NIH’s new Application Submission System & Interface for Submission Tracking (ASSIST) is available for the electronic preparation and submission of multi-project applications through Grants.gov to NIH. Applications to this FOA must be submitted electronically using ASSIST or an institutional system-to-system solution; paper applications will not be accepted.

It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

The objectives of the NIA Alzheimer’s Centers Program are to foster highly interactive, cutting-edge Alzheimer’s disease (AD) and related dementias research through the following:

• Create an environment that supports innovative research that has a significant impact on the field of dementia research and treatment;
• Provide core services that leverage funding and unique expertise;
• Raise awareness and interest in fundamental, clinical, and translational dementia research at institutions, as well as locally, regionally, and nationally;
• Foster interdisciplinary collaborations, especially in emerging areas of research, to catalyze new ideas and scientific approaches;
• Attract and retain early stage investigators and investigators new to dementia research;
• Promote the translation of scientific discoveries from bench to bedside to community that improve public health and provide an opportunity for feedback including validation and effectiveness measures;
• Enable bi-directional translation aimed at accelerating the development of effective treatment and prevention for AD patients at all stages of the disease;
• Provide rapid and broad sharing of analytic and research tools, as well as data, as appropriate and consistent with achieving the goals of the program;
• Enhance dementia related research education and training opportunities for people with dementia, their care partners, students, scientists, and clinicians.

NIA support of Alzheimer’s Centers is intended to foster excellence in research across a broad spectrum of scientific and medical concerns relevant to dementia. To facilitate discovery and its translation into direct benefit to people with dementia and the general public, the NIA awards ADRCs to institutions that have a critical mass of excellent dementia-relevant scientific research and share the resulting research resources widely, to have the greatest impact.

Background

Dementia is estimated to affect millions of people in the United States. Dementia is a devastating disease for individuals, their families and society, financially, medically and emotionally. It has been estimated that the United States spends well over $100 billion per year for the direct and indirect costs of care for people with AD and related dementias. 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, and in 2011, Congress passed the National Alzheimer’s Project Act (NAPA). The stated primary goal of the National Plan to address Alzheimer's Disease is, "To prevent and effectively treat Alzheimer's Disease and Related Dementias by 2025." NIA highlights a framework of specific steps/criteria towards this goal in a research implementation milestone database. This extraordinarily ambitious goal requires that substantial resources be brought to bear to help achieve it. Therefore, this funding opportunity announcement for Alzheimer's Disease Research Centers includes significantly increased funding, commensurate with increases in overall funding for Alzheimer's disease and related dementias research, as well as corresponding expectations for resource generation and sharing. In turn, this increase is expected to lead to major advances in the field.

Congressional, as well as public, interest has focused on funding for research on the causes, diagnosis, treatment, and prevention of the disease, as well as on disparities and on the cost and coordination 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 ADRC program is authorized by the Public Health Service Act, Section 445, and currently includes 30 NIA designated ADRCs.

In 2017, NIA completed a strategic planning process that resulted in a set of 166 recommendations. Leading experts from academia, industry and non-profit foundations, working in Alzheimer’s and other complex diseases, were engaged to help ensure that the next generation of AD Centers is aligned with the key recommendations from the NIH AD and ADRD Research Summits:

• Recognize the heterogeneity and the multifactorial nature of the disease.
• Support extensive molecular profiling of existing cohorts and establish new cohorts to fill the gaps in large-scale human data needed to build predictive models of disease and wellness.
• Employ new research paradigms such as systems biology and systems pharmacology.
• Enable rapid and extensive sharing of data, disease models, and biological specimens.
• Develop computational tools and infrastructure for storage, integration, and analysis of large-scale biological and other patient-relevant data.
• Build new multidisciplinary translational teams and create virtual and real spaces where these teams can operate.
• Support and enable open science.
• Develop new precompetitive public-private partnerships.
• Change academic, publishing, and funding incentives to promote collaborative, transparent, and reproducible research.
• Engage patients, caregivers and citizens as direct partners in research.

These sets of recommendations enable the NIA to strengthen the ability to capitalize on the unique resources available through the ADRC program, namely, leveraging the numerous strengths of the network of Centers to provide large numbers of samples and standardized clinical data collection from well-characterized participants followed to autopsy, as well as a large pool of potential participants for future AD-related research. At the same time, while some critical scientific questions require large numbers of research participants or multiple scientific teams, other aspects of science require scientists with specific expertise or available unique resources or opportunities. Thus, the distinctive contributions and novel directions of each individual Center remain just as central to the ADRC program as leveraging the network. Additionally, strong emphasis is now placed on opportunities for utilizing the resources within and across the ADRCs to advance and augment the fields of drug discovery and drug development for novel therapeutics for AD.

The principal aim of the ADRCs is to lead the field by enhancing the performance of cutting-edge research on AD and related topics, including research on mechanisms and biomarkers of risk and protective factors that may lead to potential disease-modifying therapy or behavioral or other symptom treatments. Centers should focus on defining the medical, biological, cognitive and functional predictors of decline; compare existing and novel outcome measures; and validate changes in known and/or novel biomarkers of disease progression. Emphasis should be placed on understanding the heterogeneity of the disease, including resilience as well as mixed dementias, overlapping neurodegenerative syndromes, or age-related changes that often occur with AD, such as vascular dementia, Dementia with Lewy Bodies, Parkinson’s disease dementia, Frontotemporal degeneration and Chronic Traumatic Encephalopathy, both to better differentiate among them and to recognize commonalities. In addition, co-occurring conditions in other organ systems that may contribute to clinical dementia can be studied.

Centers are expected to provide an environment and core resources which will enhance cutting-edge research by facilitating team science, bringing together biomedical, behavioral, computational and clinical investigators to study the etiology, pathogenesis, diagnosis, treatment, and prevention of AD, and to improve health care delivery through all stages of the disease. 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 data and samples from well-characterized people along the spectrum of dementia and control subjects. Centers are expected to incorporate contemporary biochemical/molecular techniques and conduct research in genomics, epigenomics, proteomics and metabolomics. Centers should develop scientific directions in accordance with local talents, interests, and resources, while also being responsive to national needs related to AD and related dementias. The ADRCs 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. The central focus may be translational research, clinical-pathological research, basic research or a combination; importantly, the set of proposed cores and their interaction should reflect this focus.

As part of a network, Centers are expected to participate in collaborative efforts on a national scale. Applicants must agree to collect a standard clinical data set (the Uniform Data Set, or UDS) that is common to all Centers and to transmit that data to the National Alzheimer’s Coordinating Center (NACC). New applicants should contact NACC to learn more about NACC procedures, the structure of the UDS, and the regular updates to the datasets required from all Centers; http://www.alz.washington.edu/.

To support the unique research needs of the Center, most Centers collect additional data to supplement those required by the UDS. These should also be made readily available to qualified investigators. Similarly, 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. Sample sharing may be done either locally or centrally through the National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD). Centers are a local, regional, national and international resource.

Centers should work together with other AD and ADRD research groups in collaborative research activities and cooperate with other Federal, State, and Local agency-supported AD and ADRD programs as well as community and related non-governmental organizations in furthering mutual goals. Applicants are expected to include efforts to address the needs of, and research on, ethnically and racially diverse people as well as other underserved populations. Centers should also, whenever possible, cooperate and collaborate with other NIA Centers such as Pepper, Roybal, Shock, RCMAR (Resource Centers for Minority Aging Research) and the Research Centers Collaborative Network (RCCN), as well as other NIH Centers programs, like CTSAs. The use of other NIH resources, such as those available from ADNI, AMP-AD, M2OVE-AD, MODEL-AD and the preclinical innovation programs at NCATS, is also encouraged.

Alzheimer’s Centers are required to include the following six cores and one component:

• Administrative - manage and coordinate interactions among the Director, the core leaders, the principal investigators of research projects using the cores, other researchers at the applicant institution as well as outside institutions, appropriate institutional administrative personnel, the staff of the awarding agency, and the members of the community in which the Center is located. Administer development project grant program.
• Clinical - establish and maintain a clinical enterprise that provides valuable, well-documented resources for cutting-edge clinical research for both Center personnel and the wider scientific community.
• Data Management and Statistical (DMS) - provide data management support and statistical consultation to facilitate research and sharing of other cores and research projects utilizing resources of the ADRC. Facilitate both local analyses as well as collaborations between and among Centers and with NACC and the broader research community.
• Neuropathology - provide post-mortem diagnosis on all participants enrolled in the clinical core and on other well-documented AD cases and controls that may contribute to knowledge about dementia. Manage the biospecimen collection of the Center and coordinate catalogs with NACC.
• Outreach, Recruitment and Engagement (ORE) - provide important liaison and engagement between the ADRC and people with dementia, their caregivers, and both the professional and local lay community so that information may be communicated bi-directionally, particularly in diverse populations. Augment participant and community engagement.
• Biomarker - collect, store, track, share and analyze biomarkers (fluid, image, wearable, etc). May be standard or novel biomarkers. Should contribute to understanding of heterogeneity, onset or progression of disease symptoms, and/or improved diagnosis. Catalogs of available biomarkers and relevant data should be shared with NACC and samples may be shared through NCRAD.
• Research Education Component (REC) - support research educational activities to complement the training of a workforce to meet the nation's research needs in AD and related dementias. This should include increasing expertise and developing the next generation of scientists who will be effective in leading cross-disciplinary, translational, team-science projects on AD or AD-related dementias. The Research Education Component will be supported through an RL5 award linked to the P30 Center Core Grant.

Centers are expected to propose additional cores which contribute to the overall focus of the Center, are scientifically justified, develop resources that support other research affiliated with the Center, and fit within the budget guidelines outlined in Section II. Award Information of the FOA. Additional cores are expected to be innovative and to serve the needs not only of the local research community, but ideally also the national and international research communities. These cores may be unique to an individual Center or they may collaborate with other similar cores at ADRCs across the country. Some examples of research support that core components could provide are:

• Digital phenotyping: e.g., wearable, in home, medication adherence; driving behavior;
• Molecular profiling: collect -omics data on brain specimens, identify unique biomarkers, DNA sequencing/genetics integrated with bioinformatic analysis which will create a platform for personalized AD treatments;
• Complex instrumentation: e.g., electron microscopy, mass spectrometry, electrophysiology;
• Systems biology or systems pharmacology: gain understanding of the molecular and physiological context within which potential therapeutic targets operate;
• Care research: research on formal or informal care partners, facilitate validation of care models, including palliative care and end of life care, particularly to take advantage of unique opportunities locally or nationally, such as healthcare policy changes or unique care resources;
• Implementation and dissemination: access well-coordinated community-based health care systems and clinics to expedite conduct of studies enabling evaluation of evidence-based research findings in clinical practice.
• Administrative data: supplement ongoing data collection with administrative data sets. E.g., consent study participants to allow linkages of current data with Electronic Health Records (EHRs), Social Security Administrative Data, Center for Medicare and Medicaid (CMS) and/or VA claims data. All consents must comply with HIPAA authorization (i.e., enrolled study participants need to sign a HIPAA authorization and must "opt-in" to allow the use of their personal health information (PHI) for sub-studies and future secondary analysis of PHI.)
• Workforce development: research on effectiveness of efforts to improve workforce preparedness, such as training social workers or other community health partners;
• Special populations: scientific questions about a particular at risk population or unique cohort such as people with Down Syndrome, a particular epidemiologic cohort, a group with extraordinary longevity/resilience, or a particular racial/ethnic group.
• Satellite Diagnostic and Treatment Clinics (SDTCs): These are designed to increase the heterogeneity of the research participant pool and to enhance the research capabilities of the ADRC by extending the activities of the clinical core. New satellite clinics may be proposed if they fit within the overall budget requirements. Satellite clinics are not required to conduct research but should serve as vehicles for the recruitment, diagnosis and management of people with dementia and other research volunteers from rural and diverse and underserved 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.

Applications should include, in addition, funding for one to three development project grants that are one to three years in duration. Further details on requirements for the development projects are in Section IV in the Research Plan section of the Administrative Core.

The Center may incorporate ancillary activities such as longitudinal studies and patient care necessary to support the primary research theme. 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, and studying unique aspects and subtypes of these very complex and heterogeneous disease processes. The Center should serve as a link between state-of-the-art research and care. To raise awareness about dementia, serve as a recruitment source, and provide access to populations within the defined catchment area, including diverse and underserved populations, the Center should also establish partnerships with other health delivery systems and state and community agencies for dissemination of evidence-based findings.

