Full Text CA-95-014 MULTI-INSTITUTIONAL COOPERATIVE GROUP FOR CLINICAL EVALUATION OF MAGNETIC RESONANCE IMAGING IN BREAST CANCER NIH GUIDE, Volume 24, Number 13, April 7, 1995 RFA: CA-95-014 P.T. 34 Keywords: Medical/Diagnostic Imaging Clinical Medicine, General National Cancer Institute Letter of Intent Receipt Date: May 9, 1995 Application Receipt Date: June 9, 1995 PURPOSE The Diagnostic Imaging Research Branch (DIRB), Division of Cancer Treatment (DCT) of the National Cancer Institute (NCI), invites applications from consortia of institutions for Cooperative Agreements (U01) to study the role of Magnetic Resonance Imaging (MRI) in improved detection and staging of breast cancer. The NCI is seeking talented scientists from academic, non-profit and for-profit research organizations who will interact with other members of the Consortium, and with DIRB in a concerted way to evaluate and optimize new approaches to breast cancer diagnosis. One consortium of multiple institutions, called "Multi-Institutional Cooperative Group for Clinical Evaluation of MRI in Breast Cancer", will be funded by the NCI. Scientific approaches taken by the Cooperative Group will be broad and will reflect the creativity and capabilities of consortium participants. The purpose of this Request for Applications (RFA) is to stimulate cooperative efforts through phase II clinical trials for facilitated evaluation of sensitivity, specificity and local staging accuracy of breast MRI compared to conventional radiologic approaches in women with abnormal or non-diagnostic x-ray mammograms for whom biopsy is required. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This RFA, Multi-Institutional Cooperative Group For Clinical Evaluation of Magnetic Resonance Imaging In Breast Cancer, is related to the priority area of cancer. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0 or Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign non-profit and for-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and Local governments, and eligible agencies of the Federal government. Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as Principal Investigators. Each application must be submitted from a single consortium consisting of several participating institutions to ensure accrual of about 3,000 women over a period of four years. MECHANISM OF SUPPORT The administrative and funding instrument to be used for this program will be a cooperative agreement (U01), an "assistance" mechanism (rather than an "acquisition" mechanism) in which a substantial involvement between NIH program staff and the awardee is anticipated during performance of the activity. Under the cooperative agreement, the NCI purpose is to support and/or stimulate the recipient's activity by involvement in and otherwise working jointly with the award recipient in a partner role, but it is not to assume direction, prime responsibility, or a dominant role in the activity. Details of the responsibilities, relationships and governance of the study to be funded under cooperative agreement(s) are discussed later in this document under the section "Terms and Conditions of Award". The total project period for an application submitted in response to this RFA may not exceed four years. The anticipated award date is September 30, 1995. Because the nature and scope of the research proposed in response to this RFA may vary, it is anticipated that the size of the award will vary also. Award and level of support depend on receipt of applications of high scientific merit. This RFA is a one-time solicitation. Future unsolicited competing continuation applications will compete with all investigator-initiated R01 applications and be reviewed according to the customary peer review procedures. FUNDS AVAILABLE It is anticipated that one award will be made for approximately $1,500,000 total costs per year for four years to a single consortium consisting of several participating institutions. Although this program is provided for in the financial plans of the NCI, the award of a Cooperative Agreement pursuant to this RFA is contingent upon the availability of funds for this purpose. RESEARCH OBJECTIVES Background Breast cancer is second only to lung cancer as the cause of cancer- related deaths in women in the United States. Conventional x-ray mammography has been shown to play an important role in detection and staging of breast cancer in women older than 50 years of age. However, younger women frequently have "radiodense" breast tissue, rendering breast cancer diagnosis with conventional mammography problematic. This scenario created a strong incentive for the Diagnostic Imaging Research Branch to support development and evaluation of novel breast imaging technologies. Over the last few years, contrast-enhanced MRI of the breast has emerged as one of the most promising clinical tools for detection of breast cancer and delineation of its anatomic local extent. Preliminary results in phase I, or exploratory clinical trials indicate that breast MRI may be more sensitive than conventional x-ray mammography in detecting small lesions. Breast MRI also appears to be particularly useful for detection of breast cancer in women with essentially uninterpretable x-ray mammograms (e.g., when breast tissue is "radiodense" or "radio-opaque" due to silicon implants). Contrast enhanced MRI is thus a promising adjunctive diagnostic tool and may be of particular value in