Part I Overview Information

Department of Health and Human Services

Participating Organizations
National Institutes of Health (NIH), (http://www.nih.gov)

Components of Participating Organizations
National Institute on Aging (NIA), (http://www.nia.nih.gov/)

Title: Alzheimer's Disease Core Centers

Announcement Type
This is a reissue with modification of RFA-AG-04-012, which was previously issued on January 30, 2004.

Update: The following update relating to this announcement has been issued:

Request For Applications (RFA) Number: RFA-AG-05-010

Catalog of Federal Domestic Assistance Number
93.866

Key Dates
Release Date: April 21, 2005
Letters of Intent Receipt Date(s): August 20, 2005
Application Receipt Dates(s): September 20, 2005
Peer Review Date(s): February-March, 2006
Council Review Date(s): May, 2006
Earliest Anticipated Start Date: July 1, 2006
Additional Information To Be Available Date (Url Activation Date): NA
Expiration Date: September 21, 2005

Due Dates for E.O. 12372
Not Applicable

Additional Overview Content

Executive Summary

The National Institute on Aging (NIA) invites applications from qualified institutions for support of Alzheimer's Disease Core Centers (ADCCs). These Centers are designed to serve as shared research resources that will facilitate research on Alzheimer's disease (AD) and related disorders, distinguish them from the process of normal brain aging and mild cognitive impairment (MCI), and lead to better diagnostic and treatment strategies. Using the NIH P30 grant mechanism, the NIA intends to commit approximately $10,500,000 and expects to fund approximately 8 applications. Eligible organizations include for-profit or non-profit organizations; public or private institutions, such as universities, colleges, hospitals, and laboratories; units of State and local governments; eligible agencies of the Federal government; and domestic institutions and organizations. Foreign institutions may participate as subcontractors within a Center. Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with his or her institution to develop an application for support. The PI should be a scientific leader experienced in the field of Alzheimer's and/or other neurodegenerative 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. An individual can be the PI on only one application submitted under this announcement. Application materials are available from the NIH Office of Extramural Research (OER); http://grants.nih.gov/grants/oer.htm. Telecommunications for the hearing impaired is available at: TTY 301-451-5936.

Table of Contents

Part I Overview Information

Part II Full Text of Announcement

 Section I. Funding Opportunity Description
   1. Research Objectives

 Section II. Award Information
   1. Mechanism(s) of Support
   2. Funds Available

 Section III. Eligibility Information
   1. Eligible Applicants
     A. Eligible Institutions
     B. Eligible Individuals
   2.Cost Sharing or Matching
   3. Other - Special Eligibility Criteria

 Section IV. Application and Submission Information
   1. Address to Request Application Information
   2. Content and Form of Application Submission
   3. Submission Dates and Times
     A. Receipt, Review and Anticipated Start Dates
       1. Letter of Intent
     B. Sending an Application to the NIH
     C. Application Processing
   4. Intergovernmental Review
   5. Funding Restrictions
   6. Other Submission Requirements

 Section V. Application Review Information
   1. Criteria
   2. Review and Selection Process
     A. Additional Review Criteria
     B. Additional Review Considerations
     C. Sharing Research Data
     D. Sharing Research Resources
   3. Anticipated Announcement and Award Dates

 Section VI. Award Administration Information
   1. Award Notices
   2. Administrative and National Policy Requirements
   3. Award Criteria

 Section VII. Agency Contact(s)
   1. Scientific/Research Contact(s)
   2. Peer Review Contact(s)
   3. Financial/ Grants Management Contact(s)

 Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement
Section I. Funding Opportunity Description

1. Research Objectives

The National Institute on Aging (NIA) invites applications from qualified institutions for support of Alzheimer's Disease Core Centers (ADCCs). These Centers are designed to serve as shared research resources that will facilitate research on Alzheimer's disease (AD) and related disorders, distinguish them from the process of normal brain aging and mild cognitive impairment (MCI), and lead to better diagnostic and treatment strategies.

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, treatment, and prevention 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 twelve Alzheimer's Disease Core Centers (ADCCs).

The Alzheimer's Centers provide a platform for training as well as the stimulation of research related to clinical-pathological correlations in normal aging and neurodegenerative diseases, studies of many basic research questions on AD and related dementias and strategies for prevention and treatment.

Background

Alzheimer's disease is estimated to affect around 4.5 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 has been estimated that the United States spends as much as 100 billion dollars/year for the direct and indirect 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.

Objectives and Scope

The principal aim of the ADCCs is to enhance the performance of innovative research on AD and related topics at the applicant institution and beyond. Centers are also requested to concentrate their attention on better defining normal aging, the transition from normal aging to mild cognitive impairment (MCI) to the earliest stages of dementia, whether AD itself or other dementias associated with aging. Clinical and pathological information about the earliest cognitive changes will make it possible to develop strategies to prevent the disease from developing or slow its progression. Attention should also be paid to mixed dementias and overlapping neurodegenerative syndromes that sometimes occur with AD.

In order to broaden the range of science necessary to advance AD research, Centers are being given the opportunity to diversify their clinical populations for specific scientific purposes. Centers are expected to provide an environment and core resources which will enhance cutting-edge 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 should also foster the development of new lines of research and provide a rich training 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 brain tissue and biological specimens and should incorporate contemporary biochemical/molecular techniques and support research, when feasible, in genomics and proteomics. Centers are encouraged to develop in accordance with local talents, interests, and resources, but should also be responsive to national needs related to Alzheimer's disease.

Centers should 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 as well as the Alzheimer's Association in furthering mutual goals. Centers should cooperate with other NIA Centers such as Pepper, Shock, and RCMAR Centers when possible, with Udall Centers sponsored by the National Institute of Neurological Diseases and Stroke (NINDS) and the National Alzheimer's Coordinating Center (NACC). Because of increased emphasis on collaborative research across multiple Centers, and additional required data reporting, Centers are mandated to have a Data Management Core. 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 and the flexibility to accomplish them are left to the applicant.

The main function of the ADCCs is to support cutting-edge research by providing well-characterized patients, patient and family information, and tissue and other biological samples from persons with AD and from age-matched control subjects for research projects. As research into the causes of AD has begun to address preclinical stages, Centers should now place more emphasis on the clinical and neuropathological changes that distinguish the initial stages of AD from normal aging and place less emphasis on late stage AD. In addition, since several others of the neurodegenerative diseases (such as vascular dementia, Parkinson's disease, Lewy body disease and frontotemporal dementia) have features that overlap or coexist with AD, ADCCs should organize the clinical cores to collect diagnostic information that allows differentiation among the various diseases while documenting features in common. To this end, applicants must agree to collect an expanded uniform clinical data set (UDS) common to all Centers and transmit the UDS to the National Alzheimer's Coordinating Center (NACC). Core resources from the centers should be used for pilot projects funded by the Center itself as well as for research projects funded by NIH and other Federal agency grant mechanisms and by non-federal and private organizations.

