Part I Overview Information


Department of Health and Human Services

Participating Organizations
National Institute on Aging (NIA) (www.nia.nih.gov)

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

Title: Alzheimer’s Disease Core Centers (P30)

Announcement Type
This is a reissue of RFA-AG-10-001

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

Request For Applications (RFA) Number:  RFA-AG-11-005

Catalog of Federal Domestic Assistance Number(s)
93.866

Key Dates
Release Date:  July 15, 2010
Letters of Intent Receipt Date: September 13, 2010
Application Receipt Date: October 13, 2010
Peer Review Date(s): February-March, 2011   
Council Review Date: May 2011 
Earliest Anticipated Start Date: July 1, 2011 
Additional Information To Be Available Date (Url Activation Date): Not applicable
Expiration Date: October 14, 2010

Due Dates for E.O. 12372

Not Applicable

Additional Overview Content

Executive Summary

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
   D.  Application Assignment
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements

Section V. Application Review Information
1. Criteria
2. Review and Selection Process
3. Anticipated Announcement and Award Dates

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

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

According to recent estimates, as many as 2.4 million to 5.1 million Americans have AD. Although it is occasionally identified in patients in their forties and fifties, it is most frequently associated with advancing age.  AD 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 well over 100 billion dollars/year for the direct and indirect costs of care for patients with AD.  The risk of AD increases greatly with age, and projections suggest that the numbers of people with AD will increase with the aging of the population unless effective interventions are found.

In the United States the Executive and Legislative Branches of the Federal Government have both expressed concern about the enormity of the problem posed by AD.  Congressional concern 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 AD.  The NIA Alzheimer's Disease Centers (ADCs) program is authorized by the Public Health Service Act, Section 445, and currently includes seventeen Alzheimer's Disease Research Centers (ADRCs) and twelve Alzheimer's Disease Core Centers (ADCCs).

The Alzheimer’s Disease Centers provide a mechanism for fostering and coordinating the interdisciplinary cooperation of a group of established investigators conducting programs of research on AD and related dementing disorders of older people.  The central focus may be translational research, clinical – pathological research, basic research or a combination. Applicants are strongly encouraged to include efforts to address the needs of, and research on, ethnically and racially diverse people as well as other underserved populations.

The ADC program is moving into a new era, capitalizing on the extraordinary opportunities presented by leveraging the strengths of the network of centers to provide large numbers of samples from well-characterized participants as well as a large pool of potential participants for future AD related research. At the same time, strong emphasis is placed on the unique contributions and new directions of each individual center. Additionally, renewed emphasis is placed on possibilities for utilizing the resources within and across the ADCs to advance and augment the fields of drug discovery and drug development for novel therapeutics for AD.

The principal aim of the ADCC should be to enhance the performance of innovative research on AD and related topics, including research that may lead to potential disease modifying therapy or behavioral or other symptom treatments.  Centers are requested to concentrate their attention on better defining normal aging and the transition from normal aging to 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 is now making it possible to develop strategies to prevent the disease from developing or to slow its progression.  Attention should also be paid to mixed dementias and overlapping neurodegenerative syndromes that often occur with AD, such as vascular dementiaLewy Body disease, Frontotemporal dementia and Parkinson’s dementia, in order to better differentiate among them and to recognize commonalities. In addition, co-occurring conditions in other organ systems that may contribute to clinical dementia could be studied.

Centers are expected to provide an environment and core resources which will enhance cutting-edge research by bringing together biomedical, behavioral, and clinical 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.  Centers should incorporate contemporary biochemical/molecular techniques and pursue research, when feasible, in genomics, epigenomics, proteomics and metabolomics.  Centers are encouraged to develop in accordance with local talents, interests, and resources, but should also be responsive to national needs related to AD.

As part of a network, centers should be poised to participate in cooperative efforts on a large scale within a relatively short time frame. Applicants should commit to collect a standard clinical data set (the Uniform Data Set, or UDS) that is common to all Centers and to transmit it to the National Alzheimer’s Coordinating Center (NACC). Approximately 20,000 participants are being followed longitudinally in the center network with standardized data being sent to NACC. Data on approximately 12,000 autopsies is also available at NACC. To support the unique research needs of the center, most centers collect additional data to supplement the UDS.  Centers should demonstrate a readiness to provide biological samples and data, with proper consent, from well characterized populations, to enable participation in large scale collaborative national or international research projects.

Centers should work together with other AD research groups in collaborative research activities and cooperate with other Federal, State, and Local agency-supported AD programs (such as the Alzheimer's Disease Cooperative Study (ADCS) and the Alzheimer's Disease Neuroimaging Initiative (ADNI)), as well as community organizations such as the Alzheimer’s Association in furthering mutual goals.  Centers should also, whenever possible, cooperate with other NIA Centers such as Pepper, Shock, and Resource Centers for Minority Aging Research (RCMARs), and Udall Centers sponsored by National Institute of Neurological Diseases and Stroke (NINDS).

The use of NIH resources, such as those available from the chemical genomics center (http://www.ncgc.nih.gov/) or the Biomedical Informatics Research Network (BIRN, http://www.nbirn.net/) is also encouraged. In addition, AD Centers should consider, where there are research questions in common that are consistent with the scientific goals of the center, collaboration with Centers for Drug Discovery or Clinical and Translational Science Award recipients (see http://www.ncrr.nih.gov/clinical_research_resources/clinical_and_translational_science_awards/).

