Full Text CA-94-007 NATIONAL COOPERATIVE NATURAL PRODUCTS DRUG DISCOVERY GROUPS NIH GUIDE, Volume 23, Number 21, June 3, 1994 RFA: CA-94-007 P.T. 34 Keywords: Cancer/Carcinogenesis Chemotherapeutic Agents Biomedical Research, Multidiscipl Natural Products National Cancer Institute Letter of Intent Receipt Date: July 15, 1994 Application Receipt Date: September 20, 1994 PURPOSE The Developmental Therapeutics Program, Division of Cancer Treatment, National Cancer Institute (NCI) invites applications for the continuance of National Cooperative Natural Products Drug Discovery Groups (NCNPDDGs) for the discovery of new effective anticancer treatments from natural sources. Applications are sought from both re-competing NCNPDDGs and new applicant groups. This Request for Applications (RFA) will support innovative, multi-disciplinary approaches to the discovery of new anticancer agents derived from natural sources. Each Group will be assembled by a Principal Investigator (PI) to form a multidisciplinary and multi-institutional consortium of skills needed to execute successfully the conceptualization, development, and preclinical investigation of the new, rationally based drug candidates. A multi-institutional approach involving academic, nonprofit, and/or commercial/industrial institutions is envisaged because the existence of all of the creative talents in the required scientific disciplines will rarely be available in a single institution. The biological or molecular cancer targets for drug discovery and the sources and types of natural products to be investigated will be selected by the applicant groups. Although NCNPDDG awards will not support clinical trials, timely evaluation of drug candidates discovered by this mechanism is encouraged. The present RFA is a reissuance of 89-CA-17 issued on September 14, 1989, with the same goals. The RESEARCH OBJECTIVES of the RFA require that an NCNPDDG has the capacity within itself to conceive, create and evaluate new approaches to discovery of natural products based drug candidates and to recommend the best candidates for development towards clinical trials. Subsequent studies required for development of new treatments to clinical trial (e.g., formulation development, classical toxicology, etc.) are beyond the scope of this RFA. Within this context, scientific approaches to the achievement of the RFA goals are broad, and are limited only by the creativity and the capability of the applicant group. The development of analogues of well-studied classes of anticancer agents is not responsive to this RFA. 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, National Cooperative Natural Products Drug Discovery 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 "Healthy People 2000" (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 for-profit and non-profit organizations, public and private, such as universities, hospitals, laboratories, research institutes, units of State and local governments, and eligible units of the Federal government. Applications from women and minority investigators are encouraged. MECHANISM OF SUPPORT The administrative and funding instrument to be used for this program will be a cooperative agreement (U19), an assistance 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 recipients 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 and the relationships of the awardee and the Government during the course of a cooperative agreement are found later in this document under the section "Terms and Conditions of Award." The awardee will be responsible for the planning, direction, and execution of the proposed project, and interrelated activities. All applications must consist of at least three interrelated laboratory programs. While no maximum number of programs is stipulated, it has been observed that awards containing more than five or six components are more difficult to manage. The partnership relationship will facilitate technology transfer from Government owned data-bases and the use of appropriate NCI resources to enhance the efficiency and effectiveness of a Group's efforts. The nature of NCI staff participation is described below under "Terms and Conditions of Award." There is no intent, real or implied, for NCI staff to direct Group activities or to limit the freedom of investigators. A Group is expected to consist of a single consortium of multidisciplinary and/or multi-institutional Laboratory Programs from academic, non-profit, or commercial organizations. The interaction of academic and non-profit research institutions with commercial (including industrial) organizations and Government will favor the efficient invention of new agents for cancer. The active participation of industry is encouraged because it will allow this segment of the scientific community to contribute its considerable intellectual and material resources. Further, the interaction of academic and non-profit research institutions with industry and Government will facilitate subsequent development and marketing of new drugs, although these latter activities are not within the scope of this RFA. Each award will be made only to the Principal Investigator's institution. All Group activities will be coordinated through a Administrative Core located at the Principal Investigator's institution. The total project period for applications submitted in response to the present RFA may not exceed five years. The earliest anticipated award date is April 1, 1995. Because the nature and scope of the research proposed in response to this RFA may vary, it is anticipated that the size of awards may vary also. Awards and level of support depend on receipt of a sufficient number of