NOTE: The catchment area must be defined and justified by the applicant, based on the geographic area it serves. It must be population based, e.g. using census tracts, zip codes, county or state lines, or other geographically defined boundaries. It must include the local area surrounding the Center.

Essential Features of NIA funded Alzheimer's Disease Research Centers

A successful NIA-funded ADRC demonstrates strength in seven essential features. Together, these features maximize its scientific potential and produce a whole that is greater than the sum of its parts:

• Dementia Focus: The Center members grants and contracts, as well as the structure and objectives of its formal research programs, demonstrate a clearly defined dementia research focus, ideally adding something unique to the national ADRC program and substantially contributing to progress in the field.
• Center Director(s): The Director is a highly qualified scientist and administrator with leadership experience and expertise appropriate for establishing a vision for the Center, advancing scientific goals, and managing a complex organization. The Director is effective in using institutionally designated authorities to manage the Center and advance its scientific objectives.
• Institutional Commitment: The Center is a formal organizational component of the institution, with sufficient space, positions, and discretionary resources to ensure its stability and fulfillment of the Center’s objectives. The Center Director has authorities appropriate for managing the Center and furthering its scientific mission. The institution recognizes team science in its promotion and tenure policies.
• Organizational Capabilities: The Center takes maximum advantage of institutional capabilities in dementia research, engaging in appropriate planning and evaluation of Center strategies and activities. If a consortium is proposed, the consortium institution(s) add significant dementia research expertise to the Center.
• Physical Space: Physical facilities dedicated to the conduct of dementia-focused research, and to the Center’s shared resources, and administration are appropriate and adequate for the task.
• Transdisciplinary Collaboration and Coordination: Substantial coordination, interaction, and collaboration, both among Center members from a variety of disciplines and between Center members and investigators in other institutions, enhance and add value to the productivity and quality of research. As appropriate to the nature of the research, Centers facilitate transition of scientific findings through the translational continuum, via coordination of research across NIA and other funding mechanisms and through collaborations with other partners.
• Sharing: In order to maximize the availability and usability of the data and research resources generated by ADRCs and to comply with the NIH Genomic Data Sharing Policy and the NIA/NIH efforts aimed at increasing transparency, reproducibility and translatability of research findings, awardees are expected to engage in broad sharing of data and biological samples, analytical methodology and disease models prior to publication with appropriate consent, consistent with achieving the goals of the program.". Also see Section IV.

Major Research Areas of Alzheimer's Disease Research Centers and Types of Interactions

Centers should feature vigorous interactions across research areas, facilitating collaboration between basic laboratory, clinical, and prevention research, as well as population-based science and data science researchers and the formal research programs of which they are a part. The organizational approach should serve the science of the institution, with reasonable breadth and depth of dementia-focused scientific faculty and dedicated research facilities. There should be selected attention given to specific research goals of the NAPA research implementation milestones and a discussion as to which goals are featured in the Center.

In addition, Centers should ensure that they are both fostering basic discovery and, as applicable, facilitating transition of scientific findings through the translational pipeline (i.e., basic to pre-clinical and early clinical development, then to Phase III trials or other types of definitive studies appropriate to the nature of the research). Discoveries may be advanced through NIA and other peer-reviewed translational science and clinical trial funding mechanisms (e.g., grants for clinical trials, program projects, phase I/II consortia, and the NIA Alzheimer s Clinical Trials Consortium or ACTC) and other collaborative strategies, including external partnerships. All Centers are expected to establish collaborative links that maximize productivity and result in appropriate application of findings. The form and extent of these activities may vary but should include both pharmaceutical interventions and non-pharmaceutical interventions such as trials of novel assessment methods, diagnostics, or care models.

Consortium Centers

NIA supports consortium Centers in which investigators from distinct scientific institutions partner together to contribute actively to the development and actualization of the dementia research agenda; these formalized relationships have the potential to both strengthen the science of the Center and further extend the benefits of its dementia research. Partnerships between research institutions serving special populations or located in geographic areas not currently served by an ADRC are particularly encouraged.

Consortium arrangements in the context of the NIA ADRC designation should include the following:

• Each member institution adds strategic value to the research mission of the ADRC, i.e., holds a portfolio of peer-reviewed, dementia-related research grants that contribute to the Center’s scientific goals.
• The consortium partner must contribute continuing tangible commitments to the Center. These may include: direct financial support of related research; protected research time to support programmatic goals; leadership positions in the Center’s cores or other components; common strategic planning and priorities (recruitment, clinical trials, grants, etc.); physical space for related research, etc.
• At the time of application for an ADRC, the partnering institutions should have prior evidence of successful collaboration. Their research should be integrated (as evidenced by a history of collaboration, including joint grants and publications), and mechanisms should exist for including geographically dispersed members in programmatic activities. Common fundraising and a joint Internal Review Board for evaluation of all dementia research across the partner institutions are encouraged, but not required.
• A formal, written agreement should be in place to ensure the stability and integration of the consortium partnership. The agreement should include:
• A process for resolution of differences at the highest levels of institutional leadership.
• An integrated planning and evaluation process that enables achievement of the Center’s research goals, (e.g. identification of future recruitment needs, shared resources, and other activities).
• Ongoing, tangible institutional commitments to the ADRC from all consortium partners. Such commitments should be appropriate to the nature of the consortium and may be demonstrated in a number of ways, including financial and in-kind contributions based on agreed upon formulas; housing and funding of Center cores; accrual to Center-wide affiliated research studies; active representation and engagement of members in Center programs and committees, etc.
• Full eligibility for membership in formal scientific programs and leadership positions in the Center.
• Reasonable access to shared resources for all members.
• Center director(s) oversight of ADRC-supported shared resources, including those located in partner institutions.

See Section VIII. Other Information for award authorities and regulations.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

o Hispanic-serving Institutions

o Historically Black Colleges and Universities (HBCUs)

o Tribally Controlled Colleges and Universities (TCCUs)

o Alaska Native and Native Hawaiian Serving Institutions

o Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.

• System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
• NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons.If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization 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.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Only one application per institution (normally identified by having a unique DUNS number or NIH IPF number) is allowed.

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

A button to access the online ASSIST system is available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

Most applicants will use NIH’s ASSIST system to prepare and submit applications through Grants.gov to NIH. Applications prepared and submitted using applicant systems capable of submitting electronic multi-project applications to Grants.gov will also be accepted.

It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

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.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Nina B. Silverberg, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-496-6788
Email: [email protected]

Available Component Types	Research Strategy/Program Plan Page Limits
Overall	12
Admin Core (Use this component type for the Administrative Core)	12
Core (Use this component type for the Clinical Core; Data Management and Statistical Core; Neuropathology Core; Outreach, Recruitment and Engagement Core; Biomarker Core; and Additional Cores)	6
Research Education (Use this component type for the Research Education Component (RL5))	12

Additional page limits described in the SF424 Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the SF424 (R&R) Application Guide, and should be used for preparing a multi-component application.

The application should consist of the following components:

• Overall: required; maximum of one
• Administrative Core: required; maximum of one
• Clinical Core: required; maximum of one
• Data Management and Statistical Core: required; maximum of one
• Neuropathology Core: required; maximum of one
• Outreach, Recruitment and Engagement Core: required; maximum of one
• Biomarker Core: required; maximum of two
• Research Education Component: required; maximum of one
• Additional Cores: optional; maximum of six

When preparing your application in ASSIST, use Component Type Overall .

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

Complete entire form.

Note: Human Embryonic Stem Cell lines from other components should be repeated in cell line table in Overall component.

Follow standard instructions.

Project Narrative: Indicate the relevance of the Center research to public health.

Project Summary/Abstract: Briefly describe the mission, vision and research goals for the Center for the next five years and describe how these have been integrated into the research program’s specific goals.

Facilities and Other Resources: Include a description of the following in a single attachment:

• Shared facilities and resources across cores.
• Actions that ensure other institutional leaders (deans, hospital presidents, and department chairs) will provide the long-term, stable support necessary to accomplish strategic Center objectives

Other Attachments: Use summary tables to list federally and non-federally funded grants that utilized resources from the Center, funding for therapeutic trials and other grants from industry, and health disparities and diversity-related grants. Include a description of what resources were used for each. Sample summary tables are available through NACC.

Enter primary site only. An Alzheimer's Disease Research Center (ADRC) will be an identifiable organizational unit formed by a single institution or a consortium of cooperating institutions.

A summary of Project/Performance Sites in the Overall section of the assembled application image in eRA Commons compiled from data collected in the other components will be generated upon submission.

Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this FOA) for the entire application.

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

A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.

The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover.

A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.

Introduction to Application: For Resubmission applications, an Introduction to Application is required in the Overall component.

Specific Aims: Describe the aims of the overall Center and outline how the different cores will contribute to these aims. State how the cores will promote the NAPA research implementation milestones and the goals of NAPA.

Research Strategy: Organize the Research Strategy into sections on: Significance, Innovation and Approach.

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

Additionally, describe how the Center will:

• Enhance the performance of innovative research on AD and related topics;
• Contribute to the national network of Alzheimer’s Centers by providing well-characterized participants and sharing with the research community brain tissue and other biological specimens;
• Provide an environment and resources to enhance cutting-edge research by bringing together investigators from various fields to study the etiology, pathogenesis, diagnosis, treatment and prevention of AD and related dementias;
• Foster the development of new lines of research;
• Facilitate the training and career development of staff at all levels from diverse backgrounds, with the goal of increasing the diversity of leadership positions within the Center;
• Create a dynamic training environment that supports disruptive and transformative research;
• Accelerate translational research across the spectrum of disease, with a strong focus on understanding disease heterogeneity;
• Demonstrate scientifically productive interactions across related NIH, VA, and other federally supported Center programs, non-governmental organizations, and large epidemiologic studies;
• Ensure that the necessary infrastructure is in place to facilitate broad data and sample sharing.
• Define the most significant scientific accomplishments in the period (as defined by the applicant) preceding the application. If applicable, describe specific examples of how the Center has significantly influenced new approaches in understanding or addressing dementia etiology, diagnosis, treatment, care and/or prevention.

Innovation: Considering the Center as a whole, show how the proposed research seeks to shift current research or clinical practice paradigms through use of novel concepts, approaches, methodologies, instrumentation, or interventions.

Approach: Discuss the interrelation of the Center to other activities in the applicant's institution (e.g., other relevant research projects) and the extent of institutional, departmental, and interdepartmental cooperation (charts and tables may be included). In addition, describe the administrative relations of the proposed ADRC to the institution. Demonstrate: 1) strong institutional commitment through organizational status for the Center that is comparable or superior to that of departments, 2) funding from institution, and 3) assurance from institutional leaders (deans, hospital presidents and department chairs) that they will provide long-term, stable support including physical space, control over faculty recruitments, and commitment to facilitate research by clinician scientists. Describe how cores complement each other or are interdependent. Describe the mechanisms that will ensure the coherence of the Center and maintain a multidisciplinary focus. Provide examples of how the presence of the ADRC has brought new investigators into the field and has stimulated non-ADRC 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.

Letters of Support: As the attachments, include letters of support signed by the Dean and/or Hospital President and/or other appropriate institutional officials documenting specifics of institutional commitment both for the long-term future of the Center and for this award period.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

In order to maximize the availability and usability of the data and research resources generated by NIA’s ADRC Program, and to comply with the NIH Genomic Data Sharing Policy and the NIA/NIH efforts aimed at increasing transparency, reproducibility and translatability of research findings, the awardees are expected to engage in broad sharing of data and biological samples, analytical methodology and disease models prior to publication, consistent with achieving the goals of the program.

To this end, ADRCs should demonstrate efforts to make:

• All datasets used/generated by this project accessible and reusable by qualified individuals other than the original data generators via web-based resources with the capacity to store large and diverse datasets (such as data about clinical phenotypes and high-dimensional omic data - genomic, proteomic, and metabolomic) to enable multiple parallel approaches to data analysis and interpretation;
• All disease models generated in the course of the award available to qualified investigators to accelerate their characterization, validation, and translational utility; and
• All biological samples obtained or used to generate data with this award available to qualified investigators.

To fulfill the above data- and resource-sharing expectations, the grantees can utilize the following NIA-supported repositories: NACC, NCRAD, NIAGADS and the AMP-AD Knowledge Portal. Data can be made accessible via open or controlled access depending on the data type and data source and as determined by the informed consent documents for each study guided by the local IRB. A comprehensive listing of NIH data sharing repositories is available at: https://www.nlm.nih.gov/NIHbmic/nih_data_sharing_repositories.html

The Steering Committee of the NACC, in conjunction with the ADRC Directors and the NIA, sets policies that allow the individual Centers to conduct unique research with participants while also sharing common data sets with NACC.

