NATIONAL COOPERATIVE DRUG DISCOVERY GROUPS FOR THE TREATMENT OF MOOD DISORDERS OR NICOTINE ADDICTION (NCDDG-MD/NA) Release Date: August 27, 2002 (see addendum NOT-MH-02-011) RFA: MH-03-008 National Institute of Mental Health (NIMH) (http://www.nimh.nih.gov/) National Institute on Drug Abuse (NIDA) (http://www.nida.nih.gov/) Letter of Intent Receipt Date: October 25, 2002 Application Receipt Date: November 26, 2002 THIS RFA CONTAINS THE FOLLOWING INFORMATION o Purpose of this RFA o Research Objectives o Mechanism of Support o Funds Available o Eligible Institutions o Individuals Eligible to Become Principal Investigators o Special Requirements o Where to Send Inquiries o Letter of Intent o Submitting an Application o Peer Review Process o Review Criteria o Receipt and Review Schedule o Award Criteria o Required Federal Citations PURPOSE The intent of this solicitation is to invite applications from academic and pharmaceutical industry investigators interested in participating with National Institute of Mental Health (NIMH) and the National Institute on Drug Abuse (NIDA) in a National Cooperative Drug Discovery Group (NCDDG-MD/NA) Program to accelerate innovative drug discovery, the development of pharmacologic tools for basic and clinical research in mood disorders or nicotine addiction, and, in the case of mood disorders, the development and validation of models for evaluating novel therapeutics. NIMH and NIDA are interested in jointly advancing the discovery of new ligands because we anticipate that there are targets in common and overlap in the expertise that can be brought to bear. The goal of the NCDDG-MD/NA Program is to establish long-term partnerships between NIH, academia, and industry that will advance the development and testing of fundamentally new, rationally designed medications and treatments for mental disorders and nicotine addiction. Academic and/or pharmaceutical industry components of each NCDDG-MD/NA should contribute unique scientific expertise towards the common goal of translating basic science findings into innovative pharmacologic treatments for mental disorders and drug addiction. Each partnership or group must consist of a multi- disciplinary team of scientists with appropriate expertise to address the development and evaluation of novel ligands, and the development of testing models where required. Scientists from both academia and pharmaceutical industry are encouraged to participate within an NCDDG-MD/NA. Scientists from foreign institutions and NIH Intramural laboratories may participate in some aspects, as noted in other sections of this application. The NCDDG-MD/NA Program is most appropriate for applications that include collaborations, Research Projects or core components from academia and the private sector (e.g., pharmaceutical, chemical, or biotechnological companies). It is anticipated that the interaction of academic and non-profit research institutions with industry and NIH via the NCDDG-MD/NA model will: 1) accelerate the discovery of new therapeutics for mood disorders and nicotine addiction; 2) increase the availability of pharmacologic research tools for basic and clinical research; and 3) facilitate the development and validation of models to evaluate novel therapeutics in mood disorders. Small businesses without academic and/or industry partners are encouraged to respond to parallel Program Announcements: Pharmacologic Agents and Drugs for Mental Disorders (SBIR Award) [http://grants.nih.gov/grants/guide/pa-files/PA-02-027.html], Development of PET and SPECT Ligands for Brain Imaging (SBIR Award) [http://grants.nih.gov/grants/guide/pa-files/PA-02-028.html], and Innovative Toxicology Models: SBIR/STTR - Addendum to PA-02-075, Notice NOT-MH-02-005 [http://grants.nih.gov/grants/guide/notice-files/NOT-MH-02-005.html]. RESEARCH OBJECTIVES A. Background Significant advances in neuroscience, genetics, and basic behavioral science, together with technological developments, have provided a rich knowledge base for understanding pathophysiology, identifying new molecular targets for drug discovery, and developing rational pharmacotherapies for the treatment of mood and substance abuse disorders. With the wealth of potential new drug targets, the opportunity exists to accelerate the process of discovery to make quantum leaps toward novel and effective treatments for mood disorders (depression and bipolar disorder) and drug addiction. NIMH recently convened a panel of experts to assess the state of the science and to identify opportunities and priorities in key areas of research relevant to mood disorders. The following priorities identified in the area of pharmacologic treatment development for mood disorders are relevant to this RFA: 1) development of neurochemical tools for understanding disease pathophysiology (e.g., expanding chemical repositories to increase the availability of imaging ligands and probes for basic and clinical research); 2) exploration, development, and evaluation of cellular, circuit-based, and pathophysiology-based models for drug development; and 3) facilitation of partnerships between NIMH, academia, and industry to support innovative approaches for drug discovery and the development of behavioral assays using the NCDDG-MD/NA model established by the National Cancer Institute (NCI). The NIMH Strategic Plan for Mood Disorders Research is available at http://www.nimh.nih.gov/strategic/strategicplanmenu.cfm. NIDA's interests are broadly consistent with the NIMH Strategy Plan (above), but with a particular interest at this time in drug discovery for nicotine addiction. The use of tobacco products is believed to be due in large part to addiction to nicotine, which acts through nicotinic cholinergic receptors (nAChRs). In recent years there have been real advances in our understanding of the structure of the various subunits of these receptors, and of the ways in which the subunits combine to form diverse nAChR subtypes. In particular, evidence suggests that the widely distributed alpha4/beta2 subtype plays a central role in nicotine addiction. In addition, studies have suggested roles for other subtypes, for example the homomeric alpha7 nAChR and various complex heteromeric receptors that have been shown to modulate the release of addiction-relevant neurotransmitters, or are of interest because of their anatomical locations. Establishment of a program to develop ligands that target nAChR subtypes is compelling for several reasons. First, the response of nAChRs to nicotine is complex and subtype dependent; this complexity may provide an opportunity to develop ligands that may be particularly useful in treating nicotine addiction. Second, it is possible that ligands with a particular profile of action at nAChRs may be developed – for example, partial agonists – a profile that may ultimately be useful in developing the molecule as a medication for treatment of nicotine addiction. Third, it is possible that ligands with a particular pharmacokinetic profile may be developed that would support their use in novel nicotine replacement devices. In general, novel ligands developed for the nAChR target may afford greater specificity and safety in treatment. Finally, ligands with a particular nAChR receptor profile will be of use as tools with which to advance knowledge of the basic processes of nicotine addiction. In addition, there have been concrete advances in our understanding of the circuitry involved in nicotine addiction, in behavioral phenomena that associate with and/or modulate addiction, and in the effects of nicotine on CNS processes that may be associated with addictive behavior, such as learning and plasticity. Furthermore, knowledge of drug addiction in general suggests that