Part 1. Overview Information

Key Dates

No late applications will be accepted for this Notice of Funding Opportunity.

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 NOFO or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Key Definitions for This Notice of Funding Opportunity (NOFO)

AD/ADRD: Alzheimer’s disease (AD) and Alzheimer’s disease-related dementias (ADRD). ADRD include, but are not limited to, Frontotemporal dementia (FTD), Vascular Contributions to Cognitive Impairment and Dementia (VCID), Lewy Body Dementias (LBD), and Multiple Etiology Dementias (MED).

Underserved populations: Groups identified as Priority Populations in the National Institute on Aging’s (NIA's) Health Disparities Framework and/or other groups known to experience barriers to accessing needed health care services or to have inadequate health care coverage. A full description of Priority Populations can be found on NIA’s Health Disparities Framework webpage.

Medically and/or socially vulnerable populations: Residents of nursing homes and assisted living facilities, and individuals in adult day care centers or other professional care settings that serve individuals living with with AD/ADRD.

Clinical trials: NIH definition of clinical trials, which is inclusive of digital, pragmatic, hybrid, and decentralized trials.

Real-world data (RWD): Data relating to patient health status and/or the delivery of health care from a variety of sources that are collected in the context of the routine delivery of care, as opposed to data collected within a clinical trial where study design controls variability in ways that are not representative of real-world care and outcomes (FDA: Real-World Evidence, 2018). For the purpose of this NOFO, RWD sources include, but are not limited to: electronic health records (EHR); labs (e.g., blood test results); claims and billing data; registry data; natality data; mortality data; public health data; medical images (e.g., MRI, CT scans, etc.); patient-generated data in home-use settings; data generated and collected from mobile devices and wearables; and data collected from Digital Health Technologies (DHTs).

Platform: This initiative will include a federated platform with:

1. A centralized data warehouse which will integrate and create a longitudinal file for RWD from private sources, including social determinants of health (SDOH) data, sensors data (as appropriate), and consumption data (e.g., consumption data from grocery stores);
2. Federated or centralized (when point of care networks agree) access to clinical research networks/point of care networks for recruitment;
3. The ability to link data from (1) and (2) to support recruitment, long-term follow-up, and linkage to other funded studies by federal entities (e.g., surveys or clinical trials); and
4. The ability to link (1), (2), and (3) to Centers for Medicare & Medicaid Services (CMS) and other federal data for research conducted within a secure environment with appropriate Institutional Review Board (IRB) and security oversight.

The Platform can also be used for recruitment of human subjects from clinical research networks and will provide access to various software, tools and dashboards to facilitate research.

Data rights and location: Private data purchased for this platform are expected to reside in three locations, with the following data provision rights:

1. Within platform, centralized longitudinal data warehouse that is expected to cover approximately 80 percent of the U.S. AD/ADRD population and 70-90 percent of the total U.S. population;
2. Within platform, subset of data from centralized longitudinal data linked to multiple studies in a federated environment; and
3. Outside platform linked to CMS and/or other federal data sources within a federally approved Authority to Operate (ATO) enclave where data from centralized and federated platforms can be linked for completeness of the longitudinal health trajectory. Within the ATO enclave, the primary recipient of the U54 will be delegated the responsibility of providing access to any private data purchased under the cooperative agreement. The cooperative agreement recipient is required to provide and approve access to RWD across the platform and facilitate access to private RWD within the CMS enclave.

Platform users: Federal entities participating in this NOFO, their grantees or contractors, federal researchers (e.g., NIA intramural staff) associated with these entities, and users accessing the ATO enclave.

1. Background

NIA’s Strategic Directions for 2020 to 2025 include the goal to understand health disparities related to aging and develop strategies to improve the health status of older adults in diverse populations. Objectives to achieve this goal include developing and implementing strategies to increase inclusion of underrepresented populations in aging research, and identifying and understanding the environmental, social, cultural, behavioral, and biological factors that create and sustain health disparities among older adults. There is tremendous opportunity to leverage RWD to support health disparities research and improve the inclusion of diverse populations in the research process. This NOFO’s recipient must engage in purposeful strategies to address racial and ethnic disparities when incorporating data sources and studying health outcomes. As data scientists and shepherds of these large datasets, the recipient must also recognize their role in being good data stewards, which includes being aware of biases that are inherent to certain data sources. The development of a Platform that does not address health disparities risks perpetuating or exacerbating them.

NIA and NINDS have supported research that found AD and VCID to be more prevalent among African Americans and Hispanics than among other ethnic groups in the U.S. Despite the passage of the National Alzheimer’s Project Act in 2011, there is still an incomplete understanding of the mechanisms causing AD, ADRD, and AD/ADRD disparities, and few FDA-approved treatments, including diagnostics. Furthermore, many of the studies and clinical trials examining AD/ADRD are conducted on individuals who do not adequately represent the populations experiencing disproportionately high rates of AD/ADRD, notably at the time of regulatory approval of novel technology, devices, and medications. Scientific advancement is needed to develop effective interventions to diagnose, delay, prevent, and treat AD/ADRD. Transforming the AD/ADRD research enterprise requires addressing one of the most prevalent and costly problems in AD/ADRD research: lack of data accessibility and links between complementary data sources that capture information from larger, more inclusive, and diverse populations participating in research funded by NIA. Data accessibility is particularly important for aging and AD/ADRD research because data sufficient to answer pressing scientific questions cannot be captured solely through one discrete data source given: (1) AD/ADRD’s unique ethical considerations; (2) insufficient understanding of if and how AD/ADRD can be prevented and when prevention interventions must begin; and (3) the long duration of care typically required by AD/ADRD. A central platform for data access would help researchers evaluate therapeutic treatments and behavioral interventions more rapidly, and at lower cost.

RWD for healthcare research can be used for research purposes to reduce costs and participant burden while increasing research efficiency and the participation of diverse patient groups who have historically been excluded from healthcare research for various reasons, including ineffective recruitment protocols. Increased accessibility and usability of RWD, which are already prevalent in the private sector, may lead to the development of high-impact, scalable interventions that can be rapidly tested within a few months to a few years (instead of decades) to improve health outcomes for older adults and persons with dementia. However, as cited by presenters at the NIA-funded stakeholder workshop Gaps and Opportunities for Real-World Data Infrastructure, accessing RWD is a major challenge faced by researchers, including researchers studying AD/ADRD and aging. Most data are limited to a singular and isolated source, which limits many types of healthcare research that require analysis of multiple data sets. Private industry data are largely inaccessible for academic research because of the differing legal standards and expectations for accessing and sharing data.

2. Specific Objectives of the Platform

This Platform aims to transform the AD/ADRD research enterprise by providing a data infrastructure as a service to the research community. The Platform has the following goals:

1. Improve applicability and generalizability of findings through larger datasets that include more diverse populations;
2. Capture more complete information through linking a variety of data sources;
3. Increase the speed at which scientific questions can be answered;
4. Improve researchers ability to answer questions that cannot be feasibly or readily answered via clinical trial; and
5. Facilitate clinical trial recruitment and research participation.