Appendix:

Limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Overall)

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Section 2 - Study Population Characteristics

2.4 Inclusion of Women, Minorities, and Children

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

The inclusion of participants with different characteristics will assist investigators in providing answers to questions about dementia diagnosis, treatment, and management strategies that are likely to be applicable to the broad U.S. population. Additionally, a more diverse participant pool will facilitate investigations of different risk factors, health disparities and the neuropathology and genetics of AD and related dementias as well as studies of care giving and family burden in diverse groups. Diversity of participants may be achieved in multiple ways. One option is to have a Satellite Clinic in locations that have higher populations of underserved individuals.

Section 3 - Protection and Monitoring Plans

3.1 Protection of Human Subjects

In addition to the required content of the Protection of Human Subjects attachment, describe the procedures for obtaining informed consent for: 1) research on cognitively-impaired human subjects who may not have the capacity to consent, specifically how proxy or surrogate consent will be obtained in the context of local and state law; 2) future participation in research studies if the participant becomes unable to consent (advanced directive for research); 3) placing data in the National Alzheimer s Coordinating Center’s Uniform Data Set and sharing data and specimens with other qualified scientists consistent with achieving the goals of this program; and 4) autopsy, specifying how and by whom and with whom the topic will be discussed, when and how often. Attention should be paid to obtaining advanced directives for research and obtaining autopsy permission from participants 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 other biological samples, as well as genetic and phenotypic information. Permission should also be obtained for storage in repositories and distribution from those repositories.

See the Biospecimen Task Force guidelines on the NACC web site: https://www.alz.washington.edu/BiospecimenTaskForce.html

For further guidance on consent forms see the NCRAD sample consent form language: https://ncrad.iu.edu/recommended_consent_language.html

For sample language regarding genetics that may be used in consent forms see:

http://www.nia.nih.gov/research/dn/sharing-policy-and-guidance-research-genetics-alzheimers-disease

Delayed Onset Study

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

When preparing your application, use Component Type Admin Core.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Facilities and Other Resources: Provide a description of all resources for the Center.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• Core Leader (CL) should have demonstrated leadership and administrative skills. Specifically, the CL should be able to organize and administer the resources created by the core in such a way that they may be shared within the ADRC as well as with other interested scientists. Demonstrated leadership in training junior investigators is desirable.
• The Program Director/Principal Investigator(s) of the proposed ADRC should also be the Administrative Core Leader(s); sufficient time should be devoted to the core to ensure that the aims are met and required functions are carried out efficiently. The PD/PI’s biographical sketch should present evidence of scientific expertise relevant to the themes of the ADRC and demonstrate the capacity for the leadership of an ADRC.
• The administrative requirements of the ADRC 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 ADRC application and grant. The administrator should be able to provide consultation in matters of fiscal administration and be familiar with NIH grant-related compliance policies.
• An Associate Director may be named who will be involved in the administrative and scientific efforts of the Center.

Budget forms appropriate for the specific component will be included in the application package.

A significant time commitment (2.4 person months) should be made by the Core Leader.

If large items of equipment are requested, the application should 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.

Domestic and foreign travel of personnel directly related to the core and scientific activities of the ADRC is allowable. Budgeting should include travel and lodging for representatives of the Center to attend: 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 ADRCs or the NIA to discuss research findings and plan cooperative projects, to promulgate data sharing, and to discuss standardization of procedures among the ADRCs; 4) for at least two ad hoc meetings on special topics; and 5) for visits of Center investigators to other ADRCs for the exchange of scientific ideas, planning of multi Center research projects and to receive training in specialized techniques.

Developmental projects must be budgeted in the Administrative Core budget. A brief description of the first-year developmental project solicitation and award process plans and detailed developmental project budgets for the first year of Center funding will be requested as Just-in-Time information through the eRA Commons shortly before the award of successful applications. Future-year developmental projects should be submitted with the annual Research Performance Progress Report (RPPR). Facilities & Administrative costs will be provided in accordance with these budgets. Developmental project costs should be in the range of $50,000-$100,000 direct costs per year and may have a project term between 1 and 3 years. Developmental projects may be awarded to investigators outside of the home institution. Funds for the developmental projects should be included under the other expenses within the administrative core budget. These funds should not be listed as a separate line in the composite budget. Developmental projects are allowed for consortium arrangements.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Administrative Core)

Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for each component.

Specific Aims: Clearly state how the core will contribute to the goals of the ADRC and outline interactions of the core with each of the other components of the Center.

Provide an overview of how the core will set the overall direction of the Center and ensure optimal utilization of Center resources. State how this core will promote the NAPA research implementation milestones and the goals of NAPA.

Research Strategy: Organize the Research Strategy into sections on: Significance, Innovation and Approach.

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

Approach: Describe how the Center's administrative structure will facilitate the following:

• oversee research and grants administrative processes (including preparation of annual RPPR);
• coordination and integration of Center components and activities (for example, the clinical and data management cores with the neuropathology and education components);
• direction for future planning and optimal utilization of resources;
• faculty recruitment, retention, tenure/promotion activities (including recognition of team science) and clear leadership succession planning;
• support and advice for the Center Director in oversight of the activities of the Center;
• interaction with the scientific and lay communities to develop relevant goals for the Center;
• coordination and organization of external and internal advisory committee meetings;
• coordination and organization of development project advertisement, review, and submission of development projects to NIA for approval;
• assurance of compliance with human subjects, animal welfare, scientific integrity, data and sample sharing as appropriate, and financial policy requirements of NIH;
• interaction with other Centers and other researchers to develop trans-ADRC and outside research projects;
• timely and routine transmissions of appropriate Center data sets to the NACC;
• timely and routine submission of samples to NCRAD;
• interaction and involvement with other research programs and grant administration of the University including the provision of core resources for development of related research;
• coordination with NIA on media coverage of the latest research findings from the Center.

Present plans to establish and operate Center advisory panels including:

• An executive committee (composed of core leaders and the administrator) to advise the Director in making the scientific and administrative decisions relating to the Center. The executive committee may consist of leaders both from within the institution and from other institutions and should provide guidance on monitoring and developing the scientific content and direction of the Center;
• An External Advisory Committee (EAC) to conduct and provide annual evaluations of the programs of the ADRC, research sharing and progress, the effectiveness of communications within and outside of the ADRC, interactions with NACC and NCRAD, and any other activities for which outside expertise is required or desirable. EAC members should not be named in the application and should not be contacted for participation in the committee prior to award. The NIA program officer should be invited to attend EAC meetings as a non-voting member. A copy of the advisory committee report should be routinely sent to the NIA with the annual RPPR and should include a list of committee members after they have been appointed;
• A review panel to assist in selecting development projects. Criteria for selecting committee members, how they will be identified, the operating procedures of the groups and the frequency of meetings should be described. Review should include a biostatistician as well as scientists from outside the Center. New applications should not select committee members prior to peer review of the Center application. Members from the External Advisory Committee may serve as reviewers for the development project applications, provided their expertise is appropriate for the submitted applications.

Development Projects: A plan to support one to three developmental projects for basic or clinical biomedical, translational, and epidemiological, caregiving, educational or behavioral research should be included in the application. Describe the process that will be used for soliciting, evaluating, selecting, and monitoring the developmental projects. The announcement for developmental projects funding should include a description of data available through NACC and samples available through NCRAD, including both websites. Use of these resources should be strongly encouraged. Use of existing resources at the Center, particularly those that are unique to the Center, should also be encouraged. This funding mechanism is intended to allow an investigator the opportunity to develop preliminary data sufficient to provide the basis for an application for independent research support. They are designed for postdoctoral or junior faculty level investigators, but may be awarded to a more senior investigator whose research is primarily in areas other than AD and ADRD research, and who wants to work in the dementia 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 development project support, unless the additional proposed developmental project constitutes a real departure from the investigator's ongoing research. The development project term is 1 to 3 years.

Examples of possible developmental projects are:

• A study based on data in the NACC data set to determine the feasibility of conducting larger studies in the future.
• 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.
• Functional, mechanistic, or pre-clinical activities designed to move a basic discovery towards a translational endpoint in the near future.

Examples of unacceptable developmental projects are:

• Clinical trials. Investigators interested in clinical trials should consider applying through the NIA Alzheimer’s Disease Pilot Clinical Trials FOA.

No developmental project applications should be submitted with the Center application. Funds designated for developmental projects are restricted until the developmental projects receive NIA approval. Successful Center applicants should conduct a competition and submit the successful development project applications to NIA for the first year of developmental projects funding after receiving a notice of grant award; in subsequent years, depending on length of projects, competition for developmental project awards should be timed so successful applications can be submitted with the RPPR for NIA review. As noted above, developmental projects may be 1-3 years in length.

Describe preliminary organizational work, institutional experience with AD and other neurodegenerative disease research, potential for developing or contributing to new and exciting research, and specific plans for implementation of the new program.

Provide evidence of successful overall integration of cores to promote the theme(s) of the Center as well as interaction within the academic and local, national and international research communities.

Provide evidence of productivity of previously funded pilot grants.

Describe the most important contributions to research on AD, related dementias and aging utilizing core resources. Basic functions of the cores should be briefly summarized. Any developmental work carried out by the core should also be presented.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

In order to maximize the availability and usability of the data and research resources generated by NIA’s ADRC Program, and to comply with the NIH Genomic Data Sharing Policy and the NIA/NIH efforts aimed at increasing transparency, reproducibility and translatability of research findings, the awardees are expected to engage in broad sharing of data and biological samples, analytical methodology and disease models prior to publication, consistent with achieving the goals of the program.

To this end, ADRCs should demonstrate efforts to make:

• All datasets used/generated by this project accessible and reusable by qualified individuals other than the original data generators via web-based resources with the capacity to store large and diverse datasets (such as data about clinical phenotypes and high-dimensional omic data - genomic, proteomic, and metabolomic) to enable multiple parallel approaches to data analysis and interpretation;
• All disease models generated in the course of the award available to qualified investigators to accelerate their characterization, validation, and translational utility; and
• All biological samples obtained or used to generate data with this award available to qualified investigators.

To fulfill the above data- and resource-sharing expectations, the grantees can utilize the following NIA-supported repositories: NACC, NCRAD, NIAGADS and the AMP-AD Knowledge Portal. Data can be made accessible via open or controlled access depending on the data type and data source and as determined by the informed consent documents for each study guided by the local IRB. A comprehensive listing of NIH data sharing repositories is available at: https://www.nlm.nih.gov/NIHbmic/nih_data_sharing_repositories.html

The Steering Committee of the NACC, in conjunction with the ADRC Directors and the NIA, sets policies that allow the individual Centers to conduct unique research with participants while also sharing common data sets with NACC.

Appendix:

Limited items are allowed in the Appendix.Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Administrative Core )

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study

All instructions in the SF424 (R&R) Application Guide must be followed.

When preparing your application in ASSIST, use Component Type Core.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover (Clinical Core)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Clinical Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Clinical Core)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Clinical Core)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Clinical cores of ADRCs may be based in university medical center neurology or psychiatry department memory disorders clinics, but they may also, or instead, be based in other departments. Applicants are encouraged to include special populations such as an underrepresented population, an existing epidemiologic cohort, or a community population living in elderly housing.

Research & Related Senior/Key Person Profile (Clinical Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• The Clinical Core Leader may be a neurologist, but may be a neuropsychologist, psychiatrist, geriatrician or other clinician with expertise in diagnosing Alzheimer’s and other neurodegenerative diseases. The Clinical Core Leader should have a track record of research in some aspect of neurodegenerative disease, including interactions with key personnel from other cores and leaders in the field from other institutions.

Budget (Clinical Core)

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 ADRC may be funded through the ADRC, provided there is no overlap of funding. Only those research patient costs directly related to ADRC activities may be charged to the ADRC.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Clinical Core)

Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for each component.

Specific Aims: Clearly state how the core will contribute to the goals of the ADRC and outline interactions of the core with each of the other components of the Center.

Clearly describe the target population for which the core will provide well-characterized, longitudinally followed research participants for cutting edge research projects involving e.g., clinico-pathological correlations, comparison of disease states to normal aging (including those using biological samples or imaging), and drug/intervention studies. State whether and to what extent the selection of the target population will promote the NAPA research implementation milestones and the goals of NAPA.

