Full Text CA-95-007 COOPERATIVE NETWORK FOR EVALUATION OF MARKERS OF URINARY BLADDER CANCER NIH GUIDE, Volume 24, Number 7, February 24, 1995 RFA: CA-95-007 P.T. 34 Keywords: Urogenital System Cancer/Carcinogenesis Biochemical Markers Pathophysiology National Cancer Institute Letter of Intent Receipt Date: April 21, 1995 Application Receipt Date: June 23, 1995 PURPOSE The Cancer Diagnosis Branch of the Division of Cancer Biology, Diagnosis and Centers at the National Cancer Institute (NCI) invites applications for cooperative agreements from institutions capable of and interested in participating in the Cooperative Network for Evaluation of Markers of Urinary Bladder Cancer. The goal of the network is to evaluate biochemical, immunologic, genetic, and other quantifiable markers for diagnosis and prognosis of urinary bladder cancer. The network will perform collaborative studies requiring expertise in urology, pathology and/or basic cancer biology to evaluate appropriate quantifiable markers of urinary bladder cancer and to define relevant clinical applications. This network will develop and carry out new studies and continue the collaborative studies of bladder cancer markers currently being carried out by the existing Marker Network for Bladder Cancer. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS led national activity for setting priority areas. This RFA, Cooperative Network for Evaluation of Markers of Urinary Bladder 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 for-profit and non-profit organizations, public and private, located in the United States, Canada, or Mexico. These include universities, colleges, hospitals, laboratories, units of state and local governments, and eligible agencies of the Federal government among others. Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as Principal Investigators. MECHANISM OF SUPPORT The administrative and funding instrument to be used for this program will be a cooperative agreement (U01) (an assistance mechanism rather than an acquisition mechanism) in which substantial NCI scientific and/or programmatic involvement with the awardee is anticipated during the performance of the activity. Under this mechanism, the NCI purpose is to support and/or stimulate the recipient's activity by working jointly with the award recipients in a partnership, but not leadership role. Details of the responsibilities, relationships, and governance of the project are discussed later under the section "Terms and Conditions of Award." The NCI anticipates six awards at an average direct cost of about $150,000. However, since the nature and scope of the proposed research may vary, the requested budget should reflect the anticipated cost of the research. This RFA is a one-time solicitation. Generally future unsolicited competitive continuation applications will compete as research project applications with all other investigator initiated applications and be reviewed by the Division of Research Grants (DRG). However, if the NCI determines that there is a sufficient continuing program need, the NCI will invite recipients of awards under this RFA to submit competitive continuation cooperative agreement applications for review according to the procedures described under REVIEW CONSIDERATIONS. FUNDS AVAILABLE The NCI anticipates making up to six awards for project periods of four years. A total cost of $1,300,000 is expected to be set aside for funding these activities in the initial year. Although this project is provided for in the financial plans of the NCI, the award of cooperative agreements pursuant to this RFA is contingent on the availability of funds appropriated in fiscal year 1996. The earliest feasible start date for the initial awards will be April 1, 1996. RESEARCH OBJECTIVES Background There is a need to improve diagnostic accuracy, more adequately predict prognosis, and more effectively monitor response to therapy in bladder cancer. Advances in immunology, molecular biology and genetics have opened new possibilities for developing cell or tissue markers to detect cancer and to predict recurrence, invasion, and metastasis. These advances have led to new and more effective approaches to diagnosis and prediction. A number of potential markers exist and there is a need for organized efforts to effectively evaluate their utility. The development of additional quantitative cell or tissue markers will expand the repertoire of diagnostic and prognostic measurements available to the clinician. Different cell markers appear to correlate with particular biological behaviors of urinary bladder tumors. Separate markers may be useful for predicting recurrence, progression or metastasis in early stage disease (Ta, T1) or for detecting carcinoma in situ. Markers for prediction of treatment response may prove useful in selecting the most appropriate treatment. DNA ploidy studies of exfoliated tumor cells have demonstrated some utility in predicting tumor behavior. The addition of other quantitative markers will expand the range of diagnostic measurements and may add to the accuracy and range of diagnostic information available to the clinician. A variety of immunological, biochemical and genetic markers are currently being evaluated by the Marker Network for Bladder Cancer, which was funded in April 1992 and will end in March, 1996. While these activities are expected to continue, activities of the proposed network need not be confined to markers currently under study. Investigators are encouraged to propose promising markers and appropriate studies for their evaluation. Individual proposals by successful applicants will be evaluated by the Coordinating Committee, which will determine which should be pursued as network studies. Objectives and Scope The objective of this RFA is to invite applications for cooperative agreements to support a network of laboratories to evaluate promising diagnostic and prognostic markers of urinary bladder