NIH GUIDE ONLINE Vol. 18, No. 38, October 27, 1989 FULL TEXT OF RFAs FOR ONLINE ACCESS REQUEST FOR APPLICATIONS FOR COOPERATIVE AGREEMENT: RFA 90-CA-01 NATIONAL CANCER INSTITUTE COOPERATIVE HUMAN TISSUE NETWORK P.T. 34, FF, II; K.W. 0780000, 0780020, 0715035 National Cancer Institute Application Receipt Date: April 25, 1990 Letter of Intent Receipt date: January 12, 1990 INTRODUCTION: The Diagnosis Research Program of the Division of Cancer Biology and Diagnosis at the National Cancer Institute (NCI) invites applications for Cooperative Agreements from institutions capable of and interested in participating in The Cooperative Human Tissue Network. The purpose of this established network is to collect and distribute human tumor tissue and normal tissue to stimulate research. The Network was developed in response to a growing need by researchers for improved access to human tumor tissue. Basic and developmental studies in many areas of cancer research, including molecular biology, immunology and genetics, have been encouraged by improved access to tissue. Hundreds of investigators have taken advantage of the existence of the Network and thousands of tissue specimens have been distributed since the inception of the Network in January 1987. Awards will be made as cooperative agreements which create an assistance relationship with substantial involvement of NCI staff during the performance of the project, as outlined in this request for applications (RFA). This mechanism is used when the NCI wishes to stimulate investigator interest and proposes to advise or assist in an important and opportune area of research. The NCI anticipates making four or five awards for project periods of five years. Although this project is provided for in the financial plans of the NCI, the award of cooperative agreements pursuant to the RFA is contingent on the availability of funds appropriated in fiscal year 1991. CONTENTS A. Background Information B. Research Goals and Scope C. Mechanism of Support - Cooperative Agreement D. Terms of Award 1. Program Staff Involvement 2. Responsibilities of Awardees a. Organization and Role of the Coordinating Committee 3. Eligibility Requirements 4. Arbitration procedures E. Eligibility Requirements F. Special Instructions for Preparation of Cooperative Agreement Applications G. Review Procedures and Criteria H. Application I. Letter of Intent J. Inquiries A. BACKGROUND: Advances in molecular biology and genetics have opened new possibilities for understanding basic mechanisms in cancer development, invasion and metastasis. This understanding has led to new and more effective approaches to improve diagnostic accuracy, to make prognostic and therapeutic decisions, to more effectively monitor response to therapy, to detect cancer at earlier stages and to identify high-risk populations. Since animal models are not always appropriate for this type of research, demand for human tissue has increased greatly. The Cancer Diagnosis Branch of the Division of Cancer Biology and Diagnosis of the NCI became aware of the need for tissue by the scientific community. Recommendations of an ad hoc working group provided the basis for development of the Cooperative Human Tissue Network (CHTN). Careful attention to its handling and to the quality of tissue diagnosis is required for human tissue to have value for research. The CHTN was established January 1987 in response to an NCI request for applications (RFA). The original concept for the CHTN called for the development of a cooperative network of tissue procurement laboratories working closely with the NCI to provide tumor and normal tissue to investigators in the major biomedical research centers throughout the United States. Since its creation, the CHTN has become a vital part of the resources used by the cancer research community. The CHTN has experienced rapid growth and has provided thousands of specimens to hundreds of researchers. B. RESEARCH GOALS AND SCOPE The objective of this RFA is to continue support for a network of laboratories capable of providing improved access to adequately prepared and well documented human tumor and normal tissue. An important aspect of this project is the continuation and expansion of a model distribution network to stimulate efforts in this area. The existing Network has already demonstrated the feasibility of the network approach and the continuing need of researchers for access to human materials. Systems have been developed that allow efficient communication among laboratories regarding tissue requests and availability. The Network is not a tissue bank, but rather responds to investigator requests to meet existing tissue requirements on a current basis. Applicants may plan for limited storage of rare tumors that would otherwise not be available. Special consideration will be given to ensuring access to and distribution of pediatric tumor specimens throughout the United States. The investigators in the Network will be responsible for future planning and direction of the program, building on previous efforts. NCI staff will assist in setting priorities and in evaluating progress to ensure that the Network conforms to the objectives and conditions of the award. It is anticipated that each of the laboratories funded under this program will propose specific procedures for collecting and processing tissue and will have established the organizational structure required for its operation. The Coordinating Committee oversees the operation of the Network and resolves problems affecting the Network, while the NCI representative provides advice and functions as liaison between the participating laboratories during the intervals between meetings of the Coordinating Committee. C. MECHANISM OF SUPPORT - COOPERATIVE AGREEMENT Support of this program will be through the Cooperative Agreement, an assistance mechanism in which substantial NCI programmatic involvement with the recipients is anticipated during performance of the planned activity, as outlined in this RFA. Applicants will be responsible for the planning, direction and execution of the proposed project. Except as otherwise stated in the RFA, awards will be administered under PHS grants policy as stated in the Public Health Service Grants Policy Statement, DHHS Publication No. (OASH)) 82-50,000, revised January 1987. This RFA is a one-time solicitation. Generally future unsolicited competing 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, should the NCI determine that there is a sufficient continuing program need, the