processes such as stress may modulate addictive behaviors. For many of these, evidence for the involvement of specific neurotransmitter systems and receptors exists; hence targets for ligand development exist. Finally with respect to nicotine addiction, a number of valid cellular and animal models are currently available. It is therefore expected that responsive groups will logically include a program to evaluate the efficacy of novel ligands in the appropriate models. Examples of components of such a program could include, but are not limited to, tests of the ability of novel ligands to modulate cellular processes of plasticity in reward-relevant regions of the brain, assessment of the behavioral profile of nicotinic ligands in tests of reinforcement, relapse and withdrawal, and measurement of the effects of novel ligands on neurotransmitter release. The NCDDG-MD/NA Program will support broad, innovative, multidisciplinary, multi- project approaches to the discovery of new, rationally based treatments for mood disorders and nicotine addiction. Since the creative talents in the required scientific disciplines are rarely available in a single institution, a multi- institutional, group approach involving academic, nonprofit, commercial, and/or industrial institutions is envisioned. Academic and pharmaceutical scientists are strongly encouraged to form partnerships that take full advantage of their combined intellectual and material resources for drug discovery, lead optimization, and model development. Further, the interaction of academic and non-profit research institutions with pharmaceutical industry and NIH is expected to facilitate subsequent development and marketing of new pharmacologic treatments, although these latter activities are not within the scope of this RFA. Molecular targets for drug discovery, and the sources and types of chemical entities to be investigated, will be selected by the applying group. Both mechanism of action and disease-oriented approaches are being solicited. B. Research Scope The objective of this RFA is to establish NCDDG-MD/NA Groups to conduct innovative, high impact research focused on the discovery and testing of chemical entities for novel molecular targets implicated in the pathophysiology of mood and nicotine addiction. The NCDDG-MD/NA serves as a vehicle for pharmaceutical and academic scientists to pool intellectual and material resources for the translation of basic science findings into the conceptualization, discovery, and evaluation of new chemical entities. Groups are encouraged to select molecular targets for drug discovery based on recent findings in basic and clinical neuroscience, genetics, and proteomics relevant to the understanding of mood disorders and nicotine addiction. Research projects directed at identifying novel targets within signaling pathways involved in the regulation of emotion, reward, addiction, and cognition are encouraged. NIMH is especially interested in drug discovery for bipolar disorder and depression, and in the development of models for testing such drugs. As noted above, NIDA is interested in drug discovery primarily for nicotine addiction. Certain molecular targets may have relevance beyond drug addiction and, in particular nicotine addiction (e.g., pain, cognitive function). At the present time, and for this initiative NIDA is not interested in the development of agents for these purposes; the sole target is drug addiction. For this initiative, NIDA is NOT interested in research to develop new models of drug addiction. NIDA has an existing medication development program built around the dopamine system and further work in this area is NOT sought under this RFA. However, dopaminergic components of action may be relevant, for example, as part of research needed to understand the mechanisms of action of bupropion and related compounds that may be useful in treating tobacco (nicotine) and possibly other substance abuse disorders. Molecular targets of high programmatic interest both in terms of novel therapeutics and research tools include, but are not limited to, the following: o Nicotinic cholinergic receptor (nAChR) subtypes, especially alpha4/beta2 and alpha7, and other AChRs implicated in nicotine reward o Metabotropic glutamate receptor subtypes o Receptors mediating the action of bupropion o Serotonin receptor subtypes, especially 5-HT2A selective antagonists, and ligands for 5-HT6 and 5-HT7 o Neurokinin receptors, NK1, NK2, NK3 o Corticotropin releasing factor receptors, CRH R1, CRH R2 o Mood stabilizers o Intracellular targets: BDNF, GSK-3B inhibitors, protein kinase inhibitors, transcription factors Potential ligands of interest to NIMH and NIDA might be identified by their receptor properties (e.g., partial agonists, agonists, or antagonists), solubility, pharmacokinetics, oral or CNS bioavailability, or other characteristics to support their use as research tools or candidates for drug development. The identification of lead compounds and refining them for medication development is the principal aim of this initiative. The use of chemical libraries, structural biology and computer modeling of molecular targets to screen for compounds with activity at selected targets are examples of responsive approaches. If applicants do choose to synthesize compounds, they are encouraged to synthesize a small number, and to evaluate these compounds before making new analogs. Extensive structure-activity-relationship studies are not encouraged. Lead optimization using combinatorial chemistry or other innovative technologies is encouraged. A program to evaluate the efficacy of novel ligands for nAChRs in valid cellular and animal models of nicotine addiction needs to be considered. Such evaluation would logically address questions of the ability of the ligands to substitute for nicotine itself, to attenuate nicotine's reinforcing properties, as well as to measure the reinforcing properties of the novel ligands per se. Responsive applicants may outline plans for the development and evaluation of cellular, circuit, or pathophysiology based models for validation of novel targets (preliminary proof-of-concept) for mood disorders, and drug discovery and the identification of compounds as potential candidates for drug development for mood disorders and nicotine addiction. The development of new chemical identities is a mandatory component. It is anticipated that the interaction of academic and non-profit research institutions with NIH and pharmaceutical industry will facilitate timely evaluation and development of clinical research tools, models, and novel therapeutics. Note: The development of analogs of established or well-studied agents for the treatment of mental disorders and/or substance abuse is not responsive to this RFA. Subsequent studies required for development of new treatments (e.g., formulation development, large-scale production for clinical trials, or toxicology in support of Investigational New Drug (IND) applications, etc.) as well as early phase clinical trials, are beyond the scope of this RFA. Please contact program staff listed under Inquiries to determine program priorities and molecular targets of interest to NIMH and NIDA. MECHANISM OF SUPPORT This RFA will use National Institute of Health (NIH) U01 and U19 cooperative agreement award mechanisms. As an applicant you will be solely responsible for planning, directing, and executing the proposed project. This RFA is a one-time solicitation. The anticipated award date is July 1, 2003. If the NCDDG-MD/NA Program is funded and successful, a follow-up RFA may be issued to facilitate renewal of the Program. The NIH U01 and U19 are cooperative agreement award mechanisms in which the Principal