COLLABORATIVE CENTERS FOR PARKINSON"S DISEASE ENVIRONMENTAL RESEARCH Release Date: December 6, 2001 RFA: RFA-ES-02-003 (See Notice NOT-ES-07-002 Notice of New Round of Competition with Broadened Scope) (see NOT-ES-04-007) National Institute of Environmental Health Sciences (http://www.niehs.nih.gov) Letter of Intent Receipt Date: February 14, 2002 Application Receipt Date: March 14, 2002 PURPOSE OF PROGRAM A variety of lines of evidence suggest that both environmental and genetic factors contribute to sporadic Parkinson"s Disease (PD), the most common form of the disease. Identification of the full complement of relevant environmental and genetic components, and an understanding of their interactive roles in the neurodegenerative process, is lacking. Such information is critical for designing effective prevention and intervention strategies. To accelerate the pace of progress in this important area and the translation of findings into the public health arena, the NIEHS is creating a Collaborative Centers for Parkinson"s Disease Environmental Research (CCPDER) Consortium Program to foster multidisciplinary research approaches to elucidate gene-environment interactions in PD. This program seeks to provide the science-based foundation for efforts to prevent and/or ameliorate the devastating effects of this disease. The NIEHS CCPDER Consortium Program will consist of a highly interactive national network that will be formed from up to three individual CCPDERs. The network will function to share data and resources and engage in the planning and conduct of collaborative studies to understand the joint contribution of genes and environment in the etiology of PD. In addition to its role in the larger network, each CCPDER will engage in a self-contained program of research activities that focus on gene-environment interactions in PD. Each CCPDER will consist of a multidisciplinary team with expertise in several of the following areas: (1) basic cellular and molecular neurobiology, (2) human genetics, (3) epidemiology, (4) clinical research, and (5) community outreach and education. Each CCPDER will support several integrative research projects and core services/facilities as may be needed for the proposed research. An integrative research project is one that proposes new work to amplify, extend or bridge an existing external peer reviewed and funded grant or grants in PD and that will incorporate multidisciplinary research approaches. Taken together, the integrative projects contained within a CCPDER will address an overarching gene-environment hypothesis or set of hypotheses in PD. To facilitate joint activities among CCPDERs, one CCPDER will be selected to serve as a Coordinating Center (CCPDER-CC). The CCPDER-CC will develop a formal mechanism for ongoing information exchange with PD patient advocates that includes opportunities for advocates to provide input concerning research directions and priorities. Collaborative activities among CCPDERs will be overseen by a CCPDER Consortium Program Steering Committee involving representation from each CCPDER and from the NIEHS. The individual CCPDERs will be funded through an NIH Cooperative Agreement U54 mechanism, the goal of which is to maximize the collaborative utilization of the unique resources in infrastructure and expertise that will be created. 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 Request for Applications, Collaborative Centers for Parkinson"s Disease Environmental Research, is related to the priority area of environmental health. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople/. ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic non-profit and for-profit organizations, private and public, such as universities, colleges, private companies, hospitals, laboratories, units of state or local governments, and eligible agencies of the Federal government. The applicant institution must be domestic. Foreign institutions are not eligible for U54 grants. Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as Principal Investigators. Applicants will be allowed to propose multi-institutional arrangements within the context of a single CCPDER application. At the time of submission, at least two of the integrative research projects for a CCPDER must be from investigators at the applicant organization. MECHANISM OF SUPPORT This RFA will use the National Institutes of Health (NIH) Cooperative Agreement (U54 Specialized Cooperative Center program award mechanism). The total project period requested for applications responding to this RFA is five years. A U54 mechanism provides support for both research project components and core facilities. A cooperative agreement is an "assistance" mechanism (rather than an "acquisition" mechanism) in which substantial NIH scientific or programmatic involvement with the awardee is anticipated during the performance of the activity. Under the cooperative agreement, the NIEHS role is to support and/or stimulate the recipient"s activity by working jointly with the award recipient as a partner, but it is not to assume direction, prime responsibility, or a dominant role in the activity. Details of the responsibilities, relationships and governance of the studies to be funded under a cooperative agreement are discussed later in this document under the section "Terms and Conditions of Award". The anticipated award date is August 2002. This RFA is a one-time solicitation. The NIEHS has not yet determined whether this or a related RFA will be issued in the future to continue the program described in this RFA. FUNDS AVAILABLE The NIEHS has budgeted total costs of up to $4 million (overall program) for each of the five years for awards made in response to this RFA. The NIEHS expects to make up to 3 awards as a result of this RFA. Two of the three CCPDER awards may receive up to $860,000 (Direct Cost) in each of the five years. One CCPDER will be selected (see AWARD CRITERIA) to serve as a Coordinating Center (CCPDER-CC), an additional $122,000 (Direct Cost) may be requested for activities associated with this function. Thus, the CCPDER-CC may receive up to $982,000 ($860,000 plus $122,000 Direct Costs) in each of five years. Because the nature and scope of the research posed in applications may vary, it is anticipated that the size of the awards may vary. The number of awards and the level of awarded support depend on the receipt of a sufficient number of applications of high scientific merit. Although this RFA program is provided for in the financial plans of the NIEHS, awards pursuant to this RFA are contingent upon the availability of funds for this purpose. Unless otherwise noted, all NIH grant policies apply. RESEARCH OBJECTIVES Background Spurred by recent landmark scientific findings, there is now an emerging appreciation that Parkinson"s disease, like most human diseases, reflects the interaction of genetic susceptibility with environmental exposure(s). What is lacking, however, is a clear mechanistic understanding of the nature of such interactions in disease causation. Such information is essential for developing rational approaches to disease prevention and intervention. It is envisioned that the CCPDER Consortium Program will provide a formal mechanism to strengthen the integrative collaboration among scientists engaged in fundamental laboratory research in PD and geneticists, clinicians and epidemiologists. Historically, such integration has provided some of the most significant advances in the field of Parkinson"s disease. As one example, the initial clinical observations of MPTP-exposed subjects in the 1980"s led to the best available animal model of PD, opened fruitful lines of investigation into other potential environmental exposures and provided a mechanistic framework for studying nigral cell death mechanisms. Likewise, the recent identification of alpha synuclein mutations in rare familial PD stimulated intense mechanistic investigations of the functional roles of this protein family and its interaction with potential environmental risk factors. The aim of the Consortium would be to increase the speed with which newly promising lines of investigation such as these can be identified and pursued at multiple levels of analysis and for which greater resources can be targeted. The three main research objectives of the CCPDER Consortium Program are to: o Identify genetic and environmental factor interactions that contribute to PD. o Provide a mechanistic understanding of how gene-environment interactions trigger the pathophysiological processes that ultimately produce PD. o Develop the knowledge base to enable translation of research findings into rational prevention and intervention strategies for PD. Research Opportunities: An NIEHS sponsored scientific workshop was held in Colorado Springs prior to the International Neurotoxicology Society"s 2001 conference. Both the workshop and the conference focused on gene-environment interactions in PD. After consideration of the research findings and knowledge gaps identified at these meetings, a number