ADCCs are required to include administrative, data management, clinical, and education cores. Another required function is neuropathological diagnosis that can be accomplished either by establishing a core or by subcontracting this function to other Centers or local organizations that have the capacity to carry out this function. Other cores can be proposed if they contribute to the overall mission of the Center, are scientifically justified, support projects funded by other grants, and fit within the budget guidelines for the cores. Funding for small one year pilot grants should also be requested.

ADCCs provide a mechanism for integrating, coordinating, fostering and developing 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 biological specimen resources to support collaborative interactions among scientists in the local Center, other Alzheimer's Centers and the research community at large. A prime objective of the Center Grant is to provide an environment that will strengthen research on AD and related disorders at the institution, increase productivity, and generate new ideas through formal interdisciplinary collaborative efforts both locally and nationally. The central focus may be clinical – pathological research, basic research or a combination. Applicants are strongly encouraged to include efforts to address the needs of, and research on, ethnically diverse populations.

The Center Grant may incorporate ancillary activities such as longitudinal studies and 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. An important role of Centers is to perform collaborative studies on particular research topics and to serve as a regional or national resource for special purpose research. Currently many of the Centers are active participants in NIA multi-disciplinary/multi-Center studies such as the initiative on the genetics of late onset AD and are contributing subjects and blood samples for multiplex family projects. All Centers are required to be linked with the NACC and the network of Centers linked to NACC is being used to standardize clinical and pathological diagnostic procedures, to pool patient information more effectively and to study unique aspects and subtypes of this very complex and heterogeneous disease process. Many Centers are also participating sites for other NIA-supported activities such as the Alzheimer's Disease Cooperative Study (ADCS) for clinical trials, and the Alzheimer's Disease Neuroimaging Initiative (ADNI).

See Section VIII, Other Information - Required Federal Citations, for policies related to this announcement.

Section II. Award Information

1. Mechanism of Support

This funding opportunity will use the NIH P30 award mechanism. As an applicant, you will be solely responsible for planning, directing, and executing the proposed project.

This funding opportunity uses the just-in-time budget concepts. It also uses the non-modular budget format described in the PHS 398 application instructions (see http://grants.nih.gov/grants/funding/phs398/phs398.html). A detailed categorical budget for the "Initial Budget Period" and the "Entire Proposed Period of Support" is to be submitted with the application. A categorical budget for each core, along with a summary budget, is required.

2. Funds Available

The NIA intends to commit approximately $10,500,000 dollars in FY 2006 to fund 8 new and/or competing continuation grants in response to this RFA. An applicant should request a project period of five years and a budget for direct costs for new applications up to $750,000 dollars per year. Competing renewal applications have no overall limit but the combined direct cost for all cores (both required and optional), the other listed required functions, satellites, and pilot grants may not exceed the combined direct costs of all presently funded core activities including satellites and pilot grants awarded during the final year of the present funding period plus a 3% increase. Although the financial plans of the NIA provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications. The anticipated start date is July 1, 2006

Facilities and administrative costs requested by consortium participants are not included in the direct cost limitation, see NOT-OD-05-004.

Section III. Eligibility Information

1. Eligible Applicants

1.A. Eligible Institutions

You may submit (an) application(s) if your organization has any of the following characteristics:

Foreign institutions may participate as subcontractors within a Center.

1.B. Eligible Individuals

The P.I. (Center Director) should be a scientific leader experienced in the field of Alzheimer's and/or other neurodegenerative 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 P.I. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH programs.

2. Cost Sharing or Matching

This program does not require cost sharing as defined in the most current Grants Policy Statement at: http://grants.nih.gov/grants/policy/nihgps_2003/nihgps_Part2.htm#matching_or_cost_sharing.

3. Other-Special Eligibility Criteria

Your institution should support an ongoing base of high-quality Alzheimer's research or research in other neurodegenerative diseases, or in aging of the nervous system. To be eligible your institution must support: at least five principal investigators with any PHS agency (or comparable peer-reviewed federal, state, or foundation) funded research grants related to neurodegenerative diseases or aging of the nervous system and each with at least two years of support remaining at the time of application.

or,

one or more program project grants (P01s) related to neurodegenerative diseases or aging of the nervous system and with at least two years of support remaining at the time of application.

To meet the eligibility criteria, you should clearly document existing support in the overview to the application by listing the principal investigators, source(s) of funding, titles of projects and amounts and duration of support for all projects that you consider to be related to neurodegenerative diseases and/or aging of the nervous system. Your institution can have only one active Alzheimer's Center receiving NIA support.

Section IV. Application and Submission Information

1. Address to Request Application Information

The PHS 398 application instructions are available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. Applicants must use the currently approved version of the PHS 398. For further assistance contact GrantsInfo, Telephone (301) 435-0714, Email: GrantsInfo@nih.gov.

Telecommunications for the hearing impaired: TTY 301-451-5936.

2. Content and Form of Application Submission

Applications must be prepared using the most current PHS 398 research grant application instructions and forms. Applications must have a D&B Data Universal Numbering System (DUNS) number as the universal identifier when applying for Federal grants or cooperative agreements. The D&B number can be obtained by calling (866) 705-5711 or through the web site at http://www.dnb.com/us/. The D&B number should be entered on line 11 of the face page of the PHS 398 form.

The title and number of this funding opportunity must be typed on line 2 of the face page of the application form and the YES box must be checked.

Special Requirements

An Alzheimer's Disease Core Center will be an identifiable organizational unit formed by a single institution or a consortium of cooperating institutions. Therefore, lines of authority must be clearly specified. 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 ADCC. 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. 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 specimens and redacted data with qualified research scientists both within and outside the Centers network and provide data concerning patients and control subjects to the NIA -sponsored National Alzheimer's Coordinating Center (NACC) where a uniform data set (UDS) from all AD Centers is centrally stored. Any genetic specimens collected by the Center should be made available to the National Cell Repository for Alzheimer's Disease (NCRAD), if they meet the criteria for inclusion in the repository, in accordance with agreed upon protocols and policies. Centers may also be requested to contribute other biological samples, such as serum and cerebrospinal fluid, using agreed upon protocols, for trans-center studies examining biomarkers that might relate to risk, diagnosis or progression of AD. The Steering Committee of the NACC in conjunction with the ADC Directors and the NIA sets policies that allow the individual Centers to conduct research on patients and control subjects collected by the individual Center while also sharing common data sets with NACC.