Alzheimer’s Centers are required to include the following five cores:

Other cores can be proposed if they contribute to the overall mission of the Center, are scientifically justified, support projects affiliated with the Center, and fit within the budget guidelines.  Funding for one to three smaller one year pilot grants should also be requested as part of the administrative core.

The Center Grant may incorporate ancillary activities such as longitudinal studies and limited patient care necessary to support the primary research effort.  The spectrum of activities should comprise a multi-disciplinary approach to the problem of AD and other neurodegenerative diseases, including activities supporting drug discovery and/or development, distinguishing early stages from normal aging, investigating mixed dementias, as well as studying unique aspects and subtypes of these very complex and heterogeneous disease processes.

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 P30 award mechanism(s).
The Project Director/Principal Investigator (PD/PI) will be solely responsible for planning, directing, and executing the proposed project.

This FOA uses “Just-in-Time” information concepts. It also uses non-modular budget formats described in the PHS 398 application instructions (see http://grants.nih.gov/grants/funding/phs398/phs398.html). 

2. Funds Available

The estimated amount of funds available for support of 8-10 projects awarded as a result of this announcement is $14 million for fiscal year 2011. Future year amounts will depend on annual appropriations.

Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size of each award will also vary. 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.

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

NIH grants policies as described in the NIH Grants Policy Statement.

3. Other-Special Eligibility Criteria

Number of Applications. Only one application per institution may be submitted.

Resubmissions.  Applications previously submitted in response to RFA-AG-10-001, but unfunded, may submit a resubmission application to the current FOA.  No other resubmissions are permitted. 

Renewals. Renewal applications are permitted in response to this FOA.

Section IV. Application and Submission Information


1. Address to Request Application Information

The current 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

Prepare all applications using the PHS 398 application forms and in accordance with the PHS 398 Application Guide (http://grants.nih.gov/grants/funding/phs398/phs398.html).

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 in item (box) 2 only of the face page of the application form and the YES box must be checked.

Additional information is available in the PHS 398 grant application instructions.

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
Letters of Intent Receipt Date: September 13, 2010
Application Receipt Date: October 13, 2010
Peer Review Date: February-March, 2011   
Council Review Date: May 2011 
Earliest Anticipated Start Date: July 1, 2011 

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 in Section IV.3.A.

The letter of intent should be sent to:

Nina B. Silverberg, Ph.D.
Alzheimer’s Disease Centers Program
Dementias of Aging Branch
Division of Neuroscience
National Institute on Aging
7201 Wisconsin Ave., Suite 350
Bethesda, MD, 20892-9205 (20814 for express shipping)
Telephone: (301) 496-9350
FAX: (301) 496-1494
Email: silverbergn@mail.nih.gov

3.B. Sending an Application to the NIH

Applications must be prepared using the forms found in the PHS 398 instructions for preparing a research grant application. 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)

Personal deliveries of applications are no longer permitted (see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-040.html).

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

Ramesh Vemuri, PhD
Chief, Scientific Review Branch
National Institute on Aging
7201 Wisconsin Avenue, Suite 2C212
Bethesda, MD 20892-9205 (20814 for express shipping)
Telephone: (301) 496-9666
FAX:  (301) 402-0066
Email: vemuri@nia.nih.gov

3.C. Application Processing

Applications must be received on or before the application receipt date described above (Section IV.3.A.). If an application is received after that date, the application may be delayed in the review process or not reviewed.  Upon receipt, applications will be evaluated for completeness by the CSR and for responsiveness by the reviewing Institute. Incomplete and/or 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. However, when a previously unfunded application, originally submitted as an investigator-initiated application, is to be submitted in response to a funding opportunity, it is to be prepared as a NEW application. That is, the application for the funding opportunity must not include an Introduction describing the changes and improvements made, and the text must not be marked to indicate the changes from the previous unfunded version of the application.

Information on the status of an application should be checked by the Principal Investigator in the eRA Commons at: https://commons.era.nih.gov/commons/.

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 NIH Grants Policy Statement.

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 renewal award if such costs: 1) are necessary to conduct the project, and 2) 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 renewal 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/archive/grants/policy/nihgps_2003/index.htm.)

6. Other Submission Requirements

Organization of the Application

Follow the instructions of the PHS Form 398, with the following additions:

Section 1: Information for the Entire Application

Table of Contents

Do not use Form Page 3, “TABLE OF CONTENTS” of Form 398 as it applies to applications for single projects. In its place, use the sample format provided in the following link http://www.nia.nih.gov/ResearchInformation/ExtramuralPrograms/NeuroscienceOfAging/ProgramInitiatives/ADCtablecontents2010.htm.

Number all pages consecutively. Because 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 the five required cores by letters as follows –

Core A = Administrative Core

Core B = Clinical Core

Core C = Data Management and Statistics Core

Core D = Neuropathology Core

Core E = Education and Information Transfer Core

Optional Cores should be identified with subsequent consecutive letters. Titles may not exceed 81 characters. Put 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.

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 five required cores and any optional cores, http://www.nia.nih.gov/NR/rdonlyres/E489A7E9-EBFA-4B9F-8C80-C10BF3676169/1997/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. Any questions about budget development may be directed to the Grants and Contracts Management Branch at the address below (Section VII, 3).

All ADCC proposals should request and provide justification for five years of support. The direct costs may be apportioned across cores and pilots at the director’s discretion in order to best serve the unique needs of the center. 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 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.  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 detailed first year and summary out year budgets for pilots in competing applications (new and renewal) will be budgeted in the Administrative Core budget.  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.

