and Human Services (HHS)
EXPIRED
Department of Health and Human Services
Participating
Organizations
National
Institutes of Health (NIH), (http://www.nih.gov)]
Components of Participating Organizations
National
Institute on Aging (NIA), (http://www.nia.nih.gov )
Title: Alzheimer s
Disease Core Centers (P30)
Announcement Type
This
is a reissue of RFA-AG-05-010.
Update: The following update relating to this announcement has been issued:
Request for Applications (RFA) Number: RFA-AG-10-001
Catalog of Federal Domestic Assistance Number(s)
93.866
Key Dates
Release Date: February 20, 2009
Letters of
Intent Receipt Date: April 6, 2009
Application Receipt Date: May 5, 2009
Peer
Review Date(s): October/November
2009
Council
Review Date: January 2010
Earliest Anticipated Start Date: April 1, 2010
Additional Information To Be
Available Date (Url Activation Date): Not
applicable
Expiration
Date: May 6, 2009
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 and Information
Section V. Application Review
Information
1. Criteria
2. Review and Selection Process
A. Additional Review Criteria
B. Additional Review
Considerations
C. Resource Sharing Plan(s)
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
AD is
estimated to affect millions of older people in the United States.
Although it is occasionally identified in patients in their forties and
fifties, it is most frequently associated with advancing age. 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 includes seventeen Alzheimer's Disease Research Centers (ADRCs) and twelve Alzheimer's Disease Core Centers (ADCCs).
The ADC program is moving into a new era, preparing to capitalize 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 ADCs 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 beginning to make it possible to develop strategies to prevent the disease from developing or slow its progression. Attention should also be paid to mixed dementias and overlapping neurodegenerative syndromes that sometimes occur with AD, as well as co-occurring conditions in other organ systems that may contribute to clinical dementia.
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.
The ADCs 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.
As part of a network, centers should be poised to participate in cooperative efforts on a massive scale within a relatively short time frame. Applicants must agree to collect a standard clinical data set (the Uniform Data Set, or UDS) that is common to all Centers and will be transmitted to the National Alzheimer’s Coordinating Center (NACC). To support the unique research needs of the center, most centers collect additional data to supplement those required by 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 the Alzheimer’s Association in furthering mutual goals. Centers should also, whenever possible, cooperate with other NIA Centers such as Pepper, Shock, and RCMAR Centers, 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 /).
ADCs are required to include administrative, data management and statistical, clinical, neuropathological and education cores. Other cores can be proposed if they contribute to the overall mission of the Center, are scientifically justified, support projects funded by the Center or by other mechanisms, and fit within the budget guidelines. Funding for one to three smaller one year pilot grants should also be requested.
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 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 2-4 projects awarded as a result of this announcement is $4.6 million for fiscal year 2010. 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 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 will apply to the applications submitted and awards made in response to this FOA.
Section III. Eligibility Information
1. Eligible Applicants
1.A. Eligible Institutions
The following
organizations/institutions are eligible to apply:
Your institution should support an ongoing base of high-quality AD research or research in other neurodegenerative diseases, or in aging of the nervous system. To be eligible your institution must support:
at least five principal investigators with any PHS agency (or comparable peer-reviewed federal, state, or foundation) funded research grants related to AD, neurodegenerative diseases or aging of the nervous system and each with at least two years of support remaining at the time of application,
or,
one or more program project grants (P01s) related to AD, neurodegenerative diseases or aging of the nervous system and with at least two years of support remaining at the time of application.
The work that you propose in the ADC should be different from the ongoing supported research. NIA will review overlap of existing support through P01s or other award mechanisms and adjust support of the center appropriately prior to any award. Your institution can have only one active Alzheimer’s Center receiving NIA support.
1.B. Eligible Individuals
Any individual with the skills, knowledge, and resources necessary to carry out the proposed research as the PD/PI is invited to work with his/her institution to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
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. A significant time commitment (at least 20%) must be made by the PI.
2. Cost Sharing or Matching
This
program does not require cost sharing as defined in the current NIH
Grants Policy Statement.
3. Other-Special Eligibility Criteria
Number of Applications. Each applicant institution may submit only one application.
