Full Text DA-98-003 STRATEGIC PROGRAM FOR INNOVATIVE RESEARCH ON COCAINE (AND OTHER PSYCHOMOTOR STIMULANTS) ADDICTION PHARMACOTHERAPY (SPIRCAP) NIH GUIDE, Volume 26, Number 21, June 20, 1997 RFA: DA-98-003 P.T. 34 Keywords: Addiction Drugs/Drug Abuse Pharmacology National Institute on Drug Abuse Letter of Intent Receipt Date: October 14, 1997 Application Receipt Date: November 14, 1997 PURPOSE This Request for Applications (RFA) will support innovative, integrated preclinical and clinical research to validate novel approaches and identify potential compounds that are safe and effective short-term (to reduce and stop cocaine and other psychomotor stimulants use) and long-term (to prolong abstinence) pharmacotherapies for the treatment of cocaine and other psychomotor stimulants addiction. A Strategic Program for Innovative Research on Cocaine (and other psychomotor stimulants) Addiction Pharmacotherapy (SPIRCAP) can focus its therapeutic research activities on, for example, modulating specific receptor sites, (e.g., the dopamine transporter, D3 receptor, a serotonin receptor, etc,) or neurotransmitters that are believed to be involved in cocaine and other psychomotor stimulants addiction, or on development of biologically based anti-cocaine medications, such as antibodies, enzymes, and catalytic antibodies, or on advancing the neurobiological understanding of cocaine and other psychomotor stimulants addiction that will construct new therapeutic concepts. Studies submitted in response to this RFA should have a truly novel or innovative approach. The SPIRCAP Program thus complements existing, more traditional preclinical and clinical programs for the development of cocaine and other psychomotor stimulants treatment medications, managed by the Medications Development Division of NIDA [e.g., the Medications Development Research Units (MDRUs, P-50)], the medicinal chemistry synthesis contracts, and the preclinical medications testing contracts. Of greatest significance, each SPIRCAP applicant is required to form a collaborative enterprise between preclinical and clinical scientists in the conceptualization and proof-of-concept of an identified therapeutic strategy. This will entail interactive research and information exchange between preclinical and clinical investigators in order to ensure effective development and refinement of the therapeutic concept. The applicant's Group (defined in Section VII) must, therefore, possess the expertise necessary to (i) evaluate the proposed strategy in preclinical systems, and (ii) conduct pilot clinical study(ies) using the proposed therapeutic approach. A SPIRCAP should be dedicated to the expedited transition of ground-breaking research from advanced preclinical findings to clinical application in developing an anti-cocaine and other psychomotor stimulants medication. A SPIRCAP is encouraged to include investigators from commercial (pharmaceutical, chemical, or biotechnological companies) organizations. 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, Strategic Program for Innovative Research on Cocaine (and other psychomotor stimulants) Addiction Pharmacotherapy, is related to the priority areas of "tobacco, alcohol and other drugs, and HIV infection". 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, D.C. 20402-9325 (telephone 202-512-1800). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic for-profit and nonprofit organizations, private and public, such as universities, colleges, hospitals, laboratories, units of State or local governments, pharmaceutical companies, 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 Awards will be made as Cooperative Agreements (U19s). The Cooperative Agreement is an assistance mechanism in which substantial NIDA programmatic involvement with the recipient during the performance of the planned activity is anticipated. The nature of NIDA staff participation is described in SECTION VIII: SPECIAL REQUIREMENTS - "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 projects conducted by at least three independent research laboratories, e.g., a preclinical laboratory, a clinical laboratory and a laboratory from a pharmaceutical or biotechnology company. For the purpose of this RFA, two (or more) projects within a single company, or projects within the same academic department will not be considered independent. If there is an overlap of (academic) departmental appointments of co- investigators, an explanation should be provided about the independence of the projects. The involvement of laboratories from commercial (pharmaceutical, chemical, or biotechnological companies) organizations as part of the project is encouraged. This limitation on the number of independent projects from the same academic or private sector organization is intended to increase the diversity and multi-disciplinary expertise available to the Group from other than the parent institution or organization. While no maximum number of projects is stipulated, it has been observed that when a multi- disciplinary grant or award exceeds six component projects the program becomes less coordinated and more difficult to manage. This RFA is a one-time solicitation. If by the end of the third year of the award, the NIDA has not announced its intent to reissue the