Part 1. Overview Information

Key Dates

No late applications will be accepted for this Funding Opportunity Announcement.

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.

There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

1. Use the NIH ASSIST system to prepare, submit and track your application online.
2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.
   
   



Table of Contents
Part 1. Overview Information
Key Dates
Part 2. Full Text of 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

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Background

Dementia is a devastating disease, and it is estimated to affect millions of people in the United States. The risk of a person being diagnosed with Alzheimer's Disease (AD) increases greatly with age, and projections suggest that the numbers of people living with AD will increase with the aging of the population unless effective interventions are found. In addition to the medical and emotional toll that the disease takes on individuals and their families, the impact of the disease spans across society. It is estimated that the United States (U.S.) spends $300 billion per year, in direct and indirect costs, caring for people with AD and AD-related dementias (ADRD).

The Executive and Legislative Branches of the U.S. Federal Government have both expressed concern about the enormity of the problem posed by AD. Congressional 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 AD Research Center (ADRC) program is authorized by the Public Health Service Act, Section 445. Additionally, in 2011, Congress passed the National Alzheimer’s Project Act (NAPA). The law calls for a National Plan to address AD/ADRD. The stated primary goal of the plan is to, " prevent and effectively treat AD/ADRD by 2025." Plans and progress towards the NAPA goals are outlined in the AD+ADRD Research Implementation Milestones Database.

In 2017, NIA engaged leading experts on AD and other complex diseases from academia, industry, and non-profit foundations to develop recommendations that help to ensure that NIA-funded ADRCs are aligned with key recommendations from NIH’s AD and ADRD Research Summits. Hereafter, NIA-funded ADRCs will also be referred to as "Centers" and/or ADRC. These sets of recommendations enable 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 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 as this remains a critical goal.

Purpose

This FOA invites applications from institutions proposing to establish, or renew, an ADRC.

NIA's support of ADRCs 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, NIA awards ADRCs to major medical institutions across the U.S that have a significant level of excellent dementia-relevant scientific research and share the resulting research resources widely in order to have the greatest impact.

NIA-funded ADRCs serve as a national resource for research related to AD/ADRD. Additionally, the ADRCs work to translate research advances into improved diagnosis and care, as well as find ways to treat, and possibly prevent, AD/ADRD. Lastly, the ADRCs collaborate and coordinate their research efforts with other programs and investigators funded by NIH.

Research Objective

The objective of NIA's ADRC Program is to foster highly interactive, cutting-edge AD/ADRD research through core services that seek to accomplish the following:

• Create an environment that supports innovative multidisciplinary, inclusive research that has a significant impact on the field of dementia research and treatment;
• Foster interdisciplinary collaborations, especially in emerging areas of research, to catalyze new ideas and scientific approaches;
• Attract, educate and/or train, and retain a group of early stage investigators and investigators new to dementia research that is richly diverse in backgrounds, and academic and technical disciplines;
• Translate scientific discoveries from bench to bedside to community that improve public health and include validation and effectiveness measures;
• Provide rapid and broad sharing of analytic and research tools, as well as data, as appropriate and as consistent with achieving the goals of the program; and
• Enhance dementia-related research education opportunities for people living with dementia, their care partners, students, scientists, and clinicians.

Functions and Activities of ADRCs

The ADRC network plays a central role in national research efforts to address AD/ADRD; therefore, ADRCs have a responsibility to support research that provides the scientific basis for understanding the multiple etiologies and risk factors that impact the presentation of disease in individuals. This requires inclusive science, not just for equity reasons, but to provide research results that improve knowledge and are applicable to all. 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 with a particular focus on populations most at risk; comparing existing and novel outcome measures; and validating 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 a rich, multidisciplinary, inclusive 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, risk factors, pathogenesis, diagnosis, treatment, and prevention of AD, and to improve healthcare delivery through all stages of the disease. Centers should also foster the development of new lines of research and provide a rich educational environment for 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 unimpaired participants. Centers are expected to incorporate advanced 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/ADRD. The ADRCs provide a mechanism for fostering and coordinating the interdisciplinary cooperation of a group of established investigators conducting programs of research on AD/ADRD. The central focus must address major issues in the field of neurodegenerative disease research; 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 (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 data sets required from all Centers. Centers must also agree to image participants with a standardized protocol managed by the Standardized Centralized Alzheimer’s & Related Dementias Neuroimaging (SCAN) infrastructure.

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. The Center may incorporate ancillary activities, such as longitudinal studies and patient care necessary to support the primary research theme. Applicants are expected to include efforts to assess the needs of, and conduct research investigating risk factors specific to, NIH-designated populations that experience health disparities. Centers should also, whenever possible, cooperate and collaborate with other NIA-funded Centers, such as the following:

• Claude D. Pepper Older Americans Independence Centers (OAICs)
• Edward R. Roybal Centers
• Nathan Shock Centers of Excellence
• Resource Centers for Minority Aging Research (RCMAR)
• Research Centers Collaborative Network (RCCN)
• Centers on the Demography and Economics of Aging (with AD focus)
• NIA’s IMPACT Collaboratory
• Artificial Intelligence and Technology Collaboratories (AITCs)

Additionally, whenever possible, Centers should cooperate and collaborate with other NIH-funded programs, such as the following:

• Clinical and Translational Science Awards (CTSA) Program
• Alzheimers Disease Neuroimaging Initiative (ADNI)
• Alzheimer's Clinical Trials Consortium (ACTC)
• Accelerating Medicines Partnership Program for Alzheimer's Disease (AMP AD)
• Molecular Mechanisms of the Vascular Etiology of Alzheimer’s Disease (M OVE-AD) Consortium
• Preclinical Innovation
• NIA’s Longitudinal Population-Based Studies
• Behavioral and Social Research Networks (with AD focus)

ADRC Structure and Governance (Required)

ADRCs are required to include the following components:

• Administrative Core - 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, NACC, NCRAD and SCAN, and the members of the community in which the Center is located. Administer a developmental project grant program.

  • As part of the Administrative Core, applicants are required to include a plan to support one to three developmental projects. Details regarding the requirements of the plan are provided in Section IV.2 of this FOA (see the Research Plan section of the Administrative Core).

• Clinical Core - Establish and maintain a clinical enterprise that provides well-characterized, longitudinally followed research participants for cutting-edge research projects for both Center personnel and the wider scientific community. Build research participant groups that address the research needs of the proposed Center as well as affiliated studies and include populations at highest risk for the diseases to be studied. Address informed consent for research, including data sharing, biosamples, and autopsy. Assure appropriate disclosure of biomarker and other results.

• Data Management and Statistical Core - Provide data management support and statistical consultation to facilitate research of other cores and research projects utilizing resources of the ADRC. Facilitate both local analyses as well as collaborations and sharing between and among Centers and with NACC and the broader research community.

• Neuropathology Core - 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 of available samples with NACC. Support broad sharing of neuropathological data to include post mortem imaging and digital neuropathological data.