Resubmissions. Applicants are not permitted to submit a resubmission application in response to this FOA.
Renewals. Renewal applications will be permitted for this FOA.
Section IV. Application and Submission Information
1. Address to
Request Application Information
The PHS 398 application
instructions are available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. Applicants must use the currently approved version of
the PHS 398. For further assistance contact GrantsInfo, Telephone (301)
710-0267, Email: [email protected].
Telecommunications for the hearing impaired: TTY
301-451-5936.
2. Content and Form of Application Submission
Applications must be
prepared using the most current PHS 398 research grant application instructions
and forms. Applications must have a D&B Data Universal Numbering System
(DUNS) number as the universal identifier when applying for Federal grants or
cooperative agreements. The D&B number can be obtained by calling (866)
705-5711 or through the web site at http://www.dnb.com/us/.
The D&B number should be entered on line 11 of the face page of the PHS 398
form.
The title and
number of this funding opportunity must be typed 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: April
6, 2009
Application Receipt Date: May 5, 2009
Peer Review Date(s): October/November
2009
Council Review Date: January 2010
Earliest
Anticipated Start Date: April
1, 2010
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: [email protected]
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: [email protected]
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. This includes previous unsuccessful P50 applications and any previous P30 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/grants/policy/nihgps_2003/NIHGPS_Part6.htm.)
6. Other Submission Requirements and Information
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 commitments 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 grants are allowed for consortium arrangements. If consortium arrangements are contemplated, the following information should be provided in the application:
1) A list of all proposed performance sites both at the applicant institution and at the collaborating institutions
2) A separate, detailed budget for the initial and future years for each institution and, where appropriate, for each unit of activity at each institution.
3) A composite budget for all units of activity at each institution for each year, as well as a composite budget for the total proposed budget for each year.
4) An explanation of the programmatic, fiscal, and administrative arrangements made between the grantee institution and the collaborating institutions.
Information that is not included with the original application may not be submitted after the receipt date except with prior approval from the responsible Scientific Review Officer. This will usually only include major corrections or changes in personnel. (Also see NOTICE-OD-08-082 on NIH Policy on Submission of Additional Grant Application Materials.)
Applicants should follow the instructions for Appendix materials below. Although the only limits on materials that may be included in the Appendix are as described in the PHS 398 form and in this FOA, the server capacity to display Appendix material and make it available to reviewers is limited to 20Mb per application. Therefore applicants should be aware that appendices exceeding 20Mb may not be available to reviewers. Appendix material should be in the form of a single PDF file, preferably with indexing. No movies in any form will be accepted (e.g. *.mov, DVD).
Submission Information
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 must 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.
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 AD Centers is centrally stored. Any genetic specimens collected by the Center should be made available to the National Cell Repository for Alzheimer s Disease (NCRAD), if they meet the criteria for inclusion in the repository, in accordance with agreed upon protocols and policies. Centers may also be requested to contribute other biological samples such as serum and cerebrospinal fluid, using agreed upon protocols, for trans-center studies examining biomarkers that might relate to risk, diagnosis or progression of AD. 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 ).
In order to assure active collaboration with other Centers, the ADC Director and other staff should attend semi-annual meetings of the ADC Directors and other ad hoc meetings arranged by the ADCs or the NIA to share research findings, participate in planning for cooperative research or help to refine and standardize operating procedures among the Centers. The ADC application should include funds for travel of the Director and other key personnel 1) to the semiannual meetings of the Center Directors, 2) for at least 2 ad hoc meetings on special topics, 3) for visits of Center investigators to other ADCs for the exchange of scientific ideas, planning of multi Center research projects and to receive training in specialized techniques, 4) for the Administrator to attend the Administrators meeting and 5) for core leaders to attend meetings with core leaders from other ADCs.
The required elements for an ADCC include five cores and pilot research projects. Required cores are described below. 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.
Specific instructions for preparing overall progress reports (for competing renewal applications), progress reports and plans for individual cores, and a list of review criteria are detailed later in this FOA.
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.