RFA, awardee should contact NIDA program staff and consider submitting investigator-initiated (R01) applications which will compete with all investigator-initiated applications and be reviewed according to the customary peer review procedures. All policies and requirements that govern the grant program of the U.S. Public Health Service (PHS) and the National Institutes of Health (NIH) apply. FUNDS AVAILABLE NIDA has set aside $2.0 million total costs for the first year of funding. This level of support is dependent on the receipt of a sufficient number and diversity of applications of high scientific merit. Two to three awards are anticipated for project periods up to four years. However, support beyond the second year of each SPIRCAP will be determined by NIDA staff based, in part, on the recommendations of an external ad hoc committee, convened to evaluate accomplishments and determine whether stated goals have been met. Because the nature and scope of the research proposed in response to this RFA may vary, it is anticipated that the size of individual awards will vary also. Awards are subject to a first year limit of $1.0 million in total costs (direct plus indirect costs). Budget requests should be carefully justified and commensurate with the complexity of the project. Although this program is provided for in the financial plans of the NIDA, awards pursuant to this RFA are contingent upon the availability of funds for this purpose. Applications in excess of $1.0 million total cost will be returned without review, unless a waiver has been granted by the SPIRCAP Program Director, Dr. Betty Tai in advance of submission. (Address listed under INQUIRIES). RESEARCH OBJECTIVES Background The NIDA and the PHS are currently supporting comprehensive extramural and intramural projects aimed at the elucidation of processes susceptible to the action of cocaine and other psychomotor stimulants and the mechanisms through which cocaine and other psychomotor stimulants affects the fundamental brain processes, and for developing safe and effective behavioral and pharmacological therapies to treat cocaine and other psychomotor stimulants addicts. Notwithstanding these efforts, no pharmacotherapeutic approaches yet been proven effective. To address this critical deficiency, NIDA has made the development of an anti-cocaine and other psychomotor stimulants medication its number one priority. The sense of urgency is prompted by the fact that cocaine abuse and dependence affect all segments of our society with devastating personal, social, and public health consequences. National surveys indicate that more than 23 million Americans have used cocaine at some time in their lives and more than 1.3 million are current cocaine users. Cocaine use is associated with potentially life-threatening cardiovascular effects; sex-for-crack exchanges that are spreading the AIDS virus among both drug-abusing and non-drug-abusing populations; possible damage to the health and development of infants born to women who abuse cocaine during pregnancy; and violence and neighborhood disintegration related to the cocaine marketplace. In recent years, the scientific information base on the neurobiology of cocaine and other psychomotor stimulants addiction has expanded and the number of technological breakthroughs has increased significantly. Advances in molecular biology, medicinal chemistry, immunology and neuroscience of cocaine and other psychomotor stimulants addiction have been made: genes for the dopamine and serotonin receptors have been cloned, novel cocaine congeners of varying affinities and pharmacokinetics properties have been synthesized and evaluated, animal models which permit the study of behavioral features of cocaine and other psychomotor stimulants addiction in the laboratory are available, relationship among protein function and regulation, brain structures, functions and behavioral end points, and how cocaine and other psychomotor stimulants affects these relationships have been elucidated, basic brain mechanisms associated with addiction behavior have been studied by clinicians, imaging scientists and psychologists. However, application of developments to clinical and treatment activities has not been commensurate with this expansion. There is a need to apply these research advances to clinical research studies, an effort that requires interactive (interdependent) research activities involving both preclinical and clinical investigators in the planning and implementation of studies whose ultimate goal is an effective pharmacotherapy for cocaine and other psychomotor stimulants addiction. A concerted effort to mobilize the nation's combined basic and clinical scientific expertise through SPIRCAP can accelerate advances in the development of effective treatments for this brain disorder. The SPIRCAP is specifically designed to support research for the development of innovative hypothesis generating and proof-of-concept pharmacological interventions and strategies for the treatment of cocaine and other psychomotor stimulants addiction. The theme of this program complements and balances present efforts pursued under existing NIDA programs, including the Medication Development Research Units (MDRUs), and the various contracts managed by the