Research Strategy: Organize the Research Strategy into sections on: Significance, Innovation and Approach.

Significance: Explain the role of the clinical core in the Center and as a resource for other ongoing activities in Alzheimer’s disease and other neurodegenerative diseases. Establish and justify sample sizes for cohort and for different subpopulations. If the clinical core will include special populations, the applicant should describe the characteristics of the population and justify the added scientific value to research at the Center resulting from the inclusion of this group, so that peer reviewers can evaluate the comparative strengths and weaknesses of the proposed clinical core. If the application includes a satellite clinic as part of the clinical core, explain its significance.

Approach: Longitudinal data, including clinical, cognitive, behavioral, functional, imaging, and biomarker characterization on participants through the spectrum from normal aging to dementia should be collected according to the UDS protocol, and transmitted in a timely manner to the Data Management and Statistics Core. Cooperation, concurrence and collaboration with the Data Management and Statistics Core should continue from the initial specification of data content through data collection to database management and data analysis. A clear linkage between clinical and neuropathological data should be described. Clearly describe the procedures for working across the Center to increase the number of participants who agree to autopsy, especially of diverse populations, cognitively unimpaired people as well as people with MCI or early in the course of AD or related dementias. Applicants should state in this section of the application that they agree to collect and provide the UDS to NACC where it will be combined with data from other Centers and made available to scientists for collaborative studies. Participants should be enrolled in the Clinical Core with the intent of longitudinal follow-up. Information on the UDS is available from NACC.

Describe procedures 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. ADRCs are strongly advised to contact NCRAD as they prepare their application, for assistance in meeting sample sharing requirements, including procedures as well as consent forms and budget issues. Particular attention should be paid to best practices for collection and use of biospecimens detailed in documents available on the NACC website (https://www.alz.washington.edu/BiospecimenTaskForce.html). Applicants should describe and follow agreed upon protocols for multi-center projects involving specimen collection.

Describe interactions with other cores. Describe the types (with specific examples) of research projects and clinical trials that use or will use the core and how other research activities will benefit from the existence of the clinical core. While supporting recruitment to clinical drug trials may be one function of a clinical core, it should not be the only major effort of the core. Whenever possible, Clinical Cores should seek opportunities to: utilize high quality data collected during clinical care; evaluate cross-correlations between research tools and clinical measures; validate biomarkers and other diagnostic measures; reduce duplication of effort, costs, and participant burden (e.g., by implementing quality assurance, process evaluation and cost-utility measures); and develop, test and validate novel and emerging endpoints for translation into practice while assuring privacy and protecting participant health information. Describe opportunities to collaborate with already well-described epidemiologic cohorts and/or initiate new cohort studies.

State how the clinical core, in addition to participant recruitment, will provide: evaluation, and diagnosis, maintain a research volunteer registry that tracks number and reasons for those lost to follow-up, and conduct longitudinal follow up of registry participants. The participants in the registry may be considered a trial-ready cohort and may be assessed remotely either by telephone, web-based assessment or other mobile assessment tool. Clearly describe how participants are recruited into the registry (i.e., catchment area, geographic recruitment, internet based, according to particular risk factors, etc.). Describe efforts to include and retain diverse participants in the registry.

Clearly summarize recent resource use in affiliated research projects (both funded by the Center and externally funded) and the new insights obtained from these studies. Describe demographic information including numbers and kinds of participants recruited, diagnosis, percentage follow up and dropout rate and reasons for drop out, and diagnostic accuracy confirmation by autopsy. Describe the most important contributions to research on AD, related dementias and aging utilizing core resources. Reports should include Core objectives and progress in meeting them.

Describe preliminary organizational work, institutional experience with AD and other neurodegenerative disease research, potential for developing transformative research, and specific plans for implementation of the new program, within a time period defined by the applicant.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

In order to maximize the availability and usability of the data and research resources generated by NIA’s ADRC Program, and to comply with the NIH Genomic Data Sharing Policy and the NIA/NIH efforts aimed at increasing transparency, reproducibility and translatability of research findings, the awardees are expected to engage in broad sharing of data and biological samples, analytical methodology and disease models prior to publication, consistent with achieving the goals of the program..

To this end, ADRCs should demonstrate efforts to make:

• All datasets used/generated by this project accessible and reusable by qualified individuals other than the original data generators via web-based resources with the capacity to store large and diverse datasets (such as data about clinical phenotypes and high-dimensional omic data - genomic, proteomic, and metabolomic) to enable multiple parallel approaches to data analysis and interpretation;
• All disease models generated in the course of the award available to qualified investigators to accelerate their characterization, validation, and translational utility; and
• All biological samples obtained or used to generate data with this award available to qualified investigators.

To fulfill the above data and resource sharing expectations the grantees can utilize the following NIA-supported repositories: NACC, NCRAD, NIAGADS and the AMP-AD Knowledge Portal. Data can be made accessible via open or controlled access depending on the data type and data source and as determined by the informed consent documents for each study guided by the local IRB. A comprehensive listing of NIH data sharing repositories is available at: https://www.nlm.nih.gov/NIHbmic/nih_data_sharing_repositories.html

The Steering Committee of the NACC in conjunction with the ADRC Directors and the NIA sets policies that allow the individual Centers to conduct unique research with participants while also sharing common data sets with NACC.

Appendix:

Limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Clinical Core)

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Other Requested Information: Each component should include an attachment that indicates that the details of the study are included in the Overall component within this attachment.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study

All instructions in the SF424 (R&R) Application Guide must be followed.

When preparing your application in ASSIST, use Component Type Core.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover (Data Management and Statistical Core)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Data Management and Statistical Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Data Management and Statistical Core)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Data Management and Statistical Core)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Data Management and Statistical Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• This Core Leader's biosketch should reflect awareness of, and experience with, database management practices, computing, statistics and bioinformatics. The Core Leader may be primarily a data manager or a statistician. The Core Leader should have the time and the authority to work administratively with other cores. The core leaders should have a publication track record with other key personnel at the Center.
• The core should include a) a systems manager for computing and database management who will be the architect of the database structure and responsible for its maintenance; b) a systems analyst with sufficient background to select and implement database management software, represent data structures, specify and organize data flow, construct detailed error-check programs, develop/implement data checking and cleaning procedures, and provide for data entry and access, as well as information distribution, through electronic means (e.g., the internet or intranet); and c) a statistician who can consult with researchers on design and analysis of their projects, if the Core Leader is not a statistician. If this core is responsible for website management, the core should reflect expertise in this domain.

Budget (Data Management and Statistical Core)

Data infrastructure, management and networking with the larger Center program is a NIA priority. Provide sufficient resources and staff for the following type of activities:

• Performing and completing required upgrades to systems
• Implementation of software programs
• Collection of NIA requested data
• Training of Center personnel on data systems
• Creation of Center network wide system of Global Unique IDentifier (GUID) in collaboration with NACC and NCRAD

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Data Management and Statistical Core)

Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for each component.

Specific Aims: Clearly state how the core will contribute to the goals of the ADRC and outline interactions of the core with each of the other components of the Center.

Describe how the core will use current data analytic and bioinformatics technologies to collect, analyze and integrate data from across the ADRC. Highlight efforts to modernize (where applicable) and standardize electronic data capture (EDC) and database structure across ADRCs to augment Center-NACC, Center-Center and Center-NIH interactions. Describe both database and statistical services that will be provided to the cores and development projects.

Research Strategy: Organize the Research Strategy into sections on: Significance, Innovation and Approach.

Significance: Explain the role of the Core in the Center as a whole and as a resource for other ongoing activities in Alzheimer’s disease and other neurodegenerative diseases.

Approach: State how the system infrastructure will improve data capture and provide accurate, timely data about the resources of the Center across all relevant cores.

Describe the promotion of access to ADRC resources, both within the ADRC program and with the larger AD and ADRD research community.

Illustrate how the core will enable access to dynamic developments, i.e., new molecular and imaging data being generated from living and deceased research participants, and new clinical data being constantly updated.

Include a data management plan that covers at least:

• data flow schemes;
• data forms (electronic or hard copy; following core and affiliated project specified content);
• a Center-wide system of subject ID numbers that meets privacy standards;
• adequate systems for storing, protecting, tracking and sharing raw data within the cores and affiliated projects and within the data core itself;
• a mechanism to track data edits;
• longitudinal follow-up data storage/retrieval consistent with the protocols of the Center.

The Core should have the capacity to prepare the UDS for transmission to the NACC which in turn will make appropriate data sets available to qualified investigators for further research. All participants should be appropriately consented to share data broadly. The institution will be responsible for monitoring the data sharing policy.

Applicants should describe how the Core will fulfill other possible functions of the core that might include:

• Create a mechanism for sharing data other than the UDS collected by the ADRC both internally and externally;
• Connect data from other grants that utilize resources of the ADRC, where relevant and make this available to other researchers;
• Enable real time data analysis;
• Manage database issues related to scheduling and prioritizing study participants and biospecimens for clinical, neuropath and other cores and associated research projects;
• Sample inventory and tracking, including requests;
• Develop, implement and maintain a tracking system for ORE core activities recruitment, retention, calls to Center, a volunteer database, pre-post assessments;
• Design, maintain, and track usage of the Center’s website;
• Develop improved mathematical models that might help e.g., identify mediation or improve understanding of the interactions of multiple variables on cognitive decline;
• Develop enhanced statistical techniques to improve study design with a focus on issues relevant to detecting cognitive decline early in the disease process;
• Provide a mechanism for training in data science relevant to neurodegenerative disease research.

Describe how the core staff will work with clinical and research personnel as well as with statisticians to assure that their data are in an appropriate form for storage, transmission and analysis.

Describe how core staff will work with primary data collectors and have their cooperation to reconcile errors and missing or incomplete data elements as discovered through error check programs or through hands-on inspection procedures.

Describe how the core staff will work cooperatively with the NACC staff and respond appropriately to data calls issued by NACC.

Demonstrate a clear plan for how the statistical consultation will:

• be involved in the design and analysis of studies using participant data and/or biomaterials from the Cores;
• work closely with the data manager to insure analysis files are produced that are consistent with the needs of the question at hand; and
• provide consultation with development project applicants and awardees as well as with affiliated research project investigators.

Describe preliminary organizational work, institutional experience with AD and other neurodegenerative disease research, potential for developing new and exciting research, and specific plans for implementation of the proposed program.

Summarize progress and activities related to data collection, data management and statistical consulting activities. Describe the most important contributions to research on AD, related dementias and aging utilizing core resources. Basic functions of the core should be briefly summarized. Include progress and interactions with NACC as well as descriptions of any novel data analysis or study design strategies that have been developed. If available, present evidence for meeting timetables for data transfer in the proper format to NACC. Any developmental work carried out by the core should also be presented. Provide evidence for advanced data analytic capabilities.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

In order to maximize the availability and usability of the data and research resources generated by NIA’s ADRC Program, and to comply with the NIH Genomic Data Sharing Policy and the NIA/NIH efforts aimed at increasing transparency, reproducibility and translatability of research findings, the awardees are expected to engage in broad sharing of data and biological samples, analytical methodology and disease models prior to publication, consistent with achieving the goals of the program.

To this end, ADRCs should demonstrate efforts to make:

• All datasets used/generated by this project accessible and reusable by qualified individuals other than the original data generators via web-based resources with the capacity to store large and diverse datasets (such as data about clinical phenotypes and high-dimensional omic data - genomic, proteomic, and metabolomic) to enable multiple parallel approaches to data analysis and interpretation;
• All disease models generated in the course of the award available to qualified investigators to accelerate their characterization, validation, and translational utility; and
• All biological samples obtained or used to generate data with this award available to qualified investigators.

To fulfill the above data and resource sharing expectations the grantees can utilize the following NIA-supported repositories: NACC, NCRAD, NIAGADS and the AMP-AD Knowledge Portal. Data can be made accessible via open or controlled access depending on the data type and data source and as determined by the informed consent documents for each study guided by the local IRB. A comprehensive listing of NIH data sharing repositories is available at: https://www.nlm.nih.gov/NIHbmic/nih_data_sharing_repositories.html

The Steering Committee of the NACC in conjunction with the ADRC Directors and the NIA sets policies that allow the individual Centers to conduct unique research with participants while also sharing common data sets with NACC.

Appendix:

Limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Data Management and Statistical Core)

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Other Requested Information: Each component should include an attachment that indicates that the details of the study are included in the Overall component within this attachment

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study

All instructions in the SF424 (R&R) Application Guide must be followed.

