ALZHEIMER'S DISEASE CORE CENTERS Release Date: May 16, 2000 RFA: AG-00-002 National Institute on Aging ( Letter of Intent Receipt Date: July 1, 2000 Application Receipt Date: September 15, 2000 PURPOSE The National Institute on Aging (NIA) invites applications from qualified institutions for support of Alzheimer's Disease Core Centers (ADCCs). These are designed to serve as shared research resources to facilitate research in Alzheimer's disease (AD) and related disorders and distinguish them from normal aging. Alzheimer's disease may presently affect as many as 4 million older people in the United States. Although it is occasionally identified in patients in their forties and fifties, it is most frequently associated with advancing age. It doubles in prevalence with every five years past the age of 65; thus, extending life by ten years quadruples the probability of the disease. Alzheimer's disease is the most frequent cause of institutionalization for long-term care. It destroys the active, productive life of its victims and devastates their families financially and emotionally. It is estimated that the United States spends as much as 100 billion dollars/year for the direct and facilities and administrative (F&A) costs of care for patients with Alzheimer's disease. With the rapidly increasing percentage of the population over the age of 65, the number of persons with AD will increase proportionately, as will the toll it takes. Both the Executive and Legislative Branches of the Federal Government have expressed concern about the enormity of the problem posed by this disease. Congressional concern about Alzheimer's disease has focused on funding for research on the causes and treatment of the disease, and on the cost of care. In 1984, Congress directed the National Institutes of Health (NIH), and in particular the National Institute on Aging (NIA), to foster further research related to Alzheimer's disease. The NIA Alzheimer's Disease Centers (ADCs) program is authorized by the Public Health Service Act, Section 445, and includes seventeen Alzheimer's Disease Research Centers (ADRCs) and eleven Alzheimer's Disease Core Centers (ADCCs). Centers are expected to provide an environment and core resources which will enhance ongoing research by bringing together biomedical, behavioral, and clinical science investigators to study the etiology, pathogenesis, diagnosis, treatment, and prevention of AD, and to improve health care delivery. Centers will also foster the development of new lines of research and provide a suitable environment for fellows and junior faculty to acquire research skills and experience in interdisciplinary AD research. The Centers provide investigators and research groups with well-characterized patients and control subjects, family information, and tissue and biological specimens for use in research projects. Each Center should develop in accordance with local talents, interests, and resources, but should also be responsive to national needs related to Alzheimer's disease. Centers are expected to work together with other Alzheimer research groups in collaborative research activities and cooperate with other Federal, State, and local agency- supported Alzheimer's disease programs in furthering mutual goals. Potential applicants are encouraged to utilize the strengths of their particular institutions in preparing an application that will cover the spectrum of required activities. While types of activities that should be included are indicated in these guidelines, specific approaches to accomplish them are left to the applicant. 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 (RFA), Alzheimer’s Disease Core Centers, is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State or local governments, and eligible agencies of the Federal government. Applications from racial/ethnic minority individuals, women, and persons with disabilities are encouraged. At the time of award, the applicant institution cannot have another Alzheimer's Disease Center funded by the NIA. Institutions eligible for Alzheimer's Disease Core Center Grants (P30s) are those at which there are (1) at least five principal investigators with any PHS agency research grant or comparable peer reviewed research project (including those funded by State governments or private foundations) related to Alzheimer’s disease, other neurodegenerative diseases or aging of the nervous system, each with at least two years of committed support remaining at the time of application or (2) one or more program project (P01) grant(s) related to Alzheimer’s disease, other neurodegenerative diseases or aging of the nervous system, which also have at least two years of committed support remaining. If P01 grant(s) exist, the work supported by the P01 should be different from that proposed in the ADCC and any overlap of the P01 cores with the P30 cores will be examined and adjustments made before funding. MECHANISM OF SUPPORT The support mechanism for this program will be the NIH Center Core Grant (P30). Investigators should request five years of support. Applications from institutions not previously funded as Alzheimer’s Centers will compete on an equal basis with competing continuation applications. The anticipated award date is July 1, 2001. FUNDS AVAILABLE The NIA intends to commit approximately $7,000,000 to fund seven new and/or competing renewal ADCC grants in Fiscal Year 2001. The specific number will depend upon the merit of the applications received and the funds available. Only applications of sufficiently high merit will be funded. The award of grants pursuant to this RFA is contingent upon the availability of funds for this purpose. RESEARCH OBJECTIVES ADCCs are required to include administrative, clinical, neuropathological, and information transfer cores. Other cores can be proposed and at least two pilot research projects per year should be requested. The ADCCs will provide well-characterized patients, patient and family information, and tissue and other biological samples primarily from persons with AD but also from persons with other neurodegenerative diseases and from age-matched control subjects for research projects. Research activities that use ADCC core resources can be supported by the NIH and other federal agency granting mechanisms, in addition to non-federal funding sources for the funding of investigator- initiated applications. The ADCCs provide a mechanism for