Required Cores and Functions
ADMINISTRATIVE CORE: The administrative core should set the overall direction of the Center and ensure optimal utilization of Center resources. Effective development of Center programs requires interaction among the Director, the leaders of the cores, the project leaders of research and pilot projects, other researchers at the applicant institution, appropriate institutional administrative personnel, the staff of the awarding agency, and the members of the community in which the Center is located. The ADRC should recognize that it is part of a large network of ADCs and be prepared to work cooperatively with the other Centers, the National Alzheimer’s Coordinating Center and the NIA.
The success of the ADC is dependent upon involving scientific and professional personnel from a variety of disciplines and subspecialties who interrelate in order to facilitate the acquisition of new knowledge. In addition to coordination of the ADC, the Director, with the advice of his or her executive committee, will be responsible for allocating and monitoring ADC funds and identifying and selecting key personnel. An executive committee (composed of core and project leaders and the administrator) will be established to assist the Director in making the scientific and administrative decisions relating to the Center. The executive committee should seek outside advice and consultation, both from within the institution and from other institutions, in its monitoring and development of the scientific content and direction of the program.
A plan to review pilot grant applications should be provided. Pilot application reviewers should include scientists from outside the ADC with expertise relevant to the types of pilot applications received by the Center. The reviewers will make funding recommendations to the Director and the Executive Committee. Unless already appointed, pilot grant reviewers should not be recruited until the NIIH review process is complete. 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.
An external advisory committee to the ADC, consisting of scientists from outside of the institution or consortium, will also be established. Unless already appointed, external advisory committee members should not be recruited until the NIH review process is complete. This committee will be used to evaluate the programs of the ADC, research progress, the effectiveness of communications within the ADC, interactions with NACC, and any other activities for which outside expertise is required or desirable. The external advisory committee may serve as reviewers for pilot grant applications. The committee should meet annually and prepare a report including recommendations to assist the ADC. A member of the NIA extramural program staff should be invited to attend each meeting. A copy of the advisory committee report should be routinely sent to the NIA with the annual progress report and should include a list of committee members.
The administrative requirements of the ADC 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 ADC application and grant. The administrator should be a member of the executive committee. While budget formulation and planning will undoubtedly begin with the Director in collaboration with the scientific staff, the administrator must be involved in the process and provide consultation in matters of fiscal administration and be familiar with NIH grant-related compliance policies. The administrator should attend the annual ADC Administrators meeting.
It is expected that the ADCC administrative structure will facilitate the following:
1) coordination and integration of ADCC components and activities; (for example, the clinical and data management cores with the neuropathology and education components)
2) direction for future planning and optimal utilization of resources
3) support and advice for the ADCC Director in his/her oversight of the activities of the Center
4) interaction with the scientific and lay communities to develop relevant goals for the ADCC
5) coordination and organization of external and internal advisory committee meetings
6) coordination and organization of pilot project advertisement, review, and submission of pilot projects to NIA for approval
7) assurance of compliance with human subjects, animal welfare, scientific integrity, data and sample sharing, and financial policy requirements of NIH
8) interaction with other Centers, the Data Coordinating Center and other researchers to develop trans-ADC and outside research projects
9) timely and routine transmissions of appropriate ADCC data sets to the NACC
10) interaction and involvement with other research programs of the University including the provision of core resources for development of related projects
11) coordination with NIA on media coverage of the latest research findings from the center
CLINICAL CORE: The chief function of the Clinical core is to 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. The Clinical core in close collaboration with the Education core of the Center is the primary contact point with the community. The Core provides resources to patients, aging control subjects, and caregivers while charting the course of the disease in patients and age-related changes in the research population being followed by the Center. Clinical cores of ADCs are usually based in university medical center neurology or psychiatry department memory disorders clinics, but they may also, or instead, include special control or elderly populations that might be available to some applicants such as an ethnic or minority population, a religious community or a community population living in elderly housing where the likelihood of being able to study the full spectrum from normal aging to mild cognitive impairment to AD would be possible.