Investigator retains the primary responsibility and dominant role for planning, directing, and executing the proposed project, with NIH staff being substantially involved as a partner with the Principal Investigator, as described under the section "Cooperative Agreement Terms and Conditions of Award". The total project period requested for applications submitted in response to the present RFA may not exceed 5 years. FUNDS AVAILABLE The NIMH and NIDA intend to commit approximately $3,000,000 (total costs) in FY 2003 to fund three to five new grants in response to this RFA (NIMH $1,500,000; NIDA $1,500,000). Because the nature and scope of the research proposed may vary, it is anticipated that the size of the awards will also vary. Although the financial plans of the IC(s) provide support for this program, awards pursuant to this RFA are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications. ELIGIBLE INSTITUTIONS You may submit an application if your institution has any of the following characteristics: o For-profit or non-profit organization o Public or private institutions, such as universities, colleges, hospitals, and laboratories o Domestic o Units of State and local governments o Eligible agencies of the Federal government INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with his/her institution to develop an application for support. Individuals from under-represented racial and ethnic groups as well as individuals with disabilities are encouraged to apply for NIH programs. DEFINITIONS AWARDEE. The institution to which the NCDDG-MD/NA award (U19 or U01) is issued. CORE (ADMINISTRATIVE). An administrative unit located at the Principal Investigator's institution that coordinates all NCDDG-MD/NA activities. It is separately budgeted from the PI's Research Project (if any) and oversees support for activities pertinent to the NCDDG-MD/NA, such as travel for intra-group meetings. CORE (SCIENTIFIC). A separately budgeted scientific service component that provides essential facilities or services to two or more of the proposed Research Projects. Core components typically use established procedures or protocols rather than generating new research. An NIH intramural laboratory may participate as a Scientific Core. CORE LEADER. The director of a scientific core component who is responsible for the conduct of that core. NATIONAL COOPERATIVE DRUG DISCOVERY GROUP (NCDDG-MD/NA). An NCDDG-MD/NA must include a Research Project to conceptualize, discover, and evaluate NEW CHEMICAL ENTITIES for the treatment of mood disorders (NCDDG-MD) and/or nicotine addiction (NCDDG-NA). The Groups may also include Research Projects to: 1) generate pharmacologic TOOLS for basic and clinical research on mood disorders and nicotine addiction (e.g., drugs or radioligands for targets implicated in the pathophysiology of mood disorders or nicotine addiction; and/or 2) for mood disorders, develop and validate cellular, circuit, or pathophysiology based MODELS for evaluating novel therapeutics. An NCDDG-MD/NA is encouraged to include high risk/high impact projects on drug discovery for mood disorders and/or nicotine addiction in one or more of the areas specified above: NEW CHEMICAL ENTITIES (required), RESEARCH TOOLS, and/or MODELS (mood disorders only). An NCDDG-MD/NA can apply using either the U01 or U19 mechanisms. A Group of collaborators focused on one or two Research Projects without Cores should use the U01 mechanism. Groups with three-to-five Research Projects as well as Core components should use the U19 mechanism. The development and strengthening of partnerships between scientists from academia and the pharmaceutical industry is a highly desirable outcome of this RFA and is strongly encouraged. Pharmaceutical scientists are encouraged to actively participate as Principal Investigator, Project Leader, and/or key personnel/collaborators in one or more Research Projects within an NCDDG-MD/NA. Scientists from foreign institutions and NIH Intramural laboratories may participate as Project Leaders or as collaborators in Research Projects or scientific cores. NIH COORDINATOR. A scientist from the NIMH and/or NIDA extramural program staff who has substantial involvement in the Group above and beyond normal program stewardship. The Coordinator interacts scientifically with the Group and facilitates the role of NIMH and/or NIDA as partner in the Group. The Coordinator will be appointed after award by NIMH and/or NIDA. NIH PROGRAM OFFICIAL. A staff member of NIMH and/or NIDA who provides normal stewardship and guidance for the overall NCDDG-MD/NA Program within the NIMH or NIDA and ensures that the NCDDG-MD/NA Program maintains its relevance to the NIMH and NIDA mission for drug discovery and treatment development research. The Program Official also may serve as an NIH Coordinator for a Group. PRINCIPAL INVESTIGATOR. The scientist who is designated by the applicant institution to direct the NCDDG-MD/NA. The PI will assume responsibility and accountability to the applicant institution and to the NIMH and NIDA for the performance and proper conduct of the NCDDG-MD/NA in accordance with the terms and conditions specified in this RFA. It is expected that the PI will contribute at least a 25% effort to the Group. Foreign scientists and NIH intramural scientists may not be a Principal Investigator. RESEARCH PROJECT. A research component headed by a Project Leader within an NCDDG-MD/NA with a separate, detailed research plan and budget. Foreign institutions and NIH intramural laboratories may participate in a Research Project. RESEARCH PROJECT LEADER. A senior scientist with proven independent research capabilities who serves as director of one of the scientific Research Projects of the Group and is responsible for the scientific conduct of that program. The Principal Investigator of the Group may be a Project Leader. Foreign scientists and NIH intramural scientists may be Project Leaders. SPECIAL REQUIREMENTS A. The NCDDG-MD/NA Program objectives and goals should be relevant to and compatible with the NIMH and/or NIDA's priorities for innovative drug discovery, development of pharmacologic tools for research, and, for NIMH, development and validation of models for mood disorders as specified in this RFA. Applicants should describe their plans to accommodate the stated NCDDG-MD/NA requirements, criteria, and NIMH and/or NIDA involvement. B. A proposed Group can consist of scientific collaborators focused on one or two Research Projects without Cores (U01 mechanism) or at least three Research Projects and Scientific and Administrative Core components (U19 mechanism). It is anticipated that the Groups will include outstanding scientists from diverse scientific disciplines within neuroscience, neuropharmacology, neurobiology, medicinal chemistry, clinical neuroscience, mood disorders research, drug addiction research, radiochemistry, and pharmacokinetics into synergistic research teams without regard to institutional affiliation. C. A plan should be described for decision-making regarding identification and evaluation of promising drug candidates for development. D. Pharmaceutical partners should include key personnel who have authority within the company to allocate resources to ensure successful completion of the proposed discovery and development efforts. E. INTELLECTUAL PROPERTY AND PATENT RIGHTS FOR NEW CHEMICAL ENTITIES Since the discovery of new pharmacological treatments for mood disorders and nicotine addiction is a major objective of this effort and active involvement by pharmaceutical laboratories is encouraged and facilitated by the existence of adequate patent coverage, it is essential that applicants provide plans to assure the protection of intellectual property for NEW CHEMICAL ENTITIES for the treatment of mood disorders and/or nicotine addiction under this RFA. Successful applicants are required to supply the following confidential materials to the NIMH and NIDA Program Officials listed under INQUIRIES. 