integrating, coordinating, and fostering the interdisciplinary cooperation of a group of established investigators conducting programs of research on Alzheimer's disease and related dementing disorders of older people. They provide financial, intellectual, patient and tissue resources to support research projects that have been reviewed and supported on an individual basis. A prime objective of the Center Grant is to provide an environment that will strengthen research, increase productivity, and generate new ideas through formal interdisciplinary collaborative efforts. The central focus may be clinical research, basic research or a combination. The Center Grant may involve ancillary supportive activities such as prolonged patient care necessary to support the primary research effort. The spectrum of activities should comprise a multi-disciplinary approach to the problem of Alzheimer's disease. The ADCCs have played and will continue to play a major role in Alzheimer's disease research by providing an infrastructure and core resources around which institutions can build innovative research programs. Centers are expected to perform collaborative studies on particular research topics or to serve as a regional or national resource for special purpose research. The ADCCs provide a unique opportunity for multi disciplinary/multi Center studies. These will be facilitated by linkage to the new National Alzheimer's Coordinating Center, which was established in 1999. This ADC network will be used to standardize clinical and pathological diagnostic procedures, to pool patient information and to study unique aspects and subtypes of this very complex and heterogeneous disease process. Particular attention should be paid to the similarities and differences in the pathogenesis and clinical presentation among the neurodegenerative disorders that may be related to and confused with Alzheimer’s disease. The NIA expects the ADCCs to participate in cooperative studies involving many or all of the Centers as well as making Center data and specimens available for collaborative studies with qualified investigators not affiliated with an Alzheimer’s Disease Center. The National Alzheimer’s Coordinating Center (NACC) will serve as a clearinghouse for requests to use data and specimens from the ADCs by outside investigators seeking to participate in collaborative projects. An Alzheimer's Disease Core Center will be an identifiable organizational unit formed by a single institution or a consortium of cooperating institutions. Such a Center will involve the interaction of broad and diverse elements. Therefore, lines of authority by the appropriate institutional officials must be clearly specified. The existence of a base of ongoing high quality research in Alzheimer's disease, other related neurodegenerative disorders or aging of the nervous system is a prerequisite for establishing an ADCC. For continuation as an Alzheimer’s center, there must be a clear emphasis on AD but involvement of research subjects with related dementias is encouraged. Each applicant institution will name an ADCC Director (P.I.) who will be the key figure in the administration, management and coordination of the ADCC grant. The Director will be responsible for the organization and operation of the Center. The Director should be a scientific leader experienced in the field of Alzheimer's disease research and must be able to coordinate, integrate, and provide guidance in the establishment of programs in Alzheimer's disease research and allied areas. A significant time commitment (at least 10%) must be made by the Director. An Associate Director may be named who will be involved in the administrative and scientific efforts of the Center. Applicants must commit to cooperate fully and to share data concerning patients, control subjects and specimen resources with the NIA -sponsored National Alzheimer's Coordinating Center (NACC) where data from all ADCs are centrally collected. The Steering Committee of the NACC in conjunction with the ADC Directors will set policies that allow the individual Centers to conduct research on patients, control subjects, and specimen resources collected by that Center while also sharing common data sets with the NACC. The required elements for an ADCC include administrative, clinical, neuropathological, and education and information transfer cores, and a pilot projects program. Additional cores may be proposed and justified as required to advance the local research effort. Applicants must demonstrate a data management capacity either by creating a data core with biostatistical expertise or having a clearly defined data management section in the administrative or clinical core, which also includes the capacity for biostatistical consulting to the scientific staff, associated with the ADCC. Specific instructions for preparing overall progress reports (competing renewal applications), progress reports and plans for individual cores, and a list of review criteria are detailed later in this RFA. Cores A core is a shared central laboratory or clinical research facility, service, or resource. Each core is directed by an investigator with substantial expertise related to the core. Facilities may be proposed that will enhance productivity or in other ways benefit a group of investigators to accomplish the stated goals. Two important and related considerations are (1) the degree to which currently funded investigators will use and will benefit from core resources and (2) the degree to which the resources will promote new and/or expanded AD research efforts locally, regionally or nationally. Applicants should document and describe briefly the projects, both existing and planned, that will depend upon resources provided by the cores (clinical and neuropathology cores, in particular). The ADCC cores support resources that allow or provide for the following: the acquisition of subjects for research; the evaluation, monitoring of clinical course, and treatment of patients; the design and support of research protocols; the neuropathological diagnosis of the disease; documentation of the cognitive, behavioral and social aspects of Alzheimer's disease; a data collection, storage and biostatistical analysis capacity; and training and outreach programs related to Alzheimer's disease. Consequently, each application should demonstrate the presence of, or propose, methods to accomplish the above tasks. Within