When preparing your application in ASSIST, use Component Type Core.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover (Neuropathology Core)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Neuropathology Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Neuropathology Core)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Facilities and Other Resources: Provide a description of all resources available for biological sample collection, storage and distribution for the Center.

Other Attachments: Provide the number of current available biological samples that can be shared in a unified federated resource sharing hub:

• Plasma
• Buffy coat
• CSF
• Serum
• DNA
• DNA at NCRAD
• Dermal fibroblasts
• Induced pluripotent stem cells
• Frozen tissue
• Fixed tissue

Project /Performance Site Location(s) (Neuropathology Core)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Neuropathology Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• The Core Leader should have a track record of research in some aspect of neurodegenerative disease, preferably including interactions with key personnel from other cores as well as other Centers. The Core Leader should have demonstrated knowledge of standard protocols as well as expertise in state of the art techniques for diagnosis of neuropathological specimens and a track record of sharing and collaboration.

Budget (Neuropathology Core)

Funds for collection and sharing of biospecimens, including postmortem tissues, from Center clinical core subjects should be included. The NIA funded biorepository, NCRAD, can help ADRCs share samples with other researchers more easily and cost effectively. Applicants are strongly encouraged to contact NCRAD during the preparation of the application. NCRAD can assist with budget questions related to sample preparation and sharing through their biorepository.

Neuropathologists from the ADRCs meet yearly to share ideas and discuss technical aspects of tissue sampling, development of standardized tissue processing for diverse research protocols, cataloging and data management, and banking and distribution of tissues and biological samples. The core leader as well as an early stage investigator interested in neuropathology should have funds budgeted to attend this meeting.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Neuropathology/Biobanking Core)

Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for each component.

Specific Aims: Clearly state how the core will contribute to the goals of the ADRC and outline interactions of the core with each of the other components of the Center.

Describe the strategy for collection and distribution of samples for cutting edge research, locally as well as in cooperative research across Centers and with other researchers outside of Centers.

All biosamples must come from individuals who have consented to banking and sharing broadly. Applicants may utilize the National Centralized Repository for Alzheimer's Disease and Related Dementias for banking and sharing of samples. Applicants are strongly advised to consult the NCRAD website for information about samples banked at the repository.

Research Strategy: Organize the Research Strategy into sections on: Significance, Innovation and Approach.

Significance: Explain the role of the core in the Center as a resource for other national and international research activities focused on Alzheimer’s disease and other neurodegenerative diseases. Describe how the Core will utilize state of the art post-mortem diagnostic procedures to understand the relationships of pathology to clinical symptoms. Define the samples/biospecimens that will be collected and how their collection will promote the NAPA research implementation milestones and the goals of NAPA.

Approach: Describe procedures 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. Biomarker storage, tracking and sharing may be included in the neuropathology core (e.g., if biomarker core is focused on imaging) or in the biomarker core.

Describe, for all autopsy cases, the facilitation of DNA extraction and collection of biosamples for storage through NCRAD. Specimen collection, data gathering and storage activities should be coordinated with those of the Clinical Core, ORE Core and the Data Management Core.

Describe how outside investigators will have access to the Center's samples and view the catalog of biospecimens for the proposed ADRC.

Indicate whether the lay public can obtain an autopsy through the Center and what information is provided to the public.

Describe procedures for obtaining consent that will allow broad sharing of biological samples.

Provide a description of interactions with the REC to help train the next generation of neuropathologists, including personnel exchanges with other Centers as well as cross-disciplinary training within the Center.

Discuss procedures to provide coded samples to investigators that protect the identity of the participants.

Describe procedures and processes to prevent catastrophic loss of stored specimens.

Describe how the core will provide a resource for research studies that include clinical-pathological correlations across Centers. To do so, ADRCs should agree to follow standardized procedures whenever possible, so that it is possible to combine data across Centers.

Discuss the procedure for prioritizing which cases are targeted for autopsy consent as well as the use of tissues and other biological samples stored at the Center and describe how it will be used to support specific research efforts of investigators affiliated with the local Center and other scientists. If collection of special material is proposed (e.g., tissues from people with other dementia diagnoses, tissues of high scientific interest, such as those from clinical trials) justification should be included. If proposing developmental work, describe the role of this work and its significance to the core, the Center and other research activities.

Provide a description of novel technologies or techniques to increase the value of stored tissues and fluids, especially those that have longitudinal data available and how this will be shared with the wider research community.

To facilitate data sharing and cross-Center comparisons of diagnosis, all Centers should use the neuropathological criteria for AD developed by the 2012 NIA-Alzheimer's Association Working Group. 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 detailed information from NACC).

Describe preliminary organizational work, institutional experience with AD and other neurodegenerative disease research, potential for developing or contributing to new and exciting research, and specific plans for implementation of the new program. Applicants should obtain the most recent best practice guidelines for biospecimens and the pathology data set from NACC: https://www.alz.washington.edu/.

Clearly summarize resource use in local or other research projects and new insights obtained from these studies, as well as type and quantity of tissue or other biosamples provided to investigators both funded by the Center and by other means. Describe the most important contributions to research on AD, related dementias and aging utilizing core resources. Basic functions of the core should be briefly summarized. Any developmental work carried out by the core should also be presented.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

In order to maximize the availability and usability of the data and research resources generated by NIA’s ADRC Program, and to comply with the NIH Genomic Data Sharing Policy and the NIA/NIH efforts aimed at increasing transparency, reproducibility and translatability of research findings, the awardees are expected to engage in broad sharing of data and biological samples, analytical methodology and disease models prior to publication, consistent with achieving the goals of the program.

To this end, ADRCs should demonstrate efforts to make:

• All datasets used/generated by this project accessible and reusable by qualified individuals other than the original data generators via web-based resources with the capacity to store large and diverse datasets (such as data about clinical phenotypes and high-dimensional omic data - genomic, proteomic, and metabolomic) to enable multiple parallel approaches to data analysis and interpretation;
• All disease models generated in the course of the award available to qualified investigators to accelerate their characterization and validation and their translational utility; and
• All biological samples obtained or used to generate data with this award available to qualified investigators.

To fulfill the above data and resource sharing expectations the grantees can utilize the following NIA-supported repositories: NACC, NCRAD, NIAGADS and the AMP-AD Knowledge Portal. Data can be made accessible via open or controlled access depending on the data type and data source and as determined by the informed consent documents for each study guided by the local IRB. A comprehensive listing of NIH data sharing repositories is available at: https://www.nlm.nih.gov/NIHbmic/nih_data_sharing_repositories.html

The Steering Committee of the NACC in conjunction with the ADRC Directors and the NIA sets policies that allow the individual Centers to conduct unique research with participants while also sharing common data sets with NACC.

Appendix:

Limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions

PHS Human Subjects and Clinical Trials Information (Neuropathology Core)

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Other Requested Information: Each component should include an attachment that indicates that the details of the study are included in the Overall component within this attachment

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study

All instructions in the SF424 (R&R) Application Guide must be followed.

When preparing your application in ASSIST, use Component Type Core.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover (Outreach, Recruitment and Engagement Core)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Outreach, Recruitment and Engagement Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Outreach, Recruitment and Engagement Core)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Other Attachments: Provide a list of recruitment materials.

Project /Performance Site Location(s) (Outreach, Recruitment and Engagement Core)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Outreach, Recruitment and Engagement Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• The Core Leader(s) should have expertise and a track record of publishing on recruitment/outreach and an understanding of what is needed for retention of participants in dementia research. The leadership team should also have experience in evaluation as it is critical to assess effectiveness of outreach/engagement programs. The Core Leader should also have experience in recruiting diverse populations.

Budget (Outreach, Recruitment and Engagement Core)

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Outreach, Recruitment and Engagement Core)

Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for each component.

Specific Aims: Clearly state how the core will contribute to the goals of the ADRC and outline interactions of the core with each of the other components of the Center.

Summarize the outreach, engagement and recruitment needs of the Center as well as local academic researchers. Outline engagement, recruitment and outreach plans in light of the needs of the research that will rely on the Center. Include a description of how the Core will enhance recruitment of volunteers into AD and ADRD research, including clinical trials. Describe how the Center will provide information and resources to the local community as well as more broadly. Define how the recruitment of the research participants will facilitate the NAPA research implementation milestones and the goals of NAPA.

Research Strategy: Organize the Research Strategy into sections on: Significance, Innovation and Approach.

Significance: Explain the role of the core in the Center and as a community resource on AD and related dementias.

Innovation: Describe novel aspects of the proposed core.

Approach: Provide an assessment of the outreach, engagement, recruitment and retention needs that are unique to the Center as well as to the geographical area in the vicinity of the ADRC, including identifying underserved groups and conducting a needs assessment in collaboration with those communities. The assessment should include information about census data, community organizations, and an evaluation of the outreach, engagement and recruitment activities and needs of each research study supported by the Center. Other proposed activities should be clearly described in the application.

Depending on the local needs identified, this core should coordinate with other cores for recruitment and retention of subjects for particular research protocols and clinical trials, with a special emphasis on underserved/underrepresented populations. An outreach/engagement plan should address the needs identified, including both strengths and barriers (e.g., parking/transportation). Efforts to avoid or address selection bias should be clearly described. Retention efforts should be clearly described, including tracking, contact and scheduling methods as well as incentives or activities to maintain engagement, particularly for hard-to-reach participants.

Describe the creation of a community advisory board, how members will be selected, their role in developing and addressing research questions, frequency of meetings, and how they will facilitate communication of findings and opportunities with the community.

The methods and techniques to be employed to disseminate information and the audience targeted to receive information should be defined including 1) descriptions of seminar or lecture series, or workshops; 2) outreach/engagement to specific communities to publicize research; 3) collaboration with other organizations such as state and local agencies, community/service groups, sports teams, hospitals, religious organizations, business groups, local medical societies, etc.; and 4) descriptions of materials (e.g., videos and printed matter) to be developed by the Center.

Attention should be directed to issues of cultural sensitivity and, where appropriate, the information should be structured so that it can effectively reach diverse populations, including non-English-speaking people. Procedures by which the education and outreach activities are closely coordinated with the clinical core and satellite(s) (if appropriate) should be described, especially in recruitment of diverse populations. Community Based Participatory Research methods should be utilized and described. The outreach activities should also be prepared to support activities of the Centers network as well as recruitment for special NIA initiatives. Collaboration with other ADRCs and the NIA Alzheimer’s Disease Education and Referral Center (ADEAR) in recruitment, education and coordinated dissemination of educational materials is expected. Collaboration and consultation with RCMARs regarding recruitment and retention of diverse elder populations are encouraged (http://www.rcmar.ucla.edu/).

Applicants should describe how they will conduct other major activities of the Outreach, Recruitment and Engagement Core, which include:

• Liaison with state agencies and community service partners regarding dementia relevant activities;
• Develop and evaluate outreach/engagement 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, pre-post event assessments, etc. Describe how the Center will determine return on investment for recruitment efforts;
• Communicate the latest research findings both locally and generally to participants, families and professionals. These efforts might include website, social media, videos, newsletters, brochures, seminars, workshops, media appearances, including TV, radio, and print;
• Work with clinical core to develop and maintain a local registry/database of potential study volunteers. Utilize the registry to facilitate rapid enrollment in clinical studies. Evaluate the effectiveness of the registry and describe how adjustments will be made, particularly with respect to inclusion of diverse populations and at risk groups as well as to meet the local research needs.

In addition to the above, describe preliminary organizational work, institutional experience with recruitment, engagement and outreach for AD and other neurodegenerative disease research, potential for developing or contributing to new and exciting methods, and specific plans for implementation of the new program.

Describe past efforts to assist the clinical core and NIA special initiatives, in participant recruitment, especially any efforts directed to recruitment of people from diverse and underrepresented backgrounds. Provide information about educational activities that effectively impart knowledge to professionals and the lay public. Describe other outreach and engagement activities. Describe the most important contributions to research on AD, related dementias and cognitive aging utilizing core resources. Basic functions of the core should be briefly summarized. Any developmental work carried out by the core should also be presented.

Letters of Support: Include Community and State organizations that will collaborate.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

In order to maximize the availability and usability of the data and research resources generated by NIA’s ADRC Program, and to comply with the NIH Genomic Data Sharing Policy and the NIA/NIH efforts aimed at increasing transparency, reproducibility and translatability of research findings, the awardees are expected to engage in broad sharing of data and biological samples, analytical methodology and disease models prior to publication, consistent with achieving the goals of the program..

