Full Text PAR-95-063 DCT CLINICAL TRIALS COOPERATIVE GROUPS NIH GUIDE, Volume 24, Number 19, May 26, 1995 PA NUMBER: PA-95-063 P.T. 34 Keywords: Cancer/Carcinogenesis Clinical Trial National Cancer Institute Application Receipt Dates: June 1, October 1, and February 1 PURPOSE The National Cancer Institute (NCI) is reannouncing its willingness to accept applications from institutions interested in conducting multi-institutional clinical trials in a Cooperative Group setting. Awards will continue to be made using the cooperative agreement mechanism (U10). Potential applicants are encouraged to contact the Cancer Therapy Evaluation Program staff to discuss and/or clarify any issues or questions regarding this announcement. The "CLINICAL TRIALS COOPERATIVE GROUP PROGRAM GUIDELINES" and the Cooperative Group Terms and Conditions of Award are available from the NCI Program Director upon request (see INQUIRIES). 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 PA, DCT Clinical Trials Cooperative Groups, 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 for-profit and non-profit organizations (including consortia of institutions), 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. MECHANISM OF SUPPORT The administrative and funding instrument used for this program is a cooperative agreement (U10), an assistance mechanism (rather than an acquisition mechanism) in which substantial NIH scientific and/or programmatic involvement with the awardee is anticipated during performance of the activity. Under the cooperative agreement, the NIH purpose is to support and/or stimulate the recipient's activity by involvement in and otherwise working jointly with the award recipient in a partner role, but it is not to assume direction, prime responsibility, or a dominant role in the activity. The "Terms and Conditions of Award," which detail the responsibilities, relationships, and governance of the studies to be funded under these cooperative agreement(s) are available from the program staff listed under INQUIRIES. Participation by NCI through the Associate Director for CTEP and selected designees provides assistance in the nature of information on NCI priorities and ongoing efforts elsewhere within the scientific community, as well as oversight, through the protocol review process and the Clinical Trials Monitoring Branch and Regulatory Affairs Branch, of methodology, feasibility, and adherence to regulatory requirements. Any subsequent updates to the terms and conditions of award will apply to any awards made under this program announcement. Because the nature and scope of the research proposed in response to this program announcement may vary, it is anticipated that the size of awards will vary also. RESEARCH OBJECTIVES Background The NCI's Clinical Trials Cooperative Groups (henceforth termed, "the Groups") were conceived in 1955 when Congress appropriated funds to the National Cancer Institute to establish the Chemotherapy National Service Center. By 1958, seventeen Groups were organized that operated under research grants from NCI; their main thrust was the testing of new anticancer agents from the NCI drug development program. Over the intervening years the Group Program has evolved into one that places major emphasis on definitive studies of combined modality approaches to the treatment of cancer. In 1980-81, the mechanism of support for the Clinical Trials Cooperative Group Program was converted from the grant to the cooperative agreement. The purpose of this change was to define the involvement of NCI program staff in the coordination of Group activities. There are currently nine NCI-funded Groups; approximately 20,000 new patients are accrued into their treatment studies each year, and many times that number are in follow-up. Thousands of individual investigators participate in Cooperative Group protocols. Currently, over $75 million is awarded annually by the NCI in support of Group research. The Groups consist of researchers at institutions affiliated with the Groups, who jointly develop and conduct cancer treatment clinical trials in multi-institutional settings. They are a major component of the extramural research effort of the Division of Cancer Treatment. Each Group is supported to continually generate new trials compatible with its particular areas of interest and expertise, as well as with national priorities for cancer treatment research. Unlike most other major NIH cooperative clinical trials efforts, Group structure and funding are not usually linked to any specific clinical trial(s). This mechanism thus has the potential for considerable flexibility in resource allocation, and for the rapid testing of promising new cancer therapies in large patient populations, since the apparatus for conducting such trials is constantly in place. The Groups have been instrumental in the development of new standards of cancer patient management and in the development of sophisticated clinical investigation techniques. The essential feature of the Clinical Trials Cooperative Group Program is the support of organizations that continually generate and conduct new clinical trials consistent with national priorities for cancer treatment research. Emphasis is placed on definitive, randomized Phase III studies and the developmental efforts preliminary to them. While a wide variety of investigational efforts are therefore