applications of high scientific merit. Although this program is provided for in the financial plans of the NCI, awards pursuant to this RFA are contingent upon continuing availability of funds for this purpose. At this time, the NCI anticipates that there will be a renewed competition of this program. If the NCI does not continue the program, awardees may submit grant applications through the usual investigator-initiated grants mechanisms. FUNDS AVAILABLE The NCI has set aside approximately $4,000,000 in total costs for the initial year's funding. This level of support is dependent on the receipt of a sufficient number and diversity of applications of high scientific merit. Five to seven awards, which will include both new awards and competing continuation awards, are anticipated for project periods up to five years. Awards are subject to a first year limit of $900,000 total costs (direct plus indirect costs). Applications in excess of $900,000 first year total costs will be returned without review. RESEARCH OBJECTIVES A. Background The search for better cancer treatments is a dynamic process dependent on the availability of new agents and strategies coupled with the development and use of more predictive models. Recent advances in modern biomedical research provide unprecedented opportunities for the discovery of novel and highly sophisticated cancer treatments. Exploitation of these exciting leads for development of more effective cancer therapy requires the organization of outstanding scientists from diverse scientific disciplines within the biological, chemical, biochemical, and pharmacological sciences into highly synergistic research teams regardless of institutional affiliation. To realize this objective as well as to utilize facilitating resources of the NCI's drug development program within these teams, the NCI established the National Cooperative Drug Discovery Group (NCDDG) program as a result of Request for Applications (RFAs) issued in July 1983 and August 1984 for the exploitation of mechanistically based differences between normal and cancer cells. October 1986 reissuances established groups focused on exploitation of specific and unique characteristics of lung and colorectal cancers. The NCDDG approach to modern drug discovery was broadened further in August 1987 by RFAs inviting applications for the creation and evaluation of both general mechanism of action based and specific disease-oriented anticancer treatments as well as for the development of innovative preclinical models for determining antitumor selectivity. National Cooperative Natural Products Drug Discovery Groups were invited by RFAs in September 1988 and October 1989 in order to enhance discovery of novel drug chemotypes for subsequent development as anticancer agents. A combined RFA was issued in August 1991 for general mechanism of action and specific disease-oriented research. NCNPDDGs are peer-reviewed projects funded through a cooperative mechanism in which the NCI, through its extramural staff, is an active partner in the group. NCI staff, represented by an NCI Coordinator, provide advice and guidance in the area of drug discovery and development and facilitate access to NCI resources including repositories, chemical searches, and screens. Resources for advanced development including scale-up isolation and/or synthesis, pharmaceutical development, toxicology and filing of Investigational New Drug Applications (INDs) can be made available through the NCI Decision Network process (M.R. Grever, S.A. Schepartz, and B.A. Chabner, Seminars in Oncology, Vol 19, No. 6 (December), 1992; pp 622-638) or through collaborating industrial partners, or through private venture capital. The present RFA is for the discovery of new therapies for cancer from the universe of natural substances, historically a fruitful source of agents effective against a wide variety of human diseases. This RFA is a reissuance of the 1988-1989 RFAs for National Cooperative Natural Products Drug Discovery Groups. A companion RFA (CA-94-008) is being issued for National Cooperative Drug Discovery Groups (NCDDGs) based on mechanistic/disease oriented approaches to discovery of new therapies. B. Objectives and Scope The goals of this RFA are to encourage the discovery and evaluation of new entities from natural sources for the treatment of cancer. Programs should utilize, to the extent possible, novel and innovative approaches to drug discovery based on recent advances in tumor biology and the molecular understanding of cancer. Programs appropriate to fulfillment of Group objectives could include, but are not limited to: discovery of natural products that selectively inhibit specific tumor types; products that may affect oncogene expression in tumors, signalling pathways for tumor growth, or the actions of hormones or growth factors on proliferation. Approaches to targets specifically present in tumor cells are encouraged. Applications that emphasize targets related to breast cancer and prostatic cancer, which are currently high priority research areas for the NCI, are encouraged but this RFA is in no way limited to these diseases. 1. The goals of the NATURAL PRODUCTS DRUG DISCOVERY GROUP PROGRAM are: a. The search for, discovery, and isolation from natural sources of novel agents to treat cancer effectively and their evaluation in appropriately developed and/or selected preclinical models. b. The development or use of preclinical models based on their ability to discriminate for antitumor activity and their ability to test the rationale for natural product selection and isolation. c. The optimization of leads sufficient to recommend viable candidate compounds for development to clinical trial. d. The design of preclinical studies that will facilitate subsequent clinical evaluation and correlation of preclinical and clinical data for validation of concept. 