To this end, ADRCs should demonstrate efforts to make:

• All datasets used/generated by this project accessible and reusable by qualified individuals other than the original data generators via web-based resources with the capacity to store large and diverse datasets (such as data about clinical phenotypes and high-dimensional omic data - genomic, proteomic, and metabolomic) to enable multiple parallel approaches to data analysis and interpretation;
• All disease models generated in the course of the award available to qualified investigators to accelerate their characterization, validation, and translational utility; and
• All biological samples obtained or used to generate data with this award available to qualified investigators.

To fulfill the above data and resource sharing expectations the grantees can utilize the following NIA-supported repositories: NACC, NCRAD, NIAGADS and the AMP-AD Knowledge Portal. Data can be made accessible via open or controlled access depending on the data type and data source and as determined by the informed consent documents for each study guided by the local IRB. A comprehensive listing of NIH data sharing repositories is available at: https://www.nlm.nih.gov/NIHbmic/nih_data_sharing_repositories.html

The Steering Committee of the NACC in conjunction with the ADRC Directors and the NIA sets policies that allow the individual Centers to conduct unique research with participants while also sharing common data sets with NACC.

Appendix:

Limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions

PHS Human Subjects and Clinical Trials Information (Outreach, Recruitment and Engagement Core)

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Other Requested Information: Each component should include an attachment that indicates that the details of the study are included in the Overall component within this attachment

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study

All instructions in the SF424 (R&R) Application Guide must be followed.

When preparing your application in ASSIST, use Component Type Core.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover (Biomarker Core)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Biomarker Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Biomarker Core)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Facilities and Other Resources: In addition to the information required in the standard instructions, highlight available facilities, equipment, tools, resources and/or services dedicated specifically to the approaches proposed in this core. Indicate on what basis these resources will be available to the ADRC investigators (e.g., in-lab, freely available, fee-for-service, etc.).

Other Attachments: Provide the standardized protocols that will be used in this core.

Project /Performance Site Location(s) (Biomarker Core)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Biomarker Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• The Core Leader(s) should have a track record of research in some aspect of neurodegenerative disease, preferably including interactions with key personnel from other cores as well as other Centers. The Core Leader(s) should have demonstrated knowledge of standard protocols as well as expertise in state of the art techniques relevant to the proposed core, and a track record of sharing and collaboration.

Budget (Biomarker Core)

Core leaders from the ADRCs will meet yearly to share ideas and discuss technical aspects of sampling, development of standardized processes for diverse research protocols, cataloging and data management, and storing, distribution and analysis of images and biological samples. The core leader as well as an early stage investigator interested in the topic should have funds budgeted to attend this meeting.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Biomarker Core)

Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for each component.

Specific Aims: Clearly state how the core will contribute to the goals of the ADRC and outline interactions of the core with each of the other components of the Center.

Define which biomarkers will be collected and/or developed and how they will be used to increase our understanding of disease heterogeneity, disease onset or progression, and/or improve diagnosis. Describe how they will be used to advance translational research, e.g., biomarkers (in combination with other data) that enable molecular profiling of individual AD dementia which eventually lead to development of personalized AD treatments. Describe the exploration of the selected biomarkers' biology that can explain etiology or heterogeneity of disease and determine the quality of the biomarker. Explain how this core will advance and promote the NAPA research implementation milestones and the goals of NAPA.

Biomarkers of interest are any that can be used for disease monitoring and novel biomarker discovery. These might include: various neuroimaging methods, fluid biomarkers, biomarkers collected in other tissues (flow, skin, ocular, olfactory etc.), as well as collection of data from mobile and/or wearable devices. An individual biomarker core may focus on collecting/developing one or more types of biomarkers. Biomarker cores can focus on collecting established, standardized biomarkers or they could be discovery-based and focus on generating high dimensional omics data (genomic, proteomic, metabolomic, glycomic etc) that will be made available to the research community at large for basic, translational and clinical research.

Research Strategy: Organize the Research Strategy into sections on: Significance, Innovation and Approach.

Significance: Explain the role of the core in the Center as a resource for other local, national and international research activities focused on Alzheimer’s disease and other neurodegenerative diseases.

Innovation: Describe novel aspects of the proposed core.

Approach: Describe how the core will provide a resource for research studies (both within and outside of the applicant institution) that seek to understand the heterogeneity of dementia through analysis of imaging and/or biomarkers. To do so, ADRCs should agree to follow standardized procedures whenever possible, so that it is possible to utilize data across Centers. There is a biospecimen best practices guidelines document available on the NACC website: https://www.alz.washington.edu/BiospecimenTaskForce.html.

Discuss the procedure for prioritizing which cases are targeted for biomarker consent as well as the use of biomarkers and data stored at the Center and describe how it will be used to support specific research efforts of investigators affiliated with the local Center and other scientists. If collection of special material is proposed (e.g., samples from people with other dementia diagnoses, samples of high scientific interest, such as those from clinical trials) justification should be included. If proposing developmental work, describe the role of this work and its significance to the core, the Center and other research activities.

Biomarker cores can focus on sample collection for biomarker discovery, generation of data using the Center’s biobanking resources that can be amenable for biomarker discovery, and/or development of analytical methods for biomarker discovery and development.

Describe the process and web-based tools to make the collected samples, data and analytics tools available to the local research community and researchers at large. Alternatively, these capabilities can be part of the Data Management and Statistics Core.

The responsibility for collection, storage, tracking and sharing of biosamples can be part of the biomarker core or the neuropath/biobanking. Biomarker and imaging data should be included in the data set transmitted to NACC.

Provide a description of interactions with the REC to help train the next generation of researchers with expertise in imaging and biomarkers and/or analytics including personnel exchanges with other Centers as well as cross-disciplinary training within the Center.

Describe preliminary organizational work, institutional experience with AD and other neurodegenerative disease research, potential for developing or contributing to new and exciting research, and specific plans for implementation of the new program.

Clearly summarize resource use in affiliated research projects and the new insights obtained from these studies, as well as type and quantity of images, data and/or samples provided to investigators both funded by the Center and by other means. Describe the most important contributions to research on AD, related dementias and aging utilizing core resources. Basic functions of the core should be briefly summarized. Any developmental work carried out by the core should also be presented.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

In order to maximize the availability and usability of the data and research resources generated by NIA’s ADRC Program, and to comply with the NIH Genomic Data Sharing Policy and the NIA/NIH efforts aimed at increasing transparency, reproducibility and translatability of research findings, the awardees are expected to engage in broad sharing of data and biological samples, analytical methodology and disease models prior to publication, consistent with achieving the goals of the program..

To this end, ADRCs should demonstrate efforts to make:

• All datasets used/generated by this project accessible and reusable by qualified individuals other than the original data generators via web-based resources with the capacity to store large and diverse datasets (such as data about clinical phenotypes and high-dimensional omic data - genomic, proteomic, and metabolomic) to enable multiple parallel approaches to data analysis and interpretation;
• All disease models generated in the course of the award available to qualified investigators to accelerate their characterization, validation, and translational utility; and
• All biological samples obtained or used to generate data with this award available to qualified investigators.

To fulfill the above data and resource sharing expectations the grantees can utilize the following NIA-supported repositories: NACC, NCRAD, NIAGADS and the AMP-AD Knowledge Portal. Data can be made accessible via open or controlled access depending on the data type and data source and as determined by the informed consent documents for each study guided by the local IRB. A comprehensive listing of NIH data sharing repositories is available at: https://www.nlm.nih.gov/NIHbmic/nih_data_sharing_repositories.html

The Steering Committee of the NACC in conjunction with the ADRC Directors and the NIA sets policies that allow the individual Centers to conduct unique research with participants while also sharing common data sets with NACC.

Appendix:

Limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions

PHS Human Subjects and Clinical Trials Information (Biomarker Core)

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Other Requested Information: Each component should include an attachment that indicates that the details of the study are included in the Overall component within this attachment

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study

All instructions in the SF424 (R&R) Application Guide must be followed.

The over-arching goal of the Research Education program is to support educational activities that complement and/or enhance the training of a workforce to meet the nation’s biomedical, behavioral and clinical needs in dementia-related research. The REC will support creative educational activities with a primary focus on providing research experiences to promote the development of future research leaders in the ADRC area of focus, particularly leaders who can integrate clinical insights with knowledge of advances in the basic and translational sciences to improve interventions for maintaining cognitive health and avoiding dementing disease conditions. REC support is intended for junior faculty and research associates.

When preparing your application in ASSIST, use Component Type Research Education .

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover (Research Education Component (RL5)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Project /Performance Site Location(s) (Research Education Component (RL5))

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Other Project Information (Research Education Component (RL5))

Follow all instructions provided in the SF424 (R&R) Application Guide with the following additional modifications:

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Facilities and Other Resources: Describe the educational environment, including the facilities, laboratories, participating departments, computer services, and any other resources to be used in the development and implementation of the proposed program. List all thematically related sources of support for research training and education following the format for Current and Pending Support.

Other Attachments: Provide a plan for the External Advisory Committee of the ADRC to monitor progress of the research education program. Describe how the effectiveness of the REC program will be evaluated.

Project /Performance Site Location(s) (Research Education Component (RL5))

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Research Education Component (RL5))

• In the PD/PI section of the form, use Project Role of Other with Category of REC Leader and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component. ASSIST only allows a single biosketch for each person. Therefore, the biosketches must be comprehensive, covering multiple roles if a single individual has multiple roles.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used

Budget (Research Education Component (RL5))

Include all personnel other than the PD(s)/PI(s) in the Other Personnel section, including clerical and administrative staff.

Use the section on Participant/Trainee Support Costs to include all allowable categories of funds requested to support participants in the program.

Funds for salaries and other expenses of the Core Lead(s), information resources, and support staff may be requested.

The REC provides the following to participants: salary, fringe benefits, coursework, travel, and research project-related expenses.

REC participant costs must be itemized in the proposed budget. Allowable participant costs depend on the educational level/career status of the individuals to be selected to participate in the program. There is no minimum salary or professional effort requirement for REC participants. REC participants may receive salary support from other federal sources consistent with the institution's salary scale as long as those sources do not specifically prohibit such salary supplementation. Individuals supported by NIH training and career development mechanisms (K, T, or F awards) may receive, and indeed are encouraged to receive, educational experiences supported by the REC as participants, but may not receive salary or stipend supplementation from the REC.

Because the RL5 program is not intended as a substitute for an NRSA institutional training program (e.g., T32), costs to support full-time participants (supported for 40 hours/week for a continuous, 12-month period) are not allowable.

Expenses for foreign travel must be exceptionally well justified.

Indirect costs (Facilities & Administrative costs) are reimbursed at 8% of modified total direct costs (exclusive of tuition and fees and expenditures for equipment).

Set aside funds to travel 3-5 participants to one cycle of the semiannual meeting of the ADRCs each year of the award.

Note: The R&R Budget form included in many of the component types allow for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Research Education Component (RL5))

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for each component.

Specific Aims: Describe the contribution of the Research Education Component (REC) to the Center's overall goals. Describe how the proposed use of REC funds for research education activities will contribute to Center's goals for research education and provide relevant preparation for a workforce in AD and related dementias research. Describe how the REC Leader(s) and other mentors will help implement the intended goals of the REC.

Research Strategy: Organize the Research Strategy into sections on:

Proposed Research Education Program. While the proposed research education program may complement ongoing research training and education occurring at the applicant institution, the proposed educational experiences must be distinct from those research training and research education programs currently receiving federal support. When research training programs are on-going in the same department, the applicant organization should clearly distinguish between the activities in the proposed research education program and the research training supported by the training program.

The research education program should include mentored research experiences that develop state-of-the-art research skills related to AD and ADRD. Outline the objectives of the program and the program activities that will be used to meet these objectives. Describe plans to accommodate differences in preparation among participants. Include information about mentored research experiences and other educational activities essential for the proposed program.

Describe the plan for recruiting, selecting, mentoring, and monitoring the progress of individuals

who will receive REC support over the proposed Center award period and describe the abilities that REC candidates will be expected to acquire. The plan should include use of the external advisory panel.

The research education plans for at least some of the junior faculty and research associates supported through the REC should provide for the development of combined competence in basic, translational and clinical research in the areas of AD and ADRD. An emphasis on development of skills for translating basic findings into clinical research, and clinical findings into mechanistic studies, is encouraged. The plan may include establishment of common courses in relation to basic and clinical AD research. Regarding the goal of developing researchers with multidisciplinary expertise in clinical, translational and basic research (including aging research), applicants should consider the previous training of the individual candidate in determining the nature and extent of research education activities for which REC support is requested. One training option might include personnel exchange among different Centers, such as ADRC, Udall, Pepper, RCMAR, and AD translational Centers.