Recent improvements in evaluation for memory disorders in normal aging and MCI present new opportunities for research on early stages of disease and decrease the necessity to enroll middle and later stage patients. In addition, our increased understanding of the relationship of AD to, or coexistence with, other neurodegenerative diseases commonly seen in the elderly population provides the opportunity to broaden the mission of the ADCs to include mixed dementias and diseases such as vascular dementia, Lewy body disease, frontotemporal dementia, and Parkinson’s dementia in order to better differentiate among them, to recognize commonalities and to study older demented individuals with mixed etiologies and medically co-morbid conditions. Therefore it is more appropriate that applicants concentrate on normal aging, MCI, preclinical AD, and early AD as well as enhancing the recruitment of research subjects with other neurodegenerative diseases rather than concentrating only on full blown or pure AD. If the clinical core will include special populations, the applicant must provide a complete description of the characteristics of the subject population and justify the added scientific value to research at the Center resulting from using a different subject population so peer reviewers can evaluate the comparative strengths and weaknesses of proposed clinical core subject populations.
A recruitment strategy for patient and age-matched control subjects should be provided including a description of how the plan fits with all of the proposed research that will make use of the core. The plan, usually developed in conjunction with the education core, 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 application should include a description of the types (with specific examples) of research projects and clinical trials that use or will use the core and what benefits will obtain to other research activities from the existence of the clinical core. While conducting clinical drug trials may be one function of a clinical core, it should not be the only major effort of the core.
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 and facilities 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.
Describe the procedures for 1) obtaining informed consent for research on cognitively impaired human subjects who may not have the capacity to consent, 2) obtaining consent for future participation in research studies if the patient becomes unable to consent (advanced directive for research) 3) obtaining consent to place data in the National Alzheimer’s Coordinating Center s minimum data set and to share data and specimens with other qualified scientists, and 4) obtaining proxy or surrogate consent in the context of local and state law. 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. Please 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 must follow the NIH policy on GWAS, available at: http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html .
Longitudinal data on preclinical stages of AD, MCI, possible and probable AD, other neurodegenerative disorders and normal aging should be collected and transmitted to the Data Management core. The data must be shared with the National Alzheimer’s Coordinating Center according to standardized protocols developed by the ADC Directors, the Clinical Core leaders and the Steering Committee of NACC. Applicants must state in this section of the application that they agree to 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. Subjects 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 as completely as possible in the application.
Efforts to recruit diverse population subgroups including minorities and/or rural populations must be outlined. One option is to set up Satellite Diagnostic and Treatment Clinics (SDTCs) designed to increase the heterogeneity of the research patient pool and to enhance the research capabilities of the ADC by extending the activities of the clinical core. Existing Centers should retain any satellites already in existence unless there are compelling reasons to restructure these components. New satellite clinics may be proposed as part of the clinical core. The satellite clinics are not required to conduct research but should serve as vehicles for the recruitment, 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. Applicants should detail appropriate strategies for outreach, in conjunction with the education and clinical cores, to recruit and retain ethnically and racially diverse subjects and describe the culturally sensitive materials that will be used. The inclusion of patients with different characteristics will assist investigators in providing answers to questions about AD diagnosis, treatment, and management strategies that are likely to be applicable to the broad U.S. population. Additionally, a more diverse patient pool will facilitate investigations of the neuropathology and genetics of AD in minority groups as well as studies of care giving and family burden in rural and minority group cohorts.
DATA MANAGEMENT and STATISTICS CORE: This core should provide data management and statistical consulting to the pilot projects and the cores of the ADC. Data cores are important to facilitate not only local analyses but also collaborations between and among Centers and with NACC. The data core must 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 must 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 /) A model for the data core might consist of two arms: 1) computing and data base management and 2) statistical consultation and liaison with other cores and pilot projects. The core director must be keenly aware of and experienced with database management practices and computing but is not necessarily the architect and day to day manager of the database. The core director must have the time and the authority to work administratively with other cores. The core should include a systems manager for computing and database management who will be the architect of the database structure and responsible for its maintenance. This person will be an experienced database programmer and systems analyst with sufficient background to select and implement database management software, represent data structures, specify and organize data flow, construct detailed error-check programs, develop/implement data checking and cleaning procedures, and provide for data entry and access, as well as information distribution, through electronic means (e.g., the internet or intranet). The systems manager should be given the authority:
1. to establish data flow schemes,
2. to construct data forms (electronic or hard copy; following core/project specified content),
3. to implement a Center-wide system of subject ID numbers that meets privacy standards
4. to require adequate filing systems for raw data within the cores/projects and within the data core itself,
5. to establish a mechanism to track data edits,
6. to provide for longitudinal follow-up data storage/retrieval consistent with the protocols of the center.