Pilot project costs should be in the range of $25,000-$35,000 direct costs per year. Pilot projects may be awarded to investigators outside of the home institution. Funds for the pilot projects should be included under the other expenses within the administrative core budgets.  These funds should not be listed as a separate line in the composite budget.

Pilot grants are allowed for consortium arrangements. 

For consortium arrangements, the application must include the following information:

1) A list of key personnel at each proposed performance site, 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 core at each institution.

3) A composite budget for all cores 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.

If an optional satellite core is included, it should have a separate budget page. If an existing satellite has been rolled into a clinical core, the budget for the satellite must still be identifiable within the clinical core budget.

Biographical Sketches

NIA staff will use the information in the biosketch to identify all personnel involved in the center and their institutional appointments. (That information is necessary to identify which possible reviewers may be in conflict with the application.) Also reviewers will use the biosketch to assess the qualifications of key personnel for their roles in the center (the “Investigators” criterion in the central review criteria). These two functions determine how the biosketches should be presented in the application.

1. Information for staff assessment of possible reviewer conflicts

Include for all Key Personnel and Other Significant Contributors a biographical sketch with the educational block at the top of the format page completed and Section B, Positions and Honors completed. List the principal investigator/program director first and then other personnel biosketches in alphabetical order. Do not include Sections A (Personal Statement) C (Selected peer-reviewed publications or manuscripts in press) or D (Research Support) in this part of the application. (See 2. below for where to place this information.) Do include reference to the part(s) (Cores) of the application and page numbers where complete biographical sketches for the personnel are located.

Also insert a completed Table II to aid in review of the application. See Attachment 4 “Distribution of Professional Effort on this application.” (MS Excel, 19K) (Accessible CSV file, 0.5K)  A significant time commitment must be made by the PI.

These biosketches and Table II should immediately precede the Introduction to the Entire Application.

2. Information for reviewer assessment of personnel qualifications for roles on core.

Following the instructions in the most recent PHS 398 form, complete full biosketches for Key Personnel and Other Significant Contributors in the part(s) of the application (Cores) where each individual contributes. When someone has a role in more than one part of the application then a complete biosketch for that person should be placed in each section where the individual has a role. As the particular qualifications for roles may differ between cores, the selected publications and the description of qualifications for the individual may differ in the several biosketches listed.

Principal Investigator: The PI should be a scientific leader experienced in the field of AD and/or other neurodegenerative disease research and must be able to coordinate, integrate, and provide guidance in the establishment of programs in AD research and allied areas.

For all cores: Core leaders should have demonstrated leadership and administrative skills. Specifically, the core leader should be able to organize and administer the resources created by the core in such a way that they may be shared within the ADCC as well as with other interested scientists. Demonstrated leadership in training young investigators is desirable. The PI of the ADCC may be a core leader, but sufficient time must be devoted to the core to ensure that the aims are met and required functions are carried out efficiently.

Administrative Core: The Principal Investigator of the proposed ADCC should also be the Administrative Core Leader. The PI’s biographical sketch should present evidence of scientific expertise relevant to the themes of the ADCC and demonstrate the capacity for the leadership of an ADCC. 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 must be able to provide consultation in matters of fiscal administration and be familiar with NIH grant-related compliance policies.

Clinical Core: The Clinical Core leader is often a neurologist, but may be a neuropsychologist, psychiatrist, geriatrician or other clinician with expertise in diagnosing Alzheimer’s and other neurodegenerative diseases. The core leader should have a track record of research in some aspect of neurodegenerative disease, preferably including interactions with key personnel from other cores.

Data Management and Statistics Core: The core leader’s biosketch should reflect awareness of and experience with database management practices, computing and statistics. The core director may be primarily a data manager or a statistician. The core director must have the time and the authority to work administratively with other cores.  The core should include a) a systems manager for computing and database management who will be the architect of the database structure and responsible for its maintenance. and b) a 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) and c) a statistician who can consult with researchers on design and analysis of their projects, if the core leader is not a statistician. 

Neuropathology Core: The core leader should have a track record of research in some aspect of neurodegenerative disease, preferably including interactions with key personnel from other cores.  The core director should have demonstrated knowledge of standard protocols as well as expertise in state of the art techniques for diagnosis of neuropathological specimens.

Education Core: The core leader should have expertise in the primary area of focus of the education core, either recruitment/outreach or professional education/training, or both.

Resources

Reviewers will use information from the Resources pages to evaluate the quality of the scientific environment for the research proposed and the quality of institutional support. Applicants should complete separate Resources pages for each core. These should be clearly labeled and may be referred to elsewhere in the application, where relevant. Shared resources across cores should be described in this section on Resources for the entire application. Reviewers will use information from the Resources page of the Administrative Core to evaluate the quality of the overall environment for the center.

Section 2: Overview of the Entire Application

An Alzheimer's Disease Core Center (ADCC) will be an identifiable organizational unit formed by a single institution or a consortium of cooperating institutions.  Therefore, lines of authority should be clearly specified.  Each applicant institution will name an ADCC Director (PI) 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.  An Associate Director may be named who will be involved in the administrative and scientific efforts of the Center.

The required elements for an ADCC are described below and include five cores and pilot research projects (which are included in the administrative core).  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 FOA.

Introduction (Resubmission Applications only) (1 page)

Resubmissions: Applications previously submitted in response to RFA-AG-10-001, but unfunded, may submit a resubmission application to the current FOA.  No other resubmissions are permitted. 

Provide an overview of major changes in the application. If cores have been deleted or added indicate that here and explain the changes under Significance (below). Address the concerns identified by the previous reviewers.