the early detection of breast cancer in women with "radiodense" and "radio-opaque" breasts and, by virtue of its ability to improve local tumor anatomic delineation, in clinical staging of local disease in women with apparent early-stage breast cancer. On the other hand, whereas current reported results appear promising, they are preliminary in nature and based on a limited patient sample in individual institutions. It is not known at this time what MRI technical approach is optimal (e.g. two- vs. three-dimensional acquisition, fat suppression vs. subtraction, trade-off between spatial and temporal resolution). While the sensitivity of breast MRI appears promising, specificity of this technology has been reported to be low. However, recent development of specialized imaging coils and MRI-guided biopsy is expected to have an important impact on tissue characterization of the MRI-detected lesions. The DIRB, NCI, with the advice of experts from academia and industry in the fields of diagnostic imaging and breast cancer treatment, has determined that a clinical trial to evaluate the sensitivity, specificity and local staging accuracy of breast MRI is, with the availability of breast-dedicated MR imaging coils and introduction of MRI-guided biopsy capability, both feasible and timely. Information from this trial may suggest future trials aimed at more clearly defining the role of MRI in breast cancer screening or clinical evaluation of women with early breast cancer. Objectives and Scope The purpose of this RFA is to facilitate cooperative efforts to evaluate MRI as a tool for improved breast cancer diagnosis through centrally coordinated multi-institutional clinical trials, with participation of multiple clinical centers for rapid patient accrual. This RFA is expected to serve a public purpose by advancing the current state-of-the-art knowledge regarding early detection and staging of breast cancer. The RFA proposes to achieve these goals through formation of one Consortium to perform phase II clinical evaluation of a new promising imaging modality and its role in breast cancer diagnosis, including sensitivity, specificity and local staging accuracy of breast MRI compared to conventional x-ray mammography, ultrasound and other related technologies in about 3,000 women in whom biopsy will be performed. The investigators will develop a clinical protocol and its modifications, if necessary, taking into account evolving scientific evidence related to the current state -of-the-art in breast MRI and its new approaches not previously mentioned in the application. Pilot studies may be performed during the initial period of this award before the phase II study protocol will be finalized. Histopathologic evaluation of MRI-detected lesions will be done for every patient, either by MRI-guided biopsies in combination with follow up imaging studies in patients with probable benign disease and/or women with breast cancer selecting breast conservation therapy (e.g. when some of the detected lesions may not be found in the lumpectomy tissue samples), or by examination of mastectomy specimens. A sufficient number of patients must be available in each participating institution for successful completion of the proposed clinical trial. Each participating institution must have experience with clinical studies in breast MRI (at least 100 previous examinations) and must demonstrate the plan for histopathologic evaluation of MRI-detected lesions. In addition, it is expected that the study participants will establish a database that would enable the Group to address vital questions such as: Can MRI reduce the number of breast biopsies, repeated lumpectomies, and/or other potentially avoidable diagnostic and therapeutic procedures? Particular emphasis will be placed on the accrual of women younger than 50 years of age and/or minority women with "radiodense" breast tissue. It is anticipated that this phase II trial, focused on evaluation of diagnostic value of MRI and its role in optimization of breast cancer detection and staging in women undergoing biopsy, may, at its completion suggest the need for phase III clinical trials to validate: (a) the impact of MRI data (e.g., improved staging accuracy through improved definition of local anatomic tumor extent) on cost-effectiveness of breast cancer management in women with early-stage disease. Particular emphasis will be placed on the accrual of women younger than 50 years of age and/or minority women with "radiodense" breast tissue as well as, (b) the role of MRI as a screening tool in reducing mortality of general (asymptomatic) population of women with "radiodense" breast tissue and patients at high genetic risk for breast cancer. SPECIAL REQUIREMENTS To promote the development of a collaborative program among the award participants, a number of issues need to be addressed in the applications, as discussed below (See APPLICATION PROCEDURES). Applicants must discuss the rationale for their choice of imaging techniques and plan for histopathologic correlation, must document their ability to recruit a sufficient number of participants, must be able to develop a plan for effective administrative management, must discuss their capability to participate in clinical trials involving breast MRI, conventional x-ray mammography and other technologies, and must state their willingness to follow the common protocol. Definitions AWARDEE - The organization