cancer. The existing network has already demonstrated the feasibility of an inter-institutional network for collaborative clinical studies of urinary bladder cancer markers. Important clinical questions include, but are not limited to: Are there markers that can predict recurrence in patients with superficial (Ta/T1) transitional cell carcinoma of the bladder? Can methods be developed to identify patients whose disease will progress from carcinoma in situ to invasive cancer? Are there ways to predict metastatic potential and or response to therapy in patients with invasive cancer? Can effective non-invasive techniques be developed to replace cystoscopy in monitoring tumor recurrence. Potential activities include, among others: (1) evaluation of additional genetic, biochemical and immunological markers of urinary bladder cancer; (2) development of techniques for quantitatively assaying those markers; and (3) development of tumor classification systems useful in patient management. The collaborative approach will optimize the research opportunities and build on the strengths of the participating institutions by facilitating sharing of clinical material and reagents. This will expand the available patient resources, improve the evaluation of potentially useful markers and allow comparison of their utility in different clinical and laboratory settings. SPECIAL REQUIREMENTS The instructions for the "Specific Aims" section of the application are modified as follows: Specific aims must be listed in priority order based on the best judgement of the applicants. A paragraph describing the rationale for the order selected must also be provided. Specific issues related to cooperative agreements must be addressed in the application as follows: Travel funds for Coordinating Committee meetings are to be set aside as a budget line item in each project budget. Applicants should include travel expenses to attend three Coordinating Committee meetings in the first year and two in each future year. For planning purposes it should be assumed that meetings will alternate between the East and the West coast. Applicants must include in the Research Plans section of the application specific plans for responding to the "Terms and Conditions of Award" section. Applicants should also state their willingness to collaborate with the other awardees and to participate as a member of the Coordinating Committee and be bound by its decisions. Applicants should also describe how they will comply with the involvement of the NCI representative and how they will fulfill the responsibilities of awardees to work together cooperatively. Applications should propose collaborative network studies as well as proposing individual laboratory studies to provide a basis for future collaborative network activities. Applicants should detail their access to patients and to clinical and outcome data since clinical studies are a critical part of network activities. It is also critical that each application completely describe the composition of patient populations in terms of gender and minority status as discussed in detail below. For competing renewal applications, a complete discussion of progress and a description of past collaborative efforts should be included in the progress report section of the application. The following terms and conditions will be incorporated into the award statement and provided to the institutional official at the time of award. Terms and Conditions of Award These special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS Grant Administration Regulations at 45 CFR Parts 74 and 92 and other HHS, PHS, and NIH Grant Administration policy statements. The administrative and funding instrument to be used for this program will be a cooperative agreement (U01) an assistance mechanism (rather than an acquisition mechanism) in which substantial NCI scientific and/or programmatic involvement with the awardee is anticipated during the performance of the activity. Under this mechanism, the NCI purpose is to support and/or stimulate the recipients activity by working jointly with the award recipients in a partnership, but not leadership role. The Cooperative Agreement mechanism will require cooperation between an NCI representative and the principal investigators of the individual projects in order to assure smooth interactions among the cooperating institutions. The NCI representative will assist in coordinating the activities of the research groups, and in facilitating exchange of information. Awardees will retain custody and primary rights to their data developed under these awards, subject to government, e.g., NCI, NIH or PHS, rights of access, consistent with current DHHS, PHS and NIH policies. 1. Awardee Rights and Responsibilities Awardees are responsible for developing individual research projects to facilitate the activities of the network and participating in the development of clinical protocols for network studies. All collaborative studies conducted under this RFA by members of the network must be approved by the Coordinating Committee. Awardees will be required to accept and implement the common protocols and procedures approved by the Coordinating Committee. Responsibility for specific aspects of collaborative network studies (e.g., statistical design and analysis) will be determined by the Committee at the time each study is planned. Two members of each research group are required to attend meetings of the Committee (as detailed below), to help formulate the Committee's policies and protocols (which will be submitted to the NCI representative for approval), and to implement those policies. Awardees are required to have access to appropriate tumor tissue and normal tissue. They are required to submit progress reports at each meeting of the Coordinating Committee. 