In order to assure active collaboration with other Centers, the ADCC Director and other staff should attend semi-annual meetings of the ADC Directors and other ad hoc meetings arranged by the ADCs or the NIA to share research findings during scientific discussions and poster sessions, participate in planning for cooperative research or help 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 Center investigators 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.

The required elements for an ADCC include four cores (Administrative; Clinical; Data Management and Statistics; and Education and Information Transfer) and two or three pilot projects. Additional cores may be proposed but only if they are needed to advance the local research effort and if they fit within the budget limits described elsewhere in this RFA. A plan to support pilot studies for basic or clinical biomedical, epidemiological, caregiving, educational or behavioral research should be included. Applicants must have the capacity to provide neuropathological confirmation of the diagnosis for all subjects who die while enrolled in the clinical core of the center and to store selected brain specimens for research. This may be accomplished by either having a neuropathology core or by using the services of another Alzheimer's Center neuropathology core or by a pathologist specializing in neurodegenerative diseases who can provide the services outlined in the neuropathology section of this RFA. Applicants should document and describe briefly the projects, both existing and planned, that will depend upon resources provided by the requested cores.

Cores

A core is a shared central laboratory or clinical research facility, service, or resource whose function is essential to the scientific purpose of the ADCC. 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 stated goals. Several important and related considerations are (1) the degree to which currently funded investigators within or outside the Center will use and will benefit from core resources, (2) the degree to which the cores coordinate with each other to further the overall Center mission and (3) the degree to which the resources will promote new and/or expanded AD research efforts locally, regionally or nationally.

Required Cores and Functions

ADMINISTRATIVE CORE (Core A): The administrative core should set the overall direction of the Center and ensure optimal utilization of Center resources. Effective development of Center programs requires interaction among the Director, the principal investigators of the cores, the principal investigators of research and pilot projects using the cores, other researchers at the applicant institution, 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 National Alzheimer's Coordinating Center.

The success of the ADCC is dependent upon involving scientific and professional personnel from a variety of disciplines and subspecialties who interrelate in order to facilitate the acquisition of new knowledge. In addition to coordination of the ADCC, the Director, with the advice of his or her executive committee, will be responsible for allocating and monitoring ADCC funds and identifying and selecting key personnel. 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.

A committee to review pilot grant applications should be established and include scientists from outside the ADCC with expertise relevant to the types of pilot applications received by the Center. This committee will make funding recommendations to the Director. Alternatively, the external advisory committee could be responsible for pilot reviews.

An external advisory committee to the ADCC, consisting of scientists from outside of the institution or consortium, will also be established. Unless already appointed, external advisory committee members should not be recruited or named until the NIH review process is complete. This committee will be used to evaluate the programs of the ADCC, research progress, the effectiveness of communications within the ADCC, interactions with NACC, 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 ADRC. A member of the NIA extramural program staff should be invited to attend each meeting as an observer. A copy of the advisory committee report should be routinely sent to the NIA with the annual progress report.

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 be 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 and be familiar with NIH grant-related compliance policies. The administrator should attend the annual ADC Administrators' meeting.

It is expected that the ADCC administrative structure will facilitate the following:

1) coordination and integration of ADCC components and activities; (for example, the clinical and data management cores with the neuropathology and education components)

2) direction for future planning and optimal utilization of resources

3) support and advice for the ADCC Director in his/her oversight of the activities of the Center

4) interaction with the scientific and lay communities to develop relevant goals for the ADCC

5) assurance of compliance with human subjects, animal welfare, scientific integrity, and financial policy requirements of NIH

6) interaction with other Centers, NACC and other researchers to develop trans-ADC and outside research projects

7) interaction and involvement with other research programs of the University including the provision of core resources for development of related projects

8) timely and routine transmissions of appropriate ADCC data sets to NACC

CLINICAL CORE (Core B): The clinical core provides well-characterized patients and control subjects for research projects involving e.g. clinicopathological correlations, comparison of disease states to normal aging, and drug/intervention studies. The clinical core in close collaboration with the Education core of the Center is the primary contact point with the community. The core provides educational and clinical resources to patients, aging control subjects, and caregivers while charting the course of the disease in patients and age-related changes in the research population being followed by the Center. Clinical cores of ADCs are usually based in university medical center neurology or psychiatry department memory disorders clinics. However, NIA is now providing the opportunity to structure clinical cores to include special control or elderly populations that might be available to some applicants such as an ethnic or minority population, a religious community or a community population living in elderly housing where the likelihood of being able to study the full spectrum from normal aging to mild cognitive impairment to AD would be possible.

Recent improvements in evaluation for memory disorders in normal aging and MCI present new opportunities for research on early stages of disease and decrease the necessity to enroll middle and later stage patients. In addition, our increased understanding of the relationship of AD to, or coexistence with, other neurogenerative diseases commonly seen in the elderly population provides the opportunity to broaden the mission of the ADCCs to include mixed dementias and diseases such as vascular dementia, Lewy body disease, frontotemporal dementia, and Parkinson's dementia in order to better differentiate among them, to recognize commonalities and to study older demented individuals with mixed etiologies and medically co-morbid conditions. Therefore it is more appropriate that applicants concentrate on preclinical AD, normal aging, MCI and early AD as well as enhancing the recruitment of research subjects with other neurodegenerative diseases rather than concentrating only on full blown or pure AD. If applicants choose to diverge from the traditional structure (memory disorders clinic model) of the clinical core by including special populations, the responsibility is on the applicant to provide a complete description of the characteristics of the subject population and to justify the added value to research at the Center resulting from using a different subject population.

The clinical core, in addition to patient and control subject recruitment, provides evaluation, and diagnosis, maintains a patient registry, conducts longitudinal follow up of patients and control subjects, and acquires clinical and laboratory data including agonal data pertaining to the last several weeks of life if post mortem material is to be used for molecular research. Procedures and facilities should be described related to collection, storage, and distribution of biological samples, including, but not limited to, cell lines, cerebrospinal fluid (CSF) and plasma. Applicants should follow agreed upon protocols for multi-center projects involving specimen collection. Details for collecting specimens, recording information about clinical status of patients immediately preceding and at time of death, and procedures for storage and distribution of human biological samples to investigators both within and outside the Center should be provided.