Component Leader(s). Describe arrangements for administration of the program. Provide evidence that the Core Leader(s) is/are actively engaged in research and/or teaching in an area related to the mission of the NIA and the ADRC Program, and can organize, administer, monitor, and evaluate the research education program. For programs proposing multiple Core Leaders, describe the complementary and integrated expertise of the Leaders, their leadership approach, and governance appropriate for the planned program.

Program Faculty. Researchers from diverse backgrounds, including racial and ethnic minorities, persons with disabilities, and women are encouraged to participate as program faculty. Faculty should have research expertise and experience relevant to AD and ADRD. Faculty must be committed to continue their involvement throughout the total period of this award.

Describe how the Program Faculty will serve as preceptors/mentors and provide guidance and expertise appropriate to the level of participants proposed in the application. Describe complementary expertise and experiences of the proposed Program Faculty, including active research and other scholarly activities in which the faculty are engaged, particularly interdisciplinary work, as well as experience mentoring and training individuals at the proposed career stage(s). For any proposed Program Faculty lacking research training experience, describe a plan to ensure successful participant guidance by these individuals. Describe the criteria used to appoint and remove individuals as Program Faculty and to evaluate their participation.

Program Participants. Applications must describe the intended participants, and the eligibility criteria and/or specific educational background characteristics that are essential for participation in the proposed research education program. Identify the career levels for which the proposed program is planned.

Present brief descriptions of the research and training background, potential research experiences, and mentoring activities for up to five candidates in the first year. Describe the goals for each candidate's career progression by the end of the award period. REC support is intended primarily for US citizens and permanent residents, unless there is strong justification otherwise based on exceptional relevance to the NIH and NIA.

REC support is intended for junior faculty and research associates. At least some participants selected for support through the REC should hold a clinical doctoral degree. Research education support should be integrated with other sources of career support that they may be receiving (e.g., career awards (NIH or not), fellowships) in concerted programs for research education. One of the goals of the research education program should be to recruit candidates from fields outside of AD and ADRD, such as technology/engineer, data sciences and traditional and emerging pharmaceutical sciences.

Recruitment Plan to Enhance Diversity: Fostering diversity in the scientific research workforce is a key component of the NIH strategy to identify, develop, support and maintain the quality of our scientific human capital (NOT-OD-15-053). Every facet of the United States scientific research enterprise from basic laboratory research to clinical and translational research to policy formation requires superior intellect, creativity and a wide range of skill sets and viewpoints. NIH’s ability to help ensure that the nation remains a global leader in scientific discovery and innovation is dependent upon a pool of highly talented scientists from diverse backgrounds who will help to further NIH's mission.

Research shows that diverse teams working together and capitalizing on innovative ideas and distinct perspectives outperform homogenous teams. Scientists and trainees from diverse backgrounds and life experiences bring different perspectives, creativity, and individual enterprise to address complex scientific problems. There are many benefits that flow from a diverse NIH-supported scientific workforce, including: fostering scientific innovation, enhancing global competitiveness, contributing to robust learning environments, improving the quality of the researchers, advancing the likelihood that underserved or health disparity populations participate in, and benefit from health research, and enhancing public trust.

Despite tremendous advancements in scientific research, information, educational and research opportunities are not equally available to all. NIH encourages institutions to diversify their student and faculty populations to enhance the participation of individuals from groups identified as underrepresented in the biomedical, clinical, behavioral and social sciences, such as:

A, Individuals from racial and ethnic groups that have been shown by the National Science Foundation to be underrepresented in health-related sciences on a national basis (see data at http://www.nsf.gov/statistics/showpub.cfm?TopID=2&SubID=27 and the report Women, Minorities, and Persons with Disabilities in Science and Engineering). The following racial and ethnic groups have been shown to be underrepresented in biomedical research: Blacks or African Americans, Hispanics or Latinos, American Indians or Alaska Natives, Native Hawaiians and other Pacific Islanders.

B. Individuals with disabilities, who are defined as those with a physical or mental impairment that substantially limits one or more major life activities, as described in the Americans with Disabilities Act of 1990, as amended. See NSF data at, http://www.nsf.gov/statistics/wmpd/2013/pdf/tab7-5_updated_2014_10.pdf

C. Individuals from disadvantaged backgrounds, defined as:

1. Individuals who come from a family with an annual income below established low-income thresholds. These thresholds are based on family size, published by the U.S. Bureau of the Census; adjusted annually for changes in the Consumer Price Index; and adjusted by the Secretary for use in all health professions programs. The Secretary periodically publishes these income levels at http://aspe.hhs.gov/poverty/index.shtml.

2. Individuals who come from an educational environment such as that found in certain rural or inner-city environments that has demonstrably and directly inhibited the individual from obtaining the knowledge, skills, and abilities necessary to develop and participate in a research career.

3. The disadvantaged background category (C1 and C2) is applicable to programs focused on high school and undergraduate candidates.

Literature shows that women from the above backgrounds (categories A, B, and C) face particular challenges at the graduate level and beyond in scientific fields. (See, e.g., Inside the Double Bind, A Synthesis of Empirical Research on Undergraduate and Graduate Women of Color in Science, Technology, Engineering, and Mathematics).

Applications must include a plan to enhance recruitment of a diverse participant pool and may include data in support of past accomplishments. The plan should be appropriate and reasonable for the nature and duration of the proposed program.

REC program is transitioning from previous ORE core linked activities in ADRCs. For previously NIA funded Alzheimer’s Centers, information should be included on successful and unsuccessful recruitment strategies including aggregate information on the distribution of:

• Individuals who applied for admission to the research education program,
• Individuals who were offered admission to the research education program,
• Individuals who participated in the research education program.

For those individuals who participated in the research education program, the report should include information about the duration of education and aggregate information on the number of individuals who finished the program in good standing, evidence of academic advancement and/or placement. Additional information on the required Recruitment and Retention Plan to Enhance Diversity is available at Frequently Asked Questions: Recruitment and Retention Plan to Enhance Diversity (Diversity FAQs).

Applications lacking a diversity recruitment plan will not be reviewed.

Plan for Instruction in the Responsible Conduct of Research. All applications must include a plan to fulfill NIH requirements for instruction in the Responsible Conduct of Research (RCR). The plan must address the five, required instructional components outlined in the NIH policy: 1) Format - the required format of instruction, i.e., face-to-face lectures, coursework, and/or real-time discussion groups (a plan with only on-line instruction is not acceptable); 2) Subject Matter - the breadth of subject matter, e.g., conflict of interest, authorship, data management, human subjects and animal use, laboratory safety, research misconduct, research ethics; 3) Faculty Participation - the role of the program faculty in the instruction; 4) Duration of Instruction - the number of contact hours of instruction, taking into consideration the duration of the program; and 5) Frequency of Instruction instruction must occur during each career stage and at least once every four years. See also NOT-OD-10-019. The plan should be appropriate and reasonable for the nature and duration of the proposed program.

Applications lacking a plan for instruction in responsible conduct of research will not be reviewed.

Evaluation Plan. Applications must include a plan for evaluating the activities supported by the research education program. A diagram or a table with milestones and timeline is encouraged. The application must specify baseline metrics (e.g., numbers, educational levels, and demographic characteristics of participants), as well as measures to gauge the short or long-term success of the research education program in achieving its objectives (e.g., publications, awards, or independent research funding). Their future career achievements should be tracked and included in the progress report. Applicants should obtain feedback from participants to help identify weaknesses and to provide suggestions for improvements.

Letters of Support: A letter of institutional commitment must be attached as part of Letters of Support. Appropriate institutional commitment should include the provision of adequate staff, facilities, and educational resources that can contribute to the planned research education program.

Progress Report Publication List: Publications resulting from resources or developmental work carried out by the REC should be listed, including those arising from research conducted by participants while they were supported by the REC.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genomic Data Sharing (GDS)) as provided in the SF424 (R&R) Application Guide, with the following modification:

Dissemination Plan: A specific plan should be provided to disseminate nationally if there are any findings resulting from or materials developed under the auspices of the research education program, e.g., sharing course curricula and related materials via web postings, presentations at scientific meetings, workshops.

Appendix: Limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions

When preparing your application in ASSIST, use Component Type Core.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

Applicants are expected to include additional cores appropriate to the theme(s) of the ADRC that both take advantage of local expertise and provide a resource to the broader research community.

SF424 (R&R) Cover (Additional Cores)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Additional Cores)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Additional Cores)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Additional Cores)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Additional Cores)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Additional Cores)

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Additional Cores)

Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for each component.

Specific Aims: Clearly state how the core will contribute to the goals of the ADRC and outline interactions of the core with each of the other cores of the Center.

Demonstrate exactly how the proposed core would augment or enhance the present capabilities of investigators using Center resources to enhance or create research at the home Center as well as other Centers and the wider research community.

Describe how the core will advance and promote the NAPA research implementation milestones and the goals of NAPA.

Research Strategy: Organize the Research Strategy into sections on: Significance, Innovation, and Approach. There should be a detailed discussion of the research that will or could use the resources of additional cores.

Describe preliminary organizational work, institutional experience with AD and other neurodegenerative disease research, potential for developing or contributing to new and exciting research, and specific plans for implementation of the new program.

Place overall summaries in the approach section of each core. Describe the most important contributions to research on AD, related dementias and aging utilizing core resources. Reports should include Core objectives and progress in meeting them. Any developmental work carried out by the core should also be presented.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

In order to maximize the availability and usability of the data and research resources generated by NIA’s ADRC Program, and to comply with the NIH Genomic Data Sharing Policy and the NIA/NIH efforts aimed at increasing transparency, reproducibility and translatability of research findings, the awardees are expected to engage in broad sharing of data and biological samples, analytical methodology and disease models prior to publication, consistent with achieving the goals of the program.

To this end, ADRCs should demonstrate efforts to make:

• All datasets used/generated by this project accessible and reusable by qualified individuals other than the original data generators via web-based resources with the capacity to store large and diverse datasets (such as data about clinical phenotypes and high-dimensional omic data - genomic, proteomic, and metabolomic) to enable multiple parallel approaches to data analysis and interpretation;
• All disease models generated in the course of the award available to qualified investigators to accelerate their characterization, validation, and translational utility; and
• All biological samples obtained or used to generate data with this award available to qualified investigators.

To fulfill the above data and resource sharing expectations the grantees can utilize the following NIA-supported repositories: NACC, NCRAD, NIAGADS and the AMP-AD Knowledge Portal. Data can be made accessible via open or controlled access depending on the data type and data source and as determined by the informed consent documents for each study guided by the local IRB. A comprehensive listing of NIH data sharing repositories is available at: https://www.nlm.nih.gov/NIHbmic/nih_data_sharing_repositories.html

The Steering Committee of the NACC in conjunction with the ADRC Directors and the NIA sets policies that allow the individual Centers to conduct unique research with participants while also sharing common data sets with NACC.

Appendix:

Limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions

PHS Human Subjects and Clinical Trials Information (Additional Cores)

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Other Requested Information: Each component should include an attachment that indicates that the details of the study are included in the Overall component within this attachment.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study

All instructions in the SF424 (R&R) Application Guide must be followed.

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov.

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies) using ASSIST or other electronic submission systems. Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

For information on how your application will be automatically assembled for review and funding consideration after submission go to: http://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) and component Project Leads must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management (SAM). Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

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

Reviewers will consider each of the review criteria below in the determination of scientific 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 Center that by its nature is not innovative may be essential to advance a field.

Does the Center address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the Center 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?

How strong is the base of ongoing high-quality research in AD and other related neurodegenerative disorders? How do the stated goals and plans demonstrate potential for contributing to cutting edge research on normal aging, MCI, AD and related disorders? How well is the Center able to participate in coordinated national efforts for collaborative research (including establishing a network of investigators, sharing data and resources within and outside the network, and holding meetings that bring together investigators from various fields)? What are the scientific interactions across federally supported Center programs, NGOs and large epidemiologic studies? What are the provided supports for the next generation of AD/ADRD researchers: postdoctoral fellows and junior faculty who are supported through different awards, including diversifying the workforce? How well does the proposed Center accelerate the research, both existing and planned, whether funded by the Center or not, that has, or will depend upon, resources provided by the requested cores? Importantly, how well does the proposed Center accelerate translational research across the spectrum of disease, with a focus on understanding the heterogeneity of AD and related dementias? Is there a clearly defined dementia research focus adding to the progress of the field? How well does the Center promote the NAPA research implementation milestones and goals?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the Center? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI , do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

How well do the investigators and staff provide creative scientific and administrative leadership of the Center and demonstrate a commitment to devote adequate time to the management of the ADRC program? What evidence is there of collaboration and interdisciplinary research among the investigators who will be associated with the ADRC? Does the group have stability and a track record of working together? Are plans for succession/recruitment of new personnel addressed? How well are the leadership transition plans clearly described and feasible? Is(Are) the PD/PI(s) a scientific leader experienced in the field of AD? Has the PD/PI(s) demonstrated that they can coordinate, integrate, and provide guidance in the establishment of programs in AD research and allied areas? How well is the PD/PI(s) effective in using institutionally designated authorities to manage and advance scientific objectives?