to which a cooperative agreement is awarded which is responsible and accountable to NCI for the use of funds provided and for performance of the cooperative agreement-supported project. Each awardee will organize a consortium that will consist of multiple participating institutions, including Clinical Sites for patient accrual. PRINCIPAL INVESTIGATOR (PI) -- The single individual designated by the awardee institution who is responsible for the scientific and administrative operations of the Cooperative Group consortium (Group). NCI PROJECT SCIENTIST - The Diagnostic Imaging Research Branch Program Director, who will have scientific/programmatic involvement, and who will also coordinate NCI interactions and administer and provide guidance for the overall program within the NCI. He/she is available for duration of research conducted through this cooperative agreement. EXECUTIVE COMMITTEE - The committee chaired by the PI and responsible for main study oversight, including protocol development and progress monitoring. In addition to the Principal Investigator and the NCI Project Scientist, the Executive Committee will be composed at the minimum of the following voting members: Director of the Data and Statistics (Coordinating) Center, Chairperson of the Quality Assurance Committee and one clinical investigator from each Clinical Site. PI may select other voting members of the Executive Committee deemed necessary for successful completion of the study. DATA AND STATISTICS (COORDINATING CENTER) responsible for development of procedures for statistical data collection, management, analysis and onsite monitoring, including audits and audit reports. Director of the Center is an individual other than the Principal Investigator. QUALITY ASSURANCE (QA) COMMITTEE - The committee, selected by the PI from among the Group members, is responsible for the development of procedures for centralized supply and quality control of contrast agents, imaging devices and approaches required by the experimental protocol. Chairperson of the Quality Assurance Committee will be selected by the Principal Investigator. IMAGING SUBCOMMITTEE of the Protocol Review Committee of the Clinical Therapy Evaluation Program will review and approve the protocol and its proposed amendments to ensure that they are within the scope of peer review and for safety considerations before implementation. The Imaging Subcommittee will consist at the minimum of the clinical radiologist, medical oncologist and surgical oncologist who will select its Chair. Other members deemed necessary for review and approval of the protocol and its amendments may be appointed by the Chair of the Imaging Subcommittee. Terms and Conditions of Award A. Applicability. These special Terms and Conditions of Award are in addition to and not in lieu of otherwise applicable OMB administrative guidelines, HHS grant administration regulations in 45 CFR Parts 74 and 92, and other HHS, PHS and NIH grant administration policy statements. The administrative and funding instrument used for this program is a cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism) in which substantial NCI scientific and/or programmatic involvement with the awardee is anticipated during performance of the activity. Under the cooperative agreement, the NCI purpose is to support and/or stimulate the recipient's activity by involvement in and otherwise working jointly with the award recipient in a partner role, but it is not to assume direction, prime responsibility, or a dominant role in the activity. Consistent with this concept, the dominant role and prime responsibility for the activity reside with the awardee 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. The NCI shall be represented in the Group by an extramural Project Scientist selected from the Diagnostic Imaging Research Branch. This representative will be referred to as the NCI Project Scientist. B. Awardee Rights and Responsibilities The Awardee will have primary rights and responsibilities to define study objectives and approaches, and to plan, conduct, analyze and publish results, interpretations, and conclusions of their studies. The Awardee will have primary and lead responsibilities for the project as a whole, including research design and protocol development, participant recruitment and follow up, data collection, quality control, interim data and safety monitoring, final data analysis and interpretation, preparation of publications, with assistance from the NCI Project Scientist. The Awardee has primary responsibilities for: 1. Establishment of procedures for all participating institutions to comply with FDA regulations for studies involving investigational drugs (e.g., contrast agents) or devices (e.g., MRI-guided biopsy equipment) and to comply with the requirements of 45 CFR Part 46 for the protection of human subjects. 