Data on preclinical stages of AD (MCI), possible and probable AD, other neurodegenerative disorders and normal aging should be collected and transmitted to the data management core. A uniform data set must be shared with the National Alzheimer's Coordinating Center according to standardized protocols developed by the ADC Directors, the clinical core leaders and the Steering Committee of NACC. Recently, a clinical task force developed the criteria for collection of the expanded uniform data set (UDS) from all Centers. Applicants may obtain details regarding the UDS from NACC, http://www.alz.washington.edu/.

Applicants must state in this section of the application that they agree to provide this expanded data set to NACC where it will be combined with data from other Centers and made available to scientists for collaborative studies.

The clinical core may perform a limited amount of developmental work, but should not directly support 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 existing diagnostic strategies, or developing 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. Procedures for communicating recruitment needs to the education core and for evaluating success should be outlined. The application should include a description of the types (with specific examples) of research projects and clinical trials that use or will use the core and what benefits will extend to other research activities from the existence of the clinical core. While conducting clinical drug trials is one function of a clinical core, it should not be the major effort of the core.

Efforts to recruit diverse population subgroups including minorities and rural populations must be outlined. 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 are not required to conduct research but should serve as vehicles for the recruitment, assessment and management of AD patients and recruitment of control subjects from rural and minority communities, who are then offered the opportunity to participate in research protocols, clinical drug trials and are followed to autopsy. Effective satellites usually include multicultural staff members who have links to the community being involved. In addition, the satellite should have clearly delineated interactions with the educational outreach activities of the Center. Applicants should detail appropriate strategies for outreach to recruit and retain ethnically diverse subjects and describe the culturally sensitive materials that will be used. The inclusion of patients with different characteristics will assist investigators in providing answers to questions about AD diagnosis, treatment, and management strategies that are likely to be applicable to the broad U.S. population. 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.

DATA MANAGEMENT and STATISTICS CORE (Core C): This core should provide data management and statistical consulting to the research projects and the cores of the ADRC. Data cores are important to facilitate local analyses and collaborations between and among Centers and with NACC. (New applicants may contact NACC to learn more about NACC procedures and the regular updates to the datasets required from all Centers; http://www.alz.washington.edu/) A model for the data core might consist of two arms: 1) computing and data base management and 2) statistical consultation and liaison with other cores. The core director must be keenly aware of and experienced with database management practices and computing but is not necessarily the architect and day to day manager of the database. The core director must have the time and the authority to work administratively with other cores. The core should include a systems manager for computing and database management who will be the architect of the database structure and responsible for its maintenance. This person will be an experienced database programmer and systems analyst with sufficient background to select and implement database management software, represent data structures, specify and organize data flow, construct detailed “error-check” programs, develop/implement data checking and cleaning procedures, and provide for data entry and access, as well as information distribution, through electronic means (e.g., the internet or intranet). Communication and cooperation with all cores where data are (or will be) generated, with NACC, and a close working relationship with the statistics arm of this core should be primary goals for this core. The systems manager should be given the authority:

1. to establish data flow schemes,

2. to construct data forms (electronic or hard copy; following core/project specified content),

3. to implement a Center-wide system of subject ID numbers that meets privacy standards

4. to require adequate filing systems for raw data within other cores and within the data core itself,

5. to establish a mechanism to track data edits,

6. to provide for longitudinal follow-up data storage/retrieval consistent with the protocols of the center.

The staff of the data core must work with clinical and research personnel to interpret their data into computer usable form, and simultaneously work with statisticians to insure that the data are represented in a fashion that will allow the desired analysis files to be produced and analyses to be accomplished. Data core staff should have a working relationship with core data collectors and must have their cooperation to reconcile errors and missing or incomplete data elements as discovered through error check programs or through ‘hands-on' inspection procedures. In addition the core staff is required to work cooperatively with the NACC staff and respond appropriately to data calls issued by NACC.

A biostatistician(s) should be involved in the design and analysis of studies using the cores and will work closely with the data manager to insure analysis files are produced consistent with the needs of the question at hand. It is expected that the clinical and other cores in the ADC, where the data are collected, will fully cooperate and participate with the data core by providing data in the form specified and in a timely way. Cooperation, concurrence and collaboration should continue from the initial specification of data content through data collection to database management and analysis.

NEUROPATHOLOGY: Neuropathology operations can be either organized as a core (Core D) or a service and are expected to provide state of the art diagnostic services and collection of well-prepared brain material appropriate for the research requirements of local research efforts as well as cooperative research across Centers and with other researchers outside of Centers. Centers must be able to provide post mortem diagnosis on cases and normal control subjects enrolled in the clinical core and on other well documented AD cases and controls. A significant value of having the Center infrastructure is the support of research studies that permit clinical-pathological correlations across Centers. Therefore, Centers should agree to follow standardized procedures so that cross-Center correlations are possible (new applicants may contact NACC to get the most recent pathology requirements). Centers can choose to establish a neuropathology core or can obtain services from outside the Center (usually another Alzheimer's Center but could be a non-center pathologist who agrees to follow procedures outlined here).

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, cell lines, cerebrospinal fluid (CSF) and plasma. While Centers are encouraged to have brain banks, less emphasis should be placed on the routine collection and storage of late stage Alzheimer's brains (unless specific research questions call for these) and more emphasis should be placed on collection of brain material that will support the specific research efforts of investigators affiliated with the local Center and other scientists. If collection of special material is proposed (e.g. tissues from Parkinson's disease, oldest old controls, frontotemporal dementia, prion diseases, mixed dementias, or stereologically prepared specimens) justification should be included. Data gathering and storage activities should be coordinated with those of the clinical core and the data management core.

To facilitate data sharing and cross-Center comparisons of diagnosis, all Centers should use the neuropathological criteria for Alzheimer's disease developed by the NIA-Reagan Institute Working Group (Neurobiology of Aging, vol. 18, suppl 4, pp S1-S2, 1997). If tissue from other diseases is collected, list the clinical diagnostic criteria used. More detailed criteria for research purposes should also be described. Pathology data should be included in the data set transmitted to NACC as recently redefined by Center neuropathologists and approved by the Center Directors group. (New applicants may get information from NACC about the pathology data set). If the applicant chooses to include a neuropathology core in the application, the core may propose a limited amount of developmental work, but should not emphasize 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 in the application. Neuropathologists from 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. All Centers are expected to send a representative to this meeting.