The Platform will improve data accessibility and quality, build investigator capacity, support AD/ADRD research and trial design using RWD, and maintain the resource and knowledge base for AD/ADRD research using RWD through the following features:

• Centralized data management and governance system that houses and integrates various data sources and provisioning rights;
• Federated data management system to integrate data from private partners and facilitate recruitment for federally funded studies;
• Clearly defined goals and objectives for using RWD to address health disparities through recruitment innovation, engagement with representatives from communities that have been historically underrepresented in research, and facilitation of research on populations from various backgrounds, including from backgrounds understudied in AD/ADRD research;
• Robust community engagement throughout platform development and implementation;
• Development and dissemination of clearly defined ethical standards for platform development, implementation, data access, and use of data for recruitment;
• Development and dissemination of trial innovation and novel methods of using RWD for Platform users;
• Development of digital and artificial intelligence tools and integration of such tools to facilitate recruitment and other activities within the platform (e.g., clinical trial risk management);
• Recruitment services that leverage RWD to enhance the size and diversity of sampling frames; and
• National competitions for incubator projects, including research studies, rapid learning research projects, challenge prizes, clinical trials, and AD/ADRD registries

These features will support researchers to: (1) securely access health data (e.g., claims, labs, genetics, imaging, consumption, contextual, and sensor data) to gain insight on AD/ADRD disease trajectory in a secure zero trust cloud computing environment; (2) access a more diverse pool of individuals for recruitment (i.e., Recruitment as a Service) for clinical research (e.g., clinical trials, AD/ADRD care interventions, and other human subject studies); (3) collaborate with health care and community health providers to enable rapid innovative trials; and (4) prepare and analyze sensitive RWD through secure cloud workspaces while protecting privacy of the study participants.

The NIA RWD Platform must be responsive to concerns expressed by some communities that have been historically marginalized and underrepresented in clinical research (e.g., African Americans; Hispanics/Latinos/Latinx; Native Americans/American Indians; Asian and Pacific Islanders). This project must take appropriate and thorough measures to inform community representatives of any plans to procure from third-party real-world sources of de-identified clinical data used for indefinite purposes well in advance of conducting research. The Platform must take appropriate measures to facilitate programmatic accountability in seeking the community representatives' input on what they perceive to be equitable and fair processes adopted to inform the use of the de-identified data for indefinite purposes. This Platform will adhere to the Tribal Health Research Office’s Tribal Consultation Policy and the Office of Science Policy’s policy for Engaging Tribal Nations.

3. Organizational Structure

The Platform will use in-house and external scientific expertise (see Section I.4. for Experience and Knowledge ), and applications are expected to contain letters of support from data vendors. At minimum, the Platform will be comprised of eight core components: (A) Administrative Core; (B) Clinical Research Networks Core; (C) Community Engagement, Data Privacy, and Ethics Core; (D) Business Case and Translation Core; (E) Health Disparities Research and Recruitment Innovation Core; (F) Trial Innovation Core; (G) Platform Access, Data Quality, and Integration Core; and (H) Incubator Core (Clinical Trial Optional). See Section IV for full details and instructions.

Applicants are encouraged to address the objectives described in Section I.2 in the eight Cores, but also have an option to propose two investigator-initiated Optional Cores (I&J) relevant to AD/ADRD research.

A. Administrative Core: Will serve as the central organizing function and provide coordination support, track objectives and key results (OKRs) and key performance indicators (KPIs) across Cores for each year, facilitate training for uptake of the infrastructure, and develop a researcher network.

B. Clinical Research Networks Core: Will nurture existing health networks and incorporate new health networks by executing partnerships. Will establish a virtual trial recruitment platform that is accessible to NIA-funded researchers and facilitate inclusive and diverse recruitment by the second year of the award for NIA-funded studies.

C. Community Engagement, Data Privacy, and Ethics Core: Will engage with diverse stakeholders and address data privacy and ethical issues such as algorithm bias, re-identification risk, and consenting for digital, decentralized, virtual, pragmatic, and clinical trials in a collaborative manner. Maintaining stakeholder engagement and ethical practices while engaging various underrepresented communities is paramount for this initiative.

D. Business Case and Translation Core: Will handle financial, regulatory, and legal aspects of the platform, while developing regulatory and legal templates for platform access and utilization. Will serve as the point of contact for public-private partnerships and develop business cases to broaden the clinical research network and engagement with the research community.

E. Health Disparities Research and Recruitment Innovation Core: Will develop strategies and programs to leverage the RWD platform to facilitate inclusive and diverse recruitment in NIA-funded studies. Will actively facilitate, support, and conduct research examining health disparities in AD/ADRD populations, and prepare reports highlighting methods of, and use cases for, using the platform to address the causes and consequences of disparate AD/ADRD care across the United States.

F. Trial Innovation Core: Will develop innovative methods and advanced cutting-edge informatics for digital, decentralized, virtual, pragmatic, and clinical trials serving older adults and their caregivers. Will cultivate the clinical trial workforce.

G. Platform Access, Data Quality, and Integration Core: Will act as the central hub for multimodal data access for clinical trials/research and analyses, develop protocols and solutions to address data quality and missingness, and link CMS claims data.

H. Incubator Core (Clinical Trial Optional): Will hold national competitions to fund and facilitate research projects (e.g., generating real-world evidence (RWE) of a new FDA-approved AD/ADRD drug, novel recruitment services, AD/ADRD registries, generating RWE on marketed devices that have been granted FDA Breakthrough Device designation, health surveillance, rapidly deploying clinical trials in real-world settings, expansion of clinical research networks). Potential Incubator Core projects can range in scope and specific goals but must address milestones specified in the NIH AD/ADRD Research Implementation Database.

I. Optional Core

Applicants have an option to propose two investigator-initiated Cores which will benefit the overall Platform. These Cores must be relevant to AD/ADRD research.

J. Optional Core

Applicants have an option to propose two investigator-initiated Cores which will benefit the overall Platform. These Cores must must be relevant to AD/ADRD research.

4. Experience and Knowledge

Platform staff are expected to have significant experience and knowledge in the following areas:

1. Regulatory requirements for conducting AD/ADRD research with the use of RWD, and experience conducting AD/ADRD research that complies with applicable regulations;
2. Conducting multi-site research studies;
3. Extracting information from a wide range of data sources (e.g., EHRs, claims, SDOH data, sensor data, etc.);
4. Bioinformatics and data linkage experience across three or more point of care networks;
5. Familiarity with ethical issues related to AD/ADRD clinical research, consents, clinical care, quality improvement, population health, surveillance, and their boundaries;
6. Experience in building digital and artificial intelligence tools for integration with RWD platform;
7. Working collaboratively with stakeholders including people living with AD/ADRD, research participants, researchers, practitioners, hospital and research informatics and technical personnel, advocacy groups, caregivers, representatives from communities that have been historically underrepresented in research, and senior managers of health care and research organizations;
8. Knowledge of workflows and health care system practices;
9. Strengths and weaknesses of current data models, algorithms, and approaches used by various networks and studies to define clinical phenotypes, extract information, define endpoints, and discover errors in data from health care systems;
10. Project management experience in taking a research question from idea through implementation;
11. Managing federated and centralized data systems, and integrating multiple data sources;
12. Study design and statistical methods;
13. Novel study designs and methods; and
14. Using creativity and innovation to promote participation by communities that have been historically underrepresented in research.

It is expected that the Platform will engage nationally with others working in similar areas to stay abreast of emerging experience, regulations, and technical advances (e.g., N3C) that impact the ability for research to be conducted in health care settings. This could include other NIH-funded AD/ADRD projects, but also other federally and privately funded efforts, such as projects funded by the Center for Medicare & Medicaid Innovation (CMMI) and/or private foundations.

The Platform will be responsible for facilitating harmonization and sharing of tools and approaches that support AD/ADRD research and clinical trials. Applicants must be willing to cooperate with the NIH in the development and design of research approaches, methods, processes, policies, and tools used in this program. Applicants should have documented prior experience of working collaboratively in research consortia and other collaborative projects to accomplish shared goals.

The activities of this award demand complex management and coordination, as many different entities will ultimately participate in the Platform. Therefore, the PD(s)/PI(s) must commit and sustain at least 9 person-months of effort per year throughout the award to manage this complex Platform. It is anticipated that a multi-PI structure may be proposed; in such structures, each PI should contribute a minimum of 6 person-months of effort per year. Multi-PD/PI leadership is highly encouraged.