these parameters, it is expected that individual Centers may develop along different lines related to local interests and expertise and that one or more cores may have unique strengths while other cores within the Center may perform more routine functions. Administrative Core (required): Effective development of Center programs requires interaction among the Director, the principal investigators of the cores, the principal investigators of research projects using the cores, appropriate institutional administrative personnel, the staff of the awarding agency, and the members of the community in which the Center is located. The ADCC should recognize that it is part of a large network of ADCs and be prepared to work cooperatively with the other Centers and the NACC. The success of the ADCC is dependent upon the involvement of scientific and professional personnel from a variety of disciplines and subspecialties who must be willing to relate to each other in order to facilitate the acquisition of new knowledge. An executive committee (composed of core leaders and the administrator) will be established to assist the Director in making the scientific and administrative decisions relating to the Center. In addition to coordination of the ADCC, the Director, with the advice of his or her executive committee, will be responsible for allocation and monitoring of ADCC funds, oversight of ethical concerns involving human subjects and animal research, and the identification and selection of key personnel. 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. In addition to the executive committee, it will be necessary to establish an ad hoc review committee advisory to the ADCC Director. The committee should be composed of scientists from outside the ADCC with expertise relevant to the programs and interest of the Center. The responsibility of this group will be to review the applications for pilot studies and to make recommendations to the ADCC Director. An external advisory committee to the ADCC, consisting of scientists from outside of the institution will also be established. Unless already appointed, external advisory committee members should not be recruited until the NIH review is complete. This committee will be used to evaluate the programs of the ADCC, research progress, the effectiveness of communications within the ADCC, 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 ADCC. However, the nature of its responsibilities may require occasional ad hoc meetings or teleconferences. A member of the NIA extramural program staff should be invited to attend each meeting as an observer and should receive a copy of the advisory committee report and recommendations of the advisory committee should be included in annual progress reports together with a short response to the recommendations. The administrative requirements of the ADCC will necessitate the assistance of an administrator with business management expertise. It is important that such an individual be identified and directly involved with the fiscal and administrative aspects of the ADCC application and grant. The administrator should be a member of the executive committee. While budget formulation and planning will undoubtedly begin with the Director in collaboration with the scientific staff, the administrator must be involved in the process and provide consultation in matters of fiscal administration. It is expected that the ADCC administrative structure will facilitate the following: 1) coordination and integration of Center components and activities; 2) plan and review utilization of funds, including funds for pilot studies; 3) support and advice for the ADCC Director in his/her efforts to oversee the activities of the Center; 4) interaction with the scientific and lay communities to develop relevant goals for the ADCC within the immediate environment of the Center; 5) interaction and involvement with other research programs of the University including the provision of core resources for development of related projects; 6) interaction with other Centers and the NACC to develop trans-ADC research projects; 7) timely and routine transmissions of the complete ADCC data set to the NACC; In order to assure active collaboration with other ADCs, the ADCC Director and other staff should attend annual meetings of the ADC Directors and other ad hoc meetings arranged by the ADCs or the NIA to share research findings and plan for cooperative research or to refine and standardize operating procedures among the Centers. The ADCC application should include funds for travel of the Director and other key personnel 1) to the semiannual meetings of the Center Directors, 2) for at least 2 ad hoc meetings on special topics, 3) for visits of investigators associated with the Center to other ADCs for the exchange of scientific ideas, planning of multi Center research projects and to receive training in specialized techniques, 4) for the Administrator to attend the Administrators' meeting and 5) for core leaders to attend meetings with core leaders from other ADCs. Pilot Studies (required): A plan to support pilot studies for basic and clinical biomedical, epidemiological, or behavioral research should be included and budgeted in the application. The description of a plan to solicit, review and administer pilot grants should be included with the Administrative Core and a separate budget including the total request for pilots should be submitted. Criteria for review of pilot studies should be developed and included in the application. These funds may be used for new investigators, investigators from other fields willing to bring their research expertise to Alzheimer's disease, and investigators whose proposed research would constitute feasibility testing. This funding mechanism is intended to provide modest support that will allow an investigator the opportunity to develop preliminary data sufficient to provide the basis for an application for independent research support through conventional granting mechanisms. Pilot studies are typically limited to a nonrenewable single year of support. If described and well justified, two years of support may be requested. Any one investigator is eligible only once for pilot support, unless the additional proposed pilot study constitutes a real departure from his or her ongoing research. Pilot study support is not intended for large undertakings of established investigators for which it would be appropriate to submit separate research grant applications. Pilot funds are not intended to support or supplement ongoing-supported research of an investigator. Since eligibility for pilot studies is difficult to define, some examples may be helpful: 1) A study proposed by an established investigator who has experience in areas other than Alzheimer’s disease research, and who wants to work in the Alzheimer research field; or study by an established investigator who wants to try a new hypothesis, method, or approach that is not an extension of ongoing research. 