• Outreach, Recruitment, and Engagement Core - Provide important liaison and engagement between the ADRC and people living with dementia, their care partners, and both the professional and local lay community to facilitate bi-directional communication, particularly in populations that are understudied and/or are at higher risk for AD/ADRD. Augment participant and community engagement to support the ADRC as well as affiliated studies.

• Biomarker Core - Collect, store, track, share, and analyze biomarkers (e.g., 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 - Support research educational activities to support a multifaceted workforce to meet the nation's research needs in AD/ADRD. This should include increasing expertise and developing the next generation of scientists who will be effective in leading cross-disciplinary, translational, team-science projects. The Research Education Component will be supported through an RL5 award linked to the P30 Center Core Grant.

Additional Core Components

Additional Core components 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 this FOA may be proposed. Additional components 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 components may be unique to an individual Center, or they may collaborate with other similar components at ADRCs across the country. Examples of research support that core components could provide include, but are not limited to, the following:

• 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, unique care resources, or associated costs
• Implementation and dissemination: access well-coordinated community-based healthcare 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 Veterans Affairs (VA) claims data. All consents must comply with the Health Insurance Portability and Accountability Act of 1996 (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, including fields such as social workers or other community health partners
• Populations with unique risk or resilience factors for AD/ADRD: scientific questions about a particular at-risk population or unique cohort, such as people living with Down Syndrome, Veterans, a particular epidemiologic cohort, a group with extraordinary longevity/resilience, or a particular racial/ethnic group

Specific details and application instructions for each component are provided sequentially in Section IV.2 of this FOA.

Plan for Enhancing Diverse Perspectives

This FOA requires a Plan for Enhancing Diverse Perspectives (PEDP) as part of the application (see further below). Applicants are strongly encouraged to read the FOA instructions carefully and view the available PEDP guidance material.

Applications must include a Plan for Enhancing Diverse Perspectives (PEDP) submitted as Other Project Information as an attachment (see Section IV). The PEDP will be assessed as part of the scientific and technical peer review evaluation, as well as considered among programmatic matters with respect to funding decisions.

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

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

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:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• 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)

Local 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)

Federal Governments

• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

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.

• System for Award Management (SAM) 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.
  • Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registration; all registrations must be in place by time of submission. 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 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 diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019.

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.

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per 2.3.7.4 Submission of Resubmission Application. 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 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST or an institutional system-to-system solution. A button to apply using ASSIST 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.

2. Content and Form of Application Submission

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.

Letter of Intent

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 NIA 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: 301-496-9350
Email: [email protected]

Page Limitations

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

Additionally, application should consist of the following components, and the components should be presented in the order listed:

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages.

Overall Component

When preparing your application, use Component Type Overall .

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

SF424(R&R) Cover (Overall)

Complete entire form.

PHS 398 Cover Page Supplement (Overall)

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

Research & Related Other Project Information (Overall)

Follow standard instructions.

Project Narrative: Describe the relevance of the Center's research to public health.

Project Summary/Abstract: Briefly describe the mission, vision, and research goals of 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: In a single attachment titled "Overall Facilities, Other Resources, and Institutional Support," include a description of the following:

• Facilities and resources that will be shared across components
• Actions taken to ensure other institutional leaders (i.e., 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 the following that utilized resources from the Center: (1) federally and non-federally funded grants; (2) therapeutic trials and other grants from industry; and (3) grants related to health disparities research and/or populations at high risk for AD/ADRD.

Include a description of what resources were used for each. Sample summary tables are available on NACC's Progress Reports to NIA webpage.

Plan for Enhancing Diverse Perspectives (PEDP)

In an "Other Attachment" entitled "Plan for Enhancing Diverse Perspectives," all applicants must include a summary of strategies to advance the scientific and technical merit of the proposed project through expanded inclusivity. The PEDP should provide a holistic and integrated view of how enhancing diverse perspectives is viewed and supported throughout the application and can incorporate elements with relevance to any review criteria (significance, investigator(s), innovation, approach, and environment) as appropriate. Where possible, applicant(s) should align their description with these required elements within the research strategy section. The PEDP will vary depending on the scientific aims, expertise required, the environment and performance site(s), as well as how the project aims are structured. The PEDP may be no more than 1-page in length and should include a timeline and milestones for relevant components that will be considered as part of the review. Examples of items that advance inclusivity in research and may be part of the PEDP can include, but are not limited to:

• Discussion of engagement with different types of institutions and organizations (e.g., research-intensive, undergraduate-focused, minority-serving, community-based).
• Description of any planned partnerships that may enhance geographic and regional diversity.
• Plan to enhance recruiting of women and individuals from groups traditionally under-represented in the biomedical, behavioral, and clinical research workforce.
• Proposed monitoring activities to identify and measure PEDP progress benchmarks.
• Plan to utilize the project infrastructure (i.e., research and structure) to support career-enhancing research opportunities for diverse junior, early- and mid-career researchers.
• Description of any training and/or mentoring opportunities available to encourage participation of students, postdoctoral researchers and co-investigators from diverse backgrounds.
• Plan to develop transdisciplinary collaboration(s) that require unique expertise and/or solicit diverse perspectives to address research question(s).
• Publication plan that enumerates planned manuscripts and proposed lead authorship.
• Outreach and planned engagement activities to enhance recruitment of individuals from diverse groups as research participants including those from under-represented backgrounds.

For further information on the Plan for Enhancing Diverse Perspectives (PEDP), please see https://braininitiative.nih.gov/about/plan-enhancing-diverse-perspectives-pedp.

Project/Performance Site Locations (Overall)

Enter primary site only.

An 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.

Research and Related Senior/Key Person Profile (Overall)

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

The PD(s)/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.

Budget (Overall)

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

PEDP implementation costs:

Applicants may include allowable costs associated with PEDP implementation (as outlined in the Grants Policy Statement section 7: https://grants.nih.gov/grants/policy/nihgps/html5/section_7/7.1_general.htm).

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.

PHS 398 Research Plan (Overall)

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

Specific Aims: The application must describe the aims of the overall Center and outline how each core component will contribute to these aims. Additionally, the application must describe how the components will promote the NAPA research implementation milestones and the goals of NAPA.

Research Strategy:

Organize the Research Strategy into the following sections: Significance, Innovation, and Approach. Below is a description of what each section should entail:

Significance: Focusing on the Center as a whole, address the following:

1. The importance of the problem or critical barrier to progress in the field that the proposed Center is focused on.
2. How the resources of the proposed Center will improve scientific knowledge, technical capability, and/or clinical practice.
3. 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 and inclusive research on neurodegenerative diseases.
• Contribute to the national network of ADRCs by providing well-characterized participants and sharing brain tissue and other biological specimens with the research community.
• 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/ADRD.
• Foster the development of new lines of research.
• Facilitate the career development of staff at all levels with the goal of promoting diverse perspectives across leadership positions within the Center.
• Create a dynamic educational environment that supports disruptive and transformative research.
• Accelerate translational research across the spectrum of disease(s), with a strong focus on understanding mixed dementias.
• Demonstrate scientifically productive interactions across related NIH, VA, and other federally-supported research; NGOs; and large epidemiologic studies.
• Ensure that the necessary infrastructure is in place to facilitate broad data and sample sharing, as well as integration with administrative data sets.
• 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.
• Provide a clear leadership succession planning for the entire Center that includes leadership mentoring for early career researchers from diverse backgrounds, including those from underrepresented groups (see Notice of NIH's Interest in Diversity, NOT-OD-20-031).