Core Directors must commit and sustain 6 person-months of effort per year to manage cross-institutional and cross-organizational activities across all years of funding. If a multi-Core Director structure is proposed, Core Directors should contribute a minimum of 4 person-months of effort per year (except for the Platform Access, Data Quality, and Integration Core). Core Director(s) for the Platform Access, Data Quality, and Integration Core must commit and sustain 6 person-months of effort to manage these cross-institutional and cross-organizational activities across all years of funding, regardless of whether a multi-Core Director structure or a singular Core Director structure is proposed.

The Executive Director and Deputy Executive Director for the Platform must each contribute full-time effort across all years of funding.

Applications must:

• Describe how the investigators will collaborate with the recipients of Incubator Core research projects.
• Describe how the investigative team is up to date on the changing landscape of data science research and participant protection regulations.
• Provide evidence of how the planned collaboration will work among a team with potentially very different backgrounds.

5. AD/ADRD Research Platform Program Governance

Platform Steering Committee

A Platform Steering Committee will be established to help guide the PDs/PIs, address issues that span across all projects, provide input towards the policies and processes of the Platform, and assist in dissemination of policies and processes that enable research in partnership with health care systems, their patients, and practitioners. The Steering Committee will be composed of a representative from NIA-funded studies, the PDs/PIs of the Platform, representatives from the Cores, Project Leads of incubator projects, seven external members which PDs/PIs will appoint with consultation with NIA, and the NIA Projects Scientist(s). All members are expected to attend and participate actively in all Steering Committee activities. The combined vote of NIH/NIA membership may never exceed 40 percent. Applications must refrain from identifying the seven external members in the application. See Section VI for full information and details.

AD/ADRD RWD Platform External Advisory Panel

An External Advisory Panel (EAP) for the Platform will be established to review the progress of all components of the program, evaluate progress towards key milestones (as described in section I.7) and provide recommendations to the Steering Committee and PDs/PIs. NIA will appoint members of the EAP. Membership may include study investigators, representatives from relevant federal agencies, and independent scientific experts in areas appropriate to the multidisciplinary content of the Platform. The EAP is expected to have 10-15 permanent members; however, membership may expand permanently or on an ad hoc basis as needed. The EAP will meet quarterly each year, either virtually or in person. After each meeting, the EAP will make recorded programmatic recommendations to NIA, the Steering Committee, and the PDs/PIs. These recommendations may include revising KPIs, key risk indicators (KRIs), and/or milestones (see Section I.7 for more details), and/or Core consolidation for NIA to consider. At the end of Year 4, the EAP will provide recommendations for the continuation, continuation with conditions, or termination of the Platform, including possible models for sustainability, if continuation is recommended.

NIA will appoint an executive secretary who will take notes and facilitate any travel for any in-person meetings. Additionally, applications should budget appropriately for secretarial support for notetaking and travel services for all other Platform activities, including secretarial services for Steering Committee meetings. See Section VI for full information and details.

Staff in the Office of Planning, Analysis, and Evaluation at NIA may evaluate the Platform and may provide recommendations for continuation of the Platform.

6. Consortium Requirement

Consortium Agreement Requirement

Applications that lack a consortium agreement at the time of submission will be considered incomplete and will not be reviewed. The consortium agreement should bring together multiple RWD providers that are willing to participate in this Platform. The application must contain letters of support indicating institutions willing to join the Platform (if funded by NIA in the first year), minimally from large pharmacy chains and health systems which will form clinical research networks. Starting in Year 2, the application must show plans, and demonstrate the ability (e.g., via letter of support from future collaborators indicating their willingness to participate in the Platform), to bring in additional point of care network partners (e.g., health care systems, home health care providers, pharmacy chains, physician-based networks, outpatient clinics, memory clinics, federally designated health centers, data vendors, hospital networks, etc.). It is expected that by the end of Year 1, RWD from private data vendors will be integrated and made available for research, and by Year 4, the Platform will be widely accessible to Platform users for recruitment and secondary data analyses.

7. Milestones

This grant will include milestones that must be met at the end of Years 1, 2, and 3 of the award. If milestones are not achieved, as determined by an internal NIA assessment of recipient progress informed by the EAP’s recommendations, NIA can choose to terminate the award, provide a mid-project extension (without additional funds), or modify aspects or conditions of the Platform at NIA’s discretion. The EAP will evaluate progress towards these milestones along with KPIs and KRIs, which will result in a report that the NIA RWD Planning Group will present to the National Advisory Council on Aging each year. Applications may suggest additional milestones for consideration by NIA program staff and peer reviewers.

Year 1 Milestones include:

1. Propose Steering Committee members to NIA program staff within the first 2 weeks of the award.
2. Establish a public-facing website within the first month of the award. The website should minimally include an overview of Platform goals and projected timelines when users can access the Platform, as well as Platform development across all cores.
3. Data agreements executed with private data vendors within the first 3 months of the award.
4. Data governance operating model developed within the first 6 months of the award (centralized data access; federated data access with point of care networks within the clinical research network; access to CMS data linked with centralized data).
5. Core ethical principles for data sharing established within the first 6 months.
6. Conduct integration, linkage, and data harmonization of RWD within the first 9 months.
7. Beta test the Platform’s data accessibility with the research community by Month 10.
8. Estimate population coverage (i.e., without duplicates) of the U.S. population by AD/ADRD conditions and representativeness in the centralized database and clinical research networks by Month 11.
9. Present findings from community engagement efforts to NIA program staff by Month 6. Periodic community engagement (e.g., every 2 months) of key stakeholders must inform the development of the platform and should include outreach to representatives from communities that have been historically unrepresented in research, advocacy groups, AD/ADRD patients and their caregivers, and the Tribal Health Research Office by end of Year 1.
10. Issue a Request for Information (RFI) for potential research projects funded under the Incubator Core by Month 6.
11. Issue Notice for National Competition (within the Incubator Core described in Section IV) by Month 9.
12. Provide NIA program staff quarterly progress updates on KPIs and KRIs.
13. Provide NIA program staff an internal evaluation of progress towards goals and the milestones specified in this application (or added by NIA program staff) by the end of Year 1.

Year 2 Milestones include:

1. Maintain and track data agreements with private data vendors and add new data sources.
2. Establish AD/ADRD registry by Year 2 (Y2) Month 9.
3. Facilitate access and usage of the registry data for researchers by the end of Y2.
4. Beta test the recruitment of research subject via the platform’s clinical research networks by Y2 Month 10.
5. Provide NIA program staff a report detailing how Clinical Research Networks (CRNs) were expanded each quarter.
6. Issue an RFI for potential research projects funded under the Incubator Core by Y2 Month 3.
7. Issue last year’s National Competition winner awards by Y2 Month 2.
8. Issue at least one Notice for National Competition (within the Incubator Core described in Section IV) by Y2 Month 6, and issue the resulting awards by Y2 Month 9.
9. Provide NIA program staff quarterly progress updates on KPIs and KRIs.
10. Provide NIA program staff an internal evaluation of progress towards key objectives and milestones specified in this application (or added by NIA program staff) by the end of Y2.
11. Initiate linkages of RWD to two NIA-funded studies by Y2 Month 12.

Year 3 Milestones include:

1. Facilitate broad accessibility (e.g., data analyses, recruitment) of the Platform to Platform users by Y3 Month 11.
2. Expand linkages of RWD to NIA-funded studies by the end of Y3 Month 9.
3. Expand CRNs through each quarter.
4. Submit at least one RFI soliciting ideas for large incubator projects exceeding $1 million in direct cost and not defined in this NOFO.
5. Provide NIA program staff quarterly progress updates on KPIs and KRIs.
6. Provide NIA program staff an internal evaluation of progress towards key objectives and milestones specified in this application (or added by NIA program staff) by the end of Year 3.