The staff of the data core must work with clinical and research personnel to transfer their data into computer usable form, and simultaneously work with statisticians to insure that the data are represented in a fashion that will allow the desired analysis files to be produced and analyses to be accomplished. Data core staff should have a working relationship with core data collectors and must have their cooperation to reconcile errors and missing or incomplete data elements as discovered through error check programs or through hands-on inspection procedures. In addition the core staff is required to work cooperatively with the NACC staff and respond appropriately to data calls issued by NACC.
A biostatistician(s) should be involved in the design and analysis of studies within the Cores and will work closely with the data manager to insure analysis files are produced that are consistent with the needs of the question at hand. A biostatistician should be available for consultation with pilot project applicants and awardees as well as with affiliated research project investigators. It is expected that the Clinical and other cores in the ADC, where data are collected, will fully cooperate and participate with the data core by providing data in the form specified and in a timely way. Cooperation, concurrence and collaboration should continue from the initial specification of data content through data collection to database management and data analysis.
Other possible functions of the core might include:
NEUROPATHOLOGY CORE: The chief function of the Neuropathology core is to provide state of the art diagnostic services, collection of 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. Centers must be able to provide post mortem diagnosis on cases and normal control subjects enrolled in the clinical core and on other well documented AD cases and controls. A significant value of having the Center infrastructure is the support of research studies that permit clinical-pathological correlations across Centers. Therefore, Centers should agree to follow standardized procedures 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 ).
Procedures and facilities should be described related to criteria for diagnosis, and the collection, storage, and distribution of brain tissue and other biological samples, including, but not limited to, cell lines, cerebrospinal fluid (CSF) and plasma. While Centers are required to have brain banks, less emphasis should be placed on the routine collection and storage of late stage Alzheimer’s brains (unless specific research questions, such as genetic and expression studies, call for these) and more emphasis placed on collection of brain material in a fashion that will support the specific research efforts of investigators affiliated with the local Center and other scientists. If collection of special material is proposed (e.g. tissues from Parkinson s disease, oldest old controls, frontotemporal dementia, prion diseases, mixed dementias, or stereologically prepared specimens) justification should be included. Specimen collection, data gathering and storage activities should be coordinated with those of the Clinical Core and the Data Management Core.
To facilitate data sharing and cross-Center comparisons of diagnosis, all Centers should use the neuropathological criteria for 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). The neuropathology core may propose a limited amount of developmental work, but should not emphasize research per se. The developmental work allowable must be directly related to the function of the core. It may be directed toward improving and expanding the core functions, e.g., improving existing, or developing additional methodologies, techniques or services. Proposed developmental work should be described in the application. Neuropathologists from the ADCs meet yearly to share ideas and discuss technical aspects of tissue sampling, development of standardized tissue processing for diverse research protocols, cataloging and data management, and banking and distribution of tissues and biological samples. All Centers are expected to send a representative to this meeting.
The procedure for prioritizing the use of tissues and other biological samples stored at the Center should be discussed along with a brief description of potential research projects that will use the samples. Best practice guidelines for handling biospecimens have been developed and are posted on the NACC website: https://www.alz.washington.edu/BiospecimenTaskForce.html . Provisions for obtaining informed consent and protecting the privacy of research subjects must be detailed. Procedures to provide coded samples to investigators that protect the identity of the patients should be described.
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: The core should 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. An outreach plan should address the needs identified, including both strengths and barriers (e.g., parking/transportation).
Depending on the local needs as identified in the analysis, 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 minorities and other underserved 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.
Other major activities of the Education Core might include:
1) Spearhead effective outreach programs that will publicize the ADCC and its contributions to research and care of AD patients and their families both locally and globally and will educate families and caregivers.