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

Approach: Describe 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.

The application must provide evidence of the following:

1. Institutional commitment to enhancing diverse perspectives in the workforce;
2. Strong institutional commitment through organizational status for the Center that is comparable or superior to that of departments;
3. Funding from the institution; and
4. Assurance from institutional leaders (i.e., 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.

5. Institutional policies, including those related to promotion and tenure, that shows a commitment to team science.

Describe how cores complement each other and how they 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: Provide 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. Submit the letters as attachments.

Other Plan(s):

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages.

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

All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan.

All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.

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 data sets 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 multi-faceted datasets (e.g., 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, the National Institute on Aging Genetics of Alzheimer's Disease Data Storage (NIAGADS), and AMP AD's 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 Institutional Review Board(IRB). A comprehensive listing of NIH data sharing repositories is available here.

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

Appendix:

Only 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 human subjects research, clinical research, and/or NIH-defined 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.

Section 2 - Study Population Characteristics

2.3.a Inclusion of Individuals Across the Lifespan

2.4 Inclusion of Women and Minorities

Summarize strategies, with reference to the Outreach, Recruitment, and Engagement Core, to recruit and retain participants from varied 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 Outreach, Recruitment, and Engagement 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 heterogeneous participant pool will facilitate investigations of different risk factors, health disparities, and the neuropathology and genetics of AD/ADRD, as well as studies of care giving and family burden across various groups. Recruiting a heterogeneous participant pool may be achieved in multiple ways. One option is to have a site in locations that have higher populations of individuals from backgrounds understudied in AD/ADRD research.

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 the following:

1. Research on cognitively-impaired human subjects who may not have the capacity to consent--specifically. Describe 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 NACC’s UDS 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.

For information regarding best practices for the ADRCs in the acquisition, preparation, and storage of biospecimens, visit NACC's Best Practices webpage.

For information regarding consent forms, see NCRAD's sample consent form language.

For sample language regarding genetics that may be used in consent forms, see here.

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

PHS Assignment Request Form (Overall)

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

Administrative Core

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.

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages. If required, the Data Management and Sharing (DMS) Plan must be provided in the Overall component.

SF424 (R&R) Cover (Administrative 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 (Administrative Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Administrative 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) (Administrative 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 (Administrative 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 (CL) must have demonstrated leadership and administrative skills. Specifically, the CL must be able to organize and administer the resources created by the Center. Demonstrated leadership in mentoring junior investigators is desirable.
• The PD(s)/PI(s)'of the proposed ADRC must also be the Administrative CL(s); sufficient time must be devoted to the core to ensure that the aims are met and required functions are carried out efficiently. For applications with multiple PIs, at least one PD/PI must be the Administrative CL. The PD(s)/PI(s)' biographical sketch must 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 must 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 (Administrative Core)

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

• The CL of this component must commit, and sustain, a minimum of 2.4 person months of effort. For applications with multiple CLs, a minimum effort of 0.8 person-month is required per additional CL and the collective effort across the CLs must be at least 2.4 person months.
• If large items of equipment are requested, the application must document what is already available and provide clear justification in terms of use by core staff and how it relates to research projects dependent on the component. General-purpose equipment needs must 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 component and scientific activities of the ADRC is allowable. Budgeting must include travel and lodging for representatives of the Center to attend the following:

1) The semi-annual meetings of the Center Directors;
2) Annual meetings of administrators, clinical CLs, education CLs, data managers, and neuropathology CLs;
3) Ad hoc meetings called by the ADRCs or NIA to discuss research findings, and plan cooperative projects, promulgate data sharing, and discuss standardization of procedures among the ADRCs; and
4) At least two ad hoc meetings on special topics, as well as for visits of Center investigators to other ADRCs for the exchange of scientific ideas, planning of multi Center research projects, and/or to learn specialized techniques.

• Developmental projects must be budgeted in the Administrative Core budget. Detailed developmental project proposals including budgetary information will be requested as Just-in-Time (JIT) 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 in 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 AC budget. These funds should not be listed as a separate line in the composite budget. Developmental projects are allowed for consortium arrangements.
• Complete Magnetic Resonance Imaging, Amyloid positron emission topography (PET) Imaging, and Tau PET Imaging in at least 24 participants of the Clinical Core each year. All three imaging modalities must be completed for each participant. The Administrator is to ensure the minimum is met and distribute the funds appropriately to the relevant component(s) to accomplish the goals, including transmission of the data to SCAN.

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 Administrative 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 Administrative Core will set the overall direction of the Center and ensure optimal utilization of Center resources.

Research Strategy:

The Research Strategy should be organized into the following sections: Significance, Innovation, and Approach. Below is a description of what each section should entail:

Significance: Explain the role of the Administrative Core in the Center as a whole and as a resource for other ongoing activities in AD and other neurodegenerative diseases.

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

• Oversight of 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, and tenure/promotion activities, including recognition of team science;
• 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;
• Consent that will allow broad sharing of biological samples.
• Support not only local, but also broad national and international data sharing
• Interaction with other Centers and other researchers to develop trans-ADRC and outside research projects;
• Timely and routine submission of appropriate Center data sets and samples to the NACC, NCRAD and SCAN;
• Interaction and involvement with other research programs and grant administration of the University, including the provision of core resources for development of related research; and
• Coordination with NIA on media coverage of the latest research findings from the Center.

Present plans to establish and operate Center advisory panels, including the following:

• An executive committee, composed of CLs and the administrator, to advise the Director in making scientific and administrative decisions related 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, NCRAD and SCAN, 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 must be routinely sent to NIA with the annual RPPR and should include a list of committee members.
• A review panel to assist in selecting developmental projects. Criteria for selecting committee members, how they will be identified, the operating procedures of the group, 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 identify committee members in the Center application. Members from the EAC may serve as reviewers for the developmental project applications, provided their expertise is appropriate for the submitted applications.

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

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

New applications: 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.

Developmental Projects: A plan to support one to three developmental projects must 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, samples, and scans available through NACC, NCRAD and SCAN, including their 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. Developmental projects 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/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 developmental project support, unless the additional proposed developmental project constitutes a real departure from the investigator's ongoing research. The developmental project term is 1 to 3 years.

Examples of unacceptable developmental projects are:

• Clinical trials. Investigators interested in clinical trials should consider applying to PAR-21-360.

No developmental project applications should be submitted with the Center application. Funds designated for developmental projects are restricted until the developmental project applications receive NIA approval. Successful Center applicants should conduct a competition and submit the successful developmental project applications to NIA for funding after receiving a request for JIT. 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.

Provide evidence of productivity of previously funded developmental projects.