of fruitful research questions that are well suited to the multidisciplinary approach envisioned in the CCPDER Consortium program have been formulated. These specific research opportunities are: o Mutations and polymorphisms in relevant PD genes: Defining the genetic susceptibilities of this disease are critical for understanding the molecular pathways leading to PD and how environmental exposures can trigger key events in these pathways. Studies of familial PD have revealed a number of causative disease genes and/or loci with apparent Mendelian inheritance patterns, including alpha-synuclein and parkin. Other studies have sought to identify PD susceptibility genes using linkage studies in families, DNA sequencing of candidate genes, and allelic association studies. In most cases, the candidate genes tested have been those with clear relevance to potential mechanisms of PD pathogenesis, including genes involved in detoxification of exogenous agents. A number of positive genetic associations with PD have been reported (e.g., CYP2D6 and MAOB) although many findings have been inconsistent. A major difficulty in identifying susceptibility genes that confer increased risk but do not cause the disease is the need for large sample sizes, with appropriate controls and standardized diagnostic criteria. Clearly, improvements in study design are needed to tease out genetic factors that may impart small but significant risk of PD. Studies to elucidate how PD susceptibility genes may interact with environmental agents to trigger the neurodegenerative processes observed in PD are of particular interest. o Environmental risk factors: Epidemiological studies have associated occupational exposures to heavy metals and agricultural chemicals with the risk of developing PD. Though the picture is not complete, there is ample preliminary evidence to consider this a fruitful avenue of research. A related and critically important need is for improvements and standardization in exposure assessment methodologies. The long preclinical course of PD, and the consequent need for retrospective assessments, makes this an especially challenging task. The relationships between these exposures and genetically determined individual differences are of special interest. Multidisciplinary efforts to elucidate the biochemical mechanisms underlying epidemiological findings in PD are warranted. Recent studies examining the interaction of pesticides with alpha synuclein demonstrate the utility of such an approach. o Oxidative stress: There is a vast literature on the role of reactive oxygen in neuronal degeneration. The knowledge that many environmental toxicants are known and putative oxidative stressors provides a mechanistic link to PD, but a cohesive description of the primary events as well as a reason for the special selectivity of the nigral neurons in PD has thus far defied resolution. A number of factors that merit further study are (1) dopamine metabolism to isoquinones and thioethers, (2) iron metabolism, and (3) mitochondrial complex I dysfunction. The relation between oxidative stress and lipid peroxidation, DNA adducts, the generation of nitric oxide and the formation of peroxynitrites, are other areas of possible relevance to PD research. The joint effects of environmental agents and PD susceptibility genes on cellular oxidative stress, and their impact on apoptosis pathways are of special interest. o Neuroprotection: Studies to understand mechanisms of neuroprotection could have immediate relevance to the clinical setting and are especially suited to a multidisciplinary approach. Evidence exists from epidemiological studies that smokers and coffee drinkers have a lower risk of developing PD. Despite the myriad of chemicals in cigarette smoke, the most productive avenue of study appears to be on the role of nicotine. Similarly, the potential for the protective effect of caffeine in coffee has engendered the greatest interest. o Protein aggregation and metabolism: Protein overexpression and aggregation appear to be part of the cascade of events associated with PD. There is a clear need for a better understanding of which events are critical to developing PD and which are a consequence of PD development, but not implicated in its development. An understanding of Lewy body formation is essential. In addition to elucidating the process by which Lewy bodies form, it has yet to be resolved as to whether their formation plays a part in a toxic or protective process. A related need is to define pathways of alpha synuclein aggregation, its protein partners and its role in nigral cell death. Likewise, the role of ubiquitin and protein degradation/ proteosomal pathways in the neurodegenerative process merits further investigation. o Development of new animal models: Without new and better disease models, translation of research findings to the clinical setting is stymied. Models that can be used to elucidate the interaction of genetic susceptibility with environmental exposures are of special interest. A number of promising animal models of PD have been developed recently, including ones based on exposure to pesticides and agrichemicals (e.g., rotenone, paraquat and maneb) as well as transgenic models of alpha synuclein expression in mice and Drosophila. Further studies to exploit these models, and to develop new models, are needed. o Other Research Opportunities: The roles of the inflammatory process and endotoxin exposure also have been implicated in the degenerative process and deserve further study. The development of both biomarkers of exposure and disease are needed. All research areas would benefit from reliable biomarkers for accurate diagnosis. The above research opportunities are not intended as an exhaustive list, but as examples of research questions that lend themselves to the multidisciplinary approach envisioned by the CCPDER Consortium program. Applicants are urged to consider any additional research opportunities that are consistent with the stated goals of the CCPDER Consortium program. ORGANIZATION OF CCPDERs Each CCPDER will have a team of appropriate investigators, a set of integrative research projects and a collection of support cores. There must be substantive and documented departmental and institutional infrastructure, support for and commitment to the proposed CCPDER. Each CCPDER applicant must also document their willingness to cooperate in a coordinated manner within the CCPDER network. Investigators with the qualifications to be members of a CCPDER research team, and to contribute to such a unique enterprise, may be located in different geographic locations. Therefore, collaborations among different domestic institutions are encouraged, if scientifically appropriate. The terminology used throughout this document relative to CCPDERs is as follows: COLLABORATIVE CENTER FOR PARKINSON"S DISEASE ENVIRONMENTAL RESEARCH (CCPDER): The organized awardee infrastructure supporting a coordinated U54 program of NIEHS mission relevant research being conducted by an organized group of scientists. CCPDER consist of three components: integrative research projects, an administrative core and resource, service or facilities cores. CCPDER COORDINATING CENTER (CCPDER-CC): A CCPDER with the additional responsibility of providing administrative coordination of Consortium meetings and workshops and information dissemination to affected scientific and lay communities. CCPDER CONSORTIUM PROGRAM: An interacting consortium group comprised of up to three U54 CCPDERs awarded as a result of this RFA. INTEGRATIVE RESEARCH PROJECT: A research project that proposes new work to amplify, extend or bridge an existing external peer reviewed and funded grant or grants in PD and that will incorporate multidisciplinary research approaches. PRINCIPAL INVESTIGATOR. Each CCPDER will have a Director (the CCPDER Principal Investigator) who will make scientific and administrative decisions relating to the CCPDER, will oversee identification and selection of key personnel, and will be responsible for allocation and monitoring of CCPDER funds. The CCPDER Director must also direct one of the integrative research projects that comprise the CCPDER. The CCPDER Director must have significant and documented expertise in PD and a strong commitment to studying gene- environment interactions in PD. The CCPDER Director must have existing external peer-reviewed funding in PD that will continue for at least two years following the receipt of the CCPDER award (August 2002). This funding should be from regular research grants supported by NIEHS, other NIH institutes and centers, and other governmental and private agencies in the area of PD. PROJECT LEADERS. Each integrative research project (defined below) will be directed by a competent and experienced scientist with expertise in PD or a closely related area of neurodegeneration. The scientist responsible for a specific project within the overall CCPDER may be identified as that project"s Project Leader, Co-Principal Investigator or Director. Project Leader