Division's discovery programs for the synthesis, testing and screening of potential pharmacotherapeutics. Research Goals and Objectives of the SPIRCAP Program A. The principal goals of this RFA are to (i) bring together innovative, advanced preclinical research of sound scientific rationale and clinical proof-of concept of an identified therapeutic strategy for cocaine and other psychomotor stimulants addiction; and (ii) implement pilot clinical studies of a therapeutic strategy. In line with this objective, the SPIRCAP Program will support projects with a common thematic goal for which advanced preclinical data exist. These efforts are to be implemented through a concerted, interactive (interdependent) Group effort by components comprising the SPIRCAP Group. B. Applicants for SPIRCAP funding are expected to have an identified strategy - based on creative, solid scientific rationale and supported by advanced preclinical data - which is proposed for pilot clinical evaluation. Therapeutic strategies that require studies in humans as well as preclinical studies to refine the clinical approach are appropriate for funding under the SPIRCAP Program. Each SPIRCAP application must propose a well-defined central research focus consistent with the research objectives of the Program as stated in the RFA. The following approaches are provided as examples and are not intended to be inclusive or restrictive: Strategies that substantiate or refute the concept of "substitution- agonist" and/or "antagonist" therapies. Much of the current approaches for the development of anti-cocaine medications are modeled after the success of opioid addiction pharmacotherapies (the methadone, LAAM and naltrexone) or the nicotine addiction pharmacotherapies (the nicotine patch, gum, etc.), however, the differences between these addictions warrant further validations of such concepts. Strategies that validate the utility of novel classes of compounds as potential anti-cocaine and other psychomotor stimulants medications, e.g., dopamine D1 antagonists, SSRIs, or kappa opioid compounds. Strategies that validate the utility of an anti-craving medication to prevent relapse to cocaine and other psychomotor stimulants addiction. Strategies to validate the utility of novel medications to ameliorate, reverse the development of neuropsychiatric sequelae of chronic cocaine and other psychomotor stimulants abuse as anti- cocaine and other psychomotor stimulants addiction pharmacotherapy. Strategies for the development of catalytic antibodies and anti- idiotype based vaccines to treat cocaine addiction. Strategies that validate the utility of compounds which interrupt chronic cocaine and other psychomotor stimulants use based on identified neurobiological and cellular mechanisms that may promote repeated cocaine and other psychomotor stimulants use. Strategies that validate the utility of compounds that modify cocaine and other psychomotor stimulants sensitization or tolerance to treat cocaine and other psychomotor stimulants addiction. Strategies that explore the impact of other co-abused substances, e.g. nicotine, alcohol on the neurobiology of cocaine and other psychomotor stimulants addiction and the construct of new therapeutic strategies to effectively accommodate these factors. C. Applications should address advanced preclinical refinements of the proposed strategy, evaluation and demonstration of therapeutic benefit in laboratory animals, if applicable, and implementation of pilot clinical studies. The cyclic flow of information between preclinical and clinical phases is critical for maximal refinement and optimization of the proposed clinical modality, clinical evaluation of the therapeutic concept, and ultimately, to accelerate transition to clinical treatment.( Applicants are encouraged to include women whenever possible in early stage clinical concept testing.) D. Studies required for the IND-targeted preclinical development (formulation, toxicology) of proposed treatments are generally beyond the scope of this RFA, but such development through private venture capital is encouraged. Alternatively, a Group may request that the NIH assist in these developmental tasks using some of the existing NIH/NIDA contract resources. In addition, NIDA/MDD also has the capacity for clinical evaluation of therapies for cocaine addiction in its VA interagency agreement. It is envisioned that extended clinical studies of treatments developed by a SPIRCAP group can be accommodated under the clinical trial mechanisms available through Medications Development Division. However, these resources are limited. Queries about these programs should be directed to Dr. Betty Tai at the address listed under INQUIRIES. E. The Group's objectives and goals should be relevant to and compatible with the NIDA Program missions and directions as stated in this RFA. Applicants should describe their plans to accommodate the stated SPIRCAP Program requirements, criteria, and NIDA involvement. F. Applications that are not truly innovative or are covered by other NIDA programs are excluded from this RFA and will be returned to the applicants. G. Relevance to other NIDA programs: This RFA will support innovative, integrated preclinical and clinical studies to validate therapeutic concepts for