Data Management and Sharing Plan:

The Data Management and Sharing Plan submitted to the Overall component of the application must include elements to address all proposed activities of this component.

Appendix:

Only 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 human subjects research, clinical research, and/or NIH-defined 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

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

Clinical Core

When preparing your application, use Component Type Clinical Core.

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

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages. If required, the Data Management and Sharing (DMS) Plan must be provided in the Overall component.

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, or in other departments. Applicants are encouraged to include special populations, such as understudied populations and those at higher risk for AD/ADRD, an existing epidemiologic cohort, or a community population.

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 any clinician with expertise in diagnosing AD and other neurodegenerative diseases. The Clinical Core Leader must have a track record of research in some aspect of neurodegenerative disease, including interactions with key personnel from other components within the proposed center and leaders in the field from other institutions.

Budget (Clinical Core)

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

• 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.
• The CL of this component must commit and sustain a minimum of 1.2 person months of effort. For applications with multiple CLs, a minimum effort of 0.8 person-month is required per additional CL.
• Provide sufficient resources and staff for the following activities:

a. Annual participant evaluation and data capture, including social determinants of health and COVID data

b. If there is a plan to include participants who speak other languages, ensure that there are sufficient staff (coordinators, psychometrists, clinicians, etc.) to support this plan

c. EHR and CMS consent processes

d. Digital data capture including devices, licenses, and staff

e. Staff (e.g., genetic counselors and/or social workers) trained to provide tailored return of results when appropriate

f. Longitudinal blood sample collection for all participants that include staff phlebotomists and necessary materials

g. Cultural sensitivity and implicit bias training appropriate to the staff and planned participant groups

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 Clinical Core will contribute to the goals of the ADRC and outline interactions of the Clinical Core with each of the other components of the Center.

Clearly describe the target population for which the Clinical Core will provide well-characterized, longitudinally followed research participants for cutting-edge research projects. Such projects might involve: clinico-pathological correlations, comparison of disease states to normal aging (including those using biological samples or imaging) and/or distinguishing AD from other dementias, better understanding how multiple dementias present clinically, and/or drug/intervention studies. There should be a focus on populations most at risk for AD/ADRD.

Research Strategy: The Research Strategy should be organized into the following sections: Significance, Innovation, and Approach. Below is a description of what each section should entail:

Significance: Explain the role of the Clinical Core in the Center and as a resource for other research activities in AD and other neurodegenerative diseases. Establish and justify sample sizes for cohort and for different subpopulations, including how the proposed cohort reflects burden of disease. If the Clinical Core will include special populations, 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. Clearly describe the significance of additional (non-UDS) assessments to be collected.

Approach and Innovation: Define and justify the participant catchment area based on the geographic region of the proposed center and its population-based metrics (e.g. using census tracts, zip codes, county or state lines, or other geographically defined boundaries) and describe how the recruitment strategies will impact the planned analyses. Different racial and ethnic groups should not be compared if they are recruited in different manners.

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 available through NACC. 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.

Describe all non-UDS data to be collected and shared.

Clearly describe the procedures for working across the Center to increase the number of participants who agree to autopsy, especially participants from the following groups: populations understudied in AD/ADRD; populations with a higher risk of being diagnosed with AD/ADRD; cognitively unimpaired people and people living with mild cognitive impairments (MCI) or early in the course of AD/ADRD. The consent process is the responsibility of the Clinical Core.

Protocols for providing for return of results to participants should be clearly described, including to whom and which results will be provided as well as who will be providing the results.

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 expected to obtain blood samples longitudinally on all participants. 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’s website . Applicants should describe protocols for multi-center projects involving specimen collection that will be utilized by the Clinical Core.

Describe interactions with other components. Describe the types, with specific examples, of research projects and clinical trials that use or will use the component and how other research activities will benefit from the existence of the Clinical Core. Whenever possible, Clinical Cores should seek opportunities to utilize high-quality data collected during clinical care, this may include EHR and CMS data; 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 ensuring privacy and protecting participant health information. Describe opportunities to collaborate with already well-described epidemiologic cohorts and/or initiate new cohort studies.

Explain how the Clinical Core will maintain a volunteer registry that is separate from the Clinical Core. Describe how registry participants will be recruited (i.e., catchment area, geographic recruitment, internet based, according to particular risk factors, etc.), evaluated, and diagnosed. The registry should track 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 by telephone, web-based assessment, or another mobile assessment tool. Describe efforts to include and retain participants from groups traditionally understudied in research in the registry.

Clearly summarize recent resources used in affiliated research projects (both funded by the Center and externally funded) and new insights obtained from these studies. Describe demographic information, including numbers of participants recruited, diagnosis, relevant risk factors, percentage follow up, dropout rate and reasons for drop out, and diagnostic accuracy confirmation by autopsy. Describe the most important contributions to research on AD/ADRD and aging utilizing core resources.

New applications: 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.

Data Management and Sharing Plan:

The Data Management and Sharing Plan submitted to the Overall component of the application must include elements to address all proposed activities of this component.

Appendix:

Only 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 human subjects research, clinical research, and/or NIH-defined 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

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

Data Management and Statistical Core

When preparing your application, use Component Type Data Management Core.

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

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages. If required, the Data Management and Sharing (DMS) Plan must be provided in the Overall component.

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 CL's biosketch should reflect awareness of, and experience with, database management practices, computing, statistics, and bioinformatics. The CL may be primarily a data manager or a statistician. The CL should have the time and the authority to work administratively with other cores. The CLs should have a publication track record with other key personnel at the Center.
• The DMSC should include the following:

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 CL is not a statistician.

d. If this component is responsible for website management, the CL should reflect expertise in this domain.

Budget (Data Management and Statistical Core)

• The CL of this component must commit and sustain a minimum of 1.2 person months of effort. For applications with multiple CLs, a minimum effort of 0.8 person-month is required per additional CL.
• Data infrastructure, management, and networking with the larger Center program is a priority of NIA. The DMSC should have sufficient resources and staff for the following activities:

a. Ensuring data interconnectedness between the components, including tracking biosamples and images as well as integrating novel data

b. Ensuring that availability of samples and data is clear to interested investigators from within and outside the ADRC

c. Supporting data needs for all components, including those related to digital neuropathology, remote and other digital data from cognitive assessment, and electronic medical records integration

d. Performing and completing required upgrades to systems

e. Implementing software programs

f. Collecting NIA-requested data and submitting data to NACC, including changes to the UDS

g. Ensuring that Center personnel understand and can utilize data systems

h. Providing data and statistical support for Research Education Component scholars, development projects, and other affiliated research projects

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 Data Management and Statistical 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 Data Management and Statistical 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 each of the components, the Research Education Component, and developmental projects.

Research Strategy: Organize the Research Strategy into the following sections: Significance, Innovation, and Approach. Below is a description of what each section should entail:

Significance: Explain the role of the Data Management and Statistical Core in the Center as a whole, and as a resource for other ongoing activities in AD and other neurodegenerative diseases.

Approach and Innovation: 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 within the larger AD/ADRD research community.