is the preferred term. Collectively, the Project Leaders must comprise a multidisciplinary team with expertise in cellular and molecular neurobiology in addition to at least two of the following four areas of PD research: (1) human genetics, (2) epidemiology, (3) clinical research, and (4) community outreach and education. Each project leader must have existing external peer-reviewed funding in PD or a closely related neurodegenerative disease. This funding must continue for at least two years following the receipt of the CCPDER award (August 2002) and must provide the primary scientific foundation for the proposed integrative research project. This peer-reviewed funding should be from individual investigator research grants or equivalent subprojects of program grants supported by NIEHS, other NIH institutes and centers, and other governmental and private agencies in the area of PD or a conceptually related area of neurodegeneration. INTEGRATIVE RESEARCH PROJECTS. Each CCPDER will propose at least three integrative research projects in the general area of gene-environment interaction in PD. These projects must be guided by a unifying hypothesis or interrelated set of hypotheses. Although existing external peer-reviewed grant funding must provide the scientific foundation for each integrative research project, the studies proposed in each integrative research project in the CCPDER application must represent a clear and significant extension or amplification of a single existing external peer reviewed grant. Alternatively, an integrative research project may propose studies that bridge, or tie together, two or more existing external peer reviewed grants. The integrative research project cannot represent a duplication of the currently funded research contained within the parent grant(s). Each integrative research project proposed must incorporate a multidisciplinary approach. SCIENTIFIC FUNDING BASE. The collective scientific funding base for each CCPDER, defined as the set of external peer reviewed grants that provide the foundation for the integrative research projects, must total at least $500,000 in annual direct costs. This funding base must extend for at least two years following the receipt of the CCPDER award (August 2002). Each integrative research project can be based on more than one existing grant, as in the case where an integrative research project has the goal of bridging the efforts of two or more existing grants. In such cases, at least one of the grants must meet the two year funding duration requirement cited above and will serve as the qualifying grant for that integrative research project, the grant or grants that bridge to the qualifying grant must extend for at least one year following CCPDER award receipt (August 2002). Each existing grant may provide the primary basis for only one integrative research project. That is, it is not permissible to propose two or more integrative research projects that represent different extensions or different bridging efforts of the same existing grant or set of grants. CORES. A Core is a shared central laboratory or clinical research facility, service, or resource. All Cores must serve a minimum of two integrative research projects. As a minimum, each CCPDER will propose an Administrative Core and a Research Development Core. The administrative Core will provide a structure to coordinate and integrate CCPDER components and activities, plan and review utilization of funds and provide support and advice to the CCPDER Principal Investigator in his/her oversight of the activities of the CCPDER. The Research Development Core will provide a structure for developing and supporting pilot projects, including those to be conducted collaboratively with other CCPDERs. An applicant may propose additional technical/facility Cores as required to conduct the proposed integrative research projects. A CCPDER may propose new Core(s) or may describe a mechanism to access (e.g., fee for service or shared costing) existing Cores. Applicants may propose use of Core services located outside of the applicant institution through a subcontractual arrangement. Each Core is directed by a faculty investigator (the Core Director) with substantial expertise related to the core. Two important and related considerations are (1) the degree to which currently funded investigators within or outside the CCPDER will use and will benefit from core resources and (2) the degree to which the resources will promote new and/or expanded PD research efforts within the overall activities of the CCPDER Consortium Program. An Executive Committee (composed of Core directors and Project leaders) must be established in each CCPDER to assist the CCPDER Director in making scientific and administrative decisions. The executive committee should be encouraged to seek outside advice and consultation, both from within the institution and from other institutions, in its monitoring and development of the scientific content and direction of the program. An External Advisory Committee to each CCPDER, consisting of scientists from outside of the institution or consortium, must also be proposed. The External Advisory Committee members should neither be contacted nor recruited until the NIH review process is complete. This committee will be used to evaluate the programs of the CCPDER, research progress, the effectiveness of communications within the CCPDER, and any other activities for which outside expertise is required or desirable. The committee should meet annually and prepare a report including recommendations to assist the CCPDER. It is expected that this committee include significant representation from PD advocacy groups. The NIEHS Extramural Science Administrator and the NIEHS Extramural Program Administrator (see definitions under SPECIAL REQUIREMENTS FOR COOPERATIVE AGREEMENT section) for the CCPDER Consortium Program should be invited to attend each meeting as observers. A copy of the advisory committee report should be sent to the NIEHS Extramural Science Administrator and to the NIEHS Extramural Program Administrator. An applicant responding to this RFA who wishes to be considered to be a Coordinating Center (CCPDER-CC) should indicate this interest and must include additional Core components. That is, the CCPDER-CC must include an Information Dissemination/Outreach Core to provide a formal mechanism for making available information about Consortium activities to the affected scientific and lay communities. Applicants who do not wish to be considered for a CCPDER-CC should not include this Core. The Information Dissemination/Outreach Core will be responsible for creating and maintaining a listserver and website for the CCPDER Consortium Program suited for use by both the scientific and lay communities interested in PD. The website should include timely information about the CCPDER Consortium Program, activities and accomplishments. The prospects for translation of CCPDER research findings into clinical practice should be highlighted. In addition, the CCPDER-CC will have an expanded Administrative Core to provide for effective coordination of one annual CCPDER Consortium Program general scientific meeting to report and evaluate progress of the integrative research projects and one annual scientific workshop on an emerging topic in PD. The scientific topic for the annual workshop will be determined by the CCPDER Consortium Program Steering Committee. The CCPDER Consortium Program annual scientific meeting should include a forum for information exchange with PD advocacy groups, including opportunities for advocates to provide input concerning CCPDER Consortium activities. In addition to the $860,000 (Direct costs) that may be requested to support a CCPDER, an applicant may request an additional $122,000 Direct costs annually to support the additional responsibilities associated with a CCPDER-CC. Thus, an applicant for the CPDER-CC may request $982,000 ($860,000 plus $122,000) in Direct Costs, annually. I. Terms and Conditions of Award The following terms and conditions will be incorporated into the U54 award statement, and will be provided to the appropriate Institutional Official, at the time of award. Failure to abide by any of the TERMS AND CONDITIONS OF AWARD pertaining to awardee responsibilities as stipulated, may result in reduction of funding, withholding of support, or suspension or termination of award. These special TERMS AND CONDITIONS OF AWARD 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 [Part 92 is applicable when State and local Governments are eligible to apply], and other HHS, NIH, and NIH grant administration policies. A. The administrative and funding instrument used for this program will be the Cooperative Agreement (U54 Specialized Center). The cooperative agreement is an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH scientific and/or programmatic involvement with the awardee is anticipated during the performance of the activity. Under the Cooperative Agreement, the NIH purpose is to support and/or stimulate