1. Each applicant Group must 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 the NIH Extramural Technology Transfer Policies and Documents [http://ott.od.nih.gov/NewPages/602-rev2.htm]. 2. 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, must be signed and dated by the organizational official authorized to enter into patent arrangements for each Group member and member institution. The signed agreement must be submitted prior to award to Drs. Linda Brady and/or William Corrigall at the addresses provided under INQUIRIES. 3. A plan must be developed for disposition of combinatorial and compound libraries generated in Research Projects focused on discovery of NEW CLINICAL ENTITIES as clinical candidates for drug development in conformance with TERMS AND CONDITIONS OF AWARD, Item 1. D, listed below. The signed document must be submitted prior to award to Drs. Linda Brady and/or William Corrigall at the addresses provided under INQUIRIES. 4. Prior to the award, the Principal Investigator and each Project Leader must provide a signed statement of acceptance of the participation of NIMH and/or NIDA staff during performance of the award as outlined under "NIMH and/or NIDA Staff Responsibilities" below. Note: Do NOT submit documents 1-4 above with the application. However, awards will not be made until these documents are received and approved by NIMH and/or NIDA. F. DATA SHARING PLAN FOR RESEARCH TOOLS AND MODELS TO EVALUATE THERAPEUTICS The NIH is also interested in ensuring that the RESEARCH TOOLS and MODELS developed through this RFA become readily available to the scientific community for further research, development, and application, in the expectation that this will lead to knowledge of benefit to the public. These TOOLS and MODELS are ones in which there are no intellectual property rights or patent position. In these cases, it is expected that the Principal Investigator's Data Sharing Plan will include the following elements: 1) Description of mechanisms by which program-generated research resources related to RESEARCH TOOLS and MODELS (e.g., compounds, radioligands, synthesis protocols, analytical tools, IND filing information for clinical research tools) are distributed to qualified investigators in the scientific community; and 2) a timetable for distribution. There should NOT be separate data sharing plans for each research component, but rather a single plan for the Group as a whole. Applicants are invited to utilize NIH supported repositories such as the NIMH Chemical Synthesis and Drug Supply Program (http://www.sri.com/biosciences/nimh/) or the NIDA Drug Supply Program to make compounds available to the scientific community as research tools. The sharing plan will be considered part of the scientific methodology for carrying out the research and, as such, the adequacy of the plan will be considered in determining funding priorities. Reviewers will assess the adequacy of the proposed plan as detailed in the review criteria section. The sharing plan as approved, after negotiation with the applicant when necessary, will be a condition of the award. G. An NIH intramural scientist may not serve as the Principal Investigator of an NCDDG-MD/NA but may participate in a Group as a Project Leader, Scientific Core Leader, collaborator, or consultant. However, an Intramural scientist may not receive salary, equipment, supplies, or other remuneration from this RFA. The Intramural scientist must obtain written approval of his/her NIH Institute Scientific Director for the amount of resources that may be allocated to the project; this amount must be specified in the letter, and can not exceed $200,000 in direct costs of intramural resources. The approval must also specify that the conduct of the project will comply with the DHHS regulations for research involving human subjects (if applicable) and with the PHS policy on vertebrate animal research. The participation of an intramural scientist is independent of and unrelated to the role of the NIMH and/or NIDA Coordinator as described below in TERMS AND CONDITIONS OF AWARD. For NCDDG-MD/NA applications that include NIH intramural components, the intramural resource level will be included in the total cost of the overall application. The involvement of Intramural scientists needs to be consistent with NIH Policy. http://www1.od.nih.gov/oir/sourcebook/ethic-conduct/ethical-conduct-toc.htm COOPERATIVE AGREEMENT TERMS AND CONDITIONS OF AWARD The following terms and conditions will be incorporated into the award statement and provided to the Principal Investigator as well as the institutional official at the time of award. Failure to abide by any of the Terms and Conditions 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 and Conditions of Award are in addition to and not in lieu of otherwise applicable OMB administrative guidelines, DHHS Grant Administration Regulations at 45 CFR parts 74 and 92, and other DHHS, PHS, and NIH Grant Administration policy statements. 1. Cooperative Agreement Mechanism The administrative and funding instrument used for this program is a cooperative agreement (U01 or U19), 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 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 Principal Investigator for the Group, although specific tasks and activities in carrying out these studies may be shared between the awardee and the NIH Coordinators assigned to the NCDDG-MD/NA. The tasks and activities are described more fully below. 2. Awardee Rights and Responsibilities a. The Principal Investigator will have primary authority and responsibility to define objectives and approaches and to plan and conduct the proposed research. She/he will assume responsibility and accountability to the applicant organization and to the NIMH and/or NIDA for performance and proper conduct of all research supported in the NCDDG-MD/NA, including the NIH intramural component, if applicable, in accordance with the Terms and Conditions of Award. b. The Group members will meet periodically to review progress, plan and design research activities, and establish priorities. Intramural research scientists participating as Research Project Leaders or collaborators have the same rights and responsibilities as other members of the Group. The NIMH and/or NIDA Coordinators and/or Program Officials may attend. The frequency of meetings, not fewer than two per year, will be determined by the Principal Investigator who will be responsible for scheduling the time and place (generally at one of the performance sites) and for preparing concise proceedings or minutes (two or three pages) which will be delivered to the members of the Group within 30 days of the meeting. The role of the NIMH and/or NIDA Coordinator is one of substantial involvement above and beyond the normal role of a Program Official, including, for example, assisting in research planning, suggesting studies within the scope of the Group's objectives and research activities, presenting experimental findings to the Group from published sources or from relevant contract projects, participating in the design of experiments agreed to by the Group, and participating in the analysis of results. c. The Awardee Institution and/or Research Project Leader's Institution will retain primary custody of and have primary rights to data as specified under either the NIMH and/or NIDA approved INTELLECTUAL PROPERTY PATENT RIGHTS AGREEMENTS FOR NEW CHEMICAL ENTITIES or the DATA SHARING PLAN FOR