Illustrate how the Data Management and Statistical Core will enable access to dynamic developments, e.g., new molecular and imaging data being generated from living and deceased research participants, as well as new clinical data being constantly updated.

The Data Management and Statistical Core should have the capacity to prepare the current UDS for transmission to 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. Include a data management plan that covers at least the following:

• Data flow schemes;
• Data forms (electronic or hard copy; following Data Management and Statistical 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 and across the components and affiliated projects and within the Data Management and Statistical Core itself;
• A mechanism to track data edits; and
• Longitudinal follow-up data storage/retrieval consistent with the protocols of the Center.

Applicants should describe how the Data Management and Statistical Core will fulfill the following required functions, outlining collaborations where applicable:

• Ensure the availability of data, preferably individual level, collected by the ADRC in addition to the UDS to researchers both within and outside of the ADRC;
• 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;
• Support scheduling and prioritizing study participants and biospecimens for clinical, neuropath, biomarker, and other components and associated research projects;
• Sample, tissue, imaging, digital neuropath, other post-mortem imaging, and other data inventory and tracking, including requests;
• Track fulfillment data, including time, and assess requests that are not fulfilled to improve responsiveness and processes;
• Develop, implement, and maintain a tracking system for activities of the Outreach, Recruitment, and Engagement Core recruitment, retention, calls to Center, a volunteer database, and 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; and
• Provide a mechanism for data science education relevant to neurodegenerative disease research.

Describe how Data Management and Statistical Core staff, including statisticians, will work with:

• Clinical and research personnel to ensure that their data are in an appropriate form for storage, transmission, and analysis;
• 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;
• NACC staff and respond appropriately to data calls issued by NACC.

Demonstrate a clear plan for how the statistical consultant will:

• Be involved in the design and analysis of studies using participant data and/or biomaterials from the components;
• Work closely with the data manager to ensure analysis files are produced that are consistent with the needs of the question at hand; and
• Provide consultation with developmental project applicants and awardees as well as with Research Education Component scholars and affiliated research project investigators.

Summarize progress and activities related to data collection, data management, and statistical consulting activities. Describe the most important contributions to research on AD/ADRD and aging utilizing core resources. Basic functions of the Data Management and Statistical 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. Present evidence for meeting timetables for data transfer in the proper format to NACC. Any developmental work carried out by the Data Management and Statistical Core should also be presented. Provide evidence for advanced data analytic capabilities.

New applications: 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.

Data Management and Sharing Plan:

The Data Management and Sharing Plan submitted to the Overall component of the application must include elements to address all proposed activities of this component.

Appendix:

Only 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 human subjects research, clinical research, and/or NIH-defined 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

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

Neuropathology Core

When preparing your application, use Component Type Neuropathology Core.

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

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages. If required, the Data Management and Sharing (DMS) Plan must be provided in the Overall component.

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.

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 CL should have a track record of research in some aspect of neurodegenerative disease, preferably including interactions with key personnel from other components, as well as other Centers. The CL 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)

• The CL of the Neuropathology Core must commit and sustain a minimum of 1.2 person months of effort. For applications with multiple CLs, a minimum effort of 0.8 person-month is required per additional CL.
• Funds for collection, tracking and sharing of biospecimens, including postmortem tissues, from Center clinical core and any other proposed participants should be included. Funds should support staff, software and infrastructure needed for state-of-the-art tracking and an on-line catalog of available samples that is updated regularly, as well as a rapid on-line review system so that requests can be processed in a timely manner. 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 various research protocols, cataloging and data management, and banking and distribution of tissues and biological samples. The CL, 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 Core)

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

Specific Aims: Clearly describe how the component will contribute to the goals of the ADRC and outline interactions of the Neuropathology Core with each of the other components of the Center.

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

All biosamples must come from individuals who have consented to banking and sharing broadly. Although CC participants should be prioritized, clear plans to obtain additional autopsies on other people that may enhance the overall scientific endeavor may be included. These may be clinical trial participants, people at high risk for AD/ADRD, such as those living with Down Syndrome, or those from groups understudied in research in general, and in autopsy cohorts in particular. If such cases are planned, describe how they will be obtained and ensure that the samples and data can be made available to the wider research community.

Applicants may utilize NCRAD 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 the following sections: Significance, Innovation, and Approach. Below is a description of what each section should entail:

Significance: Explain the role of the Neuropathology Core in the Center as a resource for other national and international research activities focused on AD and other neurodegenerative diseases. Describe how the Neuropathology Core will utilize state-of-the-art post-mortem diagnostic procedures to understand the relationships of pathology to clinical symptoms. Define the samples/biospecimens and other data that will be collected and how their collection will support the aims of the ADRC and other research supported by the ADRC infrastructure.

Approach and Innovation: Describe procedures related to criteria for diagnosis and the collection, storage, and distribution of brain tissue and other biological samples and related data, including, but not limited to, cell lines, cerebrospinal fluid (CSF), plasma and digital neuropathological data or postmortem imaging. 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, Outreach, Recruitment, and Engagement Core, and Data Management and Statistical Core. If there is a plan to obtain clinical information from family or other source postmortem, describe the process.

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

Inform whether the lay public can obtain an autopsy through the Center and what information is provided to the public regarding brain autopsy. Describe the process for providing an autopsy report to the family.

Provide a description of interactions with the Research Education Component to help educate the next generation of neuropathologists, including personnel exchanges with other Centers as well as cross-disciplinary mentoring within the Center and any on-line educational videos or other educational materials.

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

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

Describe how the Neuropathology 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 data can be combined across Centers.

Expound on the use of tissues and other biological samples stored at the Center and describe how they will be used to support specific research efforts of investigators affiliated with the local Center and other scientists. If tissue will be obtained from people who were not part of the Clinical Core, describe the source and scientific value (e.g., tissues from people living with other dementia diagnoses or tissues of high scientific interest, such as those from participants in clinical trials). If proposing developmental work, describe the role of this work and its significance to the Neuropathology Core, the Center, and other research activities.

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

To facilitate data sharing and cross-Center comparisons of diagnosis, all Centers should follow the best practices described on NACC’s website. 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).

Clearly summarize resources used 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/ADRD and aging utilizing Neuropathology Core resources. Basic functions of the Neuropathology Core should be briefly summarized. Any developmental work carried out by the Neuropathology Core should also be presented.

New applications: 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’s website.

Data Management and Sharing Plan:

The Data Management and Sharing Plan submitted to the Overall component of the application must include elements to address all proposed activities of this component.

Appendix:

Only 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 human subjects research, clinical research, and/or NIH-defined 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

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

Outreach, Recruitment, and Engagement Core

When preparing your application, use Component Type Recruitment Core.

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

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages. If required, the Data Management and Sharing (DMS) Plan must be provided in the Overall component.

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. Do not provide recruitment materials themselves.

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 CL(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 CL should also have experience recruiting understudied and populations relevant to the proposed Center.