2) A study proposed by a new investigator, with an interest in research in Alzheimer's disease, before the study has developed to the point of being suitable to apply for individual grant support. 3) A study to determine the availability of sufficient subjects with specific characteristics, such as ethnic or minority status, before undertaking a larger study. Each pilot project is limited to no more than $30,000 direct costs each year. If the pilot project is requested and justified for two years, the direct costs are limited to $30,000 per year. No pilot applications should be submitted with the ADCC application but, instead, the number requested for each year (2 minimum, 4 maximum) and the plans for soliciting pilot proposals should be described. A plan must also be presented within the administrative core for peer review of the pilot studies including the structure and composition of the review panel. Pilot proposals should be reviewed locally and those chosen for funding should be submitted to the NIA for approval in the annual noncompeting renewal application. Clinical Core (required): The clinical core serves the functions of patient and control subject recruitment, patient registry, longitudinal follow-up of patients and control subjects, evaluation, acquisition of clinical and laboratory data including data pertaining to the last weeks of life, data coordination and biostatistical analysis (if a separate data core does not exist). A research database that maintains confidentiality of all patient and control subject records should be established at the ADCC. This will include data necessary for evaluation of differences among preclinical stages of AD, possible or probable AD, other dementias and normal aging. The data must be shared with the National Alzheimer's Coordinating Center according to standardized protocols developed by the ADC Directors and the Steering Committee of the NACC. A clinical core may perform a limited amount of developmental work, but should not directly fund research per se. The developmental work allowable in a clinical core must be directly related to the function of the core. It may be directed toward improving and expanding the core functions, e.g., improving of existing, or developing of additional methodologies, techniques or services. Proposed developmental work should be described as completely as possible in the application. Planning for patient and age- matched control subject recruitment should include sensitivity to research design and biostatistical analysis. Describe the procedures for obtaining informed consent for research on cognitively impaired human subjects and controls; attach samples of information given to patients and families and copies of all consent forms. Particular attention should be paid to obtaining autopsy permission from patients and families and informed consent for current and future use of biological samples from patients. While conducting clinical drug trials is one function of a clinical core, it should not be the major effort of the core. The application should include a description of the types (with specific examples) of research projects and clinical trials that will use the core and what benefits will obtain to other research activities from the existence of the clinical core. Efforts to recruit diverse population subgroups including minorities and women and to involve them in studies are strongly encouraged. One option is to set up Satellite Diagnostic and Treatment Clinics (SDTCs) designed to increase the heterogeneity of the research patient pool and to enhance the research capabilities of the ADC by extending the activities of the clinical core. Existing Centers should retain any satellites already in existence unless there are compelling reasons to restructure these components. New satellite clinics may be proposed as part of the clinical core. The satellite clinics do not conduct research but serve as vehicles for the recruitment, diagnosis and management of AD patients and their families from rural and minority communities, who can then be offered the opportunity to participate in research protocols and clinical drug trials. The inclusion of patients with different characteristics will assist investigators in providing answers to questions about AD diagnosis, treatment and management strategies as well as facilitate studies that address issues specific to minority populations. Additionally, a more diverse patient pool will facilitate investigations of the neuropathology and genetics of AD in minority groups as well as studies of care giving and family burden in rural and minority group cohorts. These studies can be addressed by Centers individually and/or by cooperative studies involving multiple Centers and the NACC. Neuropathology Core (required): This core will provide post mortem diagnosis on dementia cases, other cognitively impaired individuals and normal aged control subjects enrolled in the clinical core and from other well documented AD cases and controls. Procedures and facilities should be described related to criteria for diagnosis, and the collection, storage, and distribution of brain tissue and other biological samples, including, but not limited to, DNA, CSF and plasma. Data gathering and storage activities should be coordinated with those of the Clinical Core. Pathology data and a catalog of all samples should be included in the data set transmitted to the NACC by mutually agreed upon protocols. To facilitate data sharing and cross Center comparisons of diagnosis, all Centers shall state clearly which neuropathological criteria they are using for routine diagnoses and are encouraged to use NIA-Reagan Institute Criteria. (Neurobiology of Aging, vol. 18, suppl 4, pp S1-S2,1997) More detailed criteria for research purposes should also be described. The Neuropathology Core may