RESEARCH TOOLS AND MODELS TO EVALUATE THERAPEUTICS (described above). The Government, via the NIMH and/or NIDA Coordinator, will have access to data generated under this cooperative agreement and may periodically review the data consistent with current DHHS, PHS, and NIH policies. Timely publication of major findings by the Group members is encouraged. Publication or oral presentation of work done under this agreement will require appropriate acknowledgment of NIMH and/or NIDA support, including the assigned cooperative agreement award number. d. Ownership of compound libraries and/or combinatorial libraries for drug discovery acquired during the course of the research rests with the Group. Prior to award, the Group(s) must formulate a plan for final disposition of the compounds and ownership rights in the event that the compounds are transferred to other parties who make discoveries using them. This plan is to be approved by NIMH and/or NIDA. e. It is the intention that new chemical entities be fully evaluated as potential candidate drugs for mental health disorders and nicotine addiction or as potential research tools, after the Group has concluded its evaluation and before the compounds are transferred to other parties for evaluation in other therapeutic areas. The Groups must follow the NIMH and/or NIDA approved INTELLECTUAL PROPERTY PATENT RIGHTS AGREEMENTS FOR NEW CHEMICAL ENTITIES or the DATA SHARING PLAN FOR RESEARCH TOOLS AND MODELS TO EVALUATE THERAPEUTICS. 3. NIMH and NIDA Staff Responsibilities NIMH and/or NIDA Coordinators have substantial involvement in the Group above and beyond normal program stewardship. The Coordinator interacts scientifically with the Group. During performance of the award, NIMH and/or NIDA may provide appropriate assistance by participating in the design of activities, advising in the selection of sources for resources, staff, etc., and advising in management and technical performance. In all cases, the role of NIMH and/or NIDA will be to assist and facilitate and not to direct activities. The NIMH/NIDA Coordinator(s) can recommend to their Institutes to utilize their drug development resources (e.g., CNS receptor screening, chemical synthesis, and toxicology services) in support of the NCDDG-MD/NA Group research activities if such resources are required on an occasional basis. The following is a list of resources that are readily available and may be supplied if they become desirable during performance. It is not anticipated that requests of services will be considered as a continuing need. a. Reference compounds for standardization of test systems, as analytical standards, and for related purposes. b. Data from testing conducted in resource contract laboratories. c. Laboratory testing capacity, whenever appropriate and possible, in NIMH's and NIDA's current contract based preclinical testing programs. The Group is expected to provide sufficient test material for such testing. d. Additional needed resources such as test materials and information that may not otherwise be available to the Group. The NIMH/NIDA Program Officials are responsible for normal stewardship and monitoring implementation of the Data Sharing Plan for Research Tools and Models for Evaluating Therapeutics. 4. Collaborative Responsibilities The following are Collaborative Responsibilities of the Group and the NIMH and NIDA Coordinators. a. The principal end products of NCDDG-MD/NA activities are expected to include: 1) the discovery of new chemical entities, optimization of lead compounds, and the identification of clinical candidates for the treatment of mood disorders and/or nicotine addiction; as well as 2) research tools; and 3) preclinical models to evaluate novel therapeutics. Subsequent toxicity and safety studies of drug candidates and clinical developmental work through other resources are encouraged. b. NIMH and/or NIDA will retain the option to cross-file or independently file an application for an investigational clinical trial (e.g., an IND application to the United States Food and Drug Administration) of any clinical research tool or invention resulting from these NIMH and/or NIDA supported cooperative agreements. Reports of data generated by the Group or any of its members required for inclusion in IND applications and for cross-filing purposes shall be submitted promptly by the Principal Investigator to the NIMH and/or NIDA Coordinator upon request. Such reports shall include background information, methods, results, and conclusions. 5. Arbitration Any disagreement that may arise on scientific/programmatic matters (within the scope of the award, including the NIH intramural component), between the awardee and the NIMH and/or NIDA may be brought to arbitration. An arbitration panel will be composed of three members: one Group designee, one NIMH and/or NIDA designee, and a third designee with expertise in the relevant area chosen by the two designees. This special arbitration procedure in no way affects the awardee's right to appeal an adverse action in accordance with PHS regulations at 42 CFR Part 50, Subpart D, and DHHS regulations at 45 CFR Part 16. WHERE TO SEND INQUIRIES We encourage inquiries concerning this RFA and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into three areas: scientific/research, peer review, and financial or grants management issues: o Direct your questions about scientific/research issues to: Linda Brady, Ph.D. Chief, Molecular and Cellular Neuroscience Research Branch Chief, Neuropharmacology & Drug Discovery and Clinical Therapeutics Program Division of Neuroscience and Basic Behavioral Science National Institute of Mental Health 6001 Executive Boulevard, Room 7185, MSC 9641 Bethesda, MD 20892-9641 Rockville, MD 20852-9641 (for express/courier service) Telephone: (301) 443-5288 FAX: (301) 402-4740 Email: lb@helix.nih.gov William Corrigall, Ph.D. Chief, Translational Research Branch Director, Nicotine and Tobacco Addiction Program Division of Neuroscience and Behavioral Research National Institute of Drug Abuse 6001 Executive Boulevard, Room 4282, MSC 9555 Bethesda, MD 20892-9555 Rockville, MD 20852 (for express/courier service) Telephone: (301) 435-1324 FAX: (301) 594-6043 Email: wcorriga@nida.nih.gov o Direct your questions about peer review issues to: Michael Kozak, Ph.D. Chief, Extramural Review Branch Division of Extramural Activities National Institute of Mental Health 6001 Executive Boulevard, Room 6138, MSC 9608 Bethesda, MD 20892-9608 Rockville, MD 20852-9608 (for express/courier service) Telephone: (301) 443-1340 FAX: (301) 443-4720 Email: kozakm@mail.nih.gov o Direct your questions about financial or grants management matters to: Carol Robinson Grants Management Branch National Institute of Mental Health 6001 Executive Boulevard, Room 6118 Bethesda, MD 20892 Telephone: (301) 443-3858 FAX: (301) 443-6885 Email: crobinso@mail.nih.gov Gary Fleming, J.D., M.A. Grants Management Branch National Institute on Drug Abuse 6001 Executive Boulevard, Room 3131 Bethesda, MD 20892 Telephone: (301) 443-6710 FAX: (301) 594-6847 Email: gf6s@mail.nih.gov LETTER OF INTENT Prospective applicants are requested to submit a letter of intent that includes the following information: o Descriptive title of the proposed research o Name, address, and telephone number of the Principal Investigator o Names of prospective Project Leaders, other key personnel, and their respective participating institutions o Number and title of this RFA Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review. The letter of intent is to be sent by the date listed at the beginning of this document, and should be sent to: Linda Brady, Ph.D. Chief, Molecular and Cellular Neuroscience Research Branch Division of Neuroscience and Basic Behavioral Science National Institute of Mental Health 6001 Executive Boulevard, Room 7185, MSC 9641 Bethesda, MD 20892-9641 Rockville, MD 20852-9641 (for express/courier service) Telephone: (301) 443-5288 FAX: (301) 402-4740 Email: lb@helix.nih.gov APPLICATION PROCEDURES Applications must be prepared using the PHS 398 research grant application instructions and forms available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. For further assistance contact GrantsInfo, Telephone (301) 435-0714, Email: GrantsInfo@nih.gov. Potential applicants are strongly encouraged to contact NIMH/NIDA program staff early in the planning process. 