Specific Aims (1 page)

Describe the aims of the overall center and outline how the different cores will contribute to these aims.

Research Strategy

Items 1, 2 and 3 below are included in the six page limit.

1. Significance: (One to two pages recommended) Focusing on the center as a whole address (i) the importance of the problem or critical barrier to progress in the field that the proposed center is focused on, (ii) how the resources of the proposed center will improve scientific knowledge, technical capability, and/or clinical practice, (iii) how the concepts methods, technologies, treatments, services, or preventive interventions that drive this field will be changed if the proposed aims are achieved.

Additionally, (see Section I.1. Research Objectives) show how the center will:

New Applications: Follow the instructions above.

Renewals: Describe any changes in research emphasis.

Resubmissions: Follow PHS 398 instructions to mark changes in the text from the prior version.

2. Innovation: Considering the center as a whole, show how the proposed research seeks to shift current research or clinical practice paradigms through use of novel concepts, approaches, methodologies, instrumentation, or interventions. Does the proposed work refine, or improve, or apply in a new way, the concepts, approaches, methodologies, instrumentation, or interventions proposed? (One page recommended)

3. Approach: Include the major approaches and studies in the application showing how the approaches of cores complement each other or are inter-dependent. Describe the mechanisms that will ensure the coherence of the center and maintain a multidisciplinary focus. (Three to four pages recommended.)

Renewals: Provide an Overall Progress Report that addresses the major scientific achievements in research on AD, normal aging and related topics carried out by Center personnel as well as by research utilizing Center resources in the last funding period. Identify the most significant findings that were facilitated or supported directly through Center resources. Include summaries of progress in achieving the major aims of the Center and highlight major publications. Provide examples 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.  If referencing information provided in particular cores within the application, include specific page numbers to help reviewers find the appropriate information.

4. Discuss the interrelationship of the center to other activities in the applicant's institution (e.g., other relevant research projects) and the extent of institutional, departmental, and interdepartmental cooperation (charts and tables may be included). In addition, describe the administrative relationships of the proposed ADCC to the institution. Include relevant issues relating to institutional commitment and settings. Competing renewal applications from existing ADCCs may use this section to present summary tables such as those provided in the annual progress reports. Do not use this section to discuss or expand on information that belongs elsewhere in the application.

Protection of Human Subjects

Describe the procedures for obtaining informed consent for 1) research on cognitively impaired human subjects who may not have the capacity to consent, specifically how proxy or surrogate consent will be obtained in the context of local and state law 2) future participation in research studies if the patient becomes unable to consent (advanced directive for research) 3) placing data in the National Alzheimer’s Coordinating Center’s Uniform Data Set and sharing data and specimens with other qualified scientists, and 4) autopsy, specifying how and by whom and with whom the topic will be discussed, when and how often.  Attach samples of information given to patients and families and copies of all consent forms.  Attention should be paid to obtaining advanced directives for research, and obtaining autopsy permission from patients and families and informed consent for current and future use of biological samples by qualified investigators. Permission should be obtained for sharing of cells, DNA, and genetic and phenotypic information as well as for storage in repositories. See the Biospecimen Task Force guidelines on the NACC web site for further guidance on consent forms, as well as http://www.nia.nih.gov/ResearchInformation/ExtramuralPrograms/NeuroscienceOfAging/AlzheimersDiseaseGenetics.htm for sample language regarding genetics that may be used in consent forms. Also, if genome wide association studies (GWAS) are planned, applicants are expected to follow the NIH policy on GWAS, available at: http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html.

Women, Minorities and Children

This section is not part of the page limit for research strategy.

1. Describe the composition of the human subjects and the proactive plan to recruit women, minorities, and children (if appropriate).

2. List the page numbers for the relevant Women, Minorities, and Children sections.

3. For most NIA applications involving human participants, a justifiable exclusion for children is that the topic is not relevant to children.

Vertebrate Animals

1. Describe the general principles and policies that will apply to vertebrate animals.

2. List the components in the application that involve vertebrate animals and page numbers for the relevant Vertebrate Animal sections.

Section 3. 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 ADC.  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.  Applicants should document and describe briefly the research, both existing and planned, whether funded by the Center or not, that have, or will depend upon, resources provided by the requested cores.

Introduction (Resubmission applications only) (1 page)

Applications previously submitted in response to RFA-AG-10-001, but unfunded, may submit a resubmission application to the current FOA.  No other resubmissions are permitted. 

Resubmissions: The Introduction should be a summary response to the global concerns expressed about the core from the previous reviews.

Specific Aims (1 page for each core)

For all cores: Clearly state how the core will contribute to the goals of the ADCC and outline interactions of the core with each of the other cores of the center.

Optional Cores: Demonstrate the augmentation or enhancement of capabilities of center resources to make possible new activities at the applicant center as well as other centers. Provide a description of research project(s) that will use resources of the additional core(s).

Research Strategy (6 pages for each core)

Organize the Research Strategy into sections on: a. Significance; and b. Approach

Place Progress Reports (for competing renewal applications) in the approach section of each core Describe the most important contributions to research on AD, related dementias and aging utilizing core resources.  Reports should include Core objectives and progress in meeting them.  Basic functions of the cores should be briefly summarized. Any developmental work carried out by the core should also be presented. Publications resulting from resources or developmental work carried out by the core should be listed. 

If an optional core is continuing, include a progress report in that component write-up.

New applications

In lieu of progress reports, new applications will be evaluated based on preliminary organizational work, experience with AD and other neurodegenerative disease research, potential for developing new and exciting research, and specific plans for implementation of the new program.