Budget (Outreach, Recruitment, and Engagement Core)

• The CL of the Outreach, Recruitment, and Engagement Core must commit and sustain a minimum of 1.2 person months of effort. For applications with multiple CLs, a minimum effort of 0.8 person-month is required per additional CL.
• Provide resources to support a minimum of 24 person months of effort for full time recruitment specialists.

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 describe how the Outreach, Recruitment, and Engagement 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 Outreach, Recruitment, and Engagement Core will enhance recruitment and retention 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.

Research Strategy: Organize the Research Strategy into the following sections: Significance, Innovation, and Approach. Below is a description of what each section should entail:

Significance: Explain the role of the Outreach, Recruitment, and Engagement Core in the Center and as a community resource on AD/ADRD.

Innovation: Describe novel aspects of the proposed Outreach, Recruitment, and Engagement 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 understudied groups. The assessment should be conducted in collaboration with those communities and include information about census data and community organizations, as well as 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, the Outreach, Recruitment, and Engagement Core should coordinate with other components for recruitment and retention of participants for particular research protocols and clinical trials, with a special emphasis on understudied 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 the information, must be described, including the following:

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 populations relevant to the proposed Center and understudied populations, for example people who do not speak English and individuals with low literacy. Procedures by which the education and outreach activities are closely coordinated with the Clinical Core must be described. Community Based Participatory Research methods must be utilized and described. The outreach activities should 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 understudied and higher risk elder populations are encouraged.

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

• Liaising with state agencies and community service partners regarding dementia-relevant activities.
• Developing and evaluating outreach/engagement programs, which may include evaluating metrics related to the total number of participants, feedback forms, number of participants who sign up to receive information or to be contacted by the Center, pre-post event assessments, etc. Describe how the Center will determine return on investment for recruitment efforts.
• Communicating 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, or media appearances, including TV, radio, and print.
• Working with the Clinical Core to develop and maintain a local registry/database of potential study volunteers. Utilizing the registry to facilitate rapid enrollment in clinical studies. Evaluating the effectiveness of the registry and describing how adjustments will be made, including with respect to inclusion of understudied populations and/or those at higher risk for AD/ADRD as well as to meet the local research needs.

Describe past efforts to assist the Clinical Core and NIA special initiatives in participant recruitment, including any efforts directed to recruitment of people from understudied populations and/or those at higher risk for AD/ADRD. 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/ADRD 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.

New applications: 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.

Letters of Support: Include letters of support from community, state, and NGOs that will collaborate with the Center.

Data Management and Sharing Plan:

The Data Management and Sharing Plan submitted to the Overall component of the application must include elements to address all proposed activities of this component.

Appendix:

Only 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 human subjects research, clinical research, and/or NIH-defined 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

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

Biomarker Core

When preparing your application, use Component Type Biomarker Core.

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

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages. If required, the Data Management and Sharing (DMS) Plan must be provided in the Overall component.

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 the Biomarker 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 the Biomarker 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 CL(s) should have a track record of research in some aspect of neurodegenerative disease, preferably including interactions with key personnel from other components, as well as other Centers. The CL(s) should have demonstrated knowledge of standard protocols, as well as expertise in state-of-the-art techniques relevant to the Biomarker Core and a track record of sharing and collaboration.

Budget (Biomarker Core)

• The CL of the Biomarker Core must commit and sustain a minimum of 1.2 person months of effort. For applications with multiple CLs, a minimum effort of 0.8 person-month is required per additional CL.
• CLs from the ADRCs will meet yearly to share ideas and discuss technical aspects of sampling; development of standardized processes for various research protocols; cataloging and data management; and storing, distribution, and analysis of images and biological samples. The CL, 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 describe how the Biomarker Core will contribute to the goals of the ADRC and outline interactions between the core and each component of the Center.

Identify which biomarkers will be collected and/or developed and how they will be used to increase the 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 leads 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.

Biomarkers of interest are any that can be used for disease monitoring and novel biomarker discovery. These might include various neuroimaging methods, fluid biomarkers, or biomarkers collected in other tissues (e.g., flow, skin, ocular, olfactory), 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 (e.g., genomic, proteomic, metabolomic, glycomic) that will be made available to the research community at large for basic, translational, and clinical research.

Research Strategy: Organize the Research Strategy into the following sections: Significance, Innovation, and Approach. Below is a description of what each section should entail:

Significance: Explain the role of the Biomarker Core in the Center as a resource for other local, national, and international research activities focused on AD and other neurodegenerative diseases.

Innovation: Describe novel aspects of the Biomarker Core.

Approach: Describe how the Biomarker 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 NACC’s website.

Describe the procedure for prioritizing which cases will be targeted for biomarker consent as well as the use of biomarkers and data stored at the Center. Describe how the prioritization 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 or 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 Biomarker 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 Statistical Core.

The responsibility for collection, storage, tracking, and sharing of biosamples can be part of the Biomarker Core or the Neuropathology Core. Biomarker and imaging data should be included in the data set transmitted to NACC.

Provide a description of interactions with the Research Education Component to help educate 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 mentoring within the Center.

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/ADRD and aging utilizing resources of the Biomarker Core. Basic functions of the Biomarker Core should be briefly summarized. Any developmental work carried out by the Biomarker Core should also be presented.

New applications: 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.

Data Management and Sharing Plan:

The Data Management and Sharing Plan submitted to the Overall component of the application must include elements to address all proposed activities of this component.

Appendix:

Only 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 human subjects research, clinical research, and/or NIH-defined 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

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

Research Education Component - Linked Education Project (RL5)

When preparing your application, use Component Type Research Education.

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

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages. If required, the Data Management and Sharing (DMS) Plan must be provided in the Overall component.

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

PHS 398 Cover Page Supplement (Research Education Component (RL5))

Enter Human Embryonic Stem Cells in each relevant component.

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

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) (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

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Component 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 (Research Education Component (RL5))

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

• 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 Research Education Component Lead(s), information resources, and support staff may be requested.
• The Research Education Component may provide the following to participants: salary, fringe benefits, travel, and research-project-related expenses.
• Research Education Component 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 Research Education Component participants. Research Education Component 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 (i.e., K, T, or F awards) may receive, and indeed are encouraged to receive, educational experiences supported by the Research Education Component as participants, but may not receive salary or stipend supplementation from the Research Education Component.
• 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 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 (Research Education Component (RL5))

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 to the Center's overall goals. Describe how the proposed use of Research Education Component funds for research education activities will provide relevant preparation for a workforce in AD/ADRD research. Describe how the Research Education Component Leader(s) and other mentors will help implement the intended goals of the Research Education Component.

Research Strategy: The Research Strategy must include the following subsections:

Proposed Research Education Program. The application must describe how the proposed program will be distinct from training programs that already exist in the organization. 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 must include mentored research experiences that develop state-of-the-art research skills related to AD and ADRD and leverage the interdisciplinary nature of the ADRC. 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 Research Education Component support over the proposed Center award period and describe the abilities that Research Education Component candidates will be expected to acquire. The plan should include use of the external advisory committee.