also perform a limited amount of developmental work, but should not directly fund research per se. The developmental work allowable must be directly related to the function of the core. It may be directed toward improving and expanding the core functions, e.g., improving existing, or developing additional methodologies, techniques or services. Proposed developmental work should be described as completely as possible in the application. Neuropathology core leaders from all of the ADCs meet yearly to share ideas and discuss technical aspects of tissue sampling, development of standardized tissue processing for diverse research protocols, cataloging and data management, and banking and distribution of tissues and biological samples. The procedure for prioritizing the use of tissues and other biological samples should be discussed along with a description of the research projects that will use material from this core. Particular attention should be paid to obtaining autopsy permission from patients and families and appropriate informed consent for present and future use of biological samples. Provisions for protecting the privacy of research subjects must be detailed. A procedure to provide blinded samples to investigators should be described. Details for collecting specimens, recording information about clinical status of patients immediately before and at time of death, and procedures for storage and distribution of all human biological samples to investigators both within and outside the Center should be provided. Monies should be budgeted to cover the costs of distributing tissue to scientists outside of the ADC. Information about testing for infectious diseases and safe handling of tissues and samples should be included. A mechanism to publicize availability of tissue, evaluate requests for samples and prioritize their use should be detailed. Cooperation with the NACC in cataloging the holdings of biological specimens from all Centers is required. Education and Information Transfer Core (required): This core will support both the development of physicians and other professional staff to improve clinical and research skills related to Alzheimer's disease and outreach programs that will publicize the ADCC and educate families and other care givers about the disease and serve as a vehicle for recruitment of research subjects. The methods and techniques to be employed to disseminate information and the audience targeted to receive information should be defined including 1) approaches to training of physicians and other professionals including possible reciprocal exchange programs between Centers to provide access to different research environments and technologies; 2) descriptions of seminar or lecture series, workshops and continuing education programs; and 3) cooperation with other organizations such as state and local agencies and the Alzheimer's Association. Attention should be directed to issues of cultural sensitivity and, where appropriate, the information should be structured so that it can effectively reach minority populations, including non-English-speaking people. Clearly stated objectives and a systematic plan as to how these objectives will be met are required. Specific assessment methodology is also required to evaluate the effectiveness of outreach programs. Consideration should be given to cooperation with other ADCs and the ADEAR Center at NIA when developing education programs for broader distribution. Other Cores (optional): The NIA, through the ADCC, will support additional cores that provide opportunities for scientific accomplishments beyond those attainable solely through support of the mandatory cores. It is important to note that support should not be requested for cores that only replace or centralize resources supported on individual project grants. In a Center grant application, it is not sufficient for the principal investigator merely to identify such centralized resources. Rather, it must be demonstrated exactly how each core would augment or enhance the present capabilities of the investigators and make possible new activities. There should be a thorough discussion of the project(s) that will use resources of additional cores. INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification is provided that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing research involving human subjects should read the "NIH Guidelines For Inclusion of Women and Minorities as Subjects in Clinical Research," which have been published in the Federal Register of March 28, 1994 (FR 59 14508-14513) and in the NIH Guide for Grants and Contracts, Volume23, Number 11, March 18, 1994, and is available on the web at 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. 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 IC staff to estimate the potential review workload and avoid conflict of interest in the review. The letter of intent is to be sent to the program staff listed under INQUIRIES by the letter of intent receipt date listed in the heading of this RFA. APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 4/98) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research and from the Division of Extramural Outreach and Information Resources, National Institutes of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone (301) 710-0267, email: Applications are also available on the Internet at The application should be prepared using instructions in this RFA and those in supplementary instructions for preparation of multi component applications (P30 Centers version) available from the program staff listed in the Inquiries section. Page Limitation: Applications may not exceed a total of 25 pages each for the overall introduction/progress report and parts a-d of the research plan for each core. Prior to submission of the formal application, consultation with NIA program staff concerning the technical aspects of preparing the application is strongly encouraged. The RFA label available in the PHS 398 (rev. 4/98) 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 sample RFA label available at: has been modified to allow for this change. Please note that this sample label is in pdf format. Submit a signed original of the application, including the Checklist, and three signed photocopies of the application 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, send two additional copies of the application plus all appendices to: Mary Nekola, Ph.D. Chief, Scientific Review Scientific Review Office National Institute on Aging 7201 Wisconsin Avenue, Room 2C212 Bethesda, MD 20892-9205 It is important to send these copies and the appendices at the same time as the original and three copies are sent to the Center for Scientific Review. These copies are used to identify conflicts and to help ensure the appropriate and timely review of the application. 