The procedure for prioritizing the use of tissues and other biological samples stored at the Center should be discussed along with a brief description of potential research projects that will use the samples. Provisions for obtaining informed consent and protecting the privacy of research subjects must be detailed. Procedures to provide coded samples to investigators that protect the identity of the patients should be described.

EDUCATION and INFORMATION CORE (Core E): The three major activities of the education core are to 1) help recruit and retain subjects for particular research protocols and clinical trials, with a special emphasis on minorities and other underserved populations; 2) spearhead effective outreach programs that will publicize the ADCC and educate families and caregivers; 3) support development of professional staff on clinical and research skills related to Alzheimer's disease and other dementias. These efforts afford an important liaison and outreach from the ADCC to patients, their caregivers and the professional community. Collaboration with the Alzheimer's Association local chapters and other groups is expected for dissemination and transfer of information to the lay community. 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 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; 3) outreach to specific communities to publicize research; 4) collaboration with other organizations such as state and local agencies and the Alzheimer's Association and 5) descriptions of materials (e.g. videos and printed matter) developed by the Center.

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. Procedures by which the education and outreach activities are closely coordinated with the clinical core and satellite(s) (if appropriate) should be described, especially in recruitment of minorities and ethnically diverse populations. The education and outreach activities should also be prepared to support activities of the Centers group as a whole as well as recruitment for special NIA initiatives, such as subjects for genetic studies. 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. Collaboration with other ADCs and the NIA Alzheimer's Disease Education and Referral Center (ADEAR) in subject recruitment, education and coordinated dissemination of educational materials is expected.

Optional Cores

Support for additional cores that provide opportunities to support scientific research beyond those attainable solely through support of the mandatory cores and other functions can be requested. However, any optional cores must support one or more research projects and fit within the budget restrictions outlined in the budget guidelines for the application. Support should not be requested for cores that only replace or centralize resources already supported by other project grants. It must be demonstrated exactly how each core would augment or enhance the present capabilities of investigators using the center resources to make possible new activities at the home Center as well as other Centers. There should be a detailed discussion of the project(s) that will use resources of additional cores. Some examples of research support that core components could provide are: (1) imaging; (2) tissue and/or cell culture facilities; (3) complex instrumentation, e.g., electron microscopy, mass spectrometry, electrophysiology; (4) sequencing or microarray facilities (5) transgenic animal or cell preparation; (6) genetics; and (7) caregiving.

Pilot Studies

A plan to support pilot studies for basic or clinical biomedical, epidemiological, caregiving, educational 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 in 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. 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 other 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. Some examples are:

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 a 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.

4) A study based on data in the NACC data set to determine the feasibility of conducting larger new studies.

Each pilot project is limited to no more than $35,000 direct costs each year. If the pilot project is requested and justified for two years, the direct costs are limited to $35,000 per year.

No pilot applications should be submitted with the Center application but, instead, the number requested for each year (2 minimum, 3 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. The panel should include scientists from outside the Center. One option is for the External Advisory committee to serve as the review panel for the pilot applications. Following review, those pilots chosen for funding should be submitted to the NIA for approval in the annual non-competing renewal application. Successful Center applicants should conduct a competition and submit the successful applications to NIA for the first year of pilot funding after receiving notice of grant award; in subsequent years competition for pilot awards should be timed so successful applications can be submitted with the non-competing renewal application for NIA review.

Progress Reports (for competing renewal applications and amended applications)/Preliminary Studies

Overall Progress Report: Address the major scientific achievements in research on AD and related topics carried out by Center personnel and by projects utilizing Center resources in the last funding period. Identify significant findings in research on aging, AD and other neurodegenerative diseases that were facilitated by using Center resources. Include summaries of progress in achieving the major aims of the Center and highlight major publications. Include details of how the presence of the ADCC has brought new investigators into the field and has stimulated non-ADCC funded research in the last funding period. Explain the Center's role in generating new funding from grants as well as leveraging funds from donors and other private sources. Describe how the presence of the Center has facilitated and improved Alzheimer research at the Institution and beyond. When an optional core has terminated, include a final report with a summary of activities and publications. If an optional core is continuing, include a progress report in that 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) Involvement in collaborative projects with other Centers including those funded by NACC, and 4) minority enrollment into research projects or clinical trials and specifically, into any research projects addressing minority issues.

In addition to text summaries, applicants should also include summary tables detailing:

1) Funded grants and projects that use or have used major resources supplied by the ADCC, including principal investigator, source and period of funding, types and amount of resources and any resulting publications.

2) Collaborations with other AD researchers, other Centers, cooperative studies, 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 private and public resources committed to the Center and its investigators.

Clinical Core progress report: Describe the most important clinical core contributions to research on AD, related dementias and aging. Detail key findings and list publications resulting from use of core patients. Any developmental work carried out by the core should be presented and resulting publications listed. The clinical core progress report should include the clinical core objectives and progress in meeting them, including information about satellites (if applicable). Basic functions of the core should be summarized (using tables where appropriate) including numbers, race, gender, age of patients and controls recruited, diagnosis, percentage follow up and drop out rate, use of autopsy data in support of clinical correlations in research projects, and diagnostic confirmation by autopsy. Functions of clinical core in providing services to funded investigators should be clearly summarized. These would include numbers and kinds of subjects recruited and participation in clinical trials and other ongoing clinical research projects, both local and national.

Data Management and Statistics progress report: Summarize progress and activities related to data collection, data management and statistical consulting activities at the appropriate place in the application detailing where in the core(s) these activities were located. Include progress and interactions with NACC. Present evidence for meeting timetables for data transfer in the proper format to NACC. List projects and publications in which data management and statistical consulting played a role.

Education and Information Transfer Core progress report: Applications should include information about training activities that effectively impart knowledge to professionals and the lay public with the possibility of leading to improved health care for patients. Include efforts to assist the clinical core and NIA special initiatives, such as the genetics initiative, in subject recruitment, especially any efforts directed to recruitment of minority and ethnically diverse subjects. Using tables when appropriate, report 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. List educational materials developed by the core and any that may have been provided to ADEAR for national distribution.

Neuropathology progress report: Describe the most important neuropathology core contributions to research on AD, related dementias and aging. Competing renewal applications should outline previously stated core objectives and progress in meeting them. Any developmental work carried out by the core should be presented and resulting publications listed. The most important consideration in reporting progress should be reports of tissue use in research projects and the new insights obtained from these studies. Basic functions of the core such as number of AD and control autopsies, post mortem intervals (where this is important for specific research purposes), tissue dissection and storage, diagnoses, and type and quantity of tissue provided to investigators should be clearly summarized (using tables where appropriate).