2. NCI Staff Responsibilities The Program Director for Bladder Cancer of the Cancer Diagnosis Branch (hereafter referred to as the NCI representative) will coordinate and facilitate the programs supported by these Cooperative Agreements, will attend and participate in all meetings as a member of the Coordinating Committee, and will provide liaison between the Coordinating Committee, the Protocol Review Committee of the Cancer Therapy Evaluation Program, and participating research groups. The NCI representative will assist the Coordinating Committee in developing operating policies, quality control procedures and consistent policies for dealing with recurring situations that require coordinated action. The NCI representative may review the operations of individual laboratories for compliance with protocols and other operating policies developed by the Coordinating Committee. The NCI representative may recommend withholding of support, suspension or termination of an award for lack of progress or failure to adhere to policies established by the Coordinating Committee. To assure consistency and quality, the Chief, Cancer Diagnosis Branch, DCBDC, NCI must concur in operating policies and clinical protocols prior to their implementation. 3. Collaborative Responsibilities The NCI representative and the participating research groups will be responsible for forming a Coordinating Committee as defined below. Operating policies developed by the Coordinating Committee will be submitted by the NCI representative to the Branch Chief, Cancer Diagnosis Branch, NCI for concurrence prior to implementation. The NCI will facilitate the review of operating policies and clinical research protocols. Results of the review will be discussed with the Coordinating Committee and an arbitration system, as detailed below will be available to resolve disagreements between the NCI representative and the other members of the Coordinating Committee. The Coordinating Committee will review the plans proposed in their applications by the individual research groups to insure that they are compatible with the overall goals of the RFA. Members of the Coordinating Committee will be responsible for redefining research objectives and defining strategies for network studies to optimize progress and efficient use of patient and tissue resources. The Coordinating Committee will also be responsible for coordinating activities such as plans for statistical design and analyses, developing forms, distributing reagents and biological samples, data collection and data analysis, monitoring the progress of the network and maintaining quality assurance. The Coordinating Committee will consist of the NCI representative and two members from each cooperating institution, one of whom is the principal investigator. The NCI representative will be appointed by the Chief of the Cancer Diagnosis Branch, Division of Cancer Biology, Diagnosis and Centers. The Coordinating Committee will be responsible for electing a chairperson (who may not be the NCI representative). The Chairperson of the Coordinating Committee will be responsible for coordinating the Committee activities, for preparing meeting agendas, and for scheduling and chairing meetings. The NCI representative will attend and participate in all meetings of the Coordinating Committee and should be informed of major inter-group interactions. The Coordinating Committee members will evaluate progress reports from each participating research group; each group is responsible for timely preparation and presentation of its report. The Coordinating Committee will meet initially to map strategies and set up operating procedures. The Coordinating Committee will meet at least twice a year thereafter (for a total of three meetings in the first year and two per year thereafter). Meetings may be held at any of the participating institutions or at another convenient location. These meetings are aimed at coordinating the activities of the participating laboratories, establishing new policies and priorities, and reviewing progress. The NCI representative will participate in the discussions at these meetings. 4. Arbitration Any disagreement that may arise on scientific/programmatic matters (within the scope of the award), between award recipients and the NCI may be brought to arbitration. An arbitration panel will be composed of three members -- one selected by the Coordinating Committee (with the NCI member not voting), one selected by the NCI, and the third chosen by the two previously selected members. This special arbitration procedure in no way affects the awardee's right to appeal an adverse action that is otherwise appealable in accordance with 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 biomedical and behavioral research 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 Women in Study Populations, and Concerning the Inclusion of Minorities in Study Populations) which have been in effect since 1990. The new policy contains some new provisions that are substantially different from the 1990 policies. All investigators proposing research involving human subjects should read the "NIH Guide for Inclusion of Women and Minorities in Clinical Research", which have been published in the Federal Register of March 28, 1994 (FR 59 14508-14513) and reprinted the NIH Guide for Grants and Contracts, Volume 23, Number 11, March 18, 1994. Investigators may obtain copies from the sources or from the program staff or contact person listed below. Program staff may also provide additional relevant information concerning the policy. LETTER OF INTENT Prospective applicants are asked to submit, by April 21, 1995, a letter of intent that includes a descriptive title of the proposed project, the name, address and telephone number of the principal investigator, the names of other key personnel, the participating institutions, and the number and title of the RFA in response to which the application may be submitted. Although a letter of intent is not required, is not binding and does not enter into the review of subsequent applications, the