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. 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. Progress Reports Overall Progress Report: For competing renewal applications, the overall progress report should include summaries of progress in achieving the major aims of the Center during the last funding period, including major publications. If an optional core has terminated, include a final report with a summary of activities and publications. If an optional core is continuing, include the progress report in the component write-up. Applicants should include tables detailing 1) Publications and grants (source, amount and title) resulting from each component funded by the ADCC 2) Publications and grants (source amount and title) resulting from pilot projects, 3) minority enrollment into research projects or clinical trials and specifically, into any research projects addressing minority issues. The overall progress report should also include details of how the presence of the ADCC has brought new investigators into the field and has stimulated funded research in the last funding period. In addition to text summaries, applicants should also include summary tables or annotated lists detailing: 1) Funded grants and projects that use or have used major resources supplied by the ADCC, including principal investigator, source and time of funding, types and amount of resources (e.g., clinical or neuropathological diagnoses, numbers of patients, specimens etc) and any resulting publications. 2) Collaborations with other AD researchers, other Alzheimer’s Centers, the National Alzheimer’s Coordinating Center, the Alzheimer’s Disease Cooperative Study, and with biotechnology and pharmaceutical companies. 3) Clinical trial participation by patients enrolled in the Center including trial name, sponsor, number of patients, and dates. Detail separately NIH and Pharmaceutical Industry sponsored trials. 4) Institutional, state and other public and private resources committed to the Center and its investigators. Clinical Core Progress Report: For competing continuations the Clinical Core Progress report should include Clinical Core objectives and progress in meeting them, including information about satellites (if applicable). Basic functions of the core should be summarized (in tabular form, where appropriate) including numbers, race, gender, age of patients and controls recruited, diagnosis, percentage follow up and drop out rate, autopsy consent and rate, diagnostic confirmation by autopsy, and clinicopathological correlations. Functions of Clinical Core in providing services to funded investigators should be clearly summarized. Include the numbers and kinds of subjects recruited for each clinical trial and each clinical research project, both local and national. How has the clinical core contributed to AD research? What key findings and publications have resulted from use of core patients? Any developmental work carried out by the core should be presented and resulting publications listed. Neuropathology Core Progress Report: For the neuropathology core, competing renewal applications should outline core objectives and progress in meeting them. Basic functions of the core such as number of AD, related neurodegenerative disorders, and control autopsies, gender and minority status, post mortem intervals, tissue dissection and storage, diagnoses, and type and quantity of tissue provided to investigators both inside and outside the Center should be clearly summarized (in tabular form, where appropriate). Any developmental work carried out by the core should be presented and resulting publications listed. Education and Information Transfer Core Progress Report: Competing renewal applications should include evidence for training activities that effectively impart knowledge to clinicians and the lay public with the possibility of leading to improved health care for patients. Include a table presenting the nature of training activities and the types of professionals trained - physicians (including medical students, residents, fellows), nurses, social workers etc. Detail the history of cooperative ventures of the Center with state and local agencies such as the Alzheimer's Association and community groups in coordinating training and education programs. Also include recruitment and outreach programs targeting ethnic and minority groups and the success of these programs. Data Management and Statistics: Summarize progress and activities related to data collection, data management and statistical consulting activities at the appropriate place in the core(s) where these services are located. Include progress and interactions with the National Alzheimer’s Coordinating Center. List projects and publications in which data management and statistical consulting played a role. Budget Considerations All ADCC proposals should request and provide justification for five years of support. The total costs (direct + F&A) requested for new applications may not exceed $900,000 for the first year. Competing renewal applications may request an increase up to 10% over final year total costs or $900,000, which ever is higher. Direct cost requests for subsequent years may increase above the prior year direct cost award no more than 3%. The direct costs are to be distributed approximately as follows: (This proposed distribution is intended only as a general guideline and proportions may vary if needed and justified. If additional cores are proposed based on local needs, the distribution may be adjusted accordingly.) Administrative Core 10% Pilot Studies 10% Clinical Core 50% Neuropathology Core 20% Education and Information Transfer Core 10% Where expensive items of equipment are requested, the application must document what is already available and provide clear justification in terms of use by core staff and how it relates to research projects dependent on the core. General-purpose equipment needs should be included and justified only after surveying the availability