the recipient"s activity by involvement in and otherwise working jointly with the award recipient in a partner role, but it is not to assume direction, prime responsibility, or a dominant role in the activity. Consistent with this concept, the dominant role and prime responsibility for the activity supported by a cooperative agreement resides with the awardee for the project as a whole, although specific tasks and activities in carrying out the study will be shared among the awardee(s) and the NIEHS. B. Awardee Rights and Responsibilities: 1. The Principal Investigator is the scientist who is designated by the awardee institution who will direct the U54 CCPDER. The Principal Investigator will have primary authority and responsibility to define objectives and approaches, and to plan and oversee the proposed research. The Principal Investigator will assume responsibility and accountability to the applicant institution and to the NIEHS for the performance and proper conduct of the research in accordance with the TERMS AND CONDITIONS OF AWARD. The Principal Investigator of each U54 CCPDER will: o Manage the coordination of the specific integrative research projects o Oversee the management of the administrative and facilities cores o Provide yearly summaries of progress during the annual CCPDER Consortium Program Steering Committee meetings. The Principal Investigator of the U54 CCPDER-Coordinating Center (CC) will: o Manage the coordination of the Information Dissemination Outreach Core specific to this Center, including coordination with the NIEHS for the standards and practices associated with the CCPDER Website as described in the RFA. o Direct the planning and management of annual CCPDER Consortium Program general scientific meetings and workshops. o Provide yearly summaries of progress of the Information Dissemination Outreach Core during the annual CCPDER Consortium Program Steering Committee meetings. 2. The Principal Investigator or designated representative will serve as a voting member of the CCPDER Program Steering Committee and will attend meetings as scheduled. 3. Awardees will retain custody of, and have primary rights to data developed under awards, subject to Government rights of access consistent with HHS, PHS, and NIH policies. Under the terms of OMB circular A-110, data generated by grantees is now subject to the Freedom of Information Act. Data and procedures for its use developed under the U54 may be considered unique research resources. The policy of the PHS is to make available to the public results and accomplishments of activities that it funds. All awardees must adhere to PHS policy for distribution of unique research resources produced with PHS funding, which was published at: http://www.nih.gov/od/ott/RTguide_final.htm. Publication or oral presentation of work done under this agreement will require appropriate acknowledgement of NIEHS support: see Acknowledgement of Federal Funding (Section 507) in the Notice of Legislative Mandates Contained in the FY2000 Omnibus Appropriations at: http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-010.html. Dissemination of information, data or substances supplied by NIEHS will require clearance by NIEHS to assure conformity with any existing confidentiality agreements with the primary suppliers of such information, data or substances to the NIEHS. 4. Possessory rights of physical materials acquired during the course of research rests with the applicant. Prior to award, the applicant must formulate a policy for final disposition of such physical materials and ownership rights in the event that such physical materials are transferred to other parties who use them to make discoveries. C. NIEHS Extramural Staff Responsibilities 1. NIEHS EXTRAMURAL SCIENCE ADMINISTRATOR (ESA): The NIEHS extramural program staff scientist who will have substantial scientific involvement during the conduct of this CCPDER Consortium Program activities, through technical assistance, advice, and coordination above and beyond normal program stewardship for grants. The NIEHS extramural science administrator will assist in avoiding unwarranted duplication of effort across CCPDERs, help coordinate collaborative research efforts that involve multiple CCPDERs, serve on the organizing committee for the annual CCPDER Consortium Program scientific meetings and workshops, facilitate interactions between the awardee and the national PD advocacy community, provide recommendations concerning the format and content of the CCPDER Consortium Program website and other outreach materials produced by the CCPDERs, and assist in the integration of the CCPDER Consortium Program with existing NIEHS scientific resources and programs. The NIEHS Science Administrator will be selected by the NIEHS, will be distinct from the NIEHS Extramural Program Administrator and will be a voting member of the CCPDER Consortium Program Steering Committee. In all cases the role of the ESA will be to provide scientific program coordination of CCPDER research activities to assist and facilitate, but not to direct, these research activities. Upon recommendation of the ESA, NIEHS may provide a U54 CCPDER Consortium Program member access to physical and/or intellectual resources from NIEHS to support appropriate CCPDER program activities when such resources are required to meet the Terms and Conditions for Award for a CCPDER. The NIEHS ESA will serve as the CCPDER program liaison to the NIEHS and, in this capacity, the NIEHS ESA represents and makes presentations on behalf of the CCPDER program to the NIEHS for the purpose of administratively evaluating the overall effectiveness and achievements of the combined consortium laboratories contributing to the overall national CCPDER Consortium Program of the NIEHS. 2. EXTRAMURAL PROGRAM ADMINISTRATOR (EPA): The NIEHS will select one extramural program administrator to administer the cooperative agreement awards for the CCPDER program. The EPA, who is separate and distinct from the ESA, will provide the NIEHS stewardship of the cooperative agreement awards during the performance of the awarded research activities. The EPA will monitor the adequacy of each individual CCPDER award progress annually and provide the usual grant stewardship and administrative assistance for each individual cooperative agreement. The NIEHS retains the option for the EPA to recommend to the NIEHS Director the withholding or reduction of support or suspension or termination of funding for any project within a CCPDER of the Consortium that substantially fails to achieve its milestone goals. The NIEHS also retains the option for withholding or reduction of support or suspension or termination of funding for any CCPDER U54 Specialized Center cooperative agreement that materially fails to comply with the Terms and Conditions of the award D. Collaborative Responsibilities The CCPDER Consortium Program Steering Committee is the governing oversight committee of the CCPDER Consortium Program. The Steering Committee consists of the NIEHS Extramural Science Administrator and two individuals from each CCPDER: the principal investigator and one integrative Project Leader designated by each Principal Investigator. Each Steering Committee membership identified in this definition has one vote in the deliberations and actions of the Steering Committee. A chairperson, not from the NIEHS, will be selected by majority vote of the Steering Committee members. The Steering Committee will meet at least once annually at either the NIEHS in Research Triangle Park, NC or at a time and place agreed upon by the Steering Committee. The purpose of this (these) meeting(s) is(are) to set performance priorities, evaluate performance milestones, and plan for the future coordinated experimental studies of the CCPDER Consortium Program. The Steering Committee will be responsible for establishing priorities for collaborative inter-CCPDER activities that will be supported by the Research Development Cores of the individual CCPDERs. The Steering Committee will evaluate and select pilot projects, consistent with the established research priorities and scope, and will oversee and monitor the progress of these studies. The Steering Committee meetings will be coordinated with the annual general scientific meeting of the CCPDER Consortium Program. The Steering Committee may add non-voting scientific advisors to provide expert opinions on specific subject areas as deemed necessary by its deliberations. Other NIEHS program staff, as approved by the Steering Committee, may attend the Steering Committee meeting. The Steering Committee may, as deemed necessary, establish tasked subcommittees. NIEHS program staff may serve on these subcommittees. The Steering Committee will serve as the main governing board of the CCPDER Consortium Program. An arbitration process will be established, as detailed further below, to resolve any disagreement that may arise between NIEHS program scientists and the non-government membership of the Steering Committee. Members of the Steering Committee