cocaine and other psychomotor stimulants addiction. Other MDD/NIDA initiatives involving only preclinical studies for novel intervention strategies address (i) preclinical animal models development; (ii) early preclinical discovery of new drugs and therapeutic approaches for the treatment of cocaine addiction. SPIRCAP applicants must ensure that no overlap exists between the specific aims proposed under this RFA and those proposed under any of the other initiatives referenced above, if applicable. SPIRCAP applicants from an institution receiving government funds under General Clinical Research Centers (GCRC), Medication Development Research Units (MDRU), should describe how these programs are integrated with the proposed studies, and ensure that no scientific and budget overlap exists with the SPIRCAP proposal. DEFINITIONS: ADMINISTRATIVE CORE - An administrative facility that provides central operations, support and leadership for the overall management, integration, communication and coordination of the cooperative agreement and services shared by the Group as a whole. The Administrative Core should have a budget separate from that of the Principal Investigator's research project, but should be administered by the Principal Investigator's organization. The Administrative Core will have in its budget for each year travel expense to support its SPIRCAP Steering Committee members to attend scheduled Steering Committee meetings. The Administrative Core will be responsible for allocating required travel expenses to appropriate members of the Group. Only SPIRCAP-related travel will be supported under this RFA; travel funds to other domestic or foreign meetings is not provided under this RFA. (For additional details of required travel see SPECIAL REQUIREMENTS - TERMS AND CONDITIONS OF AWARD: A. and B.) COOPERATIVE AGREEMENT - An assistance mechanism in which substantial NIDA programmatic involvement is anticipated with the recipient organization during the performance of the planned activity. CORE COMPONENTS - Resources for exercising leadership and coordination, and laboratory facilities for equipment and services which are shared by two or more projects of the SPIRCAP. Examples of core components are: biochemical, cell-based, and immunological studies; animal model studies; pharmacology/toxicology studies; scale-up synthesis of the therapeutic agent. The core can be defined as a facility laboratory with established techniques and assays which performs a service function resulting in an economy of effort and savings in the overall costs of the Group. The core unit is to be described with the same detail as the research projects to enable evaluation of its scientific merit. CORE LEADER - The leader of one of the Scientific or Administrative Cores of the SPIRCAP. GROUP - see SPIRCAP, below. INVENTION - An innovative therapeutic approach that is or may be patentable under Title 35 of the United States Code. (SPIRCAP) STRATEGIC PROGRAM FOR INNOVATIVE RESEARCH ON COCAINE (AND OTHER PSYCHOMOTOR STIMULANTS) ADDICTION PHARMACOTHERAPY - In this RFA the terms STRATEGIC PROGRAM FOR INNOVATIVE RESEARCH ON COCAINE (AND OTHER PSYCHOMOTOR STIMULANTS) ADDICTION PHARMACOTHERAPY (SPIRCAP) and "Group" are synonymous. Each Group may consist of a number of scientific investigators from academic and/or non-profit research institutions as well as scientists from commercial organizations, performing research on interactive projects whose central focus is development of effective pharmacotherapies for cocaine and other psychomotor stimulants addiction. A CORE component cannot be used toward fulfillment of the three research projects requirement. NIDA SPIRCAP PROGRAM DIRECTOR - A Senior Scientist of the NIDA extramural staff who coordinates NIDA's participation in the SPIRCAP Program, oversees the operation of the entire SPIRCAP Program, maintains the program stewardship duties and who ensures that the SPIRCAP Program is consistent with the Medications Development Program and NIDA missions and goals. NIDA SCIENTIFIC COORDINATORS - Scientists of the extramural staff of the Medications Development Program, NIDA, who function as collaborators with the Principal Investigators and Project Leaders and who facilitate the partnership relationship between NIDA and each Group. Two Scientific Coordinators from the Medications Development Program - one from the preclinical program area and one from the clinical program or other related program area - will be assigned to each Group by the SPIRCAP Program Director. The Scientific Coordinators are the immediate contact persons to the Group. PRINCIPAL INVESTIGATOR - The person who assembles the SPIRCAP, who is responsible for the performance of the Group as a whole and for that of each of the Project Leaders, and who is responsible for submitting the single application in response to this RFA. The Principal Investigator will coordinate Group activities scientifically and administratively and should be the project leader of one of the Research Projects of the Group and must commit at least 20 percent effort to the Program. The awardee (Principal Investigator's) institution establishes and operates the central operations office that funds Group members and is legally and fiscally accountable for the disposition