NCI will invite recipients of awards under this RFA to submit competing continuation cooperative agreement applications for review according to the procedures described in Section G. NCI anticipates making 4 to 5 awards for project periods of up to 5 years. Funding in response to this RFA is dependent on the receipt of a sufficient number of applications of high scientific merit. The earliest feasible start date for the initial awards will be 12/1/90. Although this program 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 for fiscal year 1991. The purpose of the proposed awards is to enhance and expand the availability to the research community of human tissue. The cooperative agreement funding mechanism was selected because substantial NCI programmatic involvement is required to assist in facilitating the activities of several laboratories working toward a common goal. D. TERMS OF AWARD The Cooperative Agreements 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 by coordinating the activities of the research groups, and by facilitating exchange of information. 1. Organization and Role of the Coordinating Committee The NCI and the participating research groups will be responsible for forming a Coordinating Committee as defined below. Operating policies will be developed by the Coordinating Committee and submitted to the NCI representative for concurrence prior to implementation. NCI will facilitate the review of operating policies. Results of the NCI review will be discussed with the Coordinating Committee and an arbitration system, as detailed below, will be available to resolve disagreements between investigators and NCI staff. Under the cooperative agreement mechanism, awardees are responsible for planning and carrying out all aspects of the project and for publishing results as appropriate. The Coordinating Committee will review the operating procedures proposed by the individual research groups to insure that they are compatible with the overall goals of the RFA; will establish publication guidelines; will develop uniform procedures for tissue acquisition, processing, distribution and storage; will develop uniform methods of histopathological diagnosis, and will assure appropriate control of tissue quality. The Coordinating Committee will consist of 2 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 and Diagnosis. The Coordinating Committee will be responsible for electing a chairperson (who may not be the NCI representative). This can be a rotating position. 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 will prepare an annual progress report which will include individual reports from each participating research group; each group is responsible for timely preparation of its report. The Coordinating Committee will meet initially to plan for integration of new cooperating institutions and phaseout, if necessary, of previous institutions and will review basic operating procedures and policies. The Coordinating Committee will meet at least twice a year thereafter. These meetings are aimed at coordinating the activities of the participating laboratories, establishing new policies and priorities, and reviewing progress. The NCI representative shall participate in the discussions at these meetings. Travel funds for Coordinating Committee meetings are to be set aside as a budget line item in each project budget. 2. ROLE OF NCI REPRESENTATIVE The NCI representative will coordinate and facilitate the programs supported by these Cooperative Agreements, will attend and participate in all meetings of the Coordinating Committee, and will provide liaison between the Coordinating Committee 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. To assure consistency and quality, NCI must concur in operating policies and procedures prior to their implementation. The NCI Representative may review the operations of individual laboratories for compliance with quality control standards and with 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. 3. RESPONSIBILITIES OF AWARDEES The principal investigator (PI) of a Cooperative Human Tissue Network laboratory should be an experienced surgical pathologist with demonstrated research experience in an area related to cancer. The PI should also be actively involved in the operation of a pathology laboratory with demonstrated access to a wide range of human cancer tissues. Two members of each research group are required to attend meetings of the Committee (as detailed above), to help formulate the Committee's policies (which will be submitted to the NCI 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. Inclusion of women and minorities are encouraged. If they are excluded, reasons for this exclusion must be included in the application. 4. ARBITRATION PROCEDURES An arbitration panel of external consultants will be created as needed to resolve any irreconcilable differences of opinion between the NCI and the Coordinating Committee with respect to implementation of a proposed operating policy. The panel will include one member selected by the Coordinating Committee, one member selected by the NCI, and a third member chosen by the other two members of the arbitration panel. The NCI arbitration process for the Cooperative Agreement in no way affects the rights of awardees to appeal selected postaward administrative decisions in accordance with PHS regulations at 42 CFR part 50, subpart D and HHS regulations at 45 CFR part 16. E. ELIGIBILITY REQUIREMENTS Eligibility requirements include those listed under "Responsibilities of Awardees" in Section D.3. In addition, applicant organizations should be located in the United States. Non-profit organizations and institutions, for-profit organizations and government agencies are eligible to apply. F. SPECIAL INSTRUCTIONS FOR PREPARATION OF COOPERATIVE AGREEMENT APPLICATIONS General instructions for the preparation of the Cooperative Agreement application are contained in the Grant Application Form PHS 398 (revised 10/88). Because the Terms of Award in Section D above will be included in all awards issued as a result of the RFA, it is critical that each applicant include specific plans for responding to these terms. Plans should document that the PI is a surgical pathologist and describe the applicant's approaches to tissue collection, preparation and distribution; histopathologic diagnosis; and coordination of data collection and analysis. They should describe how they will comply with NCI Program Staff involvement and how they will fulfill their responsibilities in