information allows NCI staff to estimate the potential workload and to avoid conflict of interest in the review. The letter of intent is to be sent to Dr. Roger L. Aamodt at the address listed under INQUIRIES. APPLICATION PROCEDURES The grant application form PHS 398 (rev. 9/91) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research; from the Office of Grants Information, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone 301/710-0267; and from the NCI Program Director listed under INQUIRIES. The RFA label available in the PHS 398 application form must be affixed at 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 photocopies, in one package to: Division of Research Grants National Institutes of Health 6701 Rockledge Drive - MSC 7710 Bethesda, MD 20892-7710 Bethesda, MD 20817 (for express mail) At the time of submission two additional copies of the application must also be sent to: Referral Officer Division of Extramural Activities National Cancer Institute Executive Plaza North, Room 636A 6130 Executive Boulevard Rockville, MD 20892 Rockville, MD 20859 (for express mail) Applications must be received by June 23, 1995. If an application is received after this 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 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 an introduction addressing the previous critique. REVIEW CONSIDERATIONS General Considerations All applications will be judged on the basis of the scientific merit of the proposed project and the documented ability of the investigators to meet the RESEARCH OBJECTIVES of the RFA. Although the technical merit of the proposed activities is important, it will not be the sole criterion for evaluation of the application. Other considerations such as the importance and timeliness of the proposed studies, access to patients, and appropriateness of proposed collaborations are also part of the evaluation criteria. Factors considered to be important for review include demonstrated expertise in urology, pathology and/or basic cancer biology applied to the diagnosis and treatment of urinary bladder cancer; expertise and an active research program in cell marker studies; availability of an appropriate population of patients for study; good interaction among collaborating researchers; demonstration of adequate facilities; and willingness to interact within the terms of a Cooperative Agreement as outlined in this document. Review Method Upon receipt, applications will be reviewed for completeness by the Division of Research Grants (DRG) and for responsiveness by the NCI. Incomplete and/or non-responsive applications will be returned to the applicant without further consideration. Applications that are complete and responsive 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 merit will be discussed, assigned a priority score, and receive a second level of review by the National Cancer Advisory Board. Review Criteria Applicants are encouraged to submit and describe their own ideas about how to best meet the goals of the cooperative network and to propose their own protocols, and are expected to address the issues identified under SPECIAL REQUIREMENTS. The Review group will assess the scientific merit of the applications and related factors, including: 1. Feasibility and relevance of the proposed project to the overall goals and objectives of the RFA. 2. Demonstration of availability of and access to appropriate patients (including representative numbers of women and minorities or sufficient justification for their exclusion), tissue and appropriate patient data. 3. Proposed collaborations among urologists, pathologists, basic cancer biologists and other key personnel. 4. Qualifications, experience and proposed responsibilities of the principal investigators and of key support personnel. 5. Facilities and resources, and their availability for this project. 6. Plans for effective interaction and coordination among cooperating projects and with the NCI, including a proposed timetable. 7. Plans to protect the rights of human subjects. 8. For competing continuation applications, the reviewers will consider, in addition to the above criteria, the degree of active collaboration with the other members of the existing Network, participation in the development of proposed future studies and contributions to ongoing studies of the existing Network. This criterion must not be applied to new applicants. The review group will recommend an appropriate budget and period of support for each approved application. INQUIRIES Inquiries are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Inquiries regarding programmatic issues, including the activities of the currently funded marker network or inquiries about whether or not specific proposed research would be responsive may be directed to: Roger L. Aamodt, Ph.D. Division of Cancer Biology, Diagnosis, and Centers National Cancer Institute Executive Plaza North, Room 513 6130 Executive Boulevard Rockville, MD 20892-9904 Rockville, MD 20852 (for express mail) Telephone: (301)-496-7147 FAX: (301) 402-1037 Email: ra32u@nih.gov Direct inquiries regarding fiscal matters to: Ms. Kathleen Shino Grants Administration Branch National Cancer Institute Executive Plaza South, Room 243 6120 Executive Boulevard Rockville, MD 20892 Rockville, MD 20852 (for express mail) Telephone: (301) 496-7800 FAX: (301) 496-8601 Email: shinok@nihncigab.gov AUTHORITY AND REGULATIONS This program is described in the catalog of Federal Domestic Assistance No 93.394, Cancer Detection and Diagnosis Research. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410 as amended: 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR Part 52 and 45 CFR Part 74. 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 recipients to provide a smoke-free workplace and promote the non-use of all tobacco products. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people. .
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