Amended applications that have been previously submitted as either P30 or P50 applications should also report progress using the above guidelines.

Budget Considerations

All ADCC proposals should request and provide justification for five years of support.

The direct costs requested for new applications may not exceed $750,000 for the first year. Competing renewal applications have no fixed limit but the combined direct costs for all cores (both required and optional), the other listed required activities, satellites, and pilot grants may not exceed the combined direct costs of all presently funded core activities (required and optional) including satellites and pilot grants awarded in the final year of the present funding period plus a 3% increase. Direct cost requests for subsequent years may increase above the prior year direct cost by 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 depending on whether this is a new application or a competing renewal, on the overall budget of existing Centers, and local needs. If additional cores are proposed, the distribution should be adjusted accordingly.)

Administrative Core

10%

Pilot Studies

  5%

Clinical Core

50%

Data Management Core

15%

Neuropathology (Core or Service)

10%

Education and Information Transfer Core

10%

If large 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 other investigators 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 ADCC 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 leaders, education core leaders, data managers, and neuropathology core leaders 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 $35,000 per pilot per year (without escalation). They should not be included in the Administrative Core budget 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 non-competing renewal applications. Facilities & Administrative costs will be provided in accordance with these budgets.

1) A list of all proposed performance sites both at the applicant institution and at the collaborating institutions

2) A separate, detailed budget for the initial and future years 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.

3. Submission Dates and Times
Applications must be received on or before the receipt date described below (Section IV.3.A). Submission times N/A.

3.A. Receipt, Review and Anticipated Start Dates

Letter of Intent Receipt Date: August 20, 2005
Application Receipt Date(s): September 20, 2005
Peer Review Date: February-March, 2006
Council Review Date: May, 2006
Earliest Anticipated Start Date: July 1, 2006

3.A.1. Letter of Intent

Prospective applicants are asked to submit a letter of intent that includes the following information:

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

The letter of intent is to be sent by the date listed at the beginning of this document.

The letter of intent should be sent to:

Creighton H. Phelps, Ph.D.
Program Director, Alzheimer's Disease Centers
Neuroscience and Neuropsychology of Aging Program
National Institute on Aging
7201 Wisconsin Avenue
Suite 350
Bethesda, MD 20892-9205
Telephone: (301) 496-9350
FAX: (301) 496-1494
Email: phelpsc@nia.nih.gov

3.B. Sending an Application to the NIH

Applications must be prepared using the PHS 398 research grant application instructions and forms as described above. Submit a signed, typewritten original of the application, including the checklist, and three signed photocopies in one package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)

At the time of submission, two additional copies of the application and the CD containing the appendix material must be sent to:

Mary Nekola, Ph.D., Chief
Scientific Review Office
National Institute on Aging
7201 Wisconsin Avenue
Suite 2C212
Bethesda, MD 20892-9205
Telephone: (301) 496-9666
FAX: (301)402-0066
Email: nekolam@nia.nih.gov

Using the RFA Label: The RFA label available in the PHS 398 application instructions 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/labels.pdf. Personal deliveries of applications are no longer permitted.

3.C. Application Processing

Applications must be received on or before the application receipt date(s) described above (Section IV.3.A.). If an application is received after that date, it will be returned to the applicant without review. Upon receipt, applications will be evaluated for completeness by the CSR and responsiveness by the NIA. Incomplete and non-responsive applications will not be reviewed.

The NIH will not accept any application in response to this funding opportunity that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. For unsuccessful applicants who responded to the ADCC RFA last year, the application for this funding opportunity should include an Introduction describing the changes and improvements made. Unsuccessful applicants who responded to the ADRC RFA last year should include an Introduction describing only the changes and improvements made in the cores and required ADCC components.

Although there is no immediate acknowledgement of the receipt of an application, applicants are generally notified of the review and funding assignment within eight (8) weeks.

4. Intergovernmental Review
This initiative is not subject to intergovernmental review.

5. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm (see also Section VI.3. Reporting).

Pre-Award Costs are allowable. A grantee may, at its own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new or competing continuation award if such costs: are necessary to conduct the project, and would be allowable under the grant, if awarded, without NIH prior approval. If specific expenditures would otherwise require prior approval, the grantee must obtain NIH approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new or competing continuation award.

The incurrence of pre-award costs in anticipation of a competing or non-competing award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project. See NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part6.htm.

6. Other Submission Requirements

A Supplemental Instructions:

The page limit of 25 pages for Items a-d of the Research Plan, as stated in the PHS Form 398 instructions, applies to each core. Appendix materials should be kept to a minimum. Appendices are not provided to every member of the initial review group. Material considered essential for the review must be included in the body of the application including sharing the UDS with NACC. Information that is not included with the original application may not be submitted after the receipt date except with prior approval from the responsible Scientific Review Administrator. This will usually only include major corrections or changes in personnel.

Table of Contents

Do not use Form Page 3, “TABLE OF CONTENTS” of Form 398 since it applies to applications for single projects. In its place, use the sample format provided in the following link (disregard references to projects and list only cores) http://www.nia.nih.gov/NR/rdonlyres/E489A7E9-EBFA-4B9F-8C80-C10BF3676169/4220/PPGattachment1.doc.

Number all pages consecutively. Since the first page of the application is the “Title Page,” begin the next page with the numeral “2”. Do not use lettered numbers (e.g., 2A, 2B, etc.).

Each component core should be presented according to the Table of Contents. Identify required cores by letters as follows - Core A= Administrative Core, Core B= Clinical Core, Core C = Data Management and Statistics Core; if the application includes a Neuropathology Core, it should be Core D; the Education and Information Transfer Core should be Core E, even if there is no Neuropathology Core. Optional Cores should be identified with subsequent consecutive letters. Titles may not exceed 81 characters. Type the Core leader's name at the upper right-hand corner of each page under the principal investigator's name.

Identify appendix material, as appropriate, by the principal investigator's name, core designation, and core leader's name. Appendix materials should follow the instructions in the PHS 398 form with the following exception: The complete Appendix materials should be submitted on a compact disc (CD) that is identified with the name of the principal investigator, and the name of this RFA. All appendix materials for the complete application should be on a single CD. Appendix materials should be sent to the Chief, Scientific Review Office, NIA (see address below).