appropriate, this Program specifically does not overlap with or replace funding mechanisms for more narrowly focused, Research Project Grant activities (e.g., R01, P01, U01, U19). The Cooperative Groups are heterogeneous in their research objectives and their structures. These Groups presently are of four major types: (1) Groups that are specifically disease oriented (e.g., gynecologic oncology); (2) Groups that are designed to deal primarily with high technology, single modality studies (e.g., radiotherapy); (3) Groups in which the investigators have a particular expertise (e.g., pediatricians); and (4) multimodality Groups. The common thread, however, is the development and conduct of large- scale trials in a multi- institutional setting. The goals of the Groups are: 1. IMPROVE THERAPY: Therapeutic research aimed at improving the survival and quality of life for persons with cancer is of highest priority. 2. ADJUNCT STUDIES: The database of patient information accumulated in the course of treatment research, including the possibilities for large-scale collection of tissue samples with subsequent correlation of biologic features with patient outcome, provide the Groups with unique opportunities to address scientific questions about genetics, etiology, epidemiology, pathology and other cancer-related topics. Such ancillary investigations can add considerable strength to a Group's total scientific program, and are encouraged. While certain studies may be eligible for inclusion in a Group application for financial support, particularly when the laboratory efforts are integral to the clinical trials proposed, a variety of other funding mechanisms - including investigator-initiated grants (R01s, R03s, P01s) and cooperative agreements for discrete projects (U01s, U19s) - may also be appropriate. 3. CANCER CONTROL: Groups supported by NCI's Division of Cancer Treatment may serve as research bases for treatment and cancer control research performed by Community Clinical Oncology Program (CCOP) cooperative agreement awardees supported by the NCI's Division of Cancer Prevention and Control. While this activity, when present, should be an integrated component of the Group's total research program, peer-review of the CCOP research program including cancer control research for the purposes of NCI financial support will be advisory to the Division of Cancer Prevention and Control, and generally will be conducted separately from peer review advisory to the Division of Cancer Treatment. 4. CLINICAL TRIALS METHODOLOGY: The Groups provide a unique framework for research in clinical trials methodology. While CTEP encourages development of and experimentation with new study designs within the Group framework, purely statistical research is appropriately funded through other mechanisms. SPECIAL REQUIREMENTS Each Cooperative Group should consist of three major operational components that collaborate to conduct the research agenda of the Group: the headquarters (including the Group Chair's office), the central statistical/data management office, and the participating investigators and institutions. Each component should have general responsibilities in meeting the goals and objective of the Cooperative Group or in completing tasks necessary to accomplish those goals. Each Group must be governed by a constitution and bylaws, which describe membership criteria, procedures for selecting group leadership and other details of governance. Each Group must be led by a chairperson who is ultimately responsible for the content and conduct of the Group's research program. Beyond these requirements, the structure and management of the individual Group is the responsibility of the Group itself to determine. The headquarters is the direct responsibility of the Group chairperson. It should provide executive leadership and day-to-day administrative management of the Group. Through this office the chairperson implements the Group's scientific and organizational policies. A Group's statistical and data management staff must be integral collaborators in all stages of study development, conduct, analysis, and reporting. It is anticipated that member institutions will be, for the most part, academic centers and their affiliated institutions. In addition to patient accrual, member institutions should provide scientific and administrative contributions to the Group. Each Group must establish its own specific criteria for membership and a formal process for application for Group membership. Terms and Conditions of Award Awards will include the "Terms and Conditions of Award," which detail the responsibilities, relationships, and governance of the studies to be funded under these cooperative agreement(s). These terms and conditions are available from the program staff listed under INQUIRIES. 