2. Establishment of the Executive Committee, chaired by the Principal Investigator, responsible for research design and protocol development, progress monitoring and project administrative oversight, including definition of objectives and approaches, planning, implementation, participant recruitment and follow-up, approval of procedures for data collection, analysis, interpretation, and publication of results, and approval of methods for instrumentation supply and quality assurance. The Executive Committee is responsible for ensuring accurate and timely assessment of the progress of each study, including establishment of procedures to ensure that data collection and management are: (l) adequate for quality control and analysis; (2) as simple as appropriate in order to encourage maximum participation of physicians and patients and to avoid unnecessary expense; and (3) sufficiently staffed across the participating institutions. The Principal Investigator will define the final composition of the Executive Committee, with assistance from the NCI Project Scientist who will serve as a voting member. In addition to the Principal Investigator and the NCI Project Scientist, the Executive Committee will be composed at the minimum of the following voting members: Director of the Data and Statistics (Coordinating) Center, Chairperson of the Quality Assurance Committee and one clinical investigator from each Clinical Site. PI may select other voting members of the Executive Committee deemed necessary for successful completion of the study. Principal Investigator of the Group functions as the scientific coordinator for the protocol and shall assume responsibility for administrative operations of the Group. A degree of flexibility in the clinical trial proposed in the initial stages of the MRI evaluation may be needed. The investigators will develop a clinical protocol and its modifications, if necessary, taking into account evolving scientific evidence related to the current state-of-the-art in breast MRI and its new approaches not previously mentioned in the application. Pilot studies may be performed during the initial period of this award before the phase II study protocol will be finalized. Under the leadership of the Principal Investigator and with assistance of the NCI staff, the Executive Committee will develop a clinical protocol (and its modifications, if necessary). The proposed protocol and all modifications will be submitted by the Principal Investigator of the Group to the NCI Project Scientist in compliance with the NCI protocol approval procedure described below (see section C, part 3c of these Terms and Conditions of Award). 3. Establishment and implementation of methods developed by the Data and Statistics (Coordinating) Center and approved by the Executive Committee for statistical data collection, management, analysis and monitoring, including on-site audits and audit reports. Audit reports should be submitted by the Director of the Data and Statistics (Coordinating) Center to the Principal Investigator who will be responsible for the submission of the audit reports to the NCI Project Scientist within 10 weeks of their completion. Director of the Data and Statistics (Coordinating) Center, selected by the Principal Investigator, will be an individual other than the Principal Investigator of the Group. In the multi-institutional Group, it is the responsibility of individual Clinical Sites to accrue patients and to ensure that data will be submitted in a timely way to the central Data and Statistics (Coordinating) Center. 4. Establishment and implementation of mechanisms developed by the Quality Assurance Committee and approved by the Executive Committee for coordinated supply of contrast agents and instrumentation required by the experimental protocol, development of methods and protocols for acquisition and review of images, preparation of pathologic specimens, plan for histopathologic correlation any other relevant correlative studies, and centralized standardization of instrumentation quality control, including technical requirements and performance standards for hardware and software instrumentation. Chairperson of the Quality Assurance Committee will be selected by the Principal Investigator from among the Group participants. 5. Submission of semiannual interim progress reports to the NCI Project Scientist including as a minimum, summary data on protocol performance and accrual. Such reports are in addition to the annual progress report submitted in the noncompeting continuation applications. 6. Cooperation in the reporting of the study findings. The NCI will have access to and may periodically review all data generated under an award. Where warranted by appropriate participation, plans for joint publication with NCI of pooled data and conclusions are to be developed by the Principal Investigator or Executive Committee, as applicable. NIH policies governing possible co-authorship of publications with NCI staff will apply in all cases. In general, to warrant co-authorship, NCI staff must have contributed to the following: (a) significant intellectual contribution to the concept or experiments being tested; (b) performance of significant portions of the research activity; and, (c) preparation of pertinent manuscripts. The awardee will retain custody of and the primary rights to the data developed under these awards, subject to Government rights to access consistent with current HHS, PHS, and NIH policies. C. NCI Staff Responsibilities The NCI Project Scientist will have substantial scientific programmatic involvement during conduct of this activity, through technical assistance, advice and coordination above and beyond normal program stewardship for grants, as described below. It is expected that the dominant role and prime responsibility for the activity will reside with the awardee for the project as a whole, although specific tasks and activities in carrying out the studies will be shared between the awardee and the NCI Project Scientist who will serve as the contact point for all facets of scientific interaction with the awardee. The NCI Project Scientist responsibilities will include: 1. Interacting with the Principal Investigator of the Group on a regular basis to monitor study progress, to participate in the Executive Committee meetings and related activities. The NCI Project Scientist will be a voting member of the Executive Committee and, if applicable, subcommittees. The NCI retains, as an option, periodic external review of progress. 