Required Cores and Functions

ADMINISTRATIVE CORE:

Specific Aims: Provide an overview of how the core will set the overall direction of the Center and ensure optimal utilization of Center resources.

a) Significance: Explain the role of the Administrative core in the center as a whole and as a resource for other ongoing activities in Alzheimer’s disease and other neurodegenerative diseases. 

b) Approach:

1. Progress Report: Provide evidence of successful overall integration of cores to promote the theme(s) of the center as well as interaction within the academic and local and national communities. Provide evidence of productivity of funded pilot grants.

2. Describe how the ADCC administrative structure will facilitate the following:

Present plans to establish and operate ADCC advisory panels including:

Pilot Studies

A plan to support one to three pilot studies for basic or clinical biomedical, translational, epidemiological, caregiving, educational or behavioral research should be included and budgeted in the application. The announcement for pilot funding should include a description of data available through NACC, including their website. Use of this resource should be strongly encouraged. This funding mechanism is intended to allow an investigator the opportunity to develop preliminary data sufficient to provide the basis for an application for independent research support. They are designed for postdoctoral or junior faculty level investigators, but may be awarded to a more senior investigator who has experience in areas other than AD research, and who wants to work in the AD research field or who wants to try a new hypothesis, method, or approach that is not an extension of ongoing AD research. Any one investigator is eligible only once for pilot support, unless the additional proposed pilot study constitutes a real departure from his or her ongoing research.  Pilot studies are typically limited to a nonrenewable single year of support.  If described and well justified, two years of support may be requested.

Examples of possible pilot projects are:

No pilot applications should be submitted with the Center application. Funds designated for pilots are restricted until the pilots receive NIA approval. 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.

CLINICAL CORE:

Specific Aims: Describe the target population for which the core will provide well-characterized, longitudinally followed patients and control subjects for cutting edge research projects involving e.g., clinicopathological correlations, comparison of disease states to normal aging (including those using biological samples or imaging), and drug/intervention studies.

a) Significance: The clinical core has the responsibility of establishing and maintaining a clinical enterprise that provides valuable, well-documented resources for cutting edge clinical research for both center personnel and the wider scientific community. Explain the role of the clinical core in the center as a whole and as a resource for other ongoing activities in Alzheimer’s disease and other neurodegenerative diseases.  

If the clinical core will include special populations, the applicant must describe the characteristics of the population and justify the added scientific value to research at the Center resulting from the inclusion of this group, so that peer reviewers can evaluate the comparative strengths and weaknesses of the proposed clinical core.

If the application includes a satellite clinic as part of the clinical core, explain its significance.

b) Approach:

1. Progress Report: Clearly summarize resource use in affiliated research projects (both funded by the center and externally funded) and the new insights obtained from these studies. Describe demographic information including numbers and kinds of participants recruited, diagnosis, percentage follow up and dropout rate and reasons for drop out, and diagnostic accuracy confirmation by autopsy. List relevant publications.

2. The clinical core, in addition to patient and control subject recruitment, provides evaluation, and diagnosis, maintains a patient registry that tracks number and reasons for subjects lost to follow-up, and conducts longitudinal follow up of patients and control subjects.  Procedures should be described related to collection, storage, and distribution of biological samples, that may include, but are not limited to, cell lines, cerebrospinal fluid (CSF), blood and plasma; particular attention should be paid to an ability to share these samples both within and outside the Center as well as best practices for collection and use of biospecimens detailed in documents available on the NACC website at https://www.alz.washington.edu/BiospecimenTaskForce.html. Applicants should follow agreed upon protocols for multi-center projects involving specimen collection.

Longitudinal data on preclinical stages of AD, MCI, possible and probable AD, other neurodegenerative disorders and normal aging should be collected and transmitted in a timely manner to the Data Management and Statistics core.  Cooperation, concurrence and collaboration with the Data Management and Statistics core should continue from the initial specification of data content through data collection to database management and data analysis. A clear linkage between clinical and neuropathological data should be described. There should be a commitment to working across the center to increase the number of participants who agree to autopsy, especially of controls and persons with MCI or early in the course of AD.  Applicants must state in this section of the application that they agree to collect and provide the Uniform Data Set (UDS) to NACC where it will be combined with data from other Centers and made available to scientists for collaborative studies. Participants should be enrolled in the clinical core with the intent of longitudinal follow-up. Information on the UDS is available from NACC (https://www.alz.washington.edu/).

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 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 in the application.

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 obtain to other research activities from the existence of the clinical core. While supporting clinical drug trials may be one function of a clinical core, it should not be the only major effort of the core.

Inclusion of Women and Minorities

Summarize strategies, with reference to the education core, to recruit and retain participants from diverse backgrounds including a description of how the plan fits with all of the proposed research that will make use of the core. The plan should demonstrate sensitivity to research design and biostatistical analysis. Procedures for communicating recruitment needs to the Education Core and for evaluating success should be outlined.

The inclusion of participants 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 participant pool will facilitate investigations of the neuropathology and genetics of AD as well as studies of care giving and family burden in diverse groups. Diversity of participants may be achieved in multiple ways. One option is to have a Satellite Clinic in locations that have higher populations of underserved individuals.

Resources and Environment

Clinical cores of ADCs are usually based in university medical center neurology or psychiatry department memory disorders clinics, but they may also, or instead, include special 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.