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 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 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 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, Volume 23, Number 11, March 18, 1994. Investigators also may obtain copies of the policy from the program staff listed under INQUIRIES. Program staff may also provide additional relevant information concerning the policy. APPLICATION PROCEDURES Potential applicants are strongly encouraged to contact NCI staff (See INQUIRIES) prior to the preparation and submission of an application to discuss NCI's possible interest in supporting the proposed Cooperative Group and to request copies of the Cooperative Group Guidelines and additional information that will be helpful in preparing applications. It is strongly recommended that a letter of intent, which includes a descriptive title of the proposed research, the name, address, and telephone of the Principal Investigator, the identities of other key personnel and participating institutions, and the number and title of this program announcement be submitted six months in advance of the application submission deadline. A member institution that intends to apply or reapply out of cycle with the parent Group should submit a letter of intent as early as possible prior to the submission of the application. A letter of intent is not binding and is not a precondition for submission, review or award. Applications are to be submitted on the grant application form PHS 398 (rev. 9/91). Application kits are available at most institutional offices of sponsored research and may be obtained from the Office of Grants Information, Division of Research Grants, National Institutes of Health, 6701 Rockledge Drive, Room 3032, MSC 7762, Bethesda, MD 20892- 7762, telephone 301/710-0267. The title and number of the program announcement must be typed in Section 2a of the face page of the application. The code U10 must be entered in section 2b. The applicant must provide a statement acknowledging and agreeing to NCI staff post-award involvement in conducting the Cooperative Group's clinical trials, and must describe plans to accommodate this involvement. The completed original application and three legible copies must be sent or delivered 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 service) At the time of submission, two additional copies and all appendix material 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 Rockville, MD 20852 (for express mail) Because of the interrelatedness of various components, all of the individual applications from a particular Cooperative Group must be submitted and reviewed at the same time; similarly, funding recommendations for all of the components are usually of the same duration and time frame. Exceptions include competing supplement applications and applications from individual members submitted out of sequence with the remainder of the Group. Even in these cases, however, adjustments are made in the award such that funding periods coincide with those of the remainder of the Group. REVIEW CONSIDERATIONS Applications will be assigned to the National Cancer Institute. Applications will be reviewed for scientific and technical merit by the NCI's Cancer Clinical Investigations Review (CCIRC) Committee, in accordance with the standard NIH peer review procedures and in accordance with the "CLINICAL TRIALS COOPERATIVE GROUP PROGRAM GUIDELINES" available from the NCI Program Director upon request (see INQUIRIES). Because of their interrelatedness, all applications from all components of a particular Cooperative Group are reviewed simultaneously (except in the case of member applications submitted out-of sequence with the parent Group). The full CCIRC review is usually preceded by a site visit to the Group's statistical and data management facilities. The site visit team generally consists of a subset of CCIRC members plus ad hoc reviewers as indicated by the proposed work scope. Following scientific-technical review, the applications will receive a second- level review by the National Cancer Advisory Board. Review Criteria The three components of each proposed Cooperative Group will be reviewed by the CCIRC in accordance with the following review criteria. A. GROUP HEADQUARTERS 1. Merit of Specific Research Plans - How meritorious are the research plans and strategies for each of the major areas of study? Are they appropriate in the context of national priorities? Are guidelines for the inclusion of women and minorities as research subjects being followed? 2. Research Methodology - How well designed are the Group's planned clinical trials? Will their design allow clinically important conclusions to be drawn? 3. Efficiency of Study Development - Will the process of study development proceed in an efficient and timely manner? Will important studies be rapidly developed and implemented? 4. Timeliness of Study Completion - Will the Group be able to carry out its planned studies in a reasonable period of time? 5. Overall Group Priorities - Are the proposed priorities of the Group appropriate? Are its resources well directed? 6. Developmental Fund Plans - Are the specific plans for the developmental fund appropriate and consistent with the Group's overall goals and priorities? Has the fund been well managed and wisely used in the past? 7. Group Structure and Administration - Will the Group be well administered by the Chairperson and the Headquarters staff? Does its organization and infrastructure allow it to meet its major objectives and goals? 8. Publication Record - Is the Group's prior research (if relevant) published in a timely manner and in quality peer reviewed journals? 9. Group Cohesiveness - Will the Group function as a cohesive research team? 10. Interdisciplinary Coordination - Is there adequate interdisciplinary participation in protocol development and design? Do protocol investigators reflect the modalities utilized? 