will: o Accept and participate in the cooperative nature of the group. o Attend Steering Committee meetings to review results, evaluate data, check progress toward milestones, and conduct planning and prioritizing activities of the CCPDER Consortium. A planning meeting of the CCPDER Steering Committee will be convened by the NIEHS extramural program staff shortly after the U54 awards have been made. At this meeting, a Chair will be selected and the group may: o Draft a charter/operations manual that details policies and procedures and agree on the terms of this charter/operations manual. o Determine a plan for scheduling the time and place of future meetings. o Review criteria and performance measures for coordination activities. Subsequent meetings will conduct the Steering Committee functions described earlier in this section. E. Arbitration Panel An arbitration panel is an advisory panel formed to review scientific or programmatic disagreement (within the scope of the award) that may arise between the awardee and NIEHS. The arbitration panel will be composed of three members: (i) a designee of the Steering Committee chosen without NIEHS staff voting, (ii) one NIEHS designee, and (iii) a third designee with relevant expertise who is chosen by the other two. In the case of a disagreement between a single CCPDER and the NIEHS, the first member of the arbitration panel may be chosen by the individual CCPDER awardee. The Arbitration Panel will help resolve both scientific and programmatic issues that develop during the course of work and that could restrict progress. For U54 Center grant awardees, this special arbitration procedure in no way affects the awardee"s right to appeal an adverse action that is otherwise appealable in accordance with NIH regulations 42 CFR Part 50, Subpart D and HHS regulation at 45 CFR Part 16. DATA AND SAFETY MONITORING It is the policy of NIH that provision be made for the oversight and monitoring of all intervention studies to ensure the safety of participants and the validity and integrity of the data. The NIH policy was published in the NIH Guide to Grants and Contracts, June 10, 1998 and is available at: http://grants.nih.gov/grants/guide/notice-files/not98-084.html. NIMH guidance on data safety and monitoring is available at: http://www.nimh.nih.gov/research/safetymonitoring.cfm. For the CCPDER Consortium Program, an independent panel of experts, constituting a Data Safety and Monitoring Board, will be appointed by NIH to monitor safety, quality of data collection, and integrity of the study. 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 clinical research projects unless a clear and compelling justification is 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 are 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) investigators must report annual 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. Investigators also may obtain copies of the policy from the program staff listed under INQUIRIES. Program staff may also provide additional relevant information concerning the policy. REQUIRED EDUCATION IN THE PROTECTION OF HUMAN RESEARCH PARTICIPANTS All investigators proposing research involving human subjects should read the policy that was published in the NIH Guide for Grants and Contracts, June 5, 2000 (Revised August 25, 2000), available at the following URL address: http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html. NIH GRANTS POLICY STATEMENT The NIH Grants Policy Statement (NIHGPS) has been revised and reissued. The provisions of the revised NIHGPS are effective for all funded NIH grants and cooperative agreements with budget periods beginning on or after March 1, 2001. The revised NIHGPS is available at: http://grants.nih.gov/grants/policy/nihgps_2001. 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 a 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. http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-004.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. LETTER OF INTENT Prospective applicants are asked to submit a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, the identities of other key personnel and participating institutions, and the number and title of the RFA in response to which the application may be submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows institute staff to estimate the potential review workload and plan the review. The letter of intent should be sent by February 14, 2002 to: Ethel Jackson, DDS Chief, Scientific Review Branch Division of Extramural Research and Training 111 Alexander Drive P.O. Box 12233 Research Triangle Park, NC 27709 Phone: (919) 541-7846 Fax: (919) 541-2503 email: jackson4@niehs.nih.gov APPLICATION PROCEDURES The PHS 398 research grant application instructions and forms (rev. 5/2001) available at http://grants.nih.gov/grants/funding/phs398/phs398.html must be used in applying for these grants. This version of the PHS 398 is available in an interactive, searchable format. For further assistance contact GrantsInfo, Telephone 301/710-0267, Email: GrantsInfo@nih.gov. 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, SUITE 1040 - MSC 7710 BETHESDA, MD 20892-7710 or BETHESDA, MD 20817 (for express/courier service) At the time of submission, two additional copies of the application must also be sent to: Ethel Jackson, DDS Chief, Scientific Review Branch Division of Extramural Research and Training 111 Alexander Drive P.O. Box 12233 Research Triangle Park, NC 27709 Phone: (919) 541-7846 Fax: (919) 541-2503 email: jackson4@niehs.nih.gov Applications must be received by March 14, 2002. If an application is received after that date, it will be returned to the applicant without review. The Center for Scientific Review (CSR) will not accept any application that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. The CSR will not accept any application that is essentially the same as one already reviewed. The Center for Scientific Review (CSR) will not accept any application in response to this RFA that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. The CSR will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of substantial revisions of applications already reviewed, but such applications must include an introduction addressing the previous critique. SPECIAL INSTRUCTIONS FOR ALL APPLICANTS Applicants must consider and address the following in the preparation of applications called for in this RFA: 1. Special budget considerations Each CCPDER applicant must include a budget for travel funds for selected key personnel (named below) to attend two annual meetings. One of the meetings will be the CCPDER Consortium Program scientific meeting. This scientific meeting will be used to present and evaluate the status of CCPDER Consortium Program research projects. The annual CCPDER Consortium Program Steering Committee meeting will be coordinated with this meeting. The second meeting will be a CCPDER Consortium Program workshop that explores an emerging area of science relevant to gene-environment interactions in PD. Travel funds requested for these two annual meetings should be sufficient to allow travel of the CCPDER Principal investigator, each of the integrative research project leaders and Facility Core Directors, and when appropriate, other key scientific personnel engaged in the conduct of the integrative research projects. An amount of $75,000 must be included in the Research Development Core for each CCPDER for the funding of inter-CCPDER studies as determined by the priorities and guidelines established by the CCPDER Steering Committee. An applicant who requests consideration for the CCPDER-CC may request up to an additional $122,000 direct costs to support the additional administrative aspects associated with the this coordination role and with the activities of the required Information Dissemination Core. Thus, the costs requested for a CCPDER-CC may be up to $982,000 ($860,000 for CCPDER activities and $122,000 for additional activities as a CCPDER-CC). 