DATA MANAGEMENT and STATISTICS CORE:

Specific Aims: Describe both database and statistical services that will be provided to the cores and pilots. Outline the process for contributing data to NACC and for making data available both within and outside of the center.

a) Significance: The Data Management and Statistics core both performs data management and provides statistical consultation and liaison with other cores and projects. Data cores are important to facilitate not only local analyses but also collaborations between and among Centers and with NACC.  Explain the role of the Data Management and Statistics core in the center as a whole and as a resource for other ongoing activities in Alzheimer’s disease and other neurodegenerative diseases. 

b) Approach:

1. Progress Report: Summarize progress and activities related to data collection, data management and statistical consulting activities.  Include progress and interactions with NACC as well as descriptions of any novel data analysis or study design strategies that have been developed. 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.

2. The data core should have 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 overall impact/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. The data core should be adequately funded and staffed to allow required tasks to be carried out. (New applicants may contact NACC to learn more about NACC procedures, the structure of the uniform data set, and the regular updates to the datasets required from all Centers; http://www.alz.washington.edu/).   The data management plan should include at least:

The staff of the data core should work with clinical and research personnel to transfer their data into computer usable form, as well as with statisticians to insure that the data are represented in a fashion that will allow the analyses to be accomplished. Data core staff should have a working relationship with core data collectors and 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 should work cooperatively with the NACC staff and respond appropriately to data calls issued by NACC.

Biostatistics consultation and liaison should

Other possible functions of the core might include:

NEUROPATHOLOGY CORE: 

Specific Aims: Describe the state of the art diagnostic services, strategy for collecting well-prepared brain material, and distribution of samples for cutting edge research, locally as well as in cooperative research across Centers and with other researchers outside of Centers. 

a) Significance:  The neuropathology core has the responsibility for providing post mortem diagnosis on cases and normal control subjects enrolled in the clinical core and on other well documented AD cases and controls. Explain the role of the Neuropathology core in the center as a whole and as a resource for other ongoing activities in Alzheimer’s disease and other neurodegenerative diseases. 

b) Approach:

1. Progress Report: Clearly summarize resource use in affiliated research projects and the new insights obtained from these studies, as well as type and quantity of tissue provided to investigators both funded by the Center and by other means.

2. Procedures 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.  Specimen collection, data gathering and storage activities should be coordinated with those of the Clinical Core and the Data Management Core. Describe how the core will  provide a resource for research studies that include clinical-pathological correlations across Centers.  To do so, ADCCs should agree to follow standardized procedures whenever possible, so that cross-Center correlations are possible. (New applicants may go to the NACC to get the most recent best practice guidelines for biospecimens: https://www.alz.washington.edu/BiospecimenTaskForce.html). Unless specific research questions require brains from late stage AD patients, emphasis should be placed on collection of normal, MCI and early AD brains, in order to support specific research efforts of investigators affiliated with the local center and other scientists. If collection of special material is proposed (e.g., tissues from patients with other dementias) justification should be included. If proposing developmental work, describe the role of this work and its significance to the core, the center and other research activities.

To facilitate data sharing and cross-Center comparisons of diagnosis, all Centers should use the neuropathological criteria for AD 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 local research purposes should also be described.  Pathology data should be included in the data set transmitted to NACC as defined by the UDS.  (New applicants may get information from NACC about the pathology data set).  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.  The application should commit to sending a representative to this meeting.

Resources and Environment

Facilities and equipment for use in carrying out the activities of the core should be described in this section. 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.  Best practice guidelines for handling biospecimens have been developed and are posted on the NACC website: https://www.alz.washington.edu/BiospecimenTaskForce.html. Procedures to provide coded samples to investigators that protect the identity of the patients should be described.

Neuropathology cores should provide the infrastructure necessary for applying novel technologies, techniques and/or information to increase the value of stored tissues and fluids, especially those that have longitudinal data available.

EDUCATION and INFORMATION CORE:

Specific Aims: Summarize the outreach and education needs of the center as well as local academic and community settings. Outline recruitment plans in light of the needs of the research that will rely on the center. Provide an overview of any professional staff development activities.

a) Significance: The Education core has the responsibility for providing important liaison and outreach between the ADCC and patients, their caregivers and the professional community so that information may be communicated bidirectionally. Explain the role of the education core in the center as a whole and as a community resource on Alzheimer’s Disease.

b) Approach:

1. Progress Report: Describe 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. Provide information about training activities that effectively impart knowledge to professionals and the lay public. Describe other outreach activities.

2. Provide an assessment of the outreach and educational needs that are unique to the center as well as to the geographical area in the vicinity of the ADCC, including identifying underserved groups. The assessment might include information about census data, community organizations, and an evaluation of the educational, outreach and recruitment activities and needs of each research function of the center. Depending on the local needs as identified in the analysis of local needs, the education core may focus either on A) coordination with the clinical core for recruitment and retention of subjects for particular research protocols and clinical trials, with a special emphasis on underserved/underrepresented populations and/or B) innovative development of professional staff (including nurses, social workers, physicians, researchers, medical students, other professional carers, etc.) for clinical and research skills related to AD and other dementias. An outreach plan should address the needs identified, including both strengths and barriers (e.g., parking/transportation).

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, the Alzheimer’s Association, other community/service groups, sports teams, hospitals, religious organizations, business groups, local medical societies, etc.) and 5) descriptions of materials (e.g., videos and printed matter) to be 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 diverse 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 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. 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. Collaboration and/or consultation with RCMARs regarding recruitment and retention of diverse elder populations are encouraged (http://www.rcmar.ucla.edu/).