2) Create and maintain community advisory groups.
3) Facilitate junior investigator mentorship program development.
4) Measure success of the outreach and professional training programs which may include, e.g., number of participants, feedback forms, number of participants who sign up to receive information or be contacted by the center, etc.
5) Assist in communicating the latest research findings both locally and generally to study participants, families and professionals. These efforts might include website maintenance, newsletters, brochures, seminars, workshops, media appearances, including TV, radio and print.
6) Develop and maintain a local registry/database of potential study volunteers with and without cognitive impairment, regardless of how well-characterized. Recruitment may be coordinated with the Alzheimer s Disease Cooperative Study group if the center serves as a performance site.
These efforts afford an important liaison and outreach between the ADCC and patients, their caregivers and the professional community so that information may be communicated bidirectionally. Collaboration with the Alzheimer s Association local chapters and other groups is expected for dissemination and transfer of information to the lay community and other educational activities and assistance with subject recruitment. 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 service groups, sports teams, hospitals, religious organizations, business groups, local medical societies, etc.) and 5) descriptions of materials (e.g., videos and printed matter) developed by the Center.
Attention should be directed to issues of cultural sensitivity and, where appropriate, the information should be structured so that it can effectively reach minority populations, including non-English-speaking people. Procedures by which the education and outreach activities are closely coordinated with the clinical core and satellite(s) (if appropriate) should be described, especially in recruitment of minorities and ethnically diverse populations. The education and outreach activities should also be prepared to support activities of the Centers group as a whole as well as recruitment for special NIA initiatives, such as subjects for genetic studies. 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 Resource Centers for Minority Aging Research (RCMARs) regarding recruitment and retention of minority elder populations are encouraged (http://www.rcmar.ucla.edu /).
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: (1) development of tools and/or technologies used for therapy development (2) imaging; (3) tissue and/or cell culture facilities; (4) complex instrumentation, e.g., electron microscopy, mass spectrometry, electrophysiology; (5) sequencing or microarray facilities (6) transgenic animal or cell preparation; (7) genetics; and (8) caregiving.
Pilot Studies
A plan to support one to three pilot studies for basic or clinical biomedical, epidemiological, caregiving, educational or behavioral research should be included and budgeted in the application. The description of a plan to solicit, review and administer pilot grants should be included in the Administrative Core and a separate budget including the total request for pilots should be submitted. 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. Criteria for review of pilot studies should be developed and included in the application. This funding mechanism is intended to provide modest support that will allow an investigator the opportunity to develop preliminary data sufficient to provide the basis for an application for independent research support through other granting mechanisms. 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.
Some examples of possible pilot projects are:
1) A study based on data in the NACC data set to determine the feasibility of conducting larger studies in the future.
2) A study proposed by a new investigator, with an interest in research in AD, before the study has developed to the point of being suitable to apply for individual grant support.
3) A study to determine the availability of sufficient subjects with specific characteristics, such as ethnic or minority status, before undertaking a larger study.
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.
No pilot applications should be submitted with the Center application but, instead, the number requested for each year (1 minimum, 3 maximum) and the plans for soliciting pilot proposals should be described. A plan must also be presented within the administrative core for peer review of the pilot studies including the selection of reviewers. Review should include a biostatistician as well as scientists from outside the Center. One option is for members from the External Advisory committee to serve as reviewers for the pilot applications, provided their expertise is appropriate for the submitted applications. Following local review, those pilots chosen for funding should be submitted to the NIA for approval in the annual non-competing renewal 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.
Progress Reports (for competing renewal applications)
Overall Progress Report: Address 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 in research on aging, AD and other neurodegenerative diseases 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. Include details of how the presence of the ADCC has brought new investigators into the field and has stimulated non-ADCC funded research in the last funding period. Explain the Center’s role in generating new funding from grants as well as leveraging funds from donors and other private sources. Describe how the presence of the Center has facilitated and improved AD research at the Institution and beyond.
When a pilot or optional core has terminated, include a final report with a summary of results and publications. If an optional core is continuing, include a progress report in that component write-up.