2. Special research considerations The integrative research projects proposed in the CCPDER application must be in the general area of gene-environment interaction in PD and these projects must be guided by a clearly articulated unifying hypothesis or interrelated set of hypotheses. Thus, the integrative research projects must represent a cohesive and meaningful program of research, with clear interrelationships among project leaders and project goals. Each integrative project must employ a multidisciplinary approach. An existing peer reviewed externally funded grant or grants, with at least two years of funding remaining at the time of the CCPDER award (August 2002) must be used to provide the scientific foundation for each integrative research project. The work in the proposed integrative research projects must clearly and significantly amplify, extend or bridge the existing research grants and must not represent a mere duplication of the currently funded grant or grants. Thus, the applicant must indicate clearly how the integrative research project builds onto or bridges to the parent grant or grants yet proposes new work. c. Special information considerations Applicants must include their specific plans for responding to the "Terms and Conditions of Award" section. Applicants should state their willingness to collaborate and share data freely with the other CCPDER program awardees, to participate in planning and to serve on the CCPDER Consortium Program Steering Committee and be bound by its decisions for setting the standards and guidelines for the consortium program operations, and to be able and willing to share data and communicate with each other and the NIEHS in an internet environment. Applicants should also describe how they would comply with the involvement of an NIEHS Extramural Science Administrator. APPLICATION FORMAT Applications are to be submitted on Form PHS 398 (rev 5/2001). All instructions and guidelines accompanying the PHS 398 are to be followed, with the exception of the sections modified by the specific instructions described below. In lieu of the preprinted Table of Contents outline on Form Page 3 of PHS 398, a Table of Contents should be prepared listing all of the major sections described below and paginated to enable reviewers to find specific information readily. The Table of Contents should contain the information described below. It should be divided into the following sections: Section I - General Information, Section II - Research Plan, and Section III - Appendix. The following guidelines will provide directions and descriptions for preparing each section. Major areas to be listed and paginated in the Table of Contents are underlined. SECTION I - GENERAL INFORMATION A. FACE PAGE Complete all items on the application"s face page. This is Form Page 1 of the application, number succeeding pages consecutively. On line 2, enter the appropriate Request for Applications (RFA) number and title, for those applicants applying under the CCPDER-CC, list after the RFA title CCPDER-CC and mark the YES box. B. DESCRIPTION AND PERSONNEL On Form Page 2, describe briefly the research program, indicate the emphasis of the component research projects, and identify the purposes of the proposed cores. List key scientific and technical personnel participating in the CCPDER. Use continuation pages as necessary, numbering consecutively. C. TABLE OF CONTENTS Prepare the Table of Contents as noted above. The major areas to be listed are enumerated in these instructions. D. BUDGET ESTIMATES Prepare a series of composite Budget Tables for the CCPDER as requested below. A separate detailed budget is required for each research project and for each core unit. 1. Composite Budget a. Use Form Page 4, "DETAILED BUDGET FOR INITIAL BUDGET PERIOD," of the PHS 398 to present the total direct cost budget for all requested support for the first year. For each category, such as "PERSONNEL," "EQUIPMENT," etc., list the amount requested for each research project and for each core unit. If consortium arrangements have been made involving other institutions or organizations, include total costs (direct and F&A) associated with such third party participation in the "CONSORTIUM/CONTRACTUAL COSTS" category. Costs for purchased services should be itemized under "OTHER EXPENSES." b. Use Form Page 5, "BUDGET FOR ENTIRE PROPOSED PROJECT PERIOD," of the PHS 398 to prepare a budget, by category, that provides direct cost totals for each year of requested support. 2.Individual Project and Core Budgets a. First year (use Form Page 4 of PHS 398 for each) b. Total project period (use Form Page 5 of PHS 398 for each) Consortium Budgets (if applicable) should be presented as described in Item 1 (Composite Budget), including a budget for the entire proposed project period. Total Direct and F & A costs of sub-awardees are to be shown under "CONSORTIUM/CONTRACTUAL COSTS" on individual research project or core budgets and a detailed consortium budget is to be inserted following the appropriate research project or core budgets. Budget Justifications: Describe the specific functions of key scientific and technical personnel, consultants, collaborators, and support staff. For all years, explain and justify any unusual items such as major equipment or alterations and renovations. For future years of support requested, justify any significant increases in any category over the first 12-month budget period. Identify such significant increases with asterisks against the appropriate amounts. E. BIOGRAPHICAL SKETCH Biographical sketches are required for all key scientific personnel participating in the research projects and core units as listed on PHS 398 Format at Page 2. Beginning with the CCPDER Director, and following in alphabetical order, submit biographical sketches as described in the "Instructions for PHS-398 Format at Page 6. F. RESOURCES Overall CCPDER (two page limit). Briefly describe the features of the institutional environment that are or would be relevant to the effective implementation of the proposed program. As appropriate, describe available resources, such as clinical and laboratory facilities, participating and affiliated units, patient populations, geographical distribution of space and personnel, and consultative resources. Use continuation pages as needed. SECTION II INTEGRATIVE RESEARCH PLAN Include a detailed Table of Contents with pagination (numeric only) at the beginning of Section II. Identify each research project or core unit by title, and assign each research project a number (I, II, III) and each core unit a capital letter (A,B,C) that reflects the order in which the integrative research projects and core units are presented in the application research plan. For each integrative research project and core unit, provide the name of the Principal Investigator or Core Director, and biographical sketches for personnel not identified previously. A. INTRODUCTORY OVERVIEW (20-page limit) Provide an overview of the entire proposed CCPDER highlighting its central theme and goals with respect to gene-environment interactions in PD. Describe how the overall CCPDER can achieve its major objectives. Explain the proposed contribution of each of the projects in achieving the objectives of the CCPDER. Furthermore, the administrative arrangements and support necessary to effect the research should be carefully described in the application. Shared resources should be described. In addition, provide detailed information on collaborations, recruitment, facilities and resources. 1. Purpose and Objectives of the CCPDER. Discuss the philosophy and objectives of the CCPDER and general plans for the proposed grant period. Discuss the composite research program, highlighting its central theme. List by title and investigator the integrative research projects and core units, showing the interrelationship between the integrative research projects and the core units and their relationship to the central theme. Describe relevant history leading up to the CCPDER application. Applicants should note that the Principal Investigator and leaders of integrative research project must comprise a multidisciplinary team with expertise in cellular and molecular neurobiology in addition to at least two of the following four areas of PD research: (1) human genetics, (2) epidemiology, (3) clinical research, and (4) community outreach and education. 2. Documentation of currently funded research base (not to exceed two pages). Provide a consolidated list of the collective scientific funding base for each CCPDER. The funding base is defined as the set of external peer reviewed grants that provide the foundation for the integrative research projects. The funding base list should be organized by the integrative research projects proposed in the application. For each integrative project, the title, funding source, annual direct costs, duration of award, and brief description must be provided for each parent grant. Applicants should note that this funding base must total at least $500,000 in annual direct costs and that the funding base must extend for at least two years following the receipt of the CCPDER award (August 2002). Each integrative research project can be based on more than one existing grant, as in the case where an integrative research project has the goal of bridging the efforts of two or more existing grants. Each existing grant may provide the primary basis for only one integrative research project, however. That is, it is not permissible to propose two or more integrative research projects that represent different extensions of the same existing grant or set of grants. The funding base should be from external peer reviewed research grants supported by the NIEHS, other NIH institutes and centers, and other governmental and private agencies in the area of PD or a closely related area of neurodegeneration. 