1. SPECIFIC INSTRUCTIONS FOR PREPARING THE NCDDG-MD/NA AWARD U01 APPLICATION In addition to the details described here for U01 applications, applicants also need to be aware of information described under SPECIAL REQUIREMENTS in this announcement. Applications must be complete at the time of submission. Applicants are encouraged to organize the application by initially presenting the face page, the abstract page with key personnel, a table of contents, summary budget pages for the entire proposal, and other documentation pertaining to the entire project. This should be followed by an introductory section of no more than ten pages that provides a General Description of the NCDDG-MD/NA. The content requirements of this section are described in #3 below. Following the General Description(s), each component (the Research Projects) should be presented individually with its accompanying individual budget and justification, biographical sketches, other support pages, and research plan. For each Research Project component, there is a 25-page limit for the research plan (i.e., specific aims, background and significance, preliminary studies/progress report, and research design and methods), as indicated in the form PHS 398. Appendix material limits apply to each component separately, and appendices are limited to the contents specified in the form PHS 398. They should be bundled separately, component by component. For each individual Research Project, the research plan needs to address: o The major goals and objectives of the project and their relationship to the overall effort of the NCDDG-MD/NA. o The status of current research efforts, the limitations of existing approaches, and how the research questions posed relate to the objectives of the particular project and the NCDDG-MD/NA as a whole. o The feasibility of the proposed experiments, the advantages of new methodologies (if any), the potential pitfalls, alternative approaches, the means of assessing success of the research to meet the objectives of the project and the NCDDG-MD/NA as a whole. 2. SPECIFIC INSTRUCTIONS FOR PREPARING THE NCDDG-MD/NA AWARD U19 APPLICATION In addition to the details described here for U19 applications, applicants also need to be aware of information described under SPECIAL REQUIREMENTS in this announcement. Applications must be complete at the time of submission. Applicants are encouraged to organize the application by initially presenting the face page, the abstract page with key personnel, a table of contents, summary budget pages for the entire proposal, and other documentation pertaining to the entire project. This should be followed by an introductory section of no more than ten pages that provides a General Description of the NCDDG-MD/NA. The content requirements of this section are described below. Following the General Description(s), each component (the Research Projects and cores, if any) should be presented individually with its accompanying individual budget and justification, biographical sketches, other support pages, and research plan. For each Research Project there is a 25-page limit for the research plan (i.e., specific aims, background and significance, preliminary studies/ progress report, and research design and methods), as indicated in the form PHS 398. Appendix material limits apply to each component separately, and appendices are limited to the contents specified in the form PHS 398. They should be bundled separately, component by component. For each individual Research Project, the research plan needs to address: o The major goals and objectives of the project and their relationship to the overall effort of the NCDDG-MD/NA. o The status of current research efforts, the limitations of existing approaches, and how the research questions posed relate to the objectives of the particular project and the NCDDG-MD/NA as a whole. o The feasibility of the proposed experiments, the advantages of new methodologies (if any), the potential pitfalls, alternative approaches, the means of assessing success of the research to meet the objectives of the project and the NCDDG-MD/NA as a whole. For each core component, there is a 10-page limit. If cores are required, the applicant must describe how each Core will contribute to the goals of the overall NCDDG-MD/NA as well as how each individual Research Project will draw upon a particular Core. The description of each Core should clearly indicate the facilities, resources, services and professional skills that the facility will provide. Moreover, clearly described information must be provided about how the collective operation of the Cores will be effected in a coherent manner. 3. SPECIFIC INSTRUCTIONS FOR PREPARING THE GENERAL DESCRIPTION OF THE NCDDG-MD/NA This section is to accompany both U01 and U19 applications. The section must not exceed 10 pages, and should provided the following details: o An overview of the proposed NCDDG-MD/NA Group, its central theme and goals; this overview should describe the general objectives, and explain the proposed contribution of each of the individual Research Projects and Cores (if any) towards achieving the objectives of the Group. The administrative arrangements and research support should be described. In particular, when more than one institutional site is involved, a detailed description and supporting documentation for the administrative arrangements must be included. Detailed information on collaborations, facilities, and resources must also be provided. o A clear description of how each component Research Project is required for the attainment of the NCDDG-MD/NA Program's objectives, including available professional and technical personnel to permit efficient and successful conduct of the proposed research, and description of the contribution of each to fulfillment of group objectives. The name, organization, and scientific discipline of the Principal Investigator, Research Project Leaders, and other key personnel should be included. A clear description of the interrelationships among the members of the group needs to be made. o Evidence needs to be provided that each component Research Project and the Group as a whole have available facilities required for conduct of the proposed research. o A plan to assure the maintenance of close collaboration and effective communication among members of the group that will include letters of commitment to this plan by all Research Project Leaders. Include plans for scheduling group meetings, notifying group members (including the NIMH and NIDA), and documenting and disseminating group meeting proceedings. o Description of the steps that will be taken to ensure successful completion of the NCDDG-MD/NA's research should a key member leave the Group. 