Applicants should include tables detailing:
Federally and non-federally funded grants that utilized resources from the Center, funding for therapeutic trials and other grants from industry, collaborations (including NACC, Alzheimer’s Association and others), and minority related grants.
Core Progress Reports: Describe the most important clinical core, neuropathology, and education core contributions to research on AD, related dementias and aging. Detail key findings and list publications resulting from use of core resources, including participants. Any developmental work carried out by the core should be presented and resulting publications listed. Reports should include Core objectives and progress in meeting them. Basic functions of the cores should be summarized (using tables where appropriate) including numbers, race, gender, age of patients and controls recruited, diagnosis (including ApoE status if available), percentage follow up and dropout rate and reasons for drop out, use of autopsy data in support of clinical correlations in research projects, and diagnostic confirmation by autopsy. Attention should be paid to numbers and kinds of subjects recruited and participation in clinical trials and other ongoing clinical research projects, both local and national. Clearly summarize tissue 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 (using tables where appropriate). 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. Summarize progress and activities related to data collection, data management and statistical consulting activities at the appropriate place in the application detailing where in the core(s) these activities were located. Include progress and interactions with NACC 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.
In lieu of a progress report, 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.
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/NR/rdonlyres/E489A7E9-EBFA-4B9F-8C80-C10BF3676169/9134/PPGattachment1Revised032008.doc.
Number all pages consecutively. Since the first page of the application is the Title Page, begin the next page with the numeral 2 . Do not use lettered numbers (e.g., 2A, 2B, etc.).
Each component core should be presented according to the Table of Contents. Identify 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).
Biographical Sketches. Follow the PHS 398 instructions. Include sketches for all key personnel and place them in alphabetical order; however, place the principal investigator's/program director's biographical sketch first. To aid in the review of the application, insert completed Table II after the biographical sketches. See sample, Attachment 4 in the following link. DISTRIBUTION OF PROFESSIONAL EFFORT (%) ON THIS APPLICATION, http://www.nia.nih.gov/NR/rdonlyres/E489A7E9-EBFA-4B9F-8C80-C10BF3676169/1998/PPGAttachment4.xls.
Research Plan Page Limitations
The page limit of 25 pages for Items 2-5 of the Research Plan, as stated in the PHS Form 398 instructions, applies to each core and research project. The introduction to the center application should be limited to 10 pages.
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 of the Research Plan component. 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 must 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/.
All applicants responding to this FOA are required to have a data core with the capacity to prepare the Uniform Data Set (UDS) for transmission to the National Alzheimer's Disease Coordinating Center (NACC).
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
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 NIA and 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 following will be considered in making funding decisions:
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 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 core review criteria, and additional review criteria (as applicable for the project proposed).
Core Review Criteria. Reviewers will consider each of the five review criteria below in the determination of scientific and technical merit, and give a separate score for each. 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.
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, 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 and each component 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 RFA? 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?
In addition to the above review criteria, the following criteria will be applied to applications in the determination of scientific merit and the impact/priority score.
NIH considers the following in evaluating Center grant applications:
2.A. 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 and Minorities. When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders.
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.
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.
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.
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 score.
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.
Select Agent 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).
The adequacy of plans to share brain tissue and biological specimens with other research scientists both within and outside the AD Centers network will be assessed. Any specimens that could be used for genetics research (e.g., blood, tissue) 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 (http://www.nia.nih.gov/ResearchInformation/ExtramuralPrograms/NeuroscienceOfAging/AlzheimersDiseaseGenetics.htm ).
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 (designated in
item 12 on the Application Face Page). If a grantee is not email enabled, a
hard copy of the NoA will be mailed to the 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/grants/policy/nihgps_2003/NIHGPS_Part4.htm)
and Part II Terms and Conditions of NIH Grant Awards, Subpart B: Terms and
Conditions for Specific Types of Grants, Grantees, and Activities (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part9.htm).
3.
Reporting
Awardees will be
required to submit the 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.