Other major activities of the Education Core might include:

Optional Cores

The NIA will support additional cores that provide opportunities for scientific research beyond those attainable solely through support of the mandatory cores and other functions. 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 supported on individual project grants. In a Center grant application, it is not sufficient for the principal investigator merely to identify such centralized resources.  Rather, it must be demonstrated exactly how each core would augment or enhance the present capabilities of investigators using 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:

OPTIONAL Satellite Diagnostic and Treatment Clinic Core

Satellite Diagnostic and Treatment Clinics (SDTCs) are 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 or any special recruitment activities within the clinical and education cores previously designated as a satellite and should describe these activities in a separate section of the application labeled as a separate core.  New satellite clinics may be proposed if they fit within the overall budget requirements.  Satellite clinics are not required to conduct research but should serve as vehicles for the recruitment, diagnosis and management of AD patients and control subjects from rural and minority communities, who are then offered the opportunity to participate in research protocols, clinical drug trials and 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 all of the other cores of the center.  Satellite facilities and associated community resources may be described briefly in the clinical core section of the application under Human Subjects, and details may be provided in the section on Resources in Section 1 “Information for the Entire Application.”

PHS398 Research Plan Sections

All application instructions outlined in the PHS398 Application Instructions are to be followed, with the following additional requirements:

Budget

This FOA uses non-modular budget formats described in the PHS 398 application instructions (see http://grants.nih.gov/grants/funding/phs398/phs398.html). 

Appendix Materials

All paper PHS 398 applications submitted must provide appendix material on CDs only. Include five identical CDs in the same package with the application. See http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-031.html.

Do not use the Appendix to circumvent the page limitations.  An application that does not observe the required page limitations may be delayed in the review process.

Resource Sharing Plan(s)

NIH considers the sharing of unique research resources developed through NIH-sponsored research an important means to enhance the value of, and advance research. When resources have been developed with NIH funds and the associated research findings published or provided to NIH, it is important that they be made readily available for research purposes to qualified individuals within the scientific community. If the final data/resources are not amenable to sharing, this should be explained in Resource Sharing section of the application. See http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm.

(a) Data Sharing Plan: Regardless of the amount requested, investigators are expected to include a brief 1-paragraph description of how final research data will be shared, or explain why data-sharing is not possible. Applicants are encouraged to discuss data-sharing plans with their NIH program contact. See Data-Sharing Policy or http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html.

(b) Sharing Model Organisms: Regardless of the amount requested, all applications where the development of model organisms is anticipated are expected to include a description of a specific plan for sharing and distributing unique model organisms and related resources, or state appropriate reasons why such sharing is restricted or not possible. See Sharing Model Organisms Policy, and NIH Guide NOT-OD-04-042.

(c) Genome-Wide Association Studies (GWAS): Regardless of the amount requested, applicants seeking funding for a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible.  A genome-wide association study is defined as any study of genetic variation across the entire genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight) or the presence or absence of a disease or condition.  For further information see Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088, and http://grants.nih.gov/grants/gwas/.

Applicants should commit to cooperate fully and to share specimens with other research scientists both within and outside the Centers network as well as data concerning patients and control subjects with the NIA -sponsored National Alzheimer’s Coordinating Center (NACC) where uniform data from all NIA funded Alzheimer’s Disease 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.  Therefore, consent forms should be written to allow for this possibility as well as for the possibility of eventual data sharing with the wider research community, while maintaining participants’ confidentiality. 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. Applicants should follow NIA and NIH policies on data and sample sharing (please see the following web pages for further information, including example language that may be used in consent forms: http://grants.nih.gov/grants/policy/data_sharing/, http://www.nia.nih.gov/ResearchInformation/ExtramuralPrograms/NeuroscienceOfAging/AlzheimersDiseaseGenetics.htm and http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html).

Section V. Application Review Information


1. Criteria

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

2. Review and Selection Process

Review Process

Applications that are complete and responsive to the FOA will be evaluated for scientific and technical merit by an appropriate peer review group convened by the National Institute on Aging in accordance with NIH peer review procedures (http://grants1.nih.gov/grants/peer/), using the review criteria stated below.

As part of the scientific peer review, all applications will:

The mission of the NIH is to support science in pursuit of knowledge about the biology and behavior of living systems and to apply that knowledge to extend healthy life and reduce the burdens of illness and disability.  As part of this mission, applications submitted to the NIH for grants or cooperative agreements to support biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system. 

Overall Impact

Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following five scored review criteria, and additional review criteria (as applicable for the project proposed). 

Scored Review Criteria

Reviewers will consider each of the five review criteria below in the determination of scientific and technical merit.  An application does not need to be strong in all categories to be judged likely to have major scientific impact.  For example, a project that by its nature is not innovative may be essential to advance a field.

The proposed ADCC will be reviewed both as a whole and by each Core for each of the criteria below. For the ADCC as a whole, reviewers will give numerical impact ratings, but for each Core, reviewers will provide adjectival descriptors.

Significance.  Does the project address an important problem or a critical barrier to progress in the field?  If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved?  How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?  Is there a base of ongoing high quality research in AD and other related neurodegenerative disorders? Do the stated goals and plans demonstrate potential for contributing to cutting edge research on normal aging, MCI, early AD and related disorders? Does the center have the ability to participate in coordinated national efforts for collaborative research and data sharing with other scientists and research Centers?

Investigator(s).  Are the PD/PIs, collaborators, and other researchers well suited to the project?  If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training?  If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)?  If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?  Do the investigators and staff provide creative scientific and administrative leadership of the Center and do they demonstrate a commitment to devote adequate time to the management of the ADCC program? Is there evidence of collaboration and interdisciplinary research among the investigators who will be associated with the ADCC? Does the group have stability? Are plans for recruitment of new personnel addressed?

