related to mechanisms of action, recruitment strategies, etc. The research base applicants must describe the experience of the proposed non-CCOP member institution and its investigators and how this “prevention member” will contribute to the goals of the application. In addition, the research base applicant should describe the nature and scope of work proposed for each “prevention member” included in the application and a detailed budget. e. A designated Principal Investigator is required and his/her qualifications and experience must be described. An individual must be designated to coordinate cancer prevention and control research. His or her qualifications and experience within the research base structure should also 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 prevention and 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. f. Each applicant's ability to manage the data from multi-institutional treatment and/or cancer prevention and control clinical trials must 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/participants entered on protocols. Statistical capability must exist to develop protocol statistical parameters, analyze the data, and report results. The research base must describe its data-sharing plan. The procedures to be used and a timeline for making the data available should be included in the description of the plan. A discussion on how the rights and confidentiality of participants are protected should be included. g. Each applicant must demonstrate the ability to initiate procedures for training and maintaining the proficiency of personnel from affiliated CCOPs/Minority-Based CCOPs on techniques for successful management of treatment and/or cancer prevention and control clinical trials research. Depending on the clinical trials 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). h. Each applicant's ability to provide mechanisms for periodic review of the performance of affiliated CCOPs/Minority-Based CCOPs, including on-site monitoring (auditing) and written procedures and criteria for continued affiliations, must be described. Similar measures must be described for other member/affiliates participating in cancer prevention and control research. i. Each applicant must describe its plan for independent data and safety monitoring for all prevention and control clinical trials. j. Requests for funds must reflect operations/statistical costs for quality control and data management costs for CCOP participation in protocols. This estimate is based on the expected accrual credits of affiliated CCOPs/Minority-Based CCOPs and for member/affiliate accrual credits in cancer prevention and control. CCOP-research base affiliation agreements must be included. Each applicant should include a budget for monitoring and auditing activities. Funding can be requested for scientific development and pilot testing of new cancer prevention and control research initiatives (including support of a cancer prevention and control committee(s) for the research base), and funds can also be requested for appropriate travel to meetings directly related to study activities (such as NCI-sponsored strategy sessions/workshops). In addition, the research bases may request funding for specific non-CCOP member institutions that apply to become "prevention members". A detailed budget for each prevention member must be included in the application. Specific justification for all requested funds must also be included in the application. USING THE RFA LABEL: The RFA label available in the PHS 398 (rev. 5/2001) application form must be affixed to the bottom of the face page of the application. Type the RFA number on the label. 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. The RFA label is also available at: http://grants.nih.gov/grants/funding/phs398/labels.pdf. SENDING AN APPLICATION TO THE NIH: 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 and all five copies of the appendix material must be sent to: Referral Officer National Cancer Institute Division of Extramural Activities 6116 Executive Boulevard, Room 8041, MSC 8329 Bethesda, MD 20892-8329 Rockville, MD 20852 (for express/courier service) Appendices should be comprised of unbound materials, with separators between documents. APPLICATIONS HAND-DELIVERED BY INDIVIDUALS TO THE NATIONAL CANCER INSTITUTE WILL NO LONGER BE ACCEPTED. This policy does not apply to courier deliveries (i.e., FEDEX, UPS, DHL, etc.) (See http://grants.nih.gov/grants/guide/notice-files/NOT-CA-02-002.html). This policy is similar to and consistent with the policy for applications addressed to Centers for Scientific Review as published in the NIH Guide Notice (See http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-012.html.) APPLICATION PROCESSING: Applications must be received by the application receipt date listed in the heading of this RFA. If an application is received after that date, it will be returned to the applicant without review. Although there is no immediate acknowledgement of the receipt of an application, applicants are generally notified of the review and funding assignment within 8 weeks. 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. However, when a previously unfunded application, originally submitted as an investigator-initiated application, is to be submitted in response to an RFA, it is to be prepared as a NEW application. That is the application for the RFA must not include an Introduction describing the changes and improvements made, and the text must not be marked to indicate the changes from the previous unfunded version of the application. PEER REVIEW PROCESS Upon receipt, applications will be reviewed for completeness by the CSR and for responsiveness by the NCI program staff. Incomplete and/or non-responsive applications will not be reviewed. Applications that are complete and responsive to the RFA will be evaluated for scientific and technical merit by an appropriate peer review group convened by the Division of Extramural Activities (DEA) at NCI in accordance with the review criteria stated below. As part of the initial merit review, all applications will: o 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 and assigned a priority score o Receive a written critique o Receive a second level review by the NCI’s National Cancer Advisory Board. REVIEW CRITERIA 1. CCOP APPLICANTS All applicants will be evaluated on the following criteria: a. Adequacy of plans to include both genders and minorities and their subgroups. Plans for the recruitment and retention of participants will also be evaluated. In