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: [email protected]
or
Creighton
H. Phelps, 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: [email protected]
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: [email protected]
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: [email protected]
Section VIII. Other Information
Required Federal Citations
Use of Animals in
Research:
Recipients of
PHS support for activities involving live, vertebrate animals must comply with
PHS Policy on Humane Care and Use of Laboratory Animals (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf)
as mandated by the Health Research Extension Act of 1985 (http://grants.nih.gov/grants/olaw/references/hrea1985.htm),
and the USDA Animal Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm)
as applicable.
Human
Subjects Protection:
Federal
regulations (45CFR46) require that applications and proposals involving human
subjects must be evaluated with reference to the risks to the subjects, the
adequacy of protection against these risks, the potential benefits of the
research to the subjects and others, and the importance of the knowledge gained
or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).
Data and Safety Monitoring Plan:
Data and safety monitoring is required for all types
of clinical trials, including physiologic toxicity and dose-finding studies
(phase I); efficacy studies (Phase II); efficacy, effectiveness and comparative
trials (Phase III). Monitoring should be commensurate with risk. The
establishment of data and safety monitoring boards (DSMBs) is required for
multi-site clinical trials involving interventions that entail potential risks
to the participants (NIH Policy for Data and Safety Monitoring, NIH Guide for Grants and Contracts, http://grants.nih.gov/grants/guide/notice-files/not98-084.html).
Sharing Research Data:
Investigators submitting an NIH application seeking
$500,000 or more in direct costs in any single year are expected to include a
plan for data sharing or state why this is not possible (http://grants.nih.gov/grants/policy/data_sharing).
Investigators should seek guidance from their
institutions, on issues related to institutional policies and local IRB rules,
as well as local, State and Federal laws and regulations, including the Privacy
Rule. Reviewers will consider the data sharing plan but will not factor the
plan into the determination of the scientific merit or the priority score.
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/grants/policy/nihgps_2003/index.htm).
All investigators submitting an NIH application or contract proposal, beginning
with the October 1, 2004 receipt date, are expected to include in the
application/proposal a description of a specific plan for sharing and
distributing unique model organism research resources generated using NIH
funding or state why such sharing is restricted or not possible. This will
permit other researchers to benefit from the resources developed with public
funding. The inclusion of a model organism sharing plan is not subject to a
cost threshold in any year and is expected to be included in all applications
where the development of model organisms is anticipated.
Inclusion of Women
And Minorities in Clinical Research:
It is the policy of the
NIH that women and members of minority groups and their sub-populations must be
included in all NIH-supported clinical research projects unless a clear and
compelling justification is provided indicating that inclusion is inappropriate
with respect to the health of the subjects or the purpose of the research. This
policy results from the NIH Revitalization Act of 1993 (Section 492B of Public
Law 103-43). All investigators proposing clinical research should read the
"NIH Guidelines for Inclusion of Women and Minorities as Subjects in
Clinical Research (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html);
a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.
The amended policy incorporates: the use of an NIH definition of clinical
research; updated racial and ethnic categories in compliance with the new OMB
standards; clarification of language governing NIH-defined Phase III clinical
trials consistent with the new PHS Form 398; and updated roles and
responsibilities of NIH staff and the extramural community. The policy
continues to require for all NIH-defined Phase III clinical trials that: a) all
applications or proposals and/or protocols must provide a description of plans
to conduct analyses, as appropriate, to address differences by sex/gender
and/or racial/ethnic groups, including subgroups if applicable; and b) investigators
must report annual accrual and progress in conducting analyses, as appropriate,
by sex/gender and/or racial/ethnic group differences.
Required Education
on the Protection of Human Subject Participants:
NIH policy requires
education on the protection of human subject participants for all investigators
submitting NIH applications for research involving human subjects and
individuals designated as key personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.
Human
Embryonic Stem Cells (hESC):
Criteria for
federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html.
Only research using hESC lines that are registered in the NIH Human Embryonic
Stem Cell Registry will be eligible for Federal funding (http://escr.nih.gov). It is the responsibility
of the applicant to provide in the project description and elsewhere in the
application as appropriate, the official NIH identifier(s) for the hESC line(s)
to be used in the proposed research.
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.
Weekly TOC for this Announcement
NIH Funding Opportunities and Notices
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