2. Applications for funding as an NCNPDDG should stress creative approaches to the discovery of effective anticancer therapies and should emphasize the following: a. Objectives of the proposed NCNPDDG. b. Research approaches to the realization of objectives and the provision of comprehensive information (including citations) in support of the rationale(s) for the proposed approaches. c. Specific pertinence to cancer treatment. d. The scientific and technical areas of expertise (Program Leaders) required to attain Group objectives. Approaches to realization of the goals of this RFA are broad and limited only by the creativity and ability of the applying Group. Projects for random collection and screening of natural products without strong rationales for material selection or testing models and projects designed to produce analogues or derivatives of well known antitumor natural products are not responsive to this RFA. Applications should stress novelty of approach and strong rationale both in terms of the cancer target and the natural products to be evaluated. Each group is envisioned as containing a number of Laboratory Programs (minimum of three) whose cooperative activities may, for example, include: (1) implementation of strategies to support the selection and acquisition of natural sources of NOVEL agents; (2) preparation of crude materials for testing; (3) development and use of discriminating biological assays to select crude materials for further study; (4) utilization of biological assays and physical/chemical methods leading to the efficient isolation, purification and structure elucidation of antitumor selective moieties; (5) development of methods and models for secondary evaluation of lead compounds, both in vitro and in vivo to enable discrimination among leads and facilitate selection of compounds; (6) optimization of selected leads to facilitate selection of and priorities for the development of new agents to clinical trial. A cohesive NCNPDDG should include all of the Laboratory Programs needed to attain Group objectives. Since it is unlikely that all of the required laboratory capabilities will be found in any single institution, it is probable that most proposed Groups will be multi-institutional as well as multidisciplinary in nature. The specialized research competencies required could include scientists (e.g., ecologists, botanists, chemists, molecular biologists, and others) who have not been working primarily in cancer research. The participation of highly creative scientists from any scientific discipline appropriate to the Group objectives is encouraged. Group efforts must be focused on clear, cancer-relevant goals to which all Laboratory Programs must relate. The desired end product of the funded applications is the discovery of new drugs from novel approaches to cancer treatment and sufficient secondary evaluation and optimization of these agents to enable the Group to recommend candidate compounds for advanced preclinical development. 3. Funds for laboratory programs or cores that depend on the successful completion of other parts of the group's activities will be restricted and released only on specific approval of the NCI Program Director or NCI Coordinator. Examples of such restricted funds might be for scale up re-collections, isolations, or syntheses, use of advanced models for secondary evaluation, studies of mechanism of action of lead compounds, and lead optimization studies. 4. Studies required for development of new agents to clinical trial (e.g., formulation development, classical toxicology, etc.) are beyond the scope of this RFA. However, such development is encouraged through the NCI Decision Network process or through industrial collaborations or venture capital. 5. The Group's objectives and goals should be relevant to and compatible with the NCI's mission in cancer treatment as stated in this RFA. Applicants should describe their plans to accommodate the stated NCNPDDG requirements, criteria, and NCI involvement. C. Definitions ADMINISTRATIVE CORE - An administrative unit located at the Principal Investigator's institution that coordinates all Group activities. It is separately budgeted from the P.I.'s laboratory program (if any) and budgets for activities pertinent to the Group as a whole. CORE LEADER - The director of a core component, if any, of the NCNPDDG, who is responsible for the conduct of that core. GROUP - see NATIONAL COOPERATIVE NATURAL PRODUCTS DRUG DISCOVERY GROUP LABORATORY PROGRAM - A research component within the NCNPDDG with a separate, detailed research plan and budget. NATIONAL COOPERATIVE NATURAL PRODUCTS DRUG DISCOVERY GROUP (NCNPDDG; Group) - A number of Laboratory Programs representing diverse scientific disciplines and usually multiple organizations which consist of a Principal Investigator, Program Leaders, Core Leaders (if any) and the NCI coordinator which function as a unit with a common goal: the rational selection, isolation, and evaluation of new entities from natural sources for treatment of cancer. In this RFA the terms National Cooperative Natural Products Drug Discovery Group, NCNPDDG, and Group are used synonymously. NATURAL PRODUCT - In the context of the NCNPDDG program, a term used broadly to encompass any naturally occurring chemical or biological entity of non-human origin selected and evaluated preclinically against cancer. This, of course, excludes materials which are synthesized de novo by the investigator and also excludes