Innovation.  Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions?  Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense?  Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?  Does the proposed center have the capacity to develop critical new knowledge and unique and innovative contributions to AD research locally and nationally?

Approach.  Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project?  Are potential problems, alternative strategies, and benchmarks for success presented?   If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?
If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?  Does the proposed Center demonstrate appropriate organization and core management? Are the organizational plan and management structure adequate to meet Center goals and the requirements spelled out in this FOA? Are the procedures for internal communication and cooperation among the investigators adequate?

Environment.  Will the scientific environment in which the work will be done contribute to the probability of success?  Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed?  Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?  Are the proposed facilities adequate? Is the geographic relationship between facilities adequately described? Does the center provide an environment and core resources which will enhance cutting-edge research by bringing together multidisciplinary investigators?

Additional Review Criteria

As applicable for the project proposed, reviewers will consider the following additional items in the determination of scientific and technical merit, but will not give separate scores for these items.

Protections for Human Subjects.  For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects  and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials.

Inclusion of Women, Minorities, and Children.  When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children.

Vertebrate Animals.  The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information, see http://grants.nih.gov/grants/olaw/VASchecklist.pdf.

Biohazards.  Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmission Applications.  Applications previously submitted in response to RFA-AG-10-001, but unfunded, may submit a resubmission application to the current FOA.  No other resubmissions are permitted.  When reviewing a Resubmission application (formerly called an amended application), the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewal Applications.  When reviewing a Renewal application (formerly called a competing continuation application), the committee will consider the progress made in the last funding period.

Revision Applications. Revisions are not allowed for this FOA.

Additional Review Considerations

As applicable for the project proposed, reviewers will address each of the following items, but will not give scores for these items and should not consider them in providing an overall impact/priority score.

Applications from Foreign Organizations.  Foreign are not allowed for this FOA.

Select Agents Research. Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans.  Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable:  1) Data Sharing Plan (http://grants.nih/gov/grants/policy/data_sharing/data_sharing_guidance.htm); 2) Sharing Model Organisms (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-042.html); and 3) Genome Wide Association Studies (GWAS) (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html).

Budget and Period Support.  Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Selection Process

The following will be considered in making funding decisions:

NIH considers the following in evaluating Center grant applications:

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 PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons.

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.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization. The NoA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NoA will be generated via email notification from the awarding component to the grantee business official.

Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA 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 NoA. 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/archive/grants/policy/nihgps_2003/index.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/archive/grants/policy/nihgps_2003/index.htm).

3. Reporting

Awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and Financial Status Report are required when an award is relinquished when a recipient changes institutions or when an award is terminated.

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:

Nina B. Silverberg, Ph.D.
Alzheimer’s Disease Centers Program
Dementias of Aging Branch
Division of Neuroscience
National Institute on Aging
7201 Wisconsin Ave., Suite 350
Bethesda, MD, 20892-9205 (20814 for express shipping)
Telephone: (301) 496-9350
FAX :(301) 496-1494
Email: silverbergn@mail.nih.gov

2. Peer Review Contacts:

Ramesh Vemuri, Ph.D.
Chief, Scientific Review Branch
National Institute on Aging
7201 Wisconsin Avenue, Suite 2C212
Bethesda, MD  20892-9205 (20814 for express shipping)
Telephone:  (301) 496-9666
FAX: (301) 402-0066
Email: Vemuri@nia.nih.gov

3. Financial or Grants Management Contacts:

Joseph Ellis, Jr.
Grants and Contracts Management Branch
National Institute on Aging
7201 Wisconsin Avenue, Suite 2N212
Bethesda, MD  20892-9205 (20814 for express shipping)
Telephone:  (301) 496-1472
FAX:  (301) 402-3672
Email: ellisjoe@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.

Policy for Genome-Wide Association Studies (GWAS):
NIH is interested in advancing genome-wide association studies (GWAS) to identify common genetic factors that influence health and disease through a centralized GWAS data repository. For the purposes of this policy, a genome-wide association study is defined as any study of genetic variation across the entire human genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight), or the presence or absence of a disease or condition. All applications, regardless of the amount requested, proposing a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible. Data repository management (submission and access) is governed by the Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088. For additional information, see http://grants.nih.gov/grants/gwas/.

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 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 funding opportunity 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.

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/archive/archive/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.

Inclusion of Children as Participants in Clinical Research:
The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all clinical research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them.

All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines" on the inclusion of children as participants in research involving human subjects (http://grants.nih.gov/grants/funding/children/children.htm).

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-09-116.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.

NIH Public Access Policy Requirement:
In accordance with the NIH Public Access Policy (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-033.html) investigators must submit or have submitted for them their final, peer-reviewed manuscripts that arise from NIH funds and are accepted for publication as of April 7, 2008 to PubMed Central (http://www.pubmedcentral.nih.gov/), to be made publicly available no later than 12 months after publication. As of May 27, 2008, investigators must include the PubMed Central reference number when citing an article in NIH applications, proposals, and progress reports that fall under the policy, and was authored or co-authored by the investigator or arose from the investigator’s NIH award.  For more information, see the Public Access webpage at http://publicaccess.nih.gov/.

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. For publications listed in the appendix and/or Progress report, internet addresses (URLs) must be used for publicly accessible on-line journal articles.  Unless otherwise specified in this solicitation, Internet addresses (URLs) should not be used to provide any other information necessary for 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 FOA 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. 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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