2. Serving as a resource with respect to other ongoing NCI activities that may be relevant to the protocol to facilitate compatibility and avoid unnecessary duplication of effort. 3. Substantial involvement in the design and coordination of research activities for awardees as elaborated below: a. Providing advice in the management and technical performance of the investigations, coordinating clearances for investigational drugs (e.g. contrast agents) and devices (e.g. MRI-guided biopsy equipment) to ensure that the proposed study is in accord with FDA requirements for investigational agent and device trials. b. Assisting, through participation in the Executive Committee, in the design, development, and coordination of a common research or clinical protocol and statistical evaluations of data in the preparation of questionnaires and other data recording forms and in the publication of results. c. Submitting the experimental protocol and its revisions for review by the Imaging Subcommittee of the Protocol Review Committee of the Clinical Therapy Evaluation Program (see Special Requirements, under Definitions) that will review and approve the protocol and its amendments proposed by the Group to insure they are within the scope of peer review and for safety considerations before implementation, as required by Federal regulations. The decision of the Imaging Subcommittee will be communicated to the awardee by the NCI Project Scientist within 30 days of the Imaging Subcommittee meeting. The NCI Project Scientist will monitor protocol progress, and may request that a protocol study be closed to accrual for reasons including: (i) accrual rate insufficient to complete study in a timely fashion; (ii) accrual goals met early; (iii) poor protocol performance; (iv) patient safety and regulatory concerns; (v) study results that are conclusive before completion of full accrual; and, (vi) emergence of new information that diminishes the scientific importance of the original study question. The NCI will not permit further expenditures of NCI funds for a study after requesting closure (except for patients already on study). If disagreements develop over NCI recommended protocol closure for reasons other than patient safety or regulatory concerns NCI will establish an arbitration procedure to resolve differences between the awardee and the NCI as described below (see section E of these Terms and Conditions of Award). No expenditures of NCI funds will be allowed for protocols disapproved by NCI unless disapproval has been modified by arbitration panel. 7. Reviewing and providing advice regarding methods established by the Group for statistical data collection, management, analysis and monitoring, including audits, in accordance with the procedures approved by the Executive Committee. 8. Reviewing and providing advice regarding procedures established by the Group for coordinated supply and centralized quality control of contrast agents and instrumentation. D. Collaborative Responsibilities In addition to the interactions defined above, NCI staff and the Awardee shall share responsibility for the following activities: Executive Committee. An Executive Committee chaired by the Principal Investigator of the Group will be the main oversight body of the study. NCI Project Scientist will serve as a voting member of the Executive Committee. An initial meeting of the Executive Committee will be convened by the Principal Investigator early after the award in coordination with the NCI Project Scientist. In addition to the Principal Investigator and the NCI Project Scientist, as mentioned above, the Executive Committee will be composed at the minimum of the following voting members: Director of the Data and Statistics (Coordinating) Center, Chairperson of the Quality Assurance Committee and one clinical investigator from each Clinical Site. PI may select other voting members of the Executive Committee deemed necessary for successful completion of the study. The final structure and composition of the Executive Committee will be established at the first meeting by the Principal Investigator, with assistance from the NCI Project Scientist. A degree of flexibility in the clinical trial proposed in the initial stages of the MRI evaluation may be needed. The investigators will develop a clinical protocol and its modifications, if necessary, taking into account evolving scientific evidence and unanticipated developments in MRI contrast agents, technologies and methodologies. Pilot studies may be performed during the initial period of this award before the phase II study protocol will be finalized. With assistance of the NCI staff, the Executive Committee will develop a clinical protocol (and its modifications, if necessary), determine which correlative studies are appropriate and develop long term sequential planning, including prioritization of study goals. The Executive