of funds awarded. PROJECT LEADER - The leader of one of the scientific research projects of the SPIRCAP, who is responsible for the scientific conduct of that project. SPIRCAP GROUP STEERING COMMITTEES - Each SPIRCAP Group will form a Steering Committee (SC) which is the primary coordination center of the GROUP and will decide all major scientific/programmatic decisions. It will be composed of the Principal Investigator, the Project leaders of the Group, the Chief of NIDA MDD Regulatory Affairs Branch (non voting), the NIDA Scientific Coordinators (one from the preclinical area and one from the clinical area), and other non voting consultants (e.g. Scientists, relevant FDA and/or DEA officials) as needed. Only one NIDA Scientific Coordinator will vote. The SC will have the following responsibilities and authorities: 1) develop a detailed plan and timetable to coordinate the various research activities among the GROUP's various research laboratories to ensure the preclinical concept/strategy will advance into clinical studies in a timely fashion. 2) Identify/allocate the essential and additional studies or resources (toxicology, formulation) required for the IND targeted preclinical medication development activities. 3) formulate strategies to successfully interact with the FDA, and/or local IRBs, etc regarding the IND submission and quality control of the studies (GLP, GCP, GMP, etc). 4) develop policies on data sharing, on access to data and materials and on publication authorship. The SC will meet at least two but not to exceed four times a year and will tele-conference when requested. (For additional details on SC see SPECIAL REQUIREMENTS - TERMS AND CONDITIONS OF AWARD: B.) RESEARCH PROJECT - A discrete, specified, circumscribed project that must relate to the overall theme (refinement and proof-of-concept of high risk innovative pharmacological intervention and strategy for the treatment of cocaine and other psychomotor stimulants addiction) of the SPIRCAP. SPECIAL REQUIREMENTS: TERMS AND CONDITIONS OF AWARD NOTE: Failure to abide by any of the Terms of Award pertaining to awardee responsibilities stipulated in this Section may result in withholding of funds by the NIDA until compliance with the Terms is restored. A. Awardee Rights and Responsibilities Specifically, the Principal Investigator defines the details for the project within the guidelines of the RFA, retains primary authority and responsibility for the plan, conduct, analyze and publish results, interpretations and conclusions of their studies, and agrees to accept assistance in coordination, cooperation, and participation of NIDA staff in those areas of scientific and technical management identified under C. NIDA staff responsibilities. Awardee will participate on the SPIRCAP Steering Committee as described under Collaborative Responsibilities. Awardee will retain custody of primary rights to their data developed under the award, subject to rules formulated by the Steering Committee, and government rights of access consistent with current DHHS, PHS, and NIH policies. B. Collaborative Responsibilities Under the Cooperative Agreement, a partner relationship exists between the awardee and NIDA. In order to facilitate the collaborative effort between the awardee and the NIDA extramural staff, a Steering Committee for each SPIRCAP will be established. Each SPIRCAP Steering Committee will be composed of: 1. The Principal Investigator of the Group. 2. The Project leaders of all preclinical and clinical projects. 3. The Chief of the NIDA Regulatory Affairs Branch (or designee) as the SPIRCAP Program Director, 4. The NIDA preclinical and clinical Scientific Coordinators, 5. Additional non-voting consultants as needed NIDA will have one vote and will not be serving as the Chair of the Committee. Each SPIRCAP Steering Committee will have the following authority and Responsibilities: 1) to develop a detailed plan and timetable which will ensure active and frequent interactions among the various research laboratories and NIDA staff to expedite the transition of preclinical concept/strategy into clinical studies. 2) to identify and allocate all essential and additional studies or resources (toxicology, formulation) required for the IND targeted preclinical development. 3) to formulate strategies to interact with FDA, and/or local IRBs, regarding the IND submission and quality control of the study (GLP, GMP, GCP, etc). 4) to develop policies on data sharing, on access to data and materials and on publication authorship. The steering committee will meet two to four times a year and tele- conference when requested by the Awardee or by NIDA staff. C. NIDA Staff Responsibilities: Nature of NIDA Participation Assistance via a Cooperative Agreement differs from the traditional research grant in that, in addition to the normal programmatic and administrative stewardship responsibilities, the awarding component (NIDA) anticipates substantial scientific and programmatic involvement during performance of the research program. NIDA shall work with each Group and shall be represented by two NIDA Scientific Coordinators, both members of the professional staff of the Medications Development Program: one coordinator will be from the Cocaine Treatment Discovery Program, and