Budgets. Insert a table describing the CONSOLIDATED DIRECT COSTS FOR FIRST YEAR OF REQUESTED SUPPORT, as shown in Attachment 3 in the following link for the three required cores and any optional cores (disregard references to projects), http://www.nia.nih.gov/NR/rdonlyres/E489A7E9-EBFA-4B9F-8C80-C10BF3676169/4221/PPGAttachment3.xls.

Next, insert budgets for the first twelve months and for the entire proposed period for the overall program. Do not include detailed budgets for individual cores here; instead, place them with the corresponding core. Justify all items carefully according to the PHS 398 form instructions. A complete budget for a consortium agreement is to be developed and identified as such. The period of support may not exceed five years of support. Any questions about budget development may be directed to the Grants and Contracts Management Office at the address above.

Biographical Sketches. Follow the PHS 398 instructions. Include sketches for all key personnel and place them in alphabetical order; however, place the principal investigator's/program director's biographical sketch first. To aid in the review of the application, insert completed Table II after the biographical sketches. See sample, Attachment 4 in the following link (disregard reference to projects). “DISTRIBUTION OF PROFESSIONAL EFFORT (%) ON THIS APPLICATION,” http://www.nia.nih.gov/NR/rdonlyres/E489A7E9-EBFA-4B9F-8C80-C10BF3676169/4222/PPGAttachment4.xls.

Plan for Sharing Research Data

All applicants must include a plan for sharing research data in their application. The data sharing policy is available at http://grants.nih.gov/grants/policy/data_sharing. All investigators responding to this funding opportunity should include a description of how final research data will be shared, or explain why data sharing is not possible.

Data Sharing Plan: All applicants responding to this RFA are required to have a data core with the capacity to prepare the Uniform Data Set (UDS) for transmission to the National Alzheimer's Disease Coordinating Center (NACC) which in turn will make appropriate data sets available to qualified investigators for further research. The reasonableness of the data core plan will be assessed by the reviewers and factored into the determination of scientific merit and the priority score. This requirement for data sharing will be part of the terms and conditions of the award. The funding organization will be responsible for monitoring the data sharing policy.

Sharing Research Resources

NIH policy requires that grant award recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/index.htm and http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part7.htm#_Toc54600131). Investigators responding to this funding opportunity should include a plan for sharing research resources addressing how unique research resources will be shared or explain why sharing is not possible.

The adequacy of the resources sharing plan and any related data sharing plans will be considered by Program staff of the funding organization when making recommendations about funding applications. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590, http://grants.nih.gov/grants/funding/2590/2590.htm). See Section VI.3. Reporting.

Applicants must commit to cooperate fully and to share specimens with other research scientists both within and outside the AD Centers network. Any genetic specimens collected by the Center should be made available to the National Cell Repository for Alzheimer's Disease (NCRAD), if they meet the criteria for inclusion in the repository, in accordance with agreed upon protocols and policies. Centers may also be requested to contribute other biological samples, such as serum and cerebrospinal fluid, using agreed upon protocols, for trans-center studies examining biomarkers that may relate to risk, diagnosis or progression of AD.

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process.

The following will be considered in making funding decisions:

2. Review and Selection Process

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 NIA in accordance with the review criteria stated below.

As part of the initial merit review, all applications will:

The goals of NIH supported research are to advance our understanding of biological systems, to improve the control of disease, and to enhance health. In their written critiques, reviewers will be asked to comment on each of the following criteria in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, weighting them as appropriate for each application. Note that an application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a high priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to move a field forward.

Significance: Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge or clinical practice be advanced? What will be the effect of these studies on the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Approach: Are the conceptual or clinical framework, design, methods, and analyses adequately developed, well integrated, well reasoned, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics?

Innovation: Is the project original and innovative? For example: Does the project challenge existing paradigms or clinical practice; address an innovative hypothesis or critical barrier to progress in the field? Does the project develop or employ novel concepts, approaches, methodologies, tools, or technologies for this area?

Investigators: Are the investigators 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? Does the investigative team bring complementary and integrated expertise to the project (if applicable)?

Environment: Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed studies benefit from unique features of the scientific environment, or subject populations, or employ useful collaborative arrangements? Is there evidence of institutional support?

Applications will specifically be reviewed with respect to the following:

PROGRESS IN ACHIEVING STATED GOALS (competing renewal applications and amended resubmissions)

SCIENTIFIC POTENTIAL OF THE CENTER (competing renewal, resubmission and new applications)

ORGANIZATION OF THE CENTER (competing renewal and new applications)

CORE FACILITIES (competing renewal and new applications)

RESEARCH

These criteria will be applied to competing continuations by evaluating progress and future plans, and to new applications, by evaluating preliminary organizational work, experience with Alzheimer's and other neurodegenerative disease research, potential for developing new and exciting research, and specific plans for implementation of the new program.

2.A. Additional Review Criteria:

In addition to the above criteria, the following items will continue to be considered in the determination of scientific merit and the priority score:

Protection of Human Subjects from Research Risk: The involvement of human subjects and protections from research risk relating to their participation in the proposed research will be assessed (see the Research Plan, Section E on Human Subjects in the PHS Form 398).

Inclusion of Women and Minorities in Research: The adequacy of plans to include subjects from both genders and all racial and ethnic groups (and subgroups), as appropriate for the scientific goals of the research will be assessed. Plans for the recruitment and retention of subjects will also be evaluated (see the Research Plan, Section E on Human Subjects in the PHS Form 398).

Care and Use of Vertebrate Animals in Research: If vertebrate animals are to be used in the project, the five items described under Section F of the PHS Form 398 research grant application instructions will be assessed.

2.B. Additional Review Considerations

Budget: The reasonableness of the proposed budget and the requested period of support in relation to the proposed research. The priority score should not be affected by the evaluation of the budget.

2.C. Sharing Research Data

All investigators responding to this funding opportunity should include a description of how final research data will be shared with qualified investigators as outlined above in the data sharing plan. The reasonableness of the data sharing plan will be assessed by the reviewers and factored into the determination of scientific merit and the priority score. This requirement for data sharing will be part of the terms and conditions of the award. The funding organization will be responsible for monitoring the data sharing policy. All applicants responding to this RFA are required to have a data core with the capacity to prepare the Uniform Data Set (UDS) for transmission to the National Alzheimer's Disease Coordinating Center (NACC).

2.D. Sharing Research Resources

NIH policy requires that grant recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (See the NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps/part_ii_5.htm#availofrr and http://www.ott.nih.gov/policy/rt_guide_final.html). Investigators responding to this funding opportunity should include a sharing research resources plan addressing how unique research resources will be shared with qualified investigators.