The research education plans for at least some of the junior faculty and research associates supported through the Research Education Component must 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 Research Education Component 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 Component Leader(s) is/are actively engaged in research and/or teaching in an area related to the mission of NIA and the goals of the ADRC program, and can organize, administer, monitor, and evaluate the research education program. For programs proposing multiple Component 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, but not limited to: individuals from racial and ethnic groups underrepresented in biomedical and behavioral research, individuals with disabilities, and women (see, Notice of NIH's Interest in Diversity, NOT-OD-20-031), 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.

Research Education Component 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.

Research Education Component support is intended for junior faculty and research associates. At least some participants selected for support through the Research Education Component 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/ADRD, such as technology/engineering, 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-20-031). 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.

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

Information should be included on past 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, and
• 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 and evidence of academic advancement and/or placement.

Applications lacking a Recruitment Plan to Enhance Diversity 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 online 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, and 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 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). Research education program participants 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.

Renewal applications: In addition to above, describe any changes in formal instruction over the past project period and plans to address any weaknesses in the current instruction plan. All participating faculty who served as course directors, speakers, lecturers, and/or discussion leaders during the past project period must be named in the application.

New applications: 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.

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 Research Education Component should be listed, including those arising from research conducted by participants while they were supported by the Research Education Component.

Data Management and Sharing Plan:

The Data Management and Sharing Plan submitted to the Overall component of the application must include elements to address all proposed activities of this component.

Appendix:

Only 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 (REC)

When involving human subjects research, clinical research, and/or NIH-defined 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

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

Additional Cores

When preparing your application in ASSIST, use Component Type Additional Cores.

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.

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages. If required, the Data Management and Sharing (DMS) Plan must be provided in the Overall component.

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)

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

• The CL of this components must commit, and sustain, a minimum of 1.2 person months of effort. For applications with multiple CLs, a minimum effort of 0.8 person-month is required per additional Core Leader

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 component will contribute to the goals of the ADRC and outline interactions of the Additional Cores with each of the other component of the Center.

Demonstrate how the proposed component 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.

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

Place overall summaries in the approach section of each component. Describe the most important contributions to research on AD/ADRD and aging utilizing resources of the Additional Cores. Applicants should include objectives of the Additional Cores and progress in meeting them. Any developmental work carried out by the Additional Cores should also be presented.

New applications: 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.

Data Management and Sharing Plan:

The Data Management and Sharing Plan submitted to the Overall component of the application must include elements to address all proposed activities of this component.

Appendix:

Only 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 human subjects research, clinical research, and/or NIH-defined 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.

3. Unique Entity Identifier and System for Award Management (SAM)

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

4. Submission Dates and Times

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.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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.

7. Other Submission Requirements and Information

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 How to Apply Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. 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 form. 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 unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. 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, NIH. Applications that are incomplete or non-compliant will not be reviewed.

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

Applications must include a PEDP submitted as Other Project Information as an attachment. Applications that fail to include a PEDP will be considered incomplete and will be withdrawn before review.

Post Submission Materials

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

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) will not be evaluated at time of review.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project 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 project that by its nature is not innovative may be essential to advance a field.

Significance

Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Questions Specific to this FOA:

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 advancing 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? Are the scientific interactions across federally supported Center programs, NGOs, and large epidemiologic studies appropriate for the proposed ADRC? Are the provided supports for the next generation of AD/ADRD researchers--postdoctoral fellows and junior faculty who are supported through different awards-- sufficient, including resources to support the inclusion of diverse perspectives in the workforce?

How well does the proposed Center accelerate translational research across the spectrum of disease, with a focus on understanding the heterogeneity of AD/ADRD, as well as mixed dementias? How well does the proposed center identify factors influencing cognitive changes in populations most at risk for AD/ADRD? 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?

To what extent do the efforts described in the Plan for Enhancing Diverse Perspectives further the significance of the project?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? 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?

Questions Specific to this FOA:

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? Is there sufficient evidence of collaboration and interdisciplinary research among the investigators who will be associated with the ADRC? Are plans for succession/recruitment of new personnel addressed? To what extent are the leadership transition plans clearly described and feasible? Is the PD(s)/PI(s) a scientific leader experienced in the field of AD and/or other neurodegenerative disease research? Has the PD(s)/PI(s) demonstrated that they can coordinate, integrate, and provide guidance in the establishment of programs in AD research and allied areas?

To what extent will the efforts described in the Plan for Enhancing Diverse Perspectives strengthen and enhance the expertise required for the project?

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Questions Specific to this FOA:

To what extent 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?

To what extent will the efforts described in the Plan for Enhancing Diverse Perspectives meaningfully contribute to innovation?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? 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 project 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?

Questions Specific to this FOA:

How well does the proposed Center demonstrate appropriate organization and core management? How well do the organizational plans and management structures meet Center goals? Are the procedures for internal communication and cooperation among the investigators adequate? How strong are the Center's planning and evaluation strategies and activities? Do the proposed components successfully collaborate to support the Center's scientific theme(s)? Will the center's resources support new investigators joining the field?

Are the timeline and milestones associated with the Plan for Enhancing Diverse Perspectives well-developed and feasible?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Questions Specific to this FOA:

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? Are the institutional commitments and organizational status for the Center appropriate to carry out the goals of the proposed center? Are the assurances from institutional leaders that they will provide long-term stable support and facilitate research by clinician scientists appropriate? How well does the institutional commitment ensure the Center's stability and fulfillment of the Center's objectives?

To what extent will features of the environment described in the Plan for Enhancing Diverse Perspectives (e.g., collaborative arrangements, geographic diversity, institutional support) contribute to the success of the project?

As applicable for the project 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.

Protections for Human Subjects

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 the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Individuals Across the Lifespan

When the proposed project 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.

Vertebrate Animals

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.

Biohazards

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

Resubmissions

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.

Renewals

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

Revisions

Not Applicable

As applicable for the project 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.

Applications from Foreign Organizations

Not Applicable

Select Agent Research

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

Resource Sharing Plans

Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) will not be evaluated at time of review.

Reviewers will comment on whether the Resource Sharing Plan(s) (i.e., Sharing Model Organisms) or the rationale for not sharing the resources, is reasonable.

Authentication of Key Biological and/or Chemical Resources:

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.

Budget and Period of Support

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

As applicable for the component 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 CL demonstrate the capacity for leadership of the Center?

Investigator(s)

To what extent is the PD(s)/PI(s) effective in using institutionally designated authorities to manage and advance scientific objectives?

Approach

How well does the Administrative Core support the Center's organization and integrated core management? 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? What does the developmental projects and the plan for developmental projects accomplish for the Center? How does the administrative structure plan to recruit a pool of highly talented prospective scientists from diverse backgrounds? How does the organizational 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, samples to NCRAD and images to SCAN?

Clinical Core

Significance

How do the stated goals, plans, and targeted population (including justification for sample size and 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 experienced is the CL in the diagnosis of AD and related dementias? Does the CL have a record of research in some aspect of neurodegenerative diseases?