describing the study population, it is required that a description of the gender and minority population and subpopulation served be provided, as well as an outreach plan. This information may be based on the institutional records and/or prior experience. b. Ability to accrue a minimum of 50 credits per year to treatment clinical trials and a minimum of 50 credits per year to cancer prevention and control clinical trials. Established CCOPs will be funded at a yearly accrual goal that may be higher than 50 credits for treatment clinical trials and 50 credits for cancer prevention and control clinical trials. These established CCOPs will be evaluated for their past performance in meeting these accrual goals. The minimum accrual to treatment requirements may be waived for: 1) applicants whose specialty is pediatrics and are able to place a majority of their eligible patients on protocol; and 2) for applicants with an outstanding record in accrual to prevention and control protocols. Each applicant's ability to access the appropriate populations, professional disciplines, and facilities to participate with affiliated research bases in NCI-approved cancer prevention and control intervention protocols will be appraised. Any prior participation in cancer treatment and prevention and control research will be considered. For new CCOP applicants, the plans for implementing at least two NCI-approved protocols will be assessed for feasibility and practicality. In addition, CCOP participation in cancer prevention and control research studies supported through other federally funded mechanisms such as research project grants (R01s) and contracts will be considered in the evaluation of the CCOP’s productivity. c. 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 cancer treatment and prevention and control research as well as accrual to such protocols, and related activities. d. 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, gastroenterology, pathology, internal medicine, family practice, nursing, and nutrition) will be required. Experience or special skills in cancer prevention and control research and related activities will be considered, together with availability of other community resources and personnel for such clinical trials. e. 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 cancer treatment and prevention and control research and related activities will be considered. f. 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. g. Adequacy of quality assurance mechanisms for both cancer treatment and prevention and control interventions, and adequacy of procedures for investigational drug monitoring and data management and identification of false or otherwise unreliable data. h. Adequacy of available facilities, including laboratories, in-patient and outpatient resources, cancer registries, etc., and adequacy of space for administrative activities and personnel. i. Appropriateness of research base affiliations and of the cancer treatment and prevention and control research protocols chosen. Affiliation agreements must be provided in the application. j. Adequacy of the data-sharing plan. k. The review group will critically examine the submitted budget and will recommend an appropriate budget and period of support for each favorably recommended application. Allowable items in the budget are requests for full or part-time administrative personnel, clinical research associates, 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). Funding is not allowed for clinical support personnel (e.g. pharmacist, physicist, clinical psychologist, dosimetrist). 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. OTHER REVIEW CRITERIA For competing continuations, the review group will critically examine the adequacy of progress during the funding period, including ability to meet the accrual goals in cancer treatment and prevention and control, progress made as a CCOP, and evaluation of CCOP performance by affiliated research bases(s). Consideration will be given to previous accrual and the ability to meet the previous accrual projections for which the CCOP was funded. The research base evaluation report(s) must be provided in the application. Plans for continued accrual and follow-up of participants on protocols will be evaluated. 2. RESEARCH BASE APPLICANTS All research base applicants will be evaluated on the following criteria: a. Adequacy of plans to include both genders and minorities and their subgroups as appropriate for the scientific goals of the research. Plans for the recruitment and retention of participants will also be evaluated. In describing the study population, it is required that a description of the gender and minority population and subpopulation served be provided, as well as an outreach plan. This information may be based on the institutional records and/or prior experience. b. Experience in conducting multi-institutional clinical trials; demonstrated ability to develop such studies and act as a coordinating and statistical center; adequate facilities to conduct the clinical trials; adequate procedures to collect, monitor, and analyze the data and assure the safety of patients/participants. c. Quality and availability of cancer treatment and/or prevention and control protocols, as applicable, which are appropriate for CCOP and other cooperative group members/affiliates participation, or the potential for developing such clinical trials. For new applications, a detailed description of at least two examples of actual or planned cancer prevention and control protocols, with professional expertise to assure the quality of the proposed intervention clinical trial will be evaluated. d. The ability to accrue a minimum of 50 credits per year from affiliated CCOPs/Minority-Based CCOPs to treatment clinical trials developed by the research base applicant. For new research base applicants, the ability to develop a menu of treatment protocols that will allow the research base to meet the credit minimum in subsequent competitive segments. The ability to accrue a minimum of 50 credits per year from affiliated CCOPs/Minority-Based CCOPs, members and other affiliates to cancer prevention and control clinical trials led by the research base applicant. Experience as well as the potential for developing future clinical trials will be considered. For new research base applicants, the ability to develop a menu of cancer prevention and control protocols that will allow the research base to meet the minimum of 50 credits in subsequent competitive segments. Documentation must include