8. Non-Responsiveness Criteria

The following types of applications will be considered non-responsive and will be withdrawn prior to review:

1. Applications without a clear vision for how the Platform will address health disparities.
2. Applications that do not provide a plan for how the Platform will capture 70-90% of the total U.S. population and 80% of the U.S. AD/ADRD population by the end of Year 3.
3. Applications that propose activities that only serve investigators at one or two institutions, rather than the field at large.
4. Applications that do not provide a plan for how the Platform will facilitate the recruitment of diverse populations.
5. Applications that include plans to conduct definitive multicenter randomized clinical trials. Please note that delayed onset trials may be permitted under the Incubator core.
6. Applications that lack a consortium agreement.
7. Applications that do not provide a Data Management and Sharing Plan.
8. Applications that do not address the required Milestones for Year 1, Year 2, and Year 3.

9. Clinical Research Operations Management System

NIA supports a central resource to NIA staff and extramural investigators to facilitate/support the conduct and management of clinical research. This resource, the Clinical Research Operations Management System (CROMS), is a comprehensive data management system to support the business functions, management, and oversight responsibilities of NIA grants that support the conduct of clinical research with human subjects. It is the expectation by NIA that all successful applicants will interface, integrate, or adapt their information system(s) and processes to interact with existing and future components of the CROMS as necessary, including the use of CROMS data templates as specified.

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

Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs.

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 NOFO.

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

3. Additional Information on Eligibility

Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

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 NOFO. See the administrative office for instructions if planning 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 notice of funding opportunity 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 IC staff to estimate the potential review workload and plan the review.

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

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

The letter of intent should be sent to:

Partha Bhattacharyya, Ph.D.
National Institute on Aging (NIA)
Email: [email protected]

Page Limitations

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

Instructions for the Submission of Multi-Component Applications

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

The application should consist of the following components:

• Overall: required, maximum 1
• Administrative Core: required, maximum 1
• Clinical Research Networks Core: required, maximum 1
• Business Case and Translation Core: required, maximum 1
• Community Engagement, Data Privacy, and Ethics Core: required, maximum 1
• Health Disparities Research and Recruitment Innovation Core: required, maximum 1
• Trial Innovation Core: required, maximum 1
• Platform Access, Data Quality, and Integration Core: required, maximum 1
• Incubator Core: required, maximum 1
• Optional Investigator-Initiated Core 1: optional, maximum 1
• Optional Investigator-Initiated Core 2: optional, maximum 1

Overall Component

When preparing the 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/Performance Site Locations (Overall)

Enter primary site only.

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 NOFO) for the entire application.

Personnel must have the appropriate breadth of expertise and experience to develop and manage the Platform. This includes, but is not limited to, experience with the following:

1. Regulatory requirements for conducting AD/ADRD research with the use of RWD, and experience conducting AD/ADRD research that complies with applicable regulations;
2. Conducting multi-site research studies;
3. Extracting information from a wide range of data sources (e.g., EHRs, claims, SDOH data, sensor data, etc.);
4. Bioinformatics and data linkage experience across three or more point of care networks;
5. Familiarity with ethical issues related to AD/ADRD clinical research, consents, clinical care, quality improvement, population health, surveillance, and their boundaries;
6. Experience in building digital and artificial intelligence tools for integration with RWD platform;
7. Working collaboratively with stakeholders including people living with AD/ADRD, research participants, researchers, practitioners, hospital and research informatics and technical personnel, advocacy groups, caregivers, representatives from communities that have been historically underrepresented in research, and senior managers of health care and research organizations;
8. Knowledge of workflows and health care system practices;
9. Strengths and weaknesses of current data models, algorithms, and approaches used by various networks and studies to define clinical phenotypes, extract information, define endpoints, and discover errors in data from health care systems;
10. Project management experience in taking a research question from idea through implementation;
11. Managing federated and centralized data systems, and integrating multiple data sources;
12. Study design and statistical methods;
13. Novel study designs and methods; and
14. Using creativity and innovation to promote participation by communities that have been historically underrepresented in research.

It is expected that the Platform's leadership will engage nationally with others working in similar areas to stay abreast of emerging experience, regulations, and technical advances (e.g., N3C) that impact the ability for research to be conducted in health care settings. This could include other NIH-funded AD/ADRD projects, but also other federally and privately funded efforts, such as projects funded by the CMMI and/or private foundations.

The Platform will be responsible for facilitating harmonization and sharing of tools and approaches that support AD/ADRD research and clinical trials. Applicants must be willing to cooperate with the NIH in the development and design of research approaches, methods, processes, policies, and tools used in this program. Applicants should have documented prior experience of working collaboratively in research consortia and other collaborative projects to accomplish shared goals.

Applications must describe the proposed leadership approach, staffing, governance and organizational structure. The PD/PIs must have demonstrated an ongoing record of accomplishment in support of coordination, collaboration, and communication of large national-level inclusive Platforms, networks or consortia.

The activities of this award demand complex management and coordination, as many different entities will ultimately participate in the Platform. Therefore, the PD(s)/PI(s) must commit and sustain at least 9 person-months of effort per year throughout the award to manage the Platform. It is anticipated that a multi-PI structure may be proposed; in such structures, each PI should contribute a minimum of 6 person-months of effort per year. Multi-PD/PI leadership is highly encouraged.

Core Directors must commit and sustain 6 person-months of effort per year to manage cross-institutional and cross-organizational activities across all years of funding. If a multi-Core Director structure is proposed, Core Directors should contribute a minimum of 4 person-months of effort per year (except for the Platform Access, Data Quality, and Integration Core). Core Director(s) for the Platform Access, Data Quality, and Integration Core must commit and sustain 6 person-months of effort to manage these cross-institutional and cross-organizational activities across all years of funding, regardless of whether a multi-Core Director structure or a singular Core Director structure is proposed.

The Executive Director and Deputy Executive Director for the Platform must each contribute full-time effort across all years of funding.

Applications must:

• Describe how the investigators will collaborate with recipients of the Incubator Core research projects and clinical trials.
• Describe how the investigative team is up to date on the changing landscape of data science research and participant protection regulations.
• Provide evidence of how the planned collaboration will work among a team with potentially very different backgrounds.

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.

The PD(s)/PI(s) must commit and sustain at least 9 person-months of effort per year throughout the award to manage this complex Platform. It is anticipated that a multi-PI structure may be proposed; in such structures, each PI should contribute a minimum of 6 person-months of effort per year. Other key personnel or leadership roles, including an Executive Director and Deputy Executive Director, must contribute 12 person-months of effort per year across all years of funding.

Core Directors must commit and sustain 6 person-months of effort per year to manage cross-institutional and cross-organizational activities across all years of funding. If a multi-Core Director structure is proposed, Core Directors should contribute a minimum of 4 person-months of effort per year (except for the Platform Access, Data Quality, and Integration Core). Core Director(s) for the Platform Access, Data Quality, and Integration Core must commit and sustain 6 person-months of effort to manage cross-institutional and cross-organizational activities across all years of funding, regardless of whether a multi-Core Director structure or a singular Core Director structure is proposed.

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)

Specific Aims:

Describe the aims of the overall Platform and outline how the different core components will contribute to these aims.

Research Strategy:

Focusing on the Platform as a whole, applications should comprehensively describe how they will accomplish the following goals of this NOFO: (1) improve applicability and generalizability of findings through larger datasets that include more diverse populations; (2) capture more complete information through linking a variety of data sources; (3) increase the speed at which scientific questions can be answered; and (4) improve researchers ability to answer questions that cannot be feasibly or readily answered via clinical trial. Applications must explain how the Platform will accomplish these goals while maintaining a patient-centered approach and mission.