The adequacy of plans to share brain tissue and biological specimens with other research scientists both within and outside the AD Centers network will be assessed. Any genetic specimens collected by the Center should be made available to the National Cell Repository for Alzheimer's Disease (NCRAD), if they meet the criteria for inclusion in the repository, in accordance with agreed upon protocols and policies.

The adequacy of the resources sharing plan will be considered by Program staff of the funding organization when making recommendations about funding applications. Program staff may negotiate modifications of the data and resource sharing plans with the awardee before recommending funding of an application. The final version of the data and resource sharing plans negotiated by both will become a condition of the award of the grant. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590). See Section VI.3. Reporting.

3. Anticipated Announcement and Award Dates
Not applicable

Section VI. Award Administration Information

1. Award Notices

After the peer review of the application is completed, the Principal Investigator will also receive a written critique called a Summary Statement.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part4.htm).

A formal notification in the form of a Notice of Grant Award (NGA) will be provided to the applicant organization. The NGA signed by the grants management officer is the authorizing document.

The NGA will be sent via email or postal system to the administrative official whose name is listed in Block 12 on the Face Page of the Form PHS 398.

Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NGA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs. See Also Section IV.5. Funding Restrictions.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the notice of grant award. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part4.htm) and Part II Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part9.htm).

3. Reporting

Awardees will be required to submit the PHS Non-Competing Grant Progress Report, Form 2590 annually (http://grants.nih.gov/grants/funding/2590/2590.htm) and financial statements as required in the NIH Grants Policy Statement. When pilot grant applications have been approved for funding at the Center, copies of the information supporting the applications should be sent to the NIA for approval.

Section VII. Agency Contacts

We encourage your inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into three areas: scientific/research, peer review, and financial or grants management issues:

1. Scientific/Research Contacts:

Creighton H. Phelps, Ph.D.
Program Director, Alzheimer's Disease Centers
Neuroscience and Neuropsychology of Aging Program
National Institute on Aging
7201 Wisconsin Avenue
Suite 350
Bethesda, MD 20892-9205
Telephone: (301) 496-9350
FAX: (301) 496-1494
Email: phelpsc@nia.nih

2. Peer Review Contacts:

Mary Nekola, Ph.D., Chief
Scientific Review Office
National Institute on Aging
7201 Wisconsin Avenue
Suite 2C212
Bethesda, MD 20892-9205
Telephone: (301) 496-9666
FAX: (301)402-0066
Email: nekolam@nia.nih.gov

3. Financial or Grants Management Contacts:

Deborah Stauffer
Grants and Contracts Management Office
National Institute on Aging
7201 Wisconsin Avenue
Suite 2N212
Bethesda, MD 20892-9205
Telephone: (301) 496-1472
FAX: (301) 402-3672
Email: stauffed@nia.nih.gov

Section VIII. Other Information

Required Federal Citations

Use of Animals in Research:
Recipients of PHS support for activities involving live, vertebrate animals must comply with PHS Policy on Humane Care and Use of Laboratory Animals (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf) as mandated by the Health Research Extension Act of 1985 (http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA Animal Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm) as applicable.

Human Subjects Protection:
Federal regulations (45CFR46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

Data and Safety Monitoring Plan:
Data and safety monitoring is required for all types of clinical trials, including physiologic toxicity and dose-finding studies (phase I); efficacy studies (Phase II); efficacy, effectiveness and comparative trials (Phase III). Monitoring should be commensurate with risk. The establishment of data and safety monitoring boards (DSMBs) is required for multi-site clinical trials involving interventions that entail potential risks to the participants (NIH Policy for Data and Safety Monitoring, NIH Guide for Grants and Contracts, http://grants.nih.gov/grants/guide/notice-files/not98-084.html).

Sharing Research Data:
Investigators submitting an NIH application seeking $500,000 or more in direct costs in any single year are expected to include a plan for data sharing or state why this is not possible (http://grants.nih.gov/grants/policy/data_sharing).

Investigators should seek guidance from their institutions, on issues related to institutional policies and local IRB rules, as well as local, State and Federal laws and regulations, including the Privacy Rule. Reviewers will consider the data sharing plan but will not factor the plan into the determination of the scientific merit or the priority score.

Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with Federal funding pursuant to the Bayh Dole Act (see the NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/index.htm). All investigators submitting an NIH application or contract proposal, beginning with the October 1, 2004 receipt date, are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.

Inclusion of Women And Minorities in Clinical Research:
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 "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the new PHS Form 398; and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences.

Required Education on the Protection of Human Subject Participants:
NIH policy requires education on the protection of human subject participants for all investigators submitting NIH applications for research involving human subjects and individuals designated as key personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

Human Embryonic Stem Cells (hESC):
Criteria for federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (http://escr.nih.gov/). It is the responsibility of the applicant to provide in the project description and elsewhere in the application as appropriate, the official NIH identifier(s) for the hESC line(s)to be used in the proposed research. Applications that do not provide this information will be returned without review.

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 PA 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.

Standards for Privacy of Individually Identifiable Health Information:
The Department of Health and Human Services (DHHS) issued final modification to the "Standards for Privacy of Individually Identifiable Health Information", the "Privacy Rule", on August 14, 2002. The Privacy Rule is a federal regulation under the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable health information, and is administered and enforced by the DHHS Office for Civil Rights (OCR).

Decisions about applicability and implementation of the Privacy Rule reside with the researcher and his/her institution. The OCR website (http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including a complete Regulation Text and a set of decision tools on "Am I a covered entity?" Information on the impact of the HIPAA Privacy Rule on NIH processes involving the review, funding, and progress monitoring of grants, cooperative agreements, and research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

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. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site.

Healthy People 2010:
The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This PA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

Authority and Regulations:
This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The NIH Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.

The PHS strongly encourages all grant recipients to provide a smoke-free workplace and discourage the 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.

Loan Repayment Programs:
NIH encourages applications for educational loan repayment from qualified health professionals who have made a commitment to pursue a research career involving clinical, pediatric, contraception, infertility, and health disparities related areas. The LRP is an important component of NIH's efforts to recruit and retain the next generation of researchers by providing the means for developing a research career unfettered by the burden of student loan debt. Note that an NIH grant is not required for eligibility and concurrent career award and LRP applications are encouraged. The periods of career award and LRP award may overlap providing the LRP recipient with the required commitment of time and effort, as LRP awardees must commit at least 50% of their time (at least 20 hours per week based on a 40 hour week) for two years to the research. For further information, please see: http://www.lrp.nih.gov/.


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