Committee will meet at least twice yearly under usual circumstances. Semiannual meetings of the Executive Committee will be convened by the Principal Investigator in coordination with the NCI Project Scientist. The Principal Investigator of the Group is responsible for coordinating the Executive Committee's activities, for preparing meeting agendas, and for scheduling and chairing meetings. It is suggested that applicants be advised to include plans for meetings in the budget requests. The Executive Committee, under the leadership of the Principal Investigator, will document progress in written semiannual reports to the NCI Project Scientist, and will provide supplementary reports to designated NCI staff upon request. E. Arbitration Any disagreement that may arise on scientific/programmatic matters (within the scope of the award), between the awardee and the NCI may be brought to arbitration. An arbitration panel will be composed of three members -- one selected by the awardee, a second member selected by the NCI, and the third member elected by the two prior selected members. This special arbitration procedures in no way affect the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations at 42 CFR Part 50, subpart D, and HHS regulations at 45 CFR Part 16. INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of the NIH that women and members of minority groups and their subpopulations must be included in all NIH supported biochemical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification is provided that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This new policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43) and supersedes and strengthens the previous policies (Concerning the Inclusion of Minorities in Study Populations, and Concerning the Inclusion of Women in Study Populations), which have been in effect since 1990. The new policy contains some provisions that are substantially different from the 1990 policies. All investigators proposing research involving human subjects should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research", which was reprinted in the Federal Register of March 28, 1994 (59 FR 14508-14513) to correct typesetting errors in the earlier publication, and reprinted in the NIH GUIDE FOR GRANTS AND CONTRACTS of March 18, 1994, Volume 23, Number 11. Investigators may also obtain copies of the policy from the program staff listed under Inquiries. Program staff may also provide additional relevant information concerning the policy. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. For this study, all research subjects will be women, although a particular emphasis will be placed on recruitment of women younger than 50 years of age and minority women with "radiodense breast tissue". LETTER OF INTENT Prospective applicants are asked to submit, by May 9, 1995, a letter of intent that includes a descriptive title of the proposed research, name, address and telephone number of the Principal Investigator, the identities of other key personnel and participating institutions, and the number and title of the RFA in response to which the application is being submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows NCI staff to estimate the potential review workload and to avoid conflict of interest in the review. The letter of intent is to be sent to Dr. Faina Shtern at the address listed under INQUIRIES. APPLICATION PROCEDURES Special Instructions for Preparation of Cooperative Agreement Applications General instructions are contained in the grant application form PHS 398 (rev. 9/91), which is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research and from the Office of Grants Information, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone 301-710-0267; and from the NIH program administrator listed under INQUIRIES. Additional Materials to Include in the Application Any special information that is required as a result of the use of the cooperative agreement mechanism should be provided, such as special meetings and budgetary requirements, special instructions for multi-center or multistudy projects, etc. Applicants must describe plans to accommodate stated program requests, criteria and staff involvement. It is critical that each applicant include specific plans for responding to these Terms and Conditions of Award. Plans must describe how the applicant will comply with the program staff involvement and how all the Awardee Responsibilities will be fulfilled. To promote the development of a collaborative program among the study participants, a number of issues need to be addressed by the Applicants as described below: 1. Applicants should describe their rationale for their choice of the experimental protocol. The potential for the adequate patient accrual necessary for the achievement of the proposed study goals (and understanding of how the estimated ideal number is arrived to) should be demonstrated. 2. Applicants should present a plan for personnel and facilities capable of performing and supporting the administrative functions of a cooperative group conducting imaging trials in cancer. Applicants must demonstrate the ability to organize, conduct, and monitor clinical trials in radiology. Applicants must describe a plan for qualified support personnel to ensure timely and accurate data retrieval and reporting. Applicants must describe procedures by which institutions participating in a consortium would perform their functions, including protocols for accomplishing the clinical work and patient accrual and administrative project management. The application should include the proposed protocol for correlation of breast MRI with conventional x-ray mammography and, if applicable, other technologies (e.g. US) with histopathologic findings. 