Specifically, applications must describe how this Platform will provide tools, resources, and data that promote research studying health disparities in the AD/ADRD population and beyond. As data scientists and shepherds of these large datasets, the recipient must also recognize their role in being a good data steward, which includes being aware of biases that are inherent to certain data sources. The development of a Platform that does not address health disparities risks perpetuating or exacerbating them. Applications must explain how the Platform will mitigate this risk and serve communities that have been historically underrepresented in research.

Applications must describe how the Platform will provide national leadership and engage stakeholders (including people living with AD/ADRD, research participants, researchers, practitioners, hospital and research informatics and technical personnel, advocacy groups, caregivers, representatives from communities that have been historically underrepresented in research, and senior managers of health care and research organizations) when developing and implementing the Platform, and when designing the Platform's plan to advance data access and integration for Platform users. In addition, applications must detail how findings resulting from the Platform will be translated into clinical practice and RWE that can impact the health of, and policy for, people living with AD/ADRD and their caregivers.

Applications must detail the centralized and/or federated systems proposed for the Platform, and how Locations 1 and 3 (see section IV, Platform Access, Quality, and Integration Core for more details about Platform locations) will include enough data to cover 30-40% of the U.S. AD/ADRD population by Year 1, 50% of the U.S. AD/ADRD population by Year 2, and 80% of the U.S. AD/ADRD population by Year 3. Applications must detail which data sources can be feasibly included in the Platform, and how these sources can include representative coverage of the U.S. population.

Applications must describe how the different components of the Platform will interact to help accomplish its aims, how the approaches of the core components complement each other or are interdependent, and the mechanisms to be used in assessing progress toward the Platform's goals. Where appropriate, provide timelines and organizational charts.

Applications must explain how the Platform will be made widely available and easily accessible to a wide range of researchers by Year 4 of the award.

Applications must describe how the project will challenge and seek to impact current data management and research implementation strategies by developing novel approaches and tools, and describe how these approaches and tools will be disseminated for broader use by Platform users. Applications must describe the innovative elements, as appropriate, that enhance the Platform’s potential to advance scientific knowledge and clinical practice.

Applications must detail plans to leverage RWD to enhance representative recruitment in research and clinical trials.

Applications must address all requirements specified in this NOFO. To gauge whether all requirements are met, applicants are encouraged to review the information provided under the 8. Non-Responsiveness Criteria heading in Section 1.

Letters of Support:

Include letters of support/agreement for any consortium agreements, data vendors, point of care networks, pharmacy chains, private partnerships, clinical sites, collaborative/cooperative arrangements, subcontracts or consultants. For activities to be conducted at an institution other than the applicant institution, a letter of assurance or comparable documentation, signed by the collaborator as well as the institutional officials, must be submitted with the application.

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

The following modifications also apply:

This NOFO REQUIRES the sharing of ALL resources with a broad availability of policies, practices, materials, and tools to facilitate collaboration, reuse, and replication, as appropriate and consistent with achieving the goals of the program, unless prohibited under Bayh-Dole Regulations.

It is imperative that the data collection and permission/consents are set up in such a manner with respondents and institutions that will allow broad use of resource sharing.

This NOFO encourages sharing software and codes that are developed or modified to accomplish the aims of this program, unless prohibited under Bayh-Dole Regulations.

This NOFO requires adoption of Findable, Accessible, Interoperable, and Re-usable (FAIR) data principles when addressing each application component and encourages PD/PIs to consider obtaining a Core Trust Seal by the third year of the award.

Applications must address the following items:

• Indicate the repository/consortium/enclave where they will place the resource or have a clear plan and capacity to share from their own site(s). Working with an external repository or through a consortium can be advantageous for many investigators.
• Describe and justify the timetable to release the resource. Generally, the referenced resource from a publication should be made available by the on-line publication date unless NIH policy specifies an earlier date. Investigators should justify exceptions to that timing.
• Identify any restrictions on sharing and justify them. Restrictions might include, for example, no commercial use of the resource, only qualified users may access the material, or, no attempt to reveal personal or private information may be made. Investigators may also set different levels of access, for example, for expert users and novice users.
• Describe how all materials (e.g., real-world data sources from multiple vendors, clinical trial protocols, and all resources generated from this NOFO) will be transferred to a new entity at the end of the project period to enable long-term follow up with survey respondents and institutional representatives.
• To ensure that qualified users will have easy access to the resource, describe either (1) how the investigators will curate the resource, what documentation they will provide about the resource and the format in which it will be provided, and whether any resource will be held back, and (2) if/how the investigators will work with the identified repository/consortium/enclave to prepare the resource and documentation.
• Address considerations of privacy-preserving linkages and how such keys will be transferred to various parties (e.g., consortium members, researchers) preserving PII for future follow-up.
• Address timely (i.e., within 30 days of NIA notice) execution of the material transfer agreement within and across the Platform, and with third parties if directed by NIA. The material transfer agreement includes, but is not limited to, transfer of sampling frame and all resources generated by the cooperative agreement.

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. If required, the Data Management and Sharing (DMS) Plan must be provided in the Overall component.

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.
• It is imperative that the data collection and permission/consents are set up in such a manner with respondents and institutions that will allow broad use of data sharing.
• This NOFO requires adoption of FAIR data principles when addressing each application component and encourages PD/PIs to consider obtaining a Core Trust Seal by the third year of the award.
• Applications must address the following items:
  • Indicate the repository/consortium/enclave where the investigators will place the data or have a clear plan and capacity to share from their own site(s). Working with an external repository or through a consortium can be advantageous for many investigators.
  • Describe any transformations to the data (e.g., application of algorithms, tools) that will be applied to the data in preparing them to be shared.
  • Describe and justify the timetable to release the data. Generally, the data from a publication should be made available by the on-line publication date unless NIH policy specifies an earlier date. Investigators should justify exceptions to that timing.
  • Identify any restrictions on sharing and justify them. Restrictions might include, for example, no commercial use of the data, only qualified users may access the material, or, no attempt to reveal personal or private information may be made. Investigators may also set different levels of access, for example, for expert users and novice users.
  • Describe how all materials (e.g., real-world data generated from this NOFO) will be transferred to a new entity at the end of the project period to enable long-term follow up with survey respondents and institutional representatives.
  • For studies involving human participants, describe how the investigators will mitigate deidentification risk with the data, and generally how they will secure the personal and private information of the participants; this includes a condition on the end-user certifying that no attempts to identify participants from the de-identified data will be made.
  • To ensure that qualified users will have easy access to the data, describe either (1) how the investigators will curate the data, what documentation they will provide ( metadata ) and the format in which it will be provided, and whether any data will be held back, and (2) if/how the investigators will work with the identified repository/consortium/enclave to prepare the data and documentation.
  • Address considerations of privacy-preserving linkages and how such keys will be transferred to various parties (e.g., consortium members, researchers) preserving PII for future follow-up.
  • Address timely (i.e., within 30 days of NIA notice) execution of the material transfer agreement within and across the Platform, and with third parties if directed by NIA. The material transfer agreement includes, but is not limited to, transfer of data, sampling frame, and all data generated by the cooperative agreement.
  • Explain how the complete collection of metadata (data about the data) will be provided.
  • Explain how the complete variable metadata (variable and value labels) will be provided either directly in the data file(s) or in supporting syntax file(s).
  • Explain how documentation (e.g., codebook, questionnaire, and user guide) will be provided and how the data will be made searchable.
  • If applicable, specify how data will be provided via tiered access (e.g., public use file versus data access via enclave) based on identification risk.
  • Present milestones for various releases of data resulting from this NOFO.
  • Present a plan to review restricted data within seven business days of a data user's request.

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.

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.

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 Project 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 (Administrative Core)

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

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)

Specific Aims: State the goals of the proposed Administrative Core concisely and summarize the expected outcome(s).

A critical aspect of the Platform's administrative function is establishing and effectively managing a range of collaborations and partnerships. In the Research Plan:

• Provide one or more examples of effective collaborations the PD/PI has established, including descriptions of the motivation for initiating the collaboration, the goals defined for the collaboration, and the outcomes achieved; and
• Describe processes for problem-solving, communication, and prioritization of work.