of such items within the institution. Research patient care costs (both inpatient and outpatient expenses) will be considered in the context of other existing institutional clinical resources. Attempts should be made by the applicant institution to utilize existing clinical facilities, such as General Clinical Research Centers and individually supported beds. Costs relating to the clinical efforts of the ADCC may be funded through the ADCC, provided there is no overlap of funding. Only those research patient costs directly related to Center activities may be charged to the ADCC. Domestic and foreign travel of project personnel directly related to the core and scientific activities of the ADCC is allowable. Budgeting should include travel and lodging for 1) the semi-annual meetings of the Center Directors, 2) annual meetings of administrators, clinical core, neuropathology core, and education core leaders, data managers, and, 3) representatives of the Center to attend ad hoc meetings called by the ADCs or the NIA to discuss research findings and plan cooperative projects, to promulgate data sharing, and to discuss standardization of procedures among the ADCs. Requests and commitments for pilots in competing applications (new and renewal) will be budgeted, as a separate line in the "composite" budget at $30,000 per pilot per year (without escalation). They should not be included in the Administrative Core or elsewhere in the application. A brief description of the first year pilot research and detailed pilot budgets for the first year of Center funding will be due shortly before the award of successful applications and future year pilots should be submitted with the annual noncompeting renewal applications. F&A costs will be provided in accordance with these budgets. Pilot grants are allowed for consortium arrangements but direct cost should not exceed $30,000 with total consortium cost budgeted not to exceed $35,000 for each pilot including the facilities and administrative costs of the consortium institution. No F&A costs will be provided to the grantee for pilot projects conducted by consortia. If consortium arrangements are contemplated, the following information should be provided in the application: 1) A list of all proposed performance sites both at the applicant institution and at the collaborating institutions 2) A separate, detailed budget for each institution and, where appropriate, for each unit of activity at each institution. 3) A composite budget for all units of activity at each institution for each year, as well as a composite budget for the total proposed budget for each year. 4) An explanation of the programmatic, fiscal, and administrative arrangements made between the grantee institution and the collaborating institutions. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by the Center for Scientific Review (CSR) and responsiveness by NIA. Incomplete and/or non-responsive applications will be returned to the applicant without further consideration. Each application must be thorough and complete. Additional materials or revisions will not be accepted after the receipt date. NIH has recently revised its requirements for Institutional Review Board (IRB) approval. Now IRB approval is not required prior to the NIH peer review of an application. See This change in policy is intended to provide flexibility at the institutional level. The institution may still determine that certain lines of research (e.g., scientifically or ethically controversial research) or mechanisms of research (e.g., multicenter clinical trials) should receive IRB review prior to submission of the application. Policy on Institutional Animal Care and Use Committee (IACUC) approval has not changed. Therefore, it is strongly recommended that IACUC approval be secured before the application is submitted. Otherwise, it is the applicant's responsibility to ensure that this certification is sent to the Scientific Review Office, NIA, within 60 days of the receipt date. Applications failing to comply with this requirement will be returned without review. There will be no further notifications on this issue. 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 NIA. As part of the initial merit review, a process may be used in which all applications 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 Council on Aging. Review Criteria Applicants should clearly demonstrate the ways in which the ADCC will contribute to the growth of local research programs, support on-going projects, cooperate with ADCs and the NACC in collaborative research, and attract both senior and new investigators to AD research. Listed below are the review criteria to be used in the evaluation of the ADCC applications; these criteria will be applied to competing continuations by evaluating progress and plans for future activities and to new applications by evaluating preliminary work and plans for implementation of the new program. The following review considerations will apply: A. Center as a Whole: 1) For competitive renewal applications, impact of the Center on furthering Alzheimer's disease research locally and nationally during the last funding period including utilization of Center resources by non-Center funded scientific projects (see details under Overall Progress Report section); for new applications, the potential for such impact. 2) Extent of "Centerness", i.e., does the Center as a whole serve a purpose greater than the sum of the individual components? 3) Unique contributions of the Center, including significance, innovation, scientific productivity, and recognition, (publications, new research grants, honors and awards). 4) Extent of Center interactions with the Alzheimer community including cooperative interactions with local organizations and nationally with other ADCs and cooperative studies. B. Cores: 1) For competing continuation applications, progress in meeting stated aims of cores in previous application, publications, and securing of other funding listed separately for each core. (Refer back to overall and core progress report sections) 2) How will the cores support research and educational activities of the ADCC and what is the future anticipated use? The fit of each proposed core into the overall research program. Will it enhance collaborative and/or interdisciplinary research within the Center, across Centers (including the NACC) and the wider research community? 