one coordinator will be from the Clinical Cocaine Treatment Program or other related Programs. NIDA SPIRCAP Scientific Coordinators will be members of the SPIRCAP Steering Committee and will not be serving as the Chair of the Committee. NIDA's Chief of Regulatory Affairs Branch will serve as the Program Director oversees the operation of the entire SPIRCAP Program, maintains the program stewardship duties and who ensures that the SPIRCAP Program is consistent with the Medications Development Program and NIDA missions and goals. NIDA will have one vote. In light of the complex structure and research activities of the SPIRCAP and the medications development goal of the SPIRCAP, NIDA staff will provide technical assistance and advice in the area of pharmaceutical regulatory science and in the area of information management and project management to ensure effective and efficient progress of the study. Specifically, the responsibilities of NIDA staff are three fold: 1) By means of their project management and information management expertise to facilitate the effective communication among study laboratories to ensure expedited transition of ground-breaking research from advanced preclinical findings to applied clinical mode. 2) To provide pharmaceutical regulatory advice and support to the GROUP by serving as liaison with the Food and Drug Administration (FDA) and Drug Enforcement Administration (DEA) regarding all relevant regulatory issues; serving as consultants for the GROUP to prepare IND submissions and to conduct studies that meet FDA standards (GLP, GMP, GCP) when needed. 3) To provide appropriate assistance, advice, and guidance in general by participating in the design of Group activities; advising in the selection of sources or resources; coordinating or participating in collection and/or analysis of data and participating in the preparation of publications but will not participate in the actual implementation of the preclinical and clinical studies. D. Patent Coverage Principal worldwide patent rights to an invention supported in whole or part with Federal funds usually vest with the grantee/contractor organization. Under existing regulations 37 CFR 401, grantee/contractor organization must promptly report all inventions disclosed to them by their investigators to NIH Extramural Technology Transfer Office. A grantee can elect to retain title to any subject invention, although such title is subject to an nonexclusive, nontransferable, irrevocable, paid-up license to the government to use, and license others to use, the invention for Government purposes. If the grantee does not elect to retain title, the Government may do so. Moreover, the Government retains march-in rights that require the patent holders to license others in certain circumstances such as when the licensee has not taken effective steps within a reasonable time to achieve practical application of an invention or to alleviate a health and safety need. E. Arbitration Process NIDA will establish an arbitration process to resolve any differences of opinion between the awardee and NIDA, on scientific and programmatic matters. An arbitration panel, composed of one Group designee, one NIDA designee, and a third designee with expertise in the relevant area and chosen by the other two, will be formed to review any scientific or programmatic issue that is significantly restricting progress. These special arbitration procedures in no way affect the awardee's right to appeal an adverse action in accordance with PHS regulations at 42 CFR Part 50, Subpart D, and HHS regulations at 45 CFR Part 16. The special "TERMS AND CONDITIONS OF AWARD: " described in this Section 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 policies. 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 sub-populations 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 policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing research involving human subjects should read the "NIH Guidelines For Inclusion of Women and Minorities as Subjects in Clinical Research", which have been published in the Federal Register of March 28, 1994 (FR 59 14508-14513), and in the NIH GUIDE FOR GRANTS AND CONTRACTS of March 18, 1994, Volume 23, Number 11. LETTER OF INTENT Prospective applicants are asked to submit, by October 14, 1997, a letter of intent that includes a descriptive title of the overall proposed research; the name, address, telephone number, and institution of the Principal Investigator; names of prospective Project Leaders, other key investigators, and their respective institutions; title, project leader, and institution for each component research project, and the number and title of this RFA in response to which the application is submitted. Although the letter of intent is not required, is not binding, and is not a factor in the peer review of the application, the information it contains is helpful in planning for the review of applications. It allows NIDA staff to estimate the potential review workload and to avoid conflict of interest in the review process. The letter of intent is to be sent to: Director Office of Extramural Program Review National Institute on Drug Abuse 5600 Fishers Lane, Rm 10-42 Rockville, MD 20857 Telephone: (301) 443-2755 APPLICATION PROCEDURES