11. Quality Control - Are the Group's proposed mechanisms of quality control adequate and functioning in a manner which ensures accurate data? 12. Membership - Are the criteria for initial and continuing membership adequate? Do the Group's periodic evaluations of its members result in an optimal membership roster? 13. Adequacy of plans to include both genders and minorities and their subgroups as appropriate for the scientific goals of the research. Plans for the recruitment and retention of subjects will also be evaluated. B. STATISTICAL AND DATA MANAGEMENT OFFICE This portion of the evaluation involves 2 facets: 1) the performance and capabilities of the statistical and data management office; and 2) the Group's integration of the statistical and data management offices' roles and responsibilities into the overall research program. 1. Collaboration in Research - Is there adequate statistical and data management collaboration in the development and conduct of the Group's research? 2. Adequacy of Study Design - Are the protocols properly designed statistically? Are the sample sizes adequate to detect realistic and medically important differences? Are the assumptions adequately justified? Is the expected accrual rate carefully estimated? Are the designs used appropriate for the study questions? Are endpoint selections and sequential monitoring plans adequately described and justified? 3. Adequacy of Procedures - Are data management procedures adequate, appropriate, and consistent with accepted standards? Are procedures for the verification of data accuracy in place? Is there clinical review of study data? 4. Statistical Analyses - Are analytical techniques, procedures, and policies adequate, appropriate, and consistent with accepted standards? Do publications demonstrate thorough and state-of-the-art methodology, awareness of problems of multiple analyses, and sufficient independence and lack of bias of statistical collaborators? 5. Adequacy of Staff - Are the statistical and data management staff capable of carrying out their special responsibilities? 6. Independent Research - While not required, involvement in research related to the design, conduct and analysis of cancer clinical trials is a strength. 7. Computing resources - Are computing resources adequate and appropriate to support Group activities as needed? Participating Institutional Applications Both scientific contributions to the Group, and patient accrual and data quality enter into this evaluation. 1. Contributions to Group Science - What are the contributions of the institution's investigators to the Group's research strategies and plans? Do the investigators chair research committees and studies? 2. Participation in Group Activities and Administration - Do the institution's investigators participate in Group activities and meetings? 3. Interdisciplinary Coordination - To the extent required by the Group's research, is there adequate interdisciplinary cooperation and coordination? 4. Patient Accrual - Is the record of patient accrual appropriate in the context of Group standards? Are projections for the future reasonable and adequate? 5. Adequacy of plans to include both genders and minorities and their subgroups as appropriate for the scientific goals of the research. Plans for the recruitment and retention of subjects will also be evaluated. 6. Data Quality - Are the recent data complete, accurate, and submitted in a timely fashion? 7. Protocol Compliance - What is the recent record of the quality of protocol participation? 8. Data Management - Are the institution's data management practices and procedures adequate and appropriate? 9. Publication - Do the institution's investigators contribute to publication of Group studies? AWARD CRITERIA Applications will compete for available funds with all other approved Cooperative Group U10 applications assigned to the Cancer Therapy Evaluation Program, Division of Cancer Treatment, NCI. The following will be considered in making funding decisions: Quality of the proposed project as determined by peer review, availability of funds, and program priority. The receipt dates and review schedule are as follows: Application Receipt Dates: Feb 1 Jun 1 Oct 1 Site Visit (if applicable): Apr/May Aug/Sep Dec/Jan Review Committee Meeting: Jun/Jul Oct/Nov Feb/Mar NCAB Meetings: Sep/Oct Jan/Feb May Earliest Possible Funding: Dec 1 Apr 1 Aug 1 INQUIRIES Inquiries are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Richard S. Ungerleider, M.D. Division of Cancer Treatment National Cancer Institute Executive Plaza North, Suite 741 6130 Executive Boulevard Bethesda, MD 20892 Rockville, MD 20852 (if using express mail) Telephone: (301) 496-6056 FAX: (301) 402-0557 Email: UNGERLER@DCT.NCI.NIH.GOV Direct inquiries regarding fiscal matters to: Ms. Crystal Wolfrey Grants Management Branch National Cancer Institute Executive Plaza South, Room 242 6120 Executive Boulevard Bethesda, MD 20892 Rockville, MD 20852 (if using express mail) Telephone: (301) 496-7800, ext. 282 FAX: (301) 496-8601 Email: WOLFREYC@GAB.NCI.NIH.GOV AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 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 grant policies and Federal Regulations 42 CFR 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 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. .
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