2. Administration, Organization, and Operation of the CCPDER. Include information on the support and commitment of the parent institution for the CCPDER, the authority of the CCPDER Director, the use of the executive and external advisory committees, and the method of determining core access and space assignment. Describe organizational framework and provide an organizational chart. Applicants should note that External Advisory Committee members should not be recruited until the NIH review of applications is complete. Representation of PD patient advocates is required for the External Advisory Committee. 3. Assurances and Collaborative Agreements. Any arrangements for collaborative and cooperative endeavors or subcontracting should be highlighted. Letters of Intent to Collaborate and Letters of Agreement from consultants should be referenced here and included at the end of the appropriate research project or core unit. The applicant must include a statement of acceptance of NIEHS staff participation as described in "NIEHS Extramural Staff Responsibilities." In addition, a statement by the Principal Investigator must be included, accepting participation on the CCPDER Program Consortium Steering Committee and implementing, if applicable, the goals, procedures and policies agreed upon by this Steering Committee. B. INTEGRATIVE RESEARCH PROJECT DESCRIPTION Identify each project by a Roman numeral (I, II, III ) and a title. Integrative research projects should be organized in the standard PHS 398 format of an R01 proposal with sections for an abstract, specific aims, background and significance, preliminary results, experimental design and methods and literature cited. Each integrative research project must represent a significant amplification, extension, integration or bridging of an existing peer-reviewed and externally funded research grant or grants. In addition to a description of the specific aims of the integrative research project, the application should include a description of the original aims of the parent grant(s). Preliminary data collected under the auspices of the parent grant(s) may be included if directly relevant to the aims of the integrative research project. The primary focus, however, should be how the proposed new integrative research project extends or builds onto or bridges the parent grant(s) by incorporating or strengthening multidisciplinary approaches to the stated problem. To avoid potential for duplication of effort, the applicant must clearly articulate how the new work proposed differs from that approved in the existing grant or grants that provide the scientific foundation for the integrative research project. Each integrative research project should indicate the interrelationships with other proposed integrative research projects. Applicant should describe a plan for achieving the stated goals of the Integrated Research Project if the parent grant funding is discontinued. C. CORE DESCRIPTIONS Identify each proposed core unit by a letter (A, B, C...) and a title (GENE EXPRESSION, NEUROIMAGING, ANIMAL MODELS...). The Technical Core(s) (limited to five pages) should be organized in the standard PHS 398 format. Applicants should include a description of key professional and support staff functions, space and physical resources and current and projected services to other core units and integrated research projects, and to the CCPDER as a whole. Applicants may propose new Cores or may describe a plan for accessing existing Core facilities through fee for service or cost sharing arrangements. Applicants may propose use of Core services located outside of the applicant institution through a subcontractual arrangement. D. ADMINISTRATIVE CORE UNIT DESCRIPTION (three page limit) The Administrative Core should be organized in the standard PHS 398 format (limited to five pages). Within this section, applicants should include a description of the formation of an External Advisory Committee, its role and operational processes associated with the committee. Although a general description of the number and characteristics of committee members should be provided, External Advisory Committee members should not be recruited until the NIH review of applications is complete. Representation of PD patient advocates is required for the External Advisory Committee. Applicants who desire consideration for the CCPER-CC role should include in the Administrative Core section a clear description of a management and organization plan for the required annual scientific CCPDER Consortium program meeting and workshop. A plan for establishing a formal relationship with national PD patient advocacy groups, that includes substantive participation in the annual science CCPDER Consortium Program meetings, should be included. E. INFORMATION DISSEMINATION/OUTREACH CORE DESCRIPTION (ten page limit) An Information Dissemination/Outreach Core is a required element for CCPDER applicants who wish to be considered to be the CCPPDER-CC. Applicants who do not wish to be considered for a CCPDER-CC should omit this section. The Information Dissemination/Outreach Core should be organized in the standard PHS 398 format. The applicant should describe a plan for creating and maintaining a listserver and website that provides general information about the overall CCPDER Consortium structure and function, specific integrative research projects and other CCPDER Consortium program activities. The web pages, related databases and interactive web application pages, if any, will be housed on NIEHS web and database servers. The pages will be designed and implemented with technologies supported by NIEHS, including the Oracle database engine and Cold Fusion web application development environment. These tools will be employed on this project as necessary to meet the functional goals of the site. The applicant will develop and maintain these products in conformance with NIEHS web and database development standards and will interact with NIEHS information technology staff as required to ensure that these standards are being met. The website content must be designed for use by both the scientific and lay communities. A plan for gathering and updating information from individual CCPDERs should be included. The website should include a searchable database for accessing CCPDER-generated documents and materials, including reports and any educational/outreach materials produced by individual CCPDERs. The applicant must describe an ongoing process for soliciting input from PD patient advocate representatives concerning website design and content. The website must include a clear description of the relevance of the CCPDER Consortium program to the public health arena (i.e., prevention and intervention strategies in PD). F. RESEARCH DEVELOPMENT CORE UNIT DESCRIPTION (Six page limit) The applicant must describe a process for soliciting and evaluating the scientific merit of pilot projects, and for evaluating progress of these awards. A minimum amount of $75,000 direct costs annually should be budgeted for three one-year awards of up to $25,000. These awards will be to fund studies involving investigators at multiple CCPDERs. The solicitation and review of future applications will be overseen by the CCPDER Consortium Program Steering Committee. The applicant should include an initial pilot project description (five page limit) that demonstrates an initial pilot project expressing novel ideas and concepts for a pilot project effort. Preliminary data extensive technical justifications are not required. The focus of the pilot project should be on the novel concept and its feasibility. E. CHECKLIST - As required in Form PHS 398 SECTION III - APPENDIX Include materials as appropriate (see PHS 398). REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by the CSR and responsiveness by the program staff in the Division of Extramural Research and Training (DERT), NIEHS. Incomplete and/or non-responsive applications will be returned to the applicant without further consideration. The specific points of consideration for completeness and responsiveness to the RFA are: (1) the general completeness of the application and the organizational adequacy for review (this includes both scientific and budgetary considerations). The specific points of programmatic responsiveness to this RFA include: (1) the appropriateness of the science proposed in regard to the mission of the NIEHS and the documentation as requested in this RFA. Applications that are complete and responsive to this RFA will be evaluated for scientific and technical merit by an appropriate peer review group convened by DERT, NIEHS, in accordance with the review criteria stated below. 