This RFA requires the submission of a single application for the proposed SPIRCAP. Because of the multi-institutional nature of a SPIRCAP and the special requirements in this RFA, additional instructions regarding format are listed in the following: o Each individual research project comprising the SPIRCAP Group application is subject to the same format, 25 page limitation and a separate budget as a research project grant (R01). The research grant application form PHS 398 (rev. 5/95) must be used in applying for these cooperative agreements. Applications kits are available at most institutional offices of sponsored research and may be obtained from the Division of Extramural Outreach and Information Resources, National Institutes of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone 301/710-0267, email: ASKNIH@odrockm1.od.nih.gov. The title and number of this RFA must be typed in Item 2 on the face page of the application. o An Introductory Section should be written for the proposed SPIRCAP application describing it as a whole with respect to the overall theme, goals, objectives, and overall research plan. The Introductory Section, not to exceed three pages, should contain germane information on i) the overall research theme, leadership role of the PI, mechanisms and plans to ensure effective interactive research and information exchange between preclinical and clinical investigators in order to ensure effective development and refinement of the therapeutic concept, ii) development timelines and milestones for each projects in a graphic outline to clearly layout the sequence of research events and how it related to each other, iii) the proposed Principal Investigator or his/her institution as evidence of capability to carry out the scientific and administrative duties required in this RFA and the functions of the PI's central operations office. o The proposal, depending on the nature of the program, should also contain documents of i) justification of an IRB waiver if the proposed clinical project will commence later after the completion of the proposed preclinical studies, ii) assurance of the accessibility and availability of the proposed test compounds, iii) plan for clinical data management and adverse event reporting (AER). The RFA label available in the PHS 398 (rev. 5/95) application form must be affixed to the bottom of the face page of the application. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, TO ENSURE THE IDENTIFICATION OF YOUR APPLICATION WITH THIS RFA the "Yes" box must be marked in item 2a of the face page of the application form and the title and number of this RFA typed. Applications that are not received as a single package from the Principal Investigator and which do not conform to the instructions contained in PHS 398 (rev. 5/95) application kit will be judged non-responsive and will be returned to the applicant. The completed original, including the checklist, and three legible copies must be sent or delivered to: DIVISION OF RESEARCH GRANTS NATIONAL INSTITUTES OF HEALTH 6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC-7762 BETHESDA, MD 20892-7710 BETHESDA, MD 20817 (for courier/overnight service) At the time of submission, two additional copies of the application must be sent to: Director Office of Extramural Program Review National Institute on Drug Abuse 5600 Fishers Lane, Room 10-42 Rockville, MD 20857 Telephone: (301) 443-2755 Applications must be received by November 14, 1997. If an application is received after this date, it will be returned to the applicant without review. If the application submitted in response to this RFA is substantially similar to a grant application already submitted to the NIH for review, the applicant will be asked to withdraw either the pending application or the new one. Simultaneous submission of identical applications will not be allowed, nor will essentially identical applications be reviewed by different review committees. This restriction supersedes an NIH policy permitting concurrent submission of a duplicate R01 and a component of a multi- project application. The NIH policy however, further stipulates that should both the R01 and the multi-project application be considered for funding, the R01 will be relinquished in favor of the multi- project application. REVIEW CONSIDERATIONS A. Review procedures Applications will be reviewed by NIDA staff for completeness and programmatic responsiveness to this RFA; those judged to be non- responsive will be returned to the applicant without review. Applications with first year total costs (direct and indirect) in excess of $1.0 million will be returned without review unless the applicant has received a written waiver from the NIDA to exceed this amount (see FUNDS AVAILABLE, above). Applications that are complete and responsive to the RFA will be evaluated for scientific and technical merit by an appropriate peer review group convened in accordance with NIH peer review procedures. As part of the initial merit review, all applications will receive a written critique and undergo a process in which only those applications deemed to have the highest scientific merit, generally the top half of applications under review, will be discussed, assigned priority score, and receive a second level