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?

How well do the proposed Center and each component demonstrate the capacity to develop critical new knowledge and unique and innovative contributions to AD and related dementia research locally, nationally and internationally?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the Center? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? 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? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the Center involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

How well does the proposed Center demonstrate appropriate organization and core management? What are the organizational plans and management structures that are adequate to meet Center goals? What are the procedures for internal communication and cooperation among the investigators and are they adequate? How well are the planning and evaluation of the Center strategies and activities? Do the cores proposed support the Center scientific theme(s)? Are the cores complementary to each other and do they advance the field? How well are the proposed Centers generating new funding and leveraging funds that advance the field? How many new investigators joined the field through the resources of the Center?

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?

How adequate are the relevant facilities for the proposed work? Does the geographic relationship between facilities seem reasonable to carry out the proposed work? How strong are the environment and core resources to enhance cutting-edge research by bringing together multidisciplinary investigators? How do institutional policies, including those related to promotion and tenure, recognize team science? How well do the letters of support demonstrate institutional commitment? What are the institutional commitments through organizational status for the Center that is comparable or superior to that of departments? What are the assurances from institutional leaders that they will provide long-term stable support and facilitate research by clinician scientists? How well does the institutional commitment ensure the Center's stability and fulfillment of the Center's objectives?

As applicable for the Center proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Recruitment Plan to Enhance Diversity

Peer reviewers will separately evaluate the recruitment plan to enhance diversity after the overall score has been determined. Reviewers will examine the strategies to be used in the recruitment of individuals from underrepresented groups. The review panel’s evaluation will be included in the summary statement. Plans will be rated as acceptable or unacceptable, and the summary statement will provide the consensus of the review committee.

Training in the Responsible Conduct of Research

Taking into account the specific characteristics of the proposed research education program, the level of participant experience, the reviewers will evaluate the adequacy of the proposed RCR training in relation to the following five required components: 1) Format - the required format of instruction, i.e., face-to-face lectures, coursework, and/or real-time discussion groups (a plan with only on-line instruction is not acceptable); 2) Subject Matter - the breadth of subject matter, e.g., conflict of interest, authorship, data management, human subjects and animal use, laboratory safety, research misconduct, research ethics; 3) Faculty Participation - the role of the program faculty in the instruction; 4) Duration of Instruction - the number of contact hours of instruction, taking into consideration the duration of the program; and 5) Frequency of Instruction instruction must occur during each career stage and at least once every four years. See also: NOT-OD-10-019. The review panel’s evaluation will be included in the summary statement. Plans will be rated as acceptable or unacceptable, and the summary statement will provide the consensus of the review committee.

As applicable for the core proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Administrative Core

Significance

How strong is the administrative foundation to support the proposed activities and affiliated research projects? How well does the Core Leader demonstrate the capacity for leadership of the Center?

Approach

How well does the proposed Center demonstrate appropriate organization and core management? Are the organizational plan and management structure adequate to meet Center goals? How are the procedures for internal communication and cooperation among the investigators adequate? How well described and appropriate is the description of directions for future planning and optimal utilization of resources? How does the administrative structure facilitate faculty recruitment, retention, and tenure/promotion activities, including recognition of team science? How does the organization structure support not only local, but also broad national and international data sharing including but not limited to timely and routine submission of data to NACC and samples to NCRAD?

Clinical Core

Significance

Do the stated goals, plans and targeted population (including justification for sample size, description of demographic, medical and diagnostic characteristics for each cohort) demonstrate potential for contributing to cutting edge research on normal aging, MCI, early AD and related disorders? If any special populations are proposed, are they clearly described and does their inclusion contribute substantially to the overall goals of both the Center as well as the national network? How well experienced is the Core Leader in the diagnosis of AD and related dementias? Does the Core Leader have a record of research in some aspect of neurodegenerative diseases?

Approach

How well does the application clearly describe how the clinical core, in addition to participant recruitment, provide: regular evaluation according to UDS protocol, and diagnosis, maintain a research volunteer registry that tracks number and reasons for those lost to follow-up, contributions to other related research (including clinical trials) and conduct longitudinal follow up of participants? How appropriate are the procedures for sample collection, storage and evaluation? How appropriate are interactions and roles of other cores? Specifically, with the DMSC, is the continuum from data content through data collection to data base management and data analysis clearly described? How well is there a clear linkage between the clinical and neuropathology and biomarker data, including a clear description of procedures for working across the Center to increase the number of participants who agree to autopsy and biomarker collection and sharing, especially for diverse populations and other select groups? How clear is the description of how the UDS data will be provided in a timely manner to NACC? How clear is the description of the role of and interactions with the Community Advisory Board?

Does the core contribute to validation of biomarkers and other diagnostic measures? How well does it utilize high quality data collected during clinical care? What contributions to future patient care by developing, testing and validating novel endpoints for translation into practice are described?

Data Management and Statistical Core

Significance

What are the database and statistical services? How well will the proposed Center contribute to the goals of the ADRC as well as the national efforts of the ADRC program? How is the data service modern and capable of large scale bioinformatics? Will the Center be able to participate in big data analytics or are its systems too outdated and unable to compete? How modern are the data systems and what upgrades are required to have optimum data collection and sharing? How well do the data systems support resource access? Are all the available Center resources captured in the system and available for sharing?

Approach

What are the data management and statistical plans? Is there statistical consultation with development project applicants? How well will the staff foster working relationships with the data contributors and harmonize the data collection? How well will data be available in a useful format for both planned and future analyses? Are appropriate safety procedures in place? How appropriate and reasonable are the plans for timely transmission of UDS data to NACC? Did the core prepare for Global Unique Identifier (GUID) creation and a unified federated resource sharing hub and how well will they be able to execute the requirement?

Neuropathology Core

Significance

How will the core contribute to the goals of the ADRC and provide a resource for other local, national and international research activities focused on Alzheimer’s disease and other neurodegenerative diseases?

Approach

How state-of-the-art are the diagnostic methods and collection, storage (including procedures to prevent catastrophic loss) and distribution of samples? How well will the identity of the participants be protected? What are procedures for obtaining consent (including case prioritization)? Do these procedures allow for broad sharing of biological specimens? How well is this information made clear to families as well as to researchers interested in obtaining samples? Is there an indication that NCRAD was consulted and a plan for biospecimen distribution would utilize this NIA resource?

Outreach Recruitment and Engagement Core

Significance

How well will the core interact with other cores to contribute to the goals of the ADRC as well as the national efforts of the ADRC program? How strong is a plan to regularly review the research needs for recruitment with the clinical core?

Approach

How well does the core serve as a community resource? What are the plans for communicating the latest research findings to the public? How well does the core incorporate community advisory groups into Center strategic planning? How well does the core incorporate Community Based Participatory Research methods into its plan? How strong are plans to evaluate and adapt the proposed outreach/engagement programs? How efficient is the process for evaluating its return on investment for recruitment efforts? How strong are the contact and scheduling methods? Are the methods clearly described and do they support efforts to recruit and retain hard-to-reach participants? What are the efforts made to reduce participant burden?

How well described and sufficient is the needs assessment? How does the proposed plan meet the needs identified? What are interactions of this core with the other cores and how well will they facilitate achieving the goals? How clear and adequate is the description of how the core will enhance recruitment for both the clinical core as well as other projects that rely on the Center for research recruitment, both currently and in the future? How well will the core effectively reach diverse populations?

Biomarker Core

Significance

How well does the core interact with other cores to contribute to the goals of the ADRC as well as the national efforts of the ADRC program?

Approach

How well does the core serve as a scientific community resource? How sufficient and state of the art is the equipment proposed in the core? Are the protocol methods standardized, where appropriate and sufficient for reproducibility? How well are data from the biomarkers connected with other relevant ADRC data? How well are the resources created made available to the scientific community both locally and more broadly? How appropriate are the biomarkers, collection and analysis methods? How likely are they to lead to new discoveries?

Research Education Component

Overall Impact

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to strongly advance research education by fulfilling the goal of this Research Education Component, in consideration of the following review criteria and additional review criteria, as applicable for the project proposed.

Scored Review Criteria

Reviewers will consider each of the review criteria below in the determination of scientific 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.

Significance

Does the proposed program address a key audience and an important aspect or important need in research education? Is there convincing evidence in the application that the proposed program will significantly advance the stated goal of the program?

Investigator(s)

Is the PD/PI capable of providing both administrative and scientific leadership to the development and implementation of the proposed program? Is there evidence that an appropriate level of effort will be devoted by the program leadership to ensure the program's intended goal is accomplished? If applicable, is there evidence that the participating faculty have experience in mentoring students and teaching science? If applicable, are the faculty good role models for the participants by nature of their scientific accomplishments? 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?

Innovation

Taking into consideration the nature of the proposed research education program, does the applicant make a strong case for this program effectively reaching an audience in need of the program’s offerings? Where appropriate, is the proposed program developing or utilizing innovative approaches and latest best practices to improve the knowledge and/or skills of the intended audience?

Approach

Does the proposed program clearly state its goals and objectives, including the educational level of the audience to be reached, the content to be conveyed, and the intended outcome? Is there evidence that the program is based on a sound rationale, as well as sound educational concepts and principles? Is the plan for evaluation sound and likely to provide information on the effectiveness of the program? If the proposed program will recruit participants, are the planned recruitment, retention, and follow-up (if applicable) activities adequate to ensure a highly qualified participant pool?

Environment

Will the scientific and educational environment of the proposed program contribute to its intended goals? Is there a plan to take advantage of this environment to enhance the educational value of the program? Is there tangible evidence of institutional commitment? Is there evidence that the faculty have sufficient institutional support to create a sound educational environment for the participants? Where appropriate, is there evidence of collaboration and buy-in among participating programs, departments, and institutions?

Additional Cores

Significance

How does the core contribute to the goals of the ADRC as well as the national and international research goals focused on Alzheimer s disease and other neurodegenerative diseases?

Approach

How well-reasoned and appropriate to contribute significantly to the specific aims of the Center are the overall strategy, methodology, and analyses? How strong are the strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? What 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? How strong are the plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the core involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

How does the core augment or enhance the present capabilities of investigators using Center resources to enhance or create research at the home Center as well as other Centers and the wider research community? What is the research that will or could use the resources of the additional core?

If a Satellite clinic is proposed, how does it serve the needs identified by the ORE core needs assessment, with a particular focus on one or more underserved populations?

For research that involves human subjects but does not involve one of the 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 thecategories 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. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

When the proposed Center involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

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.

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

For Renewals, the committee will consider the progress made in the last funding period.

Not Applicable

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

Not Applicable

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).

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; 2) Sharing Model Organisms; and 3) Genomic Data Sharing Plan .

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

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

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s), convened by NIA in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
• Will receive a written critique.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Council on Aging. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

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. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. 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.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

Awardee-selected projects that involve studies involving greater than minimal risk to human subjects require prior approval by NIH prior to initiation.

The awardee institution will provide NIH with written study protocols that address risks and protections for human subjects in accordance with NIH s Instructions for Preparing the Human Subjects Section of the Research Plan.

The awardee institution will provide NIH with specific plans for data and safety monitoring, and will notify the IRB and NIH of serious adverse events and unanticipated problems, consistent with NIH DSMP policies.

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 and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

Not Applicable

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten on-time submission, and post-submission issues)

Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application processes and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

Nina B. Silverberg, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-496-9350
Email: [email protected]

Ramesh Vemuri, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-496-9666
Email: [email protected]

Jennifer Edwards
National Institute on Aging (NIA)
Telephone: 301-827-6689
Email: [email protected]

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301, 405, and 445 of the Public Health Service Act as amended (42 USC 241, 284, and 285e-2) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.