Research Strategy:

Applications must address the following required objectives and features of this Core. Applicants are encouraged to provide any additional objectives or features as appropriate. Required objectives and features include:

1. Ensuring completion of stated milestones.
2. Providing a public website for communication and sharing of activities, events, trainings, publications, and program resources.
3. Hosting AD/ADRD RWD Grand Rounds.
4. Convening an annual meeting that includes Cores, Steering Committee members, EAP members, and NIA program staff.
5. Managing quarterly meetings with the Steering Committee, including by providing a meeting summary to NIA program staff.
6. Coordinating and collaborating with Core leaders to facilitate the alignment of tactical and strategic process goals.
7. Providing organizational and logistical support for Cores, Project Scientist(s), Steering Committee activities, and EAP activities.
8. Managing the Resource Sharing Plan, as listed in Section IV.2.
9. Developing high-quality communication materials, including guidance documents, training materials, promotional materials, and presentations.
10. Producing quarterly (during Y1-Y3) and biannual (during Y4-Y6) progress reports for submission to NIA program staff.
11. Developing and tracking OKRs, KPIs, and KRIs applicable to each Core, and providing the resulting data monthly to NIA program staff.
12. Creating dashboards highlighting KPIs and KRIs associated with execution risk of the platform (e.g., risk associated with execution of data agreements, risk associated with data reviews, risk associated with using clinical research networks).
13. Providing NIA program staff an annual internal evaluation report that evaluates progress towards study goals, milestones, KPIs, and KRIs.
14. Facilitating, creating, and supporting the development and execution of ALL material transfer agreements within 30 days of NIA notice.

In addition to explaining how the Administrative Core will develop, track, and report the OKRs, KPIs, and KRIs applicable to each Core (see 11 above), applications must address the following required Administrative Core KPIs and KRIs:

• Number of meetings, workshops, and trainings held annually
• Speed at which events are conducted and posted to the website
• Timely adherence to milestones (as listed in Section I.7)
• Number of grantees accessing the Platform each month
• Adherence to Resource Sharing Plan and Data Management and Sharing Plan across all Cores
• Response time by Authorized Organizational Representative (AOR), PD/PI, core leaders, and the legal team at the prime institution with individual subcontractors and NIA
• Risk indicators to ensure safe implementation of the Platform, including clear documentation of standard operating procedures (SOPs) for the following: noncompliance to Platform data privacy and security standards; number of data or software security breaches; breach of identifiable information; data leakage; IT infrastructure interruptions; lack of representative coverage in data available for access; and bias in algorithms developed by the Platform

Applications are encouraged to provide additional KPIs/KRIs applicable to each Core.

Letters of Support: Only letters of support specific to "Administrative Core" should be attached to this section.

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 Research Networks Core

When preparing your application, use Component Type CRN Core.

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

SF424 (R&R) Cover (Clinical Research Networks 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 Research Networks Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Clinical Research Networks 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 Research Networks 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 (Clinical Research Networks Core)

In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project 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 (Clinical Research Networks Core)

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

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 Research Networks Core)

Specific Aims: State the goals of the proposed Clinical Research Networks Core concisely and summarize the expected outcome(s).

Research Strategy:

Applications must address the following required objectives and features of this Core. Applications are encouraged to provide any additional objectives or features as appropriate. Required objectives and features include:

1. Executing Platform partnerships to incorporate new health networks and nurture existing health network partnerships.
2. Establishing a virtual trial recruitment tool that is accessible to Platform users and will facilitate inclusive and diverse recruitment by the second year of the award.
3. Establishing three point of care networks, including national pharmacy chains, by the end of Y1 (as listed in Section 1.7).
4. In coordination with the Health Disparities Research and Recruitment Innovation Core and Trial Innovation Core, leveraging CRNs to support recruitment.
5. Integrating multiple clinical research organizations (CROs) within the Platform for supporting human subjects studies.
6. Integrating appropriate sensor API and FHIR API with individual point of care networks.
7. In coordination with the Health Disparities Research and Recruitment Innovation Core, addressing overlap of sampling frames across health organizations so that prospective study participants are not contacted more than once.
8. Providing support services for recruitment of studies funded by NIA by the second year of the award.

Applicants are also encouraged to explain how they will develop partnerships with PCORnet health care organizations.

In addition, applications must address how the Clinical Research Networks Core will report the following required KPIs and KRIs to the Administrative Core:

• Number of partnerships executed
• Use of Clinical Research Networks across the United States by federally funded studies
• Diversity of the participants in, and types of, Clinical Research Networks
• Number of federally funded studies using data from Clinical Research Networks for recruitment (starting in Y3)

Applications are encouraged to provide additional KPIs/KRIs applicable to the Core.

Letters of Support: Only letters of support specific to "Clinical Research Networks Core" should be attached to this section.

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 Research Networks 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.

Business Case and Translation Core

When preparing your application, use Component Type BCT Core.

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

SF424 (R&R) Cover (Business Case and Translation 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 (Business Case and Translation Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Business Case and Translation 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) (Business Case and Translation 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 (Business Case and Translation Core)

In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project 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 (Business Case and Translation Core)

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

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 (Business Case and Translation Core)

Specific Aims: State the goals of the proposed Business Case and Translation Core concisely and summarize the expected outcome(s).

Research Strategy:

Applications must address the following required objectives and features of this Core. Applications are encouraged to provide any additional objectives or features as appropriate. Required objectives and features include:

1. Developing business cases that project the long-term financial viability of the Platform.
2. Handling financial, regulatory, and legal aspects of the Platform.
3. Developing regulatory, reimbursement, and legal templates for Platform access and utilization.
4. Serving as the point of contact for public-private partnerships.
5. Developing and sharing use cases for partners.
6. Returning results to partners, as appropriate;
7. Developing reimbursement metrics for negotiating and paying partners within the CRNs for facilitating screening and recruitment.
8. Developing business cases that track how Platform results generate RWE applicable to clinical practice and policy.

In addition, applications must address how the Business Case and Translation Core will report the following required KPIs and KRIs to the Administrative Core:

• Financial and nonfinancial business benefits for Platform partners (e.g., RWD vendors, CRNs)
• Number of Platform users leveraging the Platform’s data sources and tools to inform which data sources and tools are most and least used
• Cost savings based on utilization of the Platform, including cost savings associated with each clinical trial and the implementation of digital and artificial intelligence (AI) tools
• Metrics associated with the value of the Platform in producing RWE that has the potential to impact health outcomes and policy

Applications are encouraged to provide additional KPIs/KRIs applicable to the Core.

Letters of Support: Only letters of support specific to "Business Case and Translation Core" should be attached to this section.

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 (Business Case and Translation 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.

Community Engagement, Data Privacy, and Ethics Core

When preparing your application, use Component Type CEDPE Core.

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

SF424 (R&R) Cover (Community Engagement, Data Privacy, and Ethics 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 (Community Engagement, Data Privacy, and Ethics Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Community Engagement, Data Privacy, and Ethics 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) (Community Engagement, Data Privacy, and Ethics 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 (Community Engagement, Data Privacy, and Ethics Core)

In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project 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 (Community Engagement, Data Privacy, and Ethics Core)

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

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 (Community Engagement, Data Privacy, and Ethics Core)

Specific Aims: State the goals of the proposed Community Engagement, Data Privacy, and Ethics Core concisely and summarize the expected outcome(s).