semi-synthetic derivatives of known antitumor agents. NCI COORDINATOR - A scientist from the NCI extramural staff, appointed by the NCI Program Director after award, who participates as a member of the Group, interacts scientifically with the Group, and facilitates the role of NCI as partner in the NCNPDDG. The NCI Program Director may also serve as the NCI coordinator for a Group. NCI PROGRAM DIRECTOR - The senior staff member of the Grants and Contracts Operations Branch, Developmental Therapeutics Program, Division of Cancer Treatment, who provides leadership and guidance for the overall NCNPDDG program within the NCI, maintains overall scientific balance in the NCNPDDG program, and ensures that the NCNPDDG program is consistent with the NCI mission for treatment research. PROGRAM LEADER - The director of one of the Laboratory Programs of the NCNPDDG, who is responsible for the scientific conduct of that program. The Principal Investigator may also be one of the Program Leaders. SCIENTIFIC CORE - A separately budgeted scientific service component which provides essential facilities or services to two or more of the proposed Laboratory Programs. Core components typically use established procedures or protocols rather than generating new research. SPECIAL REQUIREMENTS 1. Since the discovery of new and improved anticancer treatments is the objective of this effort and active involvement by industrial laboratories is facilitated by the existence of adequate patent coverage, it is essential that applicants provide plans to assure such coverage. The situation could be complicated since multiple institutions are likely to be involved. Each applicant Group must, therefore, provide a detailed description of the approach to be used for obtaining patent coverage and for licensing where appropriate, in particular where the invention may involve investigators from more than one institution. Procedures must be described for resolution of legal problems should they arise. Your attention is drawn to P.L. 96-517 as amended by P.L. 98-620 and 37 CFR Part 401. Instructions were also published in the NIH GUIDE FOR GRANTS AND CONTRACTS, Vol. 19, No. 23, June 22, 1990. The proposed patent plan among the institutions comprising the Group must be included as part of the application. A formal patent agreement signed and dated by the organizational official authorized to enter into patent arrangements for each Group member and member institution must be on file at the Division of Extramural Activities, NCI prior to peer review. Note: A formal statement of Patent Agreement among all Group members and their institutions as well as a detailed description of procedures to be followed for resolution of legal problems which may develop, signed and dated by the organizational official authorized to enter into patent arrangements for each Group member and member institution is preferred with the application. If this signed agreement is not included in the application, it must be submitted to the Scientific Review Administrator prior to peer review. 2. Provide from the Principal Investigator and from each Program Leader a signed statement of acceptance of the provisions outlined under "NCI Staff Responsibilities" listed below. 3. A formal statement of agreement is desired with the application, signed by authorized representatives of all the institutions in the Group, assuring that an equitable portion of royalties or profits arising from drugs discovered by the NCNPDDG, if any, will be returned to indigenous peoples, research collaborators, research institutions, or Governmental entities as appropriate, in the country of origin of the natural product sample from which said drug was derived. If this signed agreement is not included in the application, it must be submitted to the Scientific Review Administrator prior to peer review. 4. Provide a plan for the development of agents discovered in the Group that are considered to be worthy of development towards clinical trials, even though clinical trials and certain advanced preclinical studies (as described above) are not supported under this mechanism. 5. Must have obtained and followed the special instructions for preparation of applications as described under "Letter of Intent" The following terms and conditions will be incorporated into the award statement and provided to the Principal Investigator(s) as well as the institutional official at the time of award. A. Terms and Conditions of Award NOTE: Non-compliance with any of the Terms of Award pertaining to awardee responsibilities stipulated in this Section may result in a reduction of funding, withholding of support, suspension,or termination of the 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 Part 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 (U19), 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 resides with the awardee for the project as a whole, although specific tasks and activities in carrying out the studies will be shared among the awardee(s) and the NCI coordinator. 