4. SUPPLEMENTAL INSTRUCTIONS FOR NIH INTRAMURAL RESEARCHERS NIH intramural researchers collaborating on an NCDDG-MD/NA must obtain the approval of his/her NIH Institute Scientific Director for participating under the terms and conditions of the RFA. A copy of that letter of approval must be provided in the application. NIH intramural researchers submitting an Individual Research Project as a part of an NCDDG-MD/NA, must follow the procedures for Individual Research Projects as described above, with the following additional modifications. o On the Face Page, fill out only items 1., 2., 3. (leave 3c. blank), 4., and 5. The remainder of the items should be left blank, and the application must not be signed by either the PI or an NIH Institute official. o The Individual Research Project PI must obtain the approval of his/her NIH Institute Scientific Director for participating as a component of the NCDDG-MD/NA under the terms and conditions of the RFA. A copy of that letter of approval must be provided in the application. o The Research Project component should NOT contain the "Other Support" pages. o The individual budget pages should supply the time and effort for each project participant, but no other budget figures should be included. The resources available for the Research Project and the research environment should be carefully described, but no budget figures should be included. The NIH Institute Scientific Director, as part of the letter of approval for participation, must verify that no more than $200,000 direct costs of intramural resources will be allocated to the project described in the application, and provide assurance that the conduct of the project will comply with the DHHS regulations for research involving human subjects (if applicable) and with the PHS policy on vertebrate animal research. FOR ALL APPLICATIONS The RFA label available in the PHS 398 (rev. 5/2001) application form must be affixed to the bottom of the face page of the application. Type the RFA number on the label. 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 2 of the face page of the application form and the YES box must be marked. The RFA label is also available at: http://grants.nih.gov/grants/funding/phs398/label-bk.pdf. Submit a signed, typewritten original of the application, including the Checklist, and three signed, photocopies, in one package to: CENTER FOR SCIENTIFIC REVIEW NATIONAL INSTITUTES OF HEALTH 6701 ROCKLEDGE DRIVE, ROOM 1040, MSC 7710 BETHESDA, MD 20892-7710 BETHESDA, MD 20817 (for express/courier service) At the time of submission, two additional copies of the application must be sent to: Jean G. Noronha, Ph.D. Division of Extramural Activities National Institute of Mental Health 6001 Executive Boulevard, Room 6154, MSC 9609 Bethesda, MD 20892 Rockville, MD 20852 (for express/courier service) Telephone: (301) 443-3367 FAX: (301) 443-4720 Email: jnoronha@mail.nih.gov Applications must be received by the application receipt date listed in the heading of this RFA. If an application is received after that date, it will be returned to the applicant without review. Supplemental documents containing significant revision or additions will not be accepted. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed by the CSR for completeness, and by NIMH/NIDA program staff for responsiveness. Incomplete or non-responsive applications will be returned to the applicant without review. 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 NIMH in accordance with the review criteria stated below. As part of the initial merit review, all applications will: o Receive a written critique o Undergo a process in which only those applications deemed to have the highest scientific merit, generally the top half of the applications under review, will be discussed and assigned a priority score o Receive a second level review by the NIMH and/or NIDA National Advisory Council. REVIEW CRITERIA The goals of NIH-supported research are to advance our understanding of biological systems, improve the control of disease, and enhance health. Within this framework, the specific goals of this RFA are drug discovery and preclinical evaluation of new drugs to treat mood disorders and nicotine addiction, the development of pharmacologic tools for basic and clinical research, and, for mood disorders, the development and validation of models for evaluating novel therapeutics. In the written comments reviewers will be asked to discuss the following aspects of the application in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. The scientific review group will address and consider each of the following criteria in assigning the overall score, weighting them as appropriate for each application. Individual Research Projects and Cores within the NCDDG-MD/NA, as well as the NCDDG-MD/NA as a whole, will be evaluated. REVIEW CRITERIA FOR THE NCDDG-MD/NA AS A WHOLE 1. Significance. Is the Group addressing an important problem? If the aims of the application are achieved, what is the likelihood that it will produce a new candidate drug for development? What will be the effect of these studies on the concepts or methods that drive this field? To what degree does the proposed plan for discovery of novel drugs, research tools, and/or preclinical models support the needs for the targeted disease? 2. Approach. Are the conceptual framework, design, and methods adequately developed, well integrated, and appropriate to the aims of the project? Are the scientific disciplines represented in Research Projects and Scientific Cores adequate to achieve the NCDDG-MD/NA Program objectives? Does the applicant acknowledge potential problem areas and consider alternative tactics? Are targets, screens, and preclinical models relevant to mood disorders and/or nicotine addiction? If pharmaceutical partnerships are proposed, how will they facilitate the development and evaluation of candidate drugs, tools for clinical research, and model validation for testing therapeutics? 3. Innovation. Does the NCDDG-MD/NA employ novel concepts, approaches or methods? Are the aims original and innovative? Does the NCDDG-MD/NA challenge existing paradigms, develop new research tools, models, methodologies, or technologies? Is the target under investigation for drug discovery novel? Will new paradigms for drug discovery emerge? 4. Investigators. Are the Principal Investigator, Research Project Leaders, and Core Leaders appropriately trained and well suited to direct or carry out this work? Are the time commitments for each sufficient to achieve the goals? To what extent do these investigators have complementary skills? Will the Research Project Leaders and their key personnel contribute unique skills to the NCDDG-MD/NA? Is the work proposed appropriate to the experience level of the key personnel and other researchers? Has the Principal Investigator demonstrated leadership in development, implementation, and management of comprehensive research programs? 5. Environment. Does the technical and scientific environment in which the Research Projects will be done contribute to the probability of success? Does the proposed work take advantage of unique features of the technical and scientific expertise and employ effective collaborations? Is there evidence of institutional support and competence of the applying Institution to serve as the Administrative Core for the Group? 6. Interaction. Are there adequate plans for ensuring effective intra-Group communication, interaction, cohesiveness, and coordination among the PI, Research Project Leaders, and NIH Coordinators? Do the investigators state their willingness to collaborate extensively and share information fully? Do the investigators state their willingness to abide by the policies stated in the Terms and Conditions of the Cooperative Agreement? 7. Data Sharing Plan. How appropriate are the proposed plans for making research tools, synthesis protocols, analytical tools, preclinical models, IND filing information, or other resources generated under the project widely available to the scientific community? Are the plans and timetable for distribution adequate for effective dissemination of the proposed resources? REVIEW CRITERIA FOR RESEARCH PROJECTS 1. Significance. Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge or technology be advanced? What will be the effect of these studies on the concepts or methods that drive this field? 2. Approach. Are the conceptual framework, design, and methods adequately developed, well integrated, and appropriate to the aims of the project? Are the scientific disciplines represented in Research Projects adequate to achieve the objectives? Does the applicant acknowledge potential problem areas and consider alternative tactics? Is the plan to optimize lead structures adequate to ensure that the most efficacious drug will result? If pharmaceutical partnerships are proposed, how will they facilitate the discovery and development of drugs and evaluation of research tools or models? 3. Innovation. Does the Research Project employ novel concepts, approaches or methods? Are the aims original and innovative? Does the project challenge existing paradigms or develop new tools, methodologies, or technologies? 4. Investigators. Are the Research Project Leader and key personnel appropriately trained and well suited to direct or carry out this work? Is the Project Leader's time commitment sufficient to achieve the goals? Is the work proposed appropriate to the experience level of the key personnel and other researchers? Have collaborations been established or consultants identified to provide the appropriate depth and breadth of expertise required for the project? 5. Environment. Does the technical and scientific environment in which the work will be done contribute to the probability of success? Does the proposed work take advantage of unique features of the technical and scientific expertise and employ effective collaborations? 6. Management of the Group. Especially for the U19 mechanism, does the PI have previous experience of the ability to manage an integrated scientific enterprise? Do other members of the Group have experience that will facilitate achieving the desired research outcomes. REVIEW CRITERIA FOR CORES 1. The utility of the Core to the NCDDG-MD/NA. Each Core must provide essential facilities or services to two or more Research Projects judged to have scientific merit. 2. The quality of the facilities or services provided by the Core. 3. The qualifications and experience of the personnel involved in the Core. ADDITIONAL CONSIDERATIONS In addition to the above criteria, in accordance with NIH policy, all applications will also be reviewed with respect to the following: o The review group will critically examine the budget requested for each Research Project, Core, and overall NCDDG-MD/NA and will recommend an appropriate budget and period of support. o The adequacy of plans to include genders, minorities and their subgroups, and children as appropriate for the scientific goals of the research. Plans for the recruitment and retention of subjects will also be evaluated. o The reasonableness of the proposed budget and duration in relation to the proposed research. o The adequacy of the proposed protection for humans, animals or the environment, to the extent they may be adversely affected by the project proposed in the application. RECEIPT AND REVIEW SCHEDULE Letter of Intent Receipt Date: October 25, 2002 Application Receipt Date: November 26, 2002 Peer Review Date: February/March 2003 Council Review: May 2003 Earliest Anticipated Start Date: July 1, 2003 AWARD CRITERIA Award criteria that will be used to make award decisions include: o Scientific and technical merit (as determined by peer review) o Availability of funds o Programmatic priorities REQUIRED FEDERAL CITATIONS MONITORING PLAN AND DATA SAFETY AND MONITORING BOARD: Research components involving Phase I and II clinical trials must include provisions for assessment of patient eligibility and status, rigorous data management, quality assurance, and auditing procedures. In addition, it is NIH policy that all clinical trials require data and safety monitoring, with the method and degree of monitoring being commensurate with the risks (NIH Policy for Data Safety and Monitoring, NIH Guide for Grants and Contracts, June 12, 1998: http://grants.nih.gov/grants/guide/notice-files/not98-084.html). 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 are provided indicating 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 clinical research should read the AMENDMENT "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research - Amended, October, 2001," published in the NIH Guide for Grants and Contracts on October 9, 2001 (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the new PHS Form 398; and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) all investigators must report accrual and progress in conducting analyses, as appropriate by sex/gender and/or racial/ethnic group differences. INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS: It is the policy of NIH that children (i.e., individuals under the age of 21) must be included in all human subjects research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them. This policy applies to all initial (Type 1) applications submitted for receipt dates after October 1, 1998. All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines" on the Inclusion of Children as Participants in Research Involving Human Subjects that was published in the NIH Guide for Grants and Contracts, March 6, 1998, and is available at the following URL address: http://grants.nih.gov/grants/guide/notice-files/not98-024.html. REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS: NIH policy requires education on the protection of human subject participants for all investigators submitting NIH proposals for research involving human subjects. This policy announcement is found in the NIH Guide for Grants and Contracts Announcement dated June 5, 2000, at the following website: http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html. PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT: The Office of Management and Budget (OMB) Circular A-110 has been revised to provide public access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are (1) first produced in a project that is supported in whole or in part with Federal funds, and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this RFA in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award. URLS IN NIH GRANT APPLICATIONS OR APPENDICES: All applications and proposals for NIH funding must be self-contained within specified page limitations. Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) should not be used to provide information necessary to the review because reviewers are under no obligation to view the Internet sites. Reviewers are cautioned that their anonymity may be compromised when they directly access an Internet site. HEALTHY PEOPLE 2010: The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS led national activity for setting priority areas. This RFA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople/. AUTHORITY AND REGULATIONS: This program is described in the Catalog of Federal Domestic Assistance No. 93.242 (NIMH) and 93.279 (NIDA). Awards are made under authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and administered under NIH grants policies and Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. The PHS strongly encourages all grant recipients to provide a smoke-free workplace and promote the non-use of all tobacco products. 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, 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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