the Cooperative Agreement. Detailed individual plans should be proposed in order to provide the Coordinating Committee with a basis for selecting the final operating procedures. For competing continuation applications, a complete description of past cooperative efforts is also required as part of the progress report. G. REVIEW PROCEDURES AND CRITERIA REVIEW PROCEDURES Upon receipt, applications will be reviewed initially by the Division of Research Grants for completeness. Incomplete applications will be returned to the applicant without further consideration. Evaluation for responsiveness to the program requirements and criteria stated in the RFA will be performed by NCI program. Applications judged to be nonresponsive to this RFA will be returned but may be submitted as regular investigator-initiated research grant applications at the next grant application receipt date. If the number of applications is large compared to the number of awards to be made, the NCI may conduct a preliminary scientific peer review to eliminate those which clearly are not competitive for award. The NCI will remove from competition those applications judged to be noncompetitive and notify the applicant and institutional business official. Those applications judged to be both competitive and responsive will be further evaluated according to the review criteria stated below for scientific and technical merit by an appropriate peer review group convened by the Division of Extramural Activities, NCI. The second level of review by the National Cancer Advisory Board considers the special needs of the Institute and the priorities of the National Cancer Program. REVIEW CRITERIA Factors considered to be important for review include demonstrated expertise in pathology and tissue preparation techniques; availability of a variety of cancer and normal tissues; good interaction among collaborating institutions and clinicians; adequate facilities; and willingness to interact within the terms of a Cooperative Agreement as outlined in this document. Reviewers will be asked to review the grant applications by considering the following criteria: 1) Appropriateness and relevance of the proposed project to the overall goals and objectives of the RFA. 2) Qualifications, experience and proposed responsibilities of the principal investigators and key support personnel. 3) Scientific merit and organizational plans for implementing the proposed program. 4) Demonstration of availability of and access to appropriate tissue from a wide variety of cancer sites and related control tissue and to appropriate clinical data. 5) Proposed collaborations with surgeons and other key personnel within the applicant and collaborating institutions. 6) Facilities and resources, and their availability for this project. 7) Plans for effective interaction and coordination among cooperating projects and with the NCI. 8) Plans to protect the rights of human subjects. The review group will recommend an appropriate budget and period of support for each application. H. APPLICATION Complete applications are due no later than April 25, 1990, and must address all requirements in the RFA. Applications received after this date will not be accepted. Also, the Division of Research Grants will not accept any application in response to this announcement that is the same as one currently being considered by any other review group or NIH awarding unit. Applications should be as concise as possible. The regular research grant application form PHS 398 (Revised 10/88) must be used in applying for these grants. These forms are available at most institutional business offices or from: Office of Grants Inquiries Division of Research Grants National Institutes of Health Room 449, Westwood Building 5333 Westbard Avenue Bethesda, MD 20892 or from the NCI Program Director named below. The RFA label available in the 10/88 revision of Application Form 398 must be affixed to the bottom of the face page. Failure to use this label could result in delayed processing of your application such that it may not reach the review committee in time for review. In addition, the RFA number and title, "NCI COOPERATIVE HUMAN TISSUE NETWORK, 90-CA-01," should be typed on line 2 of the face page of the application form. You should submit a signed typewritten original of the application, including the checklist, and four signed exact photocopies, in one package to: Division of Research Grants National Institutes of Health Room 240, Westwood Building Bethesda, Maryland 20892-4500** The photocopies must be clear and single sided. In addition, two copies should also be sent to: Referral Officer Division of Extramural Activities, DEA, NCI Room 848 Westwood Building 5333 Westbard Avenue Bethesda, MD 20892 I. LETTER OF INTENT Prospective applicants are asked to submit, by January 12, 1990, a letter of intent that includes a descriptive title of the proposed project, the name and address of the principal investigator, the names of other key personnel, the collaborating institutions, and the number and title of the RFA in response to which the application is being submitted. Although a letter of intent is not required, is not binding and does not enter into the review of subsequent applications, the NCI would like to emphasize the benefits to the applicant of having the principal investigator submit a letter of intent. The letter of intent allows NCI staff to estimate the potential review workload and to avoid possible conflict of interest in the review. J. INQUIRIES Written or telephone inquiries concerning the objectives and scope of the RFA, or inquiries about whether or not specific vproposed research would be responsive, are encouraged and should be directed to Dr. Roger L. Aamodt at the address shown below. The program director welcomes the opportunity to clarify any issues or questions from potential applicants. The letter of intent and inquiries should be addressed to: Roger L. Aamodt Ph.D. Program Director for Pathology and Cytology Diagnosis Program Division of Cancer Biology and Diagnosis National Cancer Institute Room 638, Executive Plaza South 6120 Executive Boulevard Rockville, MD 20892 Tel. No. (301)-496-7147 This program is described in the catalog of Federal Domestic Assistance no 13.394, Cancer Detection and Diagnosis Research. Awards are under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410 as amended: 42 USC 241) and administered under PHS grant policies and Federal Regulations 42 CFR Part 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review.