1. Awardee Rights and Responsibilities It is the primary responsibility of the Principal Investigator to state clearly the objectives of the Group, to direct the research stipulated in the proposal and to ensure that the results obtained are published in a timely manner. The Group must define its objectives and its approaches to attain these objectives in accord with its own interests and perceptions of novel and exploitable approaches to the discovery of effective anticancer treatment and must develop the details of the research design following the guidance given in this RFA. It is anticipated that decisions in all activities will be reached by consensus of the Group under the leadership of the Principal Investigator and that the NCI Coordinator will have the opportunity to offer input to this process. The Principal Investigator, Program Leaders, and NCI Coordinator will meet periodically to review progress, plan and design research activities, and establish priorities. The frequency of meetings (not fewer than two per year and preferably three or four) will be determined by the Principal Investigator who will be responsible for scheduling the time and place (generally at one of the performance sites or at the NCI). The application should also include plans for scheduling Group meetings, notifying Group members, including NCI, and documenting and disseminating Group meeting proceedings. NCI staff may not chair Group meetings. NCI experience with the Drug Discovery Group Program has shown that frequency of meetings and communications within the Group is strongly correlated to Group success in achieving its goals. Therefore, additional informal meetings among all participants as well as regular telephone and written communication will be important. a. The principal end product of NCNPDDG activities will be the discovery of new agents for development to clinical trial. Subsequent developmental work through private resources is encouraged. Applicants should provide a plan for development of agents beyond the stage of selection of candidate agents that is the terminal objective of the NCNPDDG funded research. NOTE: It is understood that the Government supports studies in the interest of promoting the transition of effective, innovative, therapies to the clinic and that identified therapies that have been derived via Government support mechanisms will be offered to the public at reasonable costs. b. The Government, via the NCI Coordinator, will have access to data generated under this Cooperative Agreement and may periodically review the data. However, the awardee will retain rights to the data under these awards subject to Government rights and access consistent with HHS, PHS, and NIH policies. Timely publication of major findings by the Group members is encouraged. Publications or oral presentation of work done under this agreement will require appropriate acknowledgement of NCI support. Dissemination of information on synthetic or natural substances supplied to the Group by NCI (e.g., for comparative testing purposes, as reference materials, etc.) will require clearance by NCI to assure conformity to existing confidentiality agreements with suppliers. c. The ownership of natural product samples acquired during the course of the research rests with the Group. The Group should formulate a policy for final disposition of the samples and ownership rights in the event that the samples are transferred to other parties who make discoveries using them. In order that the samples be fully evaluated for potential for anticancer activity and anti-AIDS activity after the Group has concluded its evaluation but before the samples are transferred to other parties for evaluation in other therapeutic areas, it is requested that the Group provide lists of completed samples to the NCI Coordinator, who will arrange for review of these lists by NCI staff involved in the Developmental Therapeutics Program's screening for anticancer and anti-AIDS activity. Should selected samples be of interest to the NCI, the Group is requested to provide these to the NCI for evaluation before release of samples for other purposes. d. The NCI recognizes that most countries, and in particular developing countries, retain interests in samples collected in their domains. All applicants who propose foreign collections of natural products must provide a plan, signed by all Group members, for equitable return of a portion of any profits or royalties derived from NCNPDDG discoveries to indigenous peoples, research collaborators, cooperating institutions, or Governmental entities in the countries of origin, as appropriate to their contributions. e. In order to facilitate Group activities the Principal Investigator shall prepare minutes of Group meetings within two weeks after each meeting and distribute copies to all Program Leaders and the NCI Coordinator. Such minutes will include a listing of action items to be carried out by each of the Group members. 2. NCI Staff Responsibilities NCI shall participate as a member of the Group and will be represented by a Coordinator. The NCI Coordinator will be selected from the scientific staff that manages extramural programs but not from the NCI intramural staff. During performance of the award, NCI staff may provide appropriate assistance, advice, and guidance by participating in the design of activities; advising in the selection of sources for resources, staff, etc.; advising or participating in management and/or technical performance; and participating in the preparation of publications. In all cases, the role of NCI will be to assist and facilitate and not to direct activities. The dominant role and prime responsibilities for the activity resides with the awardee(s) for the project as a whole. The NCI Coordinator, as well as any other Group member, may assist in research planning; may suggest studies within the scope of the Group's objectives and research activities; may present to the Group experimental findings from published sources or from contract projects in support of these suggestions; may participate in the design of experiments agreed to by the Group; and may participate in the analysis of results. The NCI Program Director or Coordinator will not conduct Laboratory Programs. Upon recommendation of the NCI Coordinator, NCI may utilize its drug