CCOP-research base affiliation agreements. Research base applicants’ participation in and/or facilitation of CCOP participation in cancer prevention and control studies supported through other federally funded mechanisms such as research projects grants (R01s) and contracts will be considered in the evaluation of the research base’s productivity. f. Organizational structure for involving appropriate personnel in the design and implementation of treatment and/or cancer prevention and control research. The organizational focus within the research base for cancer prevention and control research, including the composition and activities of the cancer prevention and control committee, and the designation of protocol chairpersons and its relationship to other clinical trial committees and activities will be assessed. The qualifications and contribution to the science of and accrual to cancer chemoprevention clinical trials will be assessed in the evaluation of the research base's request for the non-CCOP member institutions that apply for the designation of "prevention member”. g. 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 prevention and control clinical trials will also be evaluated. h. Experience in working with community oncologists, orienting community data management personnel to protocol requirements, organizing scientific and educational meetings for those participating in the clinical trials, and participating in inter-group clinical trials. i. Ability to establish quality control, quality assurance, and data management procedures. Experience in data management and analysis of multi- institutional clinical trials and adequacy of data management staff will be appraised. The use of mechanisms for periodic review of quality control, quality assurance, and data management procedures, safety monitoring, including procedures for data safety and monitoring committee and on-site auditing program will be assessed. j. The adequacy of the data-sharing plan. k. For competitive continuations, adequacy of progress in implementing a prevention and control clinical trials program including cancer prevention and control protocol development and implementation, accrual, data management, evaluation of performance sites; current status of each protocol and progress towards meeting planned accrual goals from CCOPs and research base members/affiliates; summary of prior activities with a clear presentation of annual accrual; completion of clinical trials, interim analyses, publication of findings, or other dissemination of trial findings throughout the research base; and other progress in meeting the requirements for a CCOP research base. For applicants submitting their initial competing continuation application, adequacy of progress must be demonstrated, in implementing a cancer prevention and control clinical trials program, including development of an adequate menu of NCI approved protocols, which will result in attainment of accrual goals and other requirements for a CCOP research base in the next and subsequent competitive segments. l. The review group will critically examine the submitted budget and will recommend an appropriate budget and period of support for each favorably recommended application. Requests for funds must reflect operations/statistical costs for quality control and data management costs for CCOP participation in protocols. This estimate is based on the expected accrual credits of affiliated CCOPs/Minority-Based CCOPs and for research base member/affiliate accrual credits in cancer prevention and control. Research bases should include a budget for monitoring and auditing costs. Funding may be requested for scientific development and pilot testing of new cancer prevention and control research initiatives, other costs related to implementation of specific cancer prevention and control protocols (including support of a cancer prevention and control committee for the research base), or for appropriate travel to meetings directly related to study activities (such as NCI-sponsored strategy sessions/workshops). Additionally, funding may be requested to provide infrastructure support for non-CCOP member institutions of the Research Bases that can show significant contribution to the science and/or accrual for chemoprevention trials. Specific justification must be provided. ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, the following items will be considered in the determination of scientific merit and the priority score: PROTECTION OF HUMAN SUBJECTS FROM RESEARCH RISK: The involvement of human subjects and protections from research risk relating to their participation in the proposed research will be assessed. (See criteria included in the section on Federal Citations, below). INCLUSION OF WOMEN, MINORITIES AND CHILDREN IN RESEARCH: The adequacy of plans to include subjects from both genders, all racial and ethnic groups (and subgroups), and children as appropriate for the scientific goals of the research. Plans for the recruitment and retention of subjects will also be evaluated. (See Inclusion Criteria in the sections on Federal Citations, below). ADDITIONAL REVIEW CONSIDERATIONS SHARING RESEARCH DATA Applicants requesting more than $500,000 in direct costs in any year of the proposed research must include a data sharing plan in their application. The reasonableness of the data sharing plan or the rationale for not sharing research data will be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or priority score. See the NIH Data Sharing Policy website at http://grants.nih.gov/grants/policy/data_sharing. BUDGET: The reasonableness of the proposed budget and the requested period of support in relation to the proposed research. RECEIPT AND REVIEW SCHEDULE Letter of Intent Receipt: June 14, 2004 Application Receipt Date: July 14, 2004 Peer Review Date: October/November 2004 Review by NCAB Advisory Board: February 2005 Anticipated Award Date: June 1, 2005 AWARD CRITERIA Applications recommended by the National Cancer Advisory Board will be considered by NCI program staff for award based upon: o Scientific and technical merit (as determined by peer review); o Availability of funds; o Programmatic priorities; and o Demographic and geographic distribution of applicants to assure inclusion of minority and underserved populations. Multiple CCOP respondents who are competing for the same patient population will be considered, but all may not be awarded unless warranted by the population density. REQUIRED FEDERAL CITATIONS HUMAN SUBJECTS PROTECTION: Federal regulations (45CFR46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained. See http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm. DATA SAFETY AND MONITORING PLAN: Data and safety monitoring is required for all types of clinical trials, including physiologic, toxicity, and dose- finding studies (phase I); efficacy studies (phase II); and efficacy, effectiveness and comparative trials (phase III). The establishment of data and safety monitoring boards (DSMBs) is required for multi-site clinical trials involving interventions that entail potential risk to the participants. (See NIH Policy for Data Safety and Monitoring, NIH Guide for Grants and Contracts, June 12, 1998 at http://grants.nih.gov/grants/guide/notice-files/not98-084.html.) Clinical trials supported or performed by NCI require special considerations. The method and degree of monitoring should be commensurate with the degree of risk involved in participation and the size and complexity of the clinical trial. Monitoring exists on a continuum from monitoring by the principal investigator/project manager or NCI program staff or a Data and Safety Monitoring Board (DSMB). These monitoring activities are distinct from the requirement for study review and approval by an Institutional review Board (IRB). For details about the Policy for the NCI for Data and Safety Monitoring of Clinical trials, see http://deainfo.nci.nih.gov/grantspolicies/datasafety.htm. Information concerning essential elements of data safety monitoring plans for clinical trials funded by the NCI is available at http://www.cancer.gov/clinical_trials/. SHARING RESEARCH DATA: Starting with the October 1, 2003 receipt date, investigators submitting an NIH application seeking $500,000 or more in direct costs in any single year are expected to include a plan for data sharing (http://grants.nih.gov/grants/policy/data_sharing) or state why this is not possible. Investigators should seek guidance from their institutions, on issues related to institutional policies, local IRB rules, as well as local, state, and Federal laws and regulations, including the Privacy Rule. Reviewers will consider the data sharing plan but will not factor the plan into the determination of the scientific merit or the priority score. INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH: It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH-supported clinical research projects unless a clear and compelling justification is provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing clinical research should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research - Amended, October, 2001," published in the NIH Guide for Grants and Contracts on October 9, 2001 (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines are available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the new PHS Form 398; and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences. INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS: The NIH maintains a policy 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 scientific and ethical 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 is available at http://grants.nih.gov/grants/funding/children/children.htm. REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS: NIH policy requires education on the protection of human subject participants for all investigators submitting NIH proposals for research involving human subjects. You will find this policy announcement in the NIH Guide for Grants and Contracts Announcement, dated June 5, 2000, at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html. A continuing education program in the protection of human participants in research is available online at: http://cme.nci.nih.gov/. PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT: The Office of Management and Budget (OMB) Circular A-110 has been revised to provide public access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are (1) first produced in a project that is supported in whole or in part with Federal funds and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this RFA in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award. STANDARDS FOR PRIVACY OF INDIVIDUALLY IDENTIFIABLE HEALTH INFORMATION: The Department of Health and Human Services (DHHS) issued final modification to the “Standards for Privacy of Individually Identifiable Health Information”, the “Privacy Rule,” on August 14, 2002. The Privacy Rule is a federal regulation under the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable health information, and is administered and enforced by the DHHS Office for Civil Rights (OCR). Those who must comply with the Privacy Rule (classified under the Rule as “covered entities”) must do so by April 14, 2003(with the exception of small health plans which have an extra year to comply). Decisions about applicability and implementation of the Privacy Rule reside with the researcher and his/her institution. The OCR website (http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including a complete Regulation Text and a set of decision tools on “Am I a covered entity?” Information on the impact of the HIPAA Privacy Rule on NIH processes involving the review, funding, and progress monitoring of grants, cooperative agreements, and research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html. URLs IN NIH GRANT APPLICATIONS OR APPENDICES: All applications and proposals for NIH funding must be self-contained within specified page limitations. Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) should not be used to provide information necessary to the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site. HEALTHY PEOPLE 2010: The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This RFA is related to one or more of the priority areas. Potential applicants may obtain a copy of “Healthy People” at http://www.healthypeople.gov/. AUTHORITY AND REGULATIONS: This program is described in the Catalog of Federal Domestic Assistance No.93.399 at http://www.cfda.gov/, and is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. Awards are made under authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and administered under NIH grants policies described at http://grants.nih.gov/grants/policy/policy.htm and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The NIH Grant Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm. The PHS strongly encourages all grant recipients to provide a smoke-free workplace and discourage the 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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