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 the applications under review, will be discussed, assigned a priority score and receive a second level review by the National Advisory Environmental Health Sciences Council. REVIEW CRITERIA FOR THE EVALUATION OF THE OVERALL PROGRAM APPLICATION The overall program application is evaluated by considering the integrative research projects, supporting cores, and the administrative structure, and how these multi disciplinary components function together to achieve the goals of the CCPDER program. For the application to receive an overall priority score, it must consist of at least three approved integrative research projects, each of which has multiple specific aims and are found to have significant and substantial merit. The applicant should not be penalized if the parent grant(s) for an Integrative Research Project has only the minimum (2 years) duration. Scientific relevance of the project should guide the overall merit of the project. Specific scientific consideration factors to be evaluated in the consideration of the program are as follows: o Scientific merit of the program as a whole, as well as that of the individual parts. o Significance of the overall program goals. This includes the significance and importance of the research program to furthering knowledge of gene environment interactions in PD. o Cohesiveness and multidisciplinary scope of the program and the coordination and interrelationships of all individual research projects and cores to the common theme of the CCPDER consortium program. o Leadership and scientific ability of the principal investigator and his or her commitment and ability to develop a well-defined central research focus and to devote adequate time and effort to work within the parameters of the CCPDER program research consortia. o Past accomplishments of the research team (Principal Investigator, Project and Core Leaders)in the proposed areas of research. REVIEW CRITERIA FOR INTEGRATIVE RESEARCH PROJECTS The review of the individual Integrative Research Projects is similar to the review of individual project grant applications (RO1). Accordingly, these projects must have substantial scientific merit. The review criteria (Significance, Approach, Innovation and Environment) are intended to encourage reviewers to focus on the global impacts of each project and the program overall, rather than concentrating on the experimental details and their critiques. The review criteria are as follows: o Significance: Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge be advanced? What will be the effect of these studies on the concepts or methods that drive this field? o Approach: Are the conceptual framework, design, methods, and analyses adequately developed, well-integrated, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics? What is the strength of the multidisciplinary approach for achieving the stated aims? What is the adequacy of the proposed plan for the Integrative Research Project if the parent grant funding is discontinued? o Innovation: Does the project employ novel concepts, approaches or method? Are the aims original and innovative? Does the project challenge existing paradigms or develop new, methodologies or technologies? o Investigator: Is the investigator appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers? o Environment: Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed experiments take advantage of unique features of the scientific environment or employ useful collaborative arrangements? Is there evidence of institutional support? o When human subjects are involved, the adequacy of plans to include women and minorities in the study design and the potential of that design to address scientific question(s) proposed must be addressed. REVIEW CRITERIA FOR INDIVIDUAL TECHNICAL FACILITY CORES o Utility of the core to the CCPDER, each core should provide essential facilities or service for two or more projects judged to have substantial merit (e.g., the number of projects that will benefit from centralized administrative and research services, the economy of effort that will be realized through use of shared services, etc.) o Quality of the facilities or services provided by this core (including procedures, techniques, and quality control) and criteria for prioritization of usage. o Qualifications, experience and commitment of the personnel involved in the core. o Appropriateness of the budget. REVIEW CRITERIA FOR RESEARCH DEVELOPMENT CORE o Adequacy of process described for soliciting and evaluating pilot projects, and for documenting and evaluating progress of pilot projects. o Appropriateness of the budget. o Conceptual Innovation, relevance to CCPDER goals and technical feasibility of the proposed pilot project. REVIEW CRITERIA - ADMINISTRATIVE CORE For all applications, in addition to evaluating the scientific components, the review will also assess: o Environment and resources in which the research will be conducted, including availability of space, equipment, or other resources as required, and the potential for interaction with scientists from other departments , o Institutional commitment to the requirements of the program, including fiscal responsibility and management capability of the institution to assist the principal investigator and his or her staff in following DHHS, PHS, and NIH policy, o Administrative planning and leadership capability to provide for internal quality control of ongoing research, the research needs of the consortia, allocation of funds, enhancement of internal communication and cooperation among the investigators involved in the program, communication with the consortia, and replacement if the principal investigator if required on an interim or permanent basis, o Appropriateness of the budget in relation to the proposed program, o Human subject"s protection, animal welfare, and biohazard issues. REVIEW CRITERIA FOR INFORMATION DISSEMINATION CORE (applies only to CCPDER-CC applicants) o Experience and commitment of the personnel involved in the core. Technical qualifications of the personnel to provide the desired product using specified tools and methods. (As described in the RFA under Information Disssemation/Outreach Core description) o Quality and innovation of overall plan for website design and implementation. o Appropriateness of planned content and website elements to achieve the goals of information dissemination to both scientific and lay communities. o Adequacy of plans for evaluating, updating and maintaining the website. o Cost-effectiveness of the plans for the Information Dissemination/Outreach Core. o Adequacy of plans for soliciting input from PD patient advocates. o Appropriateness of the budget. SCHEDULE Letter of Intent Receipt Date: February 14, 2002 Application Receipt Date: March 14, 2002 Peer Review Date: April 2002 Council Date: August 2002 Earliest Anticipated Award: August 2002 AWARD CRITERIA Award criteria that will be used to make award decisions include: o Scientific merit (as determined by peer review), o Programmatic priorities, and o Availability of Funds An award will not be able to be offered for applications that do not have the following approved application components as a result of the peer review outcome: o A minimum of three approved integrative research projects, and o An approved administrative Core. It should also be noted that Technical Cores that do not serve at least two approved research projects will not be able to be funded as independent Cores. INQUIRIES Inquiries are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Cindy P. Lawler, Ph.D. Scientific Program Administrator Organs and Systems Toxicology Branch Office of Program Development Division of Extramural Research and Training National Institute of Environmental Health Sciences Box 12233, MD EC-23 Research Triangle Park, NC 27709 Telephone: (919) 316-4671 Fax: (919) 541-5064 E-mail: lawler@niehs.nih.gov Annette Kirshner, Ph.D. Scientific Program Administrator Organs and Systems Toxicology Branch Office of Program Development Division of Extramural Research and Training National Institute of Environmental Health Sciences Box 12233, MD EC-23 Research Triangle Park, NC 27709 Telephone: (919) 541-0488 Fax: (919) 541-5064 E-mail: kirshner@niehs.nih.gov Direct inquiries regarding fiscal matters to: Lerlita D. Garcia Grants Management Specialist Grants Management Branch Office of Program Operations Division of Extramural Research and Training National Institute of Environmental Health Sciences Box 12233, MD EC-22 Research Triangle Park, NC 27709 Telephone: (919) 316-4638 Fax: (919) 541-2860 E-mail: garcia1@niehs.nih.gov AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.113. Awards are made under authorization of the public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public law 99-158, 42 USC 241 and 285) and administered under NIH grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74 and 92. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. The PHS encourages all grant and contract recipients to provide a smoke-free workplace and promote the non-use of tobacco products. In addition, Public law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, a 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.


Weekly TOC for this Announcement
NIH Funding Opportunities and Notices



NIH Office of Extramural Research Logo
  Department of Health and Human Services (HHS) - Home Page Department of Health
and Human Services (HHS)
  USA.gov - Government Made Easy
NIH... Turning Discovery Into Health®



Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files.