3. The PI of the Group should demonstrate expertise in the design and coordination of clinical trials, capability to provide educational workshops and ongoing training for Group participants, capacity to develop and implement an administrative and management structure for the Group, including an Executive Committee, a Quality Assurance committee, and a Data and Statistics (Coordinating) Center and Clinical Sites. The PI will supervise the administrative and scientific aspects of the Group's function. 4. The Data and Statistics (Coordinating) Center Director and staff should demonstrate experience in the management of data from multicenter clinical trials and must have expertise in statistical data collection, management, analysis, monitoring and other related issues. 5. The Quality Assurance Committee Chairperson and staff should demonstrate experience in the development of review, evaluation and quality control procedures for contrast agents, imaging devices, imaging techniques, image interpretation and experimental approaches required by the protocol. 6. Individual Clinical Sites in a consortium should demonstrate commitment to participate in multi-institutional protocols, including their willingness to follow the common protocol, their ability to participate in the study and their documentation of the facilities and professional personnel available to conduct cooperative imaging trials. This includes assignment of appropriate specialists required by the experimental protocol including, but not limited to, radiologists, surgeons and pathologists, in order to ensure complete patient evaluation. Individual Clinical Sites in a consortium should demonstrate the availability of the state-of-the-art instrumentation in breast MRI, conventional x-ray mammography and other technologies required by the protocol. Each Clinical Site must have the instruments, facilities, and capabilities for the proposed experimental protocol. Clinical Sites must be able to interact effectively with the Executive Committee, Data and Statistics (Coordinating) Center and Quality Assurance Committee. Clinical Sites must be able to correlate mammographic x-ray imaging, breast MRI, and US data with pathologic findings. Each Clinical Site must have the capability for performing biopsies of small lesions detectable only by MRI. This may consist of (but not limited to) the placement of appropriate markers with MRI guidance for surgical biopsy, or direct MRI-guided needle biopsy. Separate budgets should be provided for the Executive Committee, Data and Statistics (Coordinating) Center, Quality Assurance Committee, with detailed justification of each item; a separate budget should be also prepared as a subcontract for each participating institution for which funds are requested, including applicable indirect costs (see NIH/DHHS Guidelines for Establishing and Operating Consortium Grants of January 1989). It is also suggested that applicants include plans for meetings in the budget requests. The RFA label available in the PHS 398 (rev. 9/91) application form must be affixed to the bottom of the face page of the application. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2a of the face page of the application form and the YES box must be marked. Submit a signed, typewritten original of the application, including the Checklist, and three signed, clear, and single-sided photocopies, in one package to: Division of Research Grants National Institutes of Health 6701 Rockledge Drive, Room 1040 MSC 7710 Bethesda, MD 20892-7710 Bethesda, MD 20817 (for courier/overnight mail service) At the time of submission, two additional copies of the application must also be sent to: Ms. Toby Friedberg Division of Extramural Activities National Cancer Institute Executive Plaza North, Room 636 6130 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-3428 Applications must be received by June 9, 1995. If an application is received after that date, it will be returned to the applicant without review. The Division of Research Grants (DRG) will not accept any application in response to this RFA that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. The DRG will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of a substantial revision of an application already reviewed, but such applications must include introduction addressing the previous critique. REVIEW CONSIDERATIONS General Considerations All applications will be judged on the basis of the scientific and technical merit of the proposed project and the documented ability of the investigators to meet the RESEARCH OBJECTIVES of this RFA. Other considerations, such as the importance and timeliness of the proposed study, access to patients, and multidisciplinary nature of the studies, will be part of the evaluation criteria. Review Method Upon receipt, applications will be reviewed for completeness by DRG and for responsiveness by the NCI. Incomplete applications will be returned to the applicant without further consideration. If NCI staff find that the application is not responsive to the RFA, it will be returned to the