Research Strategy:

Applications must address the following required objectives and features of this Core. Applications are encouraged to provide any additional objectives or features as appropriate. Required objectives and features include:

1. Engaging with a wide range of stakeholders, including representatives from communities that have been historically underrepresented in research, in developing the Platform and addressing data privacy and ethical issues such as algorithm bias, re-identification risk, and consenting for human subjects studies, in a collaborative manner.
2. Integrating stakeholder feedback to develop best practices and ethical guidelines for the Platform, and ensuring the Platform is HIPAA compliant.
3. Providing a plan for when and how to, as appropriate, return results or information back to the patients providing the data. This plan must incorporate input from the Steering Committee, External Advisory Panel, and NIA program staff.
4. Coordinating with the Administrative Core to recommend a governance structure for the Platform.
5. Producing best practices and ethical guidelines related to RWD usage on topics including consent to linkage of administrative data; reproducibility standards; return of results to study participants; and regulatory structures that affect data access.
6. Collaborating with the Health Disparities Research and Recruitment Innovation Core to address challenges of algorithm bias.
7. Developing and integrating Platform consent practices adherent to the NIH Research Involving Individuals with Questionable Capacity to Consent: Points to Consider.
8. Developing patient and caregiver-reported outcomes and instruments relevant to AD/ADRD research that can be captured in RWD sources.

In addition, applications must address how the Community Engagement, Data Privacy, and Ethics Core will report the following required KPIs and KRIs to the Administrative Core:

• Range, background, and involvement of stakeholders in decision-making and Platform development and management
• Number and type of Platform users accessing each tier of data
• Metrics associated with data management and privacy trainings administered to all Platform users and administrators

Applications are encouraged to provide additional KPIs/KRIs applicable to the Core.

Letters of Support: Only letters of support specific to "Community Engagement, Data Privacy, and Ethics Core" should be attached to this section.

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 (Community Engagement, Data Privacy, and Ethics 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.

Health Disparities Research and Recruitment Innovation Core

When preparing your application, use Component Type HDRRI Core.

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

SF424 (R&R) Cover (Health Disparities Research and Recruitment Innovation 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 (Health Disparities Research and Recruitment Innovation Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Health Disparities Research and Recruitment Innovation 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) (Health Disparities Research and Recruitment Innovation 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 (Health Disparities Research and Recruitment Innovation Core)

In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project 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 (Health Disparities Research and Recruitment Innovation Core)

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

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 (Health Disparities Research and Recruitment Innovation Core)

Specific Aims: State the goals of the proposed Health Disparities Research and Recruitment Innovation Core concisely and summarize the expected outcome(s).

Research Strategy:

Applications must address the following required objectives and features of this Core. Applications are encouraged to provide any additional objectives or features as appropriate. Required objectives and features include:

1. Developing strategies and programs that leverage the Platform to facilitate inclusive and diverse recruitment for human subjects research studies.
2. Actively facilitating, supporting, and conducting research examining health disparities in AD/ADRD populations, and preparing reports that highlight the methods of, and use cases for, using the Platform to address the causes and consequences of disparate AD/ADRD care and outcomes across the U.S.
3. Developing innovative methods to improve the diversity of research and clinical trial recruitment while adhering to ethical best practices.
4. Evaluating the diversity of the population captured by each data source included in the Platform.
5. Identifying potential study participants and providing recruitment services that support real-time or near real-time recruitment and expedite study enrollment.
6. Collaborating with the Platform Access, Data Quality, and Integration Core to incorporate various data sources that capture information on the SDOH.
7. Collaborating with the Community Engagement, Data Privacy, and Ethics Core to address challenges of algorithm bias.
8. Preparing an annual report describing how the Platform has addressed gaps in AD/ADRD health disparities starting in Year 3.

In addition, applications must address how the Health Disparities Research and Recruitment Innovation Core will report the following required KPIs and KRIs to the Administrative Core:

• Number of Platform users using data to conduct health disparities research
• Time associated with participant recruitment in human subject studies using the Platform
• Number of innovative tools addressing diversity in clinical trials accessible to Platform users
• Number of human subjects studies using the Platform that are completed on time or early
• Representativeness of participants in clinical trials using the Platform

Applications are encouraged to provide additional KPIs/KRIs applicable to the Core.

Letters of Support: Only letters of support specific to "Health Disparities Research and Recruitment Innovation Core" should be attached to this section.

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 (Health Disparities Research and Recruitment Innovation 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.

Trial Innovation Core

When preparing your application, use Component Type TI Core.

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

SF424 (R&R) Cover (Trial Innovation 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 (Trial Innovation Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Trial Innovation 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) (Trial Innovation 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 (Trial Innovation Core)

In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project 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 (Trial Innovation Core)

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

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 (Trial Innovation Core)

Specific Aims: State the goals of the proposed Trial Innovation Core concisely and summarize the expected outcome(s).

Research Strategy:

Applications must address the following required objectives and features of this Core. Applications are encouraged to provide any additional objectives or features as appropriate. Required objectives and features include:

1. Advancing and incorporating cutting-edge informatics for recruitment in clinical trials.
2. Providing innovative methods for tracking patients and observing long-term follow up of clinical trial participants.
3. Developing and disseminating innovative methods for conducting clinical trials using RWD.
4. Developing and integrating electronic consent procedures.
5. Developing and integrating technology and artificial intelligence tools for clinical trials (e.g., protocol navigator, optimizing recruitment, etc.).
6. Developing digital tools that support the initiation of clinical trials.
7. Cultivating and preparing the clinical trial workforce.
8. Integrating robotic process automation (RPA) for protocol development/modification, as well as processes such as patient recruitment, onboarding, testing, data collection, scheduling, follow-ups, etc.
9. Providing support services for clinical trials funded by NIA.
10. Integrating with applications and services (e.g., rideshare companies, integrated electronic delivery of incentives, etc.) to improve the research participant experience.

In addition, applications must address how the Trial Innovation Core will report the following required KPIs and KRIs to the Administrative Core:

• Number of Platform users using each of the Platform’s innovative trial tools
• Number of innovative trial tools accessible to Platform users
• Number of Platform users using electronic consent procedures

Applications are encouraged to provide additional KPIs/KRIs applicable to the Core.

Letters of Support: Only letters of support specific to "Trial Innovation Core" should be attached to this section.

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 (Trial Innovation 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.

Platform Access, Data Quality, and Integration Core

When preparing your application, use Component Type PADQI Core.

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

SF424 (R&R) Cover (Platform Access, Data Quality, and Integration 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 (Platform Access, Data Quality, and Integration Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Platform Access, Data Quality, and Integration 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) (Platform Access, Data Quality, and Integration 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 (Platform Access, Data Quality, and Integration Core)

In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project 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 (Platform Access, Data Quality, and Integration Core)

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

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 (Platform Access, Data Quality, and Integration Core)

Specific Aims: State the goals of the proposed Platform Access, Data Quality, and Integration Core concisely and summarize the expected outcome(s).

Research Strategy:

Applications must address how they will develop and manage the Platform's three locations for data access:

(1) Centralized data warehouse that exists within the Platform and stores privately acquired datasets (e.g., pharmacy chain data, EHR vendor data)

(2) Federated environment that exists within the Platform and has linkage to health systems, clinical research networks, and various studies

(3) ATO enclave that exists outside the Platform for linkage of centralized data (Location 1) and federated data (Location 2) to federal data sources such as CMS data

Applications must explain how they will create and provide access to Platform resources as a service to the research community. Applications are encouraged to explore use of the Health and Aging Data (HaAD) Enclave as appropriate for data sharing.