Approach

How well does the application describe how the Clinical Core, in addition to participant recruitment, provides regular evaluation according to UDS protocol, provides diagnosis, maintains a research volunteer registry that tracks number and reasons for those lost to follow-up, contributes to other related research (including clinical trials), and conducts longitudinal follow up of participants? How appropriate are the procedures for sample collection, storage, and evaluation? How appropriate are interactions with other components? Specific to interactions with the Data Management and Statistical Core, is the continuum from data content through data collection to database management and data analysis clearly described? To what extent 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 populations that are understudied in AD/ADRD research and at higher risk of being diagnosed with AD/ADRD? How clear is the description of how the UDS data will be provided in a complete manner to NACC? How appropriate and realistic are the biomarker disclosure plans and the plans for longitudinal blood sample collection?

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

Data Management and Statistical Core

Significance

Are the database and statistical services appropriate? How well will the proposed Center contribute to the goals of the ADRC, as well as the national efforts of the ADRC program? How modern is the data service and is it 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 and integrated in the system and available for sharing?

Approach

Are the data management and statistical plans appropriate and likely to support a successful and integrated ADRC? Is there statistical consultation with developmental project applicants? How well will the staff foster working relationships with the data contributors and harmonize the data collection? To what extent will data be available in a useful format for both planned and future analyses? Are appropriate data safety procedures in place? How appropriate and reasonable are the plans for timely transmission of UDS data to NACC? Is there a unified federated resource sharing hub, and how well will they be able to process requests?

Neuropathology Core

Significance

How will the Neuropathology Core contribute to the goals of the ADRC and provide a resource for other local, national, and international research activities focused on AD and other neurodegenerative diseases?

Approach

How state-of-the-art are the diagnostic methods and collection, storage (including procedures to prevent catastrophic loss), tracking and distribution of samples? How well will the identity of the participants be protected? If fluid samples are proposed in this core, is there an indication that NCRAD was consulted and a plan for biospecimen distribution would utilize this NIA resource? If there is additional autopsy proposed beyond the Clinical Core participants, how feasible are the plans and how will they contribute to the themes of the center as well as the larger research endeavor?

Outreach Recruitment and Engagement Core

Significance

How well will the Outreach Recruitment and Engagement Core interact with other components 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? Are the plans for communicating the latest research findings to the public sufficient? 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 is the description of the role of and interactions with the Community Advisory Board? 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, and do they support efforts to recruit and retain underserved and understudied participants?

How well-described and sufficient is the needs assessment? How does the proposed plan meet the needs identified? Are interactions of this core with the other cores clearly described, and 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 Outreach Recruitment and Engagement Core effectively reach heterogeneous populations?

Biomarker Core

Significance

How well does the Biomarker Core interact with other components to contribute to the goals of the ADRC as well as the national efforts of the ADRC program?

Approach

How well does the Biomarker 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, tracking and analysis methods? How likely are they to lead to new discoveries or new lines of research? If the core is imaging focused, are there plans to transmit the data to the SCAN infrastructure? How appropriate are the plans to collaborate with NCRAD and submit data to NACC?

Research Education Component

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? Is there evidence that the proposed program is distinct from other training programs that already exist in the organization? How well does the application describe the differences between the proposed program and other training programs that exist in the organization?

Investigator(s)

Is the PD(s)/PI(s) 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 Review Considerations

As applicable for the project 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.

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 prospective participants 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 and 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 online 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.

Additional Cores

Significance

How does the component contribute to the goals of the ADRC, as well as the national and international research goals focused on AD and other neurodegenerative diseases?

Approach

How does the component contribute to the specific aims of the Center? How does the component contribute to the overall strategy, methodology, and analyses of the Center? How strong are the strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented and are they appropriate? 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 component 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 component 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? Will the resources of the component support important and cutting-edge research?

2. Review and Selection Process

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 will receive a written critique.

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.

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, including the PEDP.

3. Anticipated Announcement and Award Dates

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.

Section VI. Award Administration Information

1. Award Notices

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 recipient's business official.

Recipients must comply with any funding restrictions described in Section IV.6. 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.

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

Prior Approval of Developmental Projects

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

• The recipient institution will comply with the NIH Guidance on Changes That Involve Human Subjects in Active Awards and That Will Require Prior NIH Approval.
• The recipient 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, Recipients, and Activities, including of note, but not limited to:

• Federalwide Research Terms and Conditions
• Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
• Acknowledgment of Federal Funding

If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS will be required to complete an HHS Assurance of Compliance form (HHS 690) in which the recipient agrees, as a term and condition of receiving the grant, to administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, age, sex and disability, and agreeing to comply with federal conscience laws, where applicable. This includes ensuring that entities take meaningful steps to provide meaningful access to persons with limited English proficiency; and ensuring effective communication with persons with disabilities. Where applicable, Title XI and Section 1557 prohibit discrimination on the basis of sexual orientation, and gender identity. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html

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.

• Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov.

• For information on an institution’s specific legal obligations for serving qualified individuals with disabilities, including providing program access, reasonable modifications, and to provide effective communication, see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html.

• HHS funded health and education programs must be administered in an environment free of sexual harassment, see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.

• For guidance on administering programs in compliance with applicable federal religious nondiscrimination laws and applicable federal conscience protection and associated anti-discrimination laws see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.

Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.

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 and 2 CFR Part 200.206 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

Not Applicable

3. Data Management and Sharing

Note: The NIH Policy for Data Management and Sharing is effective for due dates on or after January 25, 2023.

Consistent with the NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

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

All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan.

All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.

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 data sets 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 multi-faceted datasets (e.g., 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, the National Institute on Aging Genetics of Alzheimer's Disease Data Storage (NIAGADS), and AMP AD's 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 Institutional Review Board(IRB). A comprehensive listing of NIH data sharing repositories is available here.

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

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

Progress reports should briefly describe status of pilot projects, including data and safety monitoring, and should notify NIH of serious adverse events and unanticipated problems.

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. NIH FOAs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All recipients 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 the threshold. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113and 2 CFR Part 200.113 and Appendix XII to 45 CFR Part 75 and 2 CFR Part 200, 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 75and 2 CFR Part 200 Award Term and Condition for Recipient Integrity and Performance Matters.

Other Reporting Requirements

• The institution must submit a completed Statement of Appointment (PHS Form 2271) for each participant appointed full time for eight weeks or more or the equivalent. Grantees must submit the PHS 2271 data electronically using the xTrain system. More information on xTrain is available at xTrain (eRA Commons). An appointment or reappointment may begin any time during the budget period, but not before the budget period start date of the grant year.
• Participant Termination Notice: Within 30 days of the end of the total support period for each participant, the institution must submit a Termination Notice (PHS Form 416-7) via xTrain for each participant appointed full time for eight weeks or more, or the equivalent.

Section VII. Agency Contacts

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 submission by the due date, and post-submission issues)

Finding Help Online: https://www.era.nih.gov/need-help (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-480-7075

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

Cerise Elliott, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-496-9350
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]

Philip Smith
National Institute on Aging (NIA)
Telephone: 301-555-1212
Email: [email protected]

Section VIII. Other Information

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 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75 and 2 CFR Part 200.

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.