review by the National Advisory Council of NIDA. B. Review Criteria: The review group will review the program as an integrated research effort focussed upon a central research strategy or theme including the relationship of research components to the central strategy/theme and the effectiveness of the core units in supporting the program. The review group will assess the scientific and technical merit of the proposal according to the following criteria and assign one overall priority score for the entire program. Significance and originality of the overall proposed research program and the development of a well defined central strategy relevant to The goals of the RFA; Appropriateness and adequacy of the proposed research approach, methodology, and plans to address the special goal of the SPIRCAP. The cohesiveness of a multi-disciplinary and multifaceted scope of the program and coordination of individual projects and core(s); The likelihood that innovative preclinical therapeutic strategies will be refined and pilot clinical research implemented within two years of award date; The leadership, scientific ability, and administrative competence of the Principal Investigator for the development, implementation, and management of a comprehensive preclinical and clinical research program; and the Principal Investigator's commitment to devote substantial time and effort to the program; Administrative arrangements and organizational structure, through an administrative core, to facilitate and monitor the attainment of objectives and internal quality control. For example, these factors will include plans to enhance communication and cooperation among the investigators involved in the program and mechanisms for the allocation of funds for day to day management, long term planning and periodic evaluation, contractual agreements, and procedures for the replacement of key personnel, e.g., the Principal investigators, if required on an interim or permanent basis. The qualifications, experience, and commitment of the investigators responsible for the individual research projects or core(s) (Project Leaders) and their contribution to the program, including their ability to devote adequate time and effort to the Group. It is anticipated that, due to the complexity and time required to maintain a well-coordinated and productive research effort, a minimum 20% (time) effort by the Principal Investigator and each Project Leader should be devoted to the study, unless there are compelling arguments to the contrary; Availability of the resources necessary to perform the research; Appropriateness of the proposed budget and duration in relation to the proposed research; Appropriateness of proposed methodology and demonstrated willingness to work as part of the cooperative study and with NIDA Collaborating Scientists; Documented commitment of Institutions represented by Group members; documented capability of Principal Investigator's Institution to serve as the Central Operations Office for the Group; Adequacy of provisions for the protection of animal and human subjects; and Adequacy of plans to include both genders and minorities and their subgroups as appropriate for the specific goals of the research. Plans for the recruitment and retention of subjects will also be evaluated. AWARD CRITERIA Applications recommended for further consideration by an appropriate Advisory Council will be considered for funding based on the following factors: Overall scientific and technical merit of the proposal as determined by peer review; Significance and originality of the proposed research; Appropriateness of budget estimates; Compatibility of research and data analytic approaches, administrative structures, and other features to make a successful cooperative study a reasonable likelihood; Program priorities; and Availability of funds. SCHEDULE Letter of Intent Receipt Date: October 14, 1997 Application Receipt Date: November 14, 1997 Scientific Review Date: January/February 1998 Council Meeting Date: May 1998 Earliest Award Date: July 1998 INQUIRIES Inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applications is welcome. Direct inquiries regarding programmatic issues to: Betty Tai, Ph.D. Medications Development Division National Institute on Drug Abuse Parklawn Building, Room 11A-55 5600 Fishers Lane Rockville, MD 20857 TEL: (301) 443-3318/1428 FAX: (301) 443-2599 Email: BTAI@NIH.GOV Direct inquiries regarding fiscal matters to: Gary Fleming, J.D., M.S. Chief, Grants Management Branch National Institute on Drug Abuse Parklawn Building, Room 8A-54 5600 Fishers Lane Rockville, Maryland 20857 TEL: (301) 443-6710 Email: gfleming@aoada1.ssw.dhhs.gov AUTHORITY AND REGULATIONS This program is described in the catalog of Federal Domestic Assistance No. 93.279. 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 PHS grant policies and Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92. This program is not subject to the intergovernmental review requirements of Executive Order 122372 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 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 routine education, library, day care, health care of 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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