applicant without further consideration. Applications that are complete and responsive to this RFA will be evaluated for scientific and technical merit by an appropriate peer review group convened by the NCI, in accordance with the review criteria stated below. As part of the initial merit review, all applications will receive a written critique and may undergo a process in which only those applications deemed to have the highest scientific and technical merit will be discussed, assigned a priority score, and receive a second level review by the National Cancer Advisory Board. Review Criteria Applicants are encouraged to submit and describe their own ideas about how best to meet the goals of the cooperative study and their specific protocols, and are expected to address issues identified under APPLICATION PROCEDURES of this RFA. The review group will assess the scientific and technical merit of the proposed study and related factors, including: o Scientific, technical, or medical significance and originality of proposed research; o Appropriateness and adequacy of the experimental approach and methodology proposed to carry out the research; o Qualifications and research experience of the Principal Investigator and staff, particularly, but not exclusively in the area of the proposed research; o Availability of appropriate facilities, equipment, instrumentation (including but not limited to the state-of-the-art conventional x-ray mammography, dedicated breast MR imaging coils, MRI-guided biopsy capability), and other resources to ensure that each institution participating in the consortium is capable of performing innovative cooperative trials in breast cancer diagnosis; o Appropriateness of the proposed budget and project duration in relation to the proposed research; The initial review group will also examine the provisions for the protection of human subjects, the safety of research environment, and conformance with the NIH Guidelines for the Inclusion of Women and Minorities as Subjects in Clinical Research. o Adequacy of plans to include minorities and their subgroups as appropriate for the scientific goals of the research. Plans for recruitment and retention of subjects will also be evaluated. A particular emphasis should be placed on the accrual of women younger than 50 years of age and minority women with radiodense breast tissue. Specific attention will be given to: o The overall qualifications of applicant institutions in the collaborative group as stated under the Eligibility Requirements for participants (see ELIGIBILITY REQUIREMENTS); o A record or evidence of willingness of the professional and support personnel to work as a team with other Group members and with the NCI Project Scientist; o Evidence of the ability and /or the potential of the Principal Investigator to develop multicenter clinical trials of substantial scientific and technical merit in breast MRI; o Evidence of the previous experience of the key professional personnel of Clinical Sites with clinical breast MRI studies of sound scientific quality (at least 100 examinations) and their histopathologic correlation; o Evidence of the potential of Clinical Sites for reaching the adequate patient accrual necessary for the achievement of the proposed study goal in a reasonable period of time; o Evidence of the experience of the participants of the Data and Statistics (Coordinating) Center in biostatistical study design and data collection, management, analysis and monitoring of multicenter clinical trials; o Evidence of the experience of the key personnel of the Quality Assurance Committee in the development of procedures for quality control of contrast agents and imaging devices, including standardization of instrumentation performance and technical requirements. AWARD CRITERIA Applications recommended by the National Cancer Advisory Board will be considered for award based upon (a) scientific and technical merit as reflected by the priority score; (b) availability of funds; and (c) programmatic priorities. INQUIRIES Inquiries concerning this RFA are encouraged. The opportunity to clarify issues or questions from potential applicants is welcome. Direct inquiries regarding scientific and programmatic issues to: Dr. Faina Shtern Division of Cancer Treatment National Cancer Institute Executive Plaza North, Suite 800 Bethesda, MD 20892 Telephone: (301) 496-9531 FAX: (301) 480-5785 Email: shternf@rrp.nci.nih.gov Direct inquiries regarding fiscal matters to: Ms. Joy McCauley Grants Administration Branch National Cancer Institute Executive Plaza South, Suite 243 Bethesda, MD 20892 Telephone: (301) 496-7800, Ext. 253 FAX: (301) 496-8601 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance Number 93.395, Cancer Treatment Research. Awards are made under the authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR Part 52 and 45 CFR Part 74 and 45 CFR Part 92. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. The PHS strongly encourages all grant and contract recipients to provide a smoke-free workplace and promote the non-use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routing 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. .
Return to NIH Guide Main Index
Office of Extramural Research (OER) |
National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892 |
Department of Health and Human Services (HHS) |
||||||||
Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files. |