development resources in support of Group research activities when such resources may be required on an occasional basis. The following is a list of some resources that might be supplied if they become desirable during performance, are not anticipated as a continuing need, and are readily available: a. Reference compounds for standardization of test systems, as analytical standards, and for related purposes. b. Needed resources such as test materials and information that may not otherwise be available to the Group. c. Data from testing conducted in resource contract laboratories. d. Laboratory testing capacity, whenever appropriate and possible, in the current contract based preclinical therapy-related laboratory testing program. The Group is expected to provide sufficient test material for such testing. e. Searches of computer files of materials, chemical structures and biological activity, if requests for such searches are sufficiently focused to avoid excessive costs. Information given to an NCNPDDG will be restricted by any standard confidentiality agreements between the Government and suppliers of test materials to the Government. f. Experimental animals and cultured cells, if available, to Groups whose main research activities do not require these materials on a regular basis. Groups whose experimental approach involves studies that require animals on a regular basis must budget for costs in their application. g. Computer processing and statistical evaluation if costs are not excessive. These "Terms and Conditions of Award" require that the NCI Program Director approve the following: changes in the Principal Investigator or Program Leaders; reports intended for inclusion in INDAs and Clinical Brochures; redistribution, outside the NCNPDDG, of biological and chemical materials received from the Government; dissemination of research findings resulting from the use of such materials; and release of funds restricted for use in specific circumstances or contingencies. 3. Collaborative Responsibilities The Group (Principal Investigator, Program Leaders, and NCI Coordinator) may recommend that development be co-sponsored or fully sponsored by NCI. In the latter case, it will be necessary for the Principal Investigator and NCI Coordinator to cooperate in the analysis, summarization, preparation, and presentation of data to the appropriate NCI staff through the Decision Network process. Co-development with the NCI is encouraged as part of the Government's assistance in the Cooperative agreement process. NCI will retain the option to cross-file or independently file an application for investigational clinical trial (e.g., an Investigational New Drug Application (INDA) to the United States Food and Drug Administration) of any invention resulting from these NCI supported Cooperative Agreements. Reports of data generated by the Group or any of its members required for inclusion in INDAs and Clinical Brochures and for cross-filing purposes will be submitted by the Principal Investigator to the NCI Coordinator upon request. Such reports will include background information, methods, results, and conclusions. They will be subject to approval and revision by NCI and may be augmented with test results from other Government sponsored projects prior to submission to the appropriate regulatory agency. 4. Arbitration Any disagreements arising on scientific/programmatic matters will be arbitrated by a panel composed of one Group designee, one NCI designee, and a third designee with expertise in the relevant area chosen by the other two. These 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. STUDY POPULATIONS 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 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) 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 Guidelines on the 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 obtain copies from these 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 July 15, 1994, a short letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, names of other key personnel, the participating institutions, and the number and title of the RFA 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, it is requested in order to provide an indication of the number and scope of applications to be reviewed. The letter of intent is to be sent directly to: Matthew Suffness, Ph.D. Division of Cancer Treatment National Cancer Institute Executive Plaza North, Suite 832 Bethesda, MD 20892 Telephone: (301) 496-8783 FAX: (301) 480-4883 or (301) 496-8333 APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 9/91) is to be used in applying. 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, Westwood Building Room 449, Bethesda, MD 20892, telephone (301) 710-0267. The RFA label available in the application form PHS-398 must be affixed to the bottom of the face page. 