3) Plan for recruitment of women and minority patients and control subjects to the clinical core. In competing continuation applications, has progress been made in increasing participation of diverse populations in ADCC activities? If Center had funds for satellite clinics, how effectively have they been used? Specifically include discussion of minority related research in the Center. 4) Would any proposed optional cores duplicate existing resources or services? If so, are the requested new resources justified? Do other grant funds already provide any of the requested capabilities? C. Research: 1) For new applications, the existence of a base of ongoing high quality research in Alzheimer's disease, other related neurodegenerative disorders or normal aging at the applicant institution and, for competing renewal applications, evidence for progress in increasing research on Alzheimer’s disease and related dementias. 2) For competing continuation applications, progress in meeting stated aims of cores in previous application, including utilization of subjects/specimens in other grants, publications, and securing of new funding. (Refer to progress report sections for details) 3) The feasibility of the pilot grant program proposed in new applications and the success of pilots funded in the previous award period for competing continuations as judged by documentation of subsequent success in publications and obtaining further funding. 4) The experience and commitment of the investigators responsible for the individual research projects which will be associated with the ADCC and their interrelations with the other elements of the ADCC and with other scientists at their institution and elsewhere. 5) The expected role of the ADCC in increasing the quantity and quality of research in Alzheimer's disease and related dementias within the applicant institution and cooperative studies with other ADCs and the NACC. D. Data Management: 1) Are data management and support procedures developed sufficiently to a) allow ADCC investigators to access and utilize data, b) comply with data requests from the NACC, and c) participate in cooperative studies with other ADCs and the NACC. Does the Center provide statistical design and support to aid ADCC investigators? 2) Is there a thoughtful plan to manage and utilize clinical and neuropathological data? Are adequate safeguards to protect patient confidentiality addressed? Are staffing, hardware and software adequate? 3) Statement of agreement to cooperate fully and share all core data with the National Alzheimer's Coordinating Center and to share data and specimens and participate in collaborative projects with other ADCs and outside investigators according to guidelines being developed by the NACC and the NIA. E. Program Administration: 1) The creative scientific and administrative leadership of the ADCC Director and his/her staff, and their commitment to devote adequate time to the management of the ADCC program. 2) The proposed administrative organization including: o Coordination of the ADCC resources including procedures for allocating Center resources in response to requests made by investigators and documentation of resources used and resulting publications. o Procedures for internal communication and cooperation among the investigators involved in the ADCC. o Mechanisms for reviewing the use of, and administering, funds for pilot projects. o Management capabilities that include fiscal administration, procurement, property and personnel management, planning, budgeting, etc. o For competing continuation applications, composition of the advisory board. Is it appropriate? Has it had regularly scheduled meetings? Are its responsibilities defined? How has the ADC benefited from advisory board input? o Evidence for full cooperation with the NACC. F. Investigators: 1) The qualifications of the participants. What are their academic credentials and their research records? What is the current funding of investigators associated with the ADCC? 2) Evidence of collaboration and interdisciplinary research among the investigators who will be associated with the ADCC. 3) Involvement with studies using the NACC and /or the Alzheimer’s Disease Cooperative Study. G. Facilities: 1) Facilities should be adequate. Are they reasonably contiguous or physically separated? H. Institutional Commitment: 1) Evidence for institutional commitment to the program, including provision of funding, space, faculty positions, or commitments for construction or renovation. 2) The academic environment and resources, including equipment and facilities, and the potential for interaction with scientists from other departments and components. In addition to the above criteria, in accordance with NIH policy, all applications will also be reviewed with respect to the following: o The adequacy of plans to include both genders, minorities and their subgroups as appropriate for the scientific goals of the research. Plans for the recruitment and retention of subjects will also be evaluated. 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. Schedule: Letter of Intent Receipt Date: July 1, 2000 Application Receipt Date: September 15, 2000 Date of Initial Review: February, 2001 Review by Advisory Council: May, 2001 Anticipated Award Date: July, 2001 AWARD CRITERIA Funding criteria will be scientific merit (based on the review criteria listed above), availability of funds, and programmatic priorities. INQUIRIES Inquiries concerning the RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Requests for supplementary guidelines, letters of intent and inquiries regarding programmatic issues may be directed to: Dr. Creighton H. Phelps Alzheimer's Disease Centers Program National Institute on Aging 7201 Wisconsin Avenue, Suite 3C307, MSC 9205 Bethesda, MD 20892-9205 Telephone: (301) 496-9350 FAX: (301) 496-1494 Email: Direct inquiries regarding fiscal matters to: Linda Whipp Grants Management Office National Institute on Aging Gateway Building, Room 2N-212 Bethesda, MD 20892-9205 Telephone: (301) 496-1472 FAX: (301) 402-3672 Email: AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.866. 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 and contract recipients to provide a smoke-free workplace and promote the non-use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or 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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