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 and the YES box must be marked. This RFA requires the submission of a single application for the proposed NATIONAL COOPERATIVE NATURAL PRODUCTS DRUG DISCOVERY GROUP. Because of the multi-institutional nature of an NCNPDDG and the special requirements in this RFA, additional suggestions regarding format and some modifications are necessary to provide a comprehensive yet readily reviewable application. These are found in the "Special Instructions to Applicants," which must be obtained from the Program Director listed under INQUIRIES. Submit a signed, typewritten original of the application, including a single Checklist, and three signed, exact single sided photocopies in one package to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892* At the time of submission, two additional copies of the application must 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 The deadline for receipt of applications is September 20, 1994. Applications received after this date will be considered as not responsive to this RFA and will be returned 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 that has been reviewed. This does not preclude the submission of a substantial revision of an application already reviewed, but such an application 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 studies is important, it will not be the sole criterion for evaluation of applications. Other considerations such as the likelihood of identifying candidate compounds for a clinical trials, will be part of the evaluation criteria. Review Method Upon receipt, applications will be reviewed for completeness by the 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 without further consideration. Applications that are complete and responsive to the RFA will be evaluated for scientific and technical merit by an appropriate peer review group convened by the Division of Extramural Activities, NCI in accordance with the review criteria stated below. As part of the initial merit review, a process (triage) may be used by the initial review group in which applications will be determined to be competitive or non-competitive based on their scientific merit relative to other applications received in response to the RFA. Applications judged to be competitive will be discussed and assigned a priority score. Applications determined to be non-competitive will be withdrawn from further consideration and the principal investigator and the official signing for the applicant institution will be promptly notified. Each Laboratory Program will be evaluated on its relevance to the Group's objectives well as its individual scientific merit. Review Criteria Applicants are encouraged to submit and describe their own ideas about how best to meet the goals of the cooperative study and are expected to address issues identified under SPECIAL REQUIREMENTS of the RFA. 1. Extent to which application addresses the goals and objectives of the RFA (see RESEARCH OBJECTIVES section) and the probability of discovery of novel agents for treatment of cancer. 2. Scientific merit and originality of proposed research. 3. Adequacy of Group composition relative to proposed objectives in drug discovery; adequacy of justification for all programs and cores. 4. Technical merit of proposed methods for selecting and obtaining natural products and for their evaluation. 5. Adequacy of the scientific disciplines and specific competencies represented by the Principal Investigator and Program Leaders; scientific skills, research experience, competence, commitment, and time availability of Principal Investigator, Program Leaders, and other key personnel. 6. Extent of progress on prior award (RECOMPETING GROUPS only) or preliminary results (NEW APPLICANTS). 7. Extent and effectiveness of cooperation with the NCI (recompeting Groups) and adequacy of plans for cooperation with the NCI in the event of an award (All applicants). 8. Administrative experience and competence of Principal Investigator in the development, implementation, and management of comprehensive research programs. 9. Adequacy of plans for effective intra-Group communication and for assuring Group cohesiveness. 10. Adequacy and availability of existing physical facilities and resources of the Principal Investigator and Program Leaders. 11. Evidence of availability and competence of the applying institution to serve as the Administrative Core for the Group. The review group will critically examine the submitted budget and will recommend an appropriate budget and period of support for each approved application. AWARD CRITERIA Applications recommended by the National Cancer Advisory Board (NCAB) will be considered for award based on: scientific merit as reflected in the priority score; programmatic priorities including breast and prostate cancer research; programmatic balance including balance between types of natural products to be studied, and types of assays and cancer targets; and availability of funds. Letter of Intent Receipt Date: July 15, 1994 Application Receipt Date: September 20, 1994 Scientific Review Date: January/February 1995 NCAB Meeting Date: May 31-June 2, 1995 Earliest Award Date: July 1, 1995 INQUIRIES Written, telephone, and FAX inquiries about this RFA are encouraged. The opportunity to clarify questions from potential applicants is welcomed. Direct inquiries regarding programmatic issues, requests for the Special Instructions, and address the letter of intent to: Matthew Suffness, Ph.D. Division of Cancer Treatment National Cancer Institute Executive Plaza North, Room 832 Bethesda, MD 20892 Telephone: (301) 496-8783 FAX: (301) 480-4883 or (301) 496-8333 Direct questions on budgets and grants regulations to: Barbara A. Fisher Grants Administration Branch National Cancer Institute Executive Plaza South, Suite 242 Bethesda, MD 20892 Telephone: (301) 496-7800 Ext. 229 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 authority 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 HHS grants policies. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. The Public Health Service strongly encourages all grant recipients to provide a smoke free workplace and promote the non-use of 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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Office of Extramural Research (OER) |
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Department of Health and Human Services (HHS) |
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