Applications must address the following required objectives and features of this Core. Applicants are encouraged to provide any additional objectives or features as appropriate. Required objectives and features include:

1. Acting as the central hub for multimodal data access for research recruitment and analysis.
2. Developing tools that ensure consistency in research protocols and solutions to address data quality, including through addressing the impact of missing data.
3. Securely procuring data (including from Tribal Health Centers and Federally Designated Health Centers) and securing administrative data use agreements to facilitate reuse and transfer of data within the 3 specified locations, (1) centralized within Platform, (2) federated within Platform, and (3) ATO enclave outside the Platform.
4. Securely de-identifying (e.g., privacy preserving linkages, encryption of PII, or tokenization), curating, and creating longitudinal files across multiple RWD data sources with common data elements (CDE) in the centralized data warehouse (Location 1) and the ATO enclave (Location 3).
5. For Platform Locations 1 and 2, obtaining either (1) an ATO from a federal agency for facilitating data access through a Desktop as a Service (DaaS) environment to Platform users, or (2) a FedRAMP authorization with high impact level for security controls that incorporates zero trust principles/architecture.
6. Procuring public and private SDOH data, consumption data, contextual data at various levels (e.g., geographic data), individual and household level behavioral and economic measures (e.g., income, employment, consumption, etc.), and private data sources for inclusion in Location 1.
7. Providing the ability to link federated data sources to data in Locations 1 or 3, as appropriate.
8. Performing a quarterly review of types of data accessible, data leakages, access protocol violations (based on tiered access), and open vulnerabilities to ensure high accessibility while complying with federal regulations and maintaining high ethical standards and security.
9. Addressing data interoperability across data sources.
10. Working closely with the Clinical Research Network Core to integrate appropriate API (for sensor and/or data) and FHIR API with individual point of care networks to facilitate recruitment.
11. Promoting the efficacious use of Platform data by providing trainings, tools, and support that take into account underlying biases and inaccuracies inherent to certain data sources.
12. Assessing the impact of various data sources on cohort size and representativeness.
13. Acquiring private RWD data sources as needed to have national representation while maintaining data quality and completeness.
14. Maintaining data codebooks, metadata, and other data documentation, and creating a cross-walk between these resources and their respective datasets.
15. Using a common data model, such as OMOP.
16. Enhancing and incorporating data from other NIH data resources/programs or other national sources (when applicable) (e.g., N3C, RECOVER, PCORNET, etc.).
17. Incorporating a suite of software to allow for in situ analyses of data that cannot be linked or pooled across data sources (e.g., data from multiple health systems used for recruitment).
18. Incorporating input from Platform users during the development, integration, and update of various Platform user interfaces.
19. Performing data harmonization and implementing quality assurance procedures.
20. Linking longitudinal data as appropriate (with IRB-reviewed protocols) within a federated data environment (Location 2) to Platform user studies (e.g., clinical research networks; cross-sectional and longitudinal studies; and/or clinical trials).
21. Facilitating linkages of CMS data through the currently supported NIA contract with Acumen, LLC, a new contractor (upon expiration of the current contract with Acumen, LLC), and/or CMS directly (upon expiration of the current contract with Acumen, LLC).
22. Evaluating the quality of data sources, particularly for novel data sources.
23. In collaboration with Health Disparities Research and Recruitment Innovation and Trial Innovation Cores, developing a tool to help clinical trials incorporate nudges.

The application must also provide details about how it will carry out the following Platform Access, Data Quality, and Integration Core functions that serve to facilitate Platform access to the research community:

1. In coordination with the Administration Core, Clinical Research Networks Core, Health Disparities Research and Recruitment Innovation Core, and Trial Innovation Core, providing an application (accessible via smartphone and other devices) that provides and supports easily accessible user support services, including data visualization tools, recruitment services, and AI tools that can improve the Platform’s accessibility to a broad range of researchers and research fields.
2. Optimizing access to data by utilizing data warehousing techniques and methods (e.g., data lakes).
3. Making analytical tools available for research projects (e.g., statistical software).
4. Cloud-based repository and project management tools for Platform users.
5. Facilitating large-scale data processing for batch and streaming workloads to reduce costs traditionally associated with processing large datasets.
6. Optimizing use of APIs (including FHIR API) for data transfer and connectivity.
7. Supporting standards and mechanisms to publicly share data, resources, and codes developed through use of the Platform.
8. Providing design and analysis support for AD/ADRD observational research using RWD.
9. Instituting a Data Access Committee, and monitoring and providing clearance for data requests based on research needs (i.e., Platform users will be provided with the minimum data necessary for their individual study with IRB approval).
10. Managing the full lifecycle of data requests from Platform users, including but not limited to initial data or recruitment request, issuance of data, and termination of data request.
11. Responding to technical queries and providing support to Platform users.

In addition, applications must address how the Platform Access, Data Quality, and Integration Core will report the following required KPIs and KRIs to the Administrative Core:

• Data sharing and linkage benchmarks and timeliness and frequency of data release
• Percentage of U.S. population represented in the Platform
• Percentage of U.S. population with AD/ADRD represented in the Platform
• Representativeness (by race/ethnicity, rural/urban) of the overall platform, within each Platform location (i.e., Location 1: within Platform centralized data warehouse, Location 2: within Platform federated environment, and Location 3: ATO enclave) and within individual data sources contained in the Platform
• Measures associated with data quality and harmonization, including tracking Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM) transformation or other harmonization processes across data sources
• Number of studies linked to RWD using Platform data resources, and the percentage of participants linked for each of those studies
• Benchmarking missing data and corrections across data sources
• Number and use of curated and harmonized data feeds available for analysis
• Number of Fast Health Interoperability Resources (FHIR) and other application programming interfaces (APIs) for various data feeds
• Timeliness of availability of each private and public data source and usage across research theme (e.g., surveillance; usage for trials; usage for secondary data analyses; therapeutic development, etc.)
• Metrics associated with the data governance process to acquire, audit, manage, govern, access, and share data
• Usage of various technology and AI tools by Platform users
• Timeliness of support to Platform users; user satisfaction score; total tickets and tickets per user/customer; average handle time; first contact resolution; cost per resolution

Applications are encouraged to provide additional KPIs/KRIs applicable to the Core.

Letters of Support: Only letters of support specific to "Platform Access, Data Quality, and Integration Core" should be attached to this section.

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 (Platform Access, Data Quality, and Integration 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.

Incubator Core

When preparing your application, use Component Type Incubator Core.

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

SF424 (R&R) Cover (Incubator 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 (Incubator Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Incubator 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) (Incubator 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 (Incubator Core)

In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project 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 (Incubator Core)

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

While the Incubator Core should support research on both AD/ADRD and general aging topics, no more than 15% of Incubator funds can be allocated to non-AD/ADRD projects each year.

NIA intends to commit $4 million in Y1, $6 million in Y2, $10 million in Y3, $10 million in Y4, $14 million in Y5, and $14 million in Y6 to fund research through the Incubator Core. NINDS intends to commit $2 million in each year of the award to fund research through the Incubator Core.

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

PHS 398 Research Plan (Incubator Core)

Specific Aims: State the goals of the proposed Incubator Core concisely and summarize the expected outcome(s).

Research Strategy:

This Core will internally develop an AD/ADRD registry and fund innovative research projects and clinical trials. Per milestones listed in Section 1.7, the AD/ADRD registry must be established by Year 2 Month 9 of the award. Applicants must provide a timeline for the integration of Incubator Core activities within the larger Platform.

Applications must describe how the Incubator Core will plan, coordinate, and build an AD/ADRD registry, including the following information:

1. Plans and a research strategy for building an AD/ADRD registry, making reference to the "Registries for Evaluating Patient Outcomes: A User's Guide," fourth edition.
2. How the registry will incorporate feedback from various stakeholders/communities.
3. How the registry will integrate RWD data that can provide insight into an individual’s health during the prodromal stage of AD/ADRD or MCI.
4. How registries can support drug development, regulatory approval, and the translation of research into clinical practice.
5. Which data sources will be incorporated.
6. How the registry will be linked with CMS data.
7. How the registry will serve key stakeholders, including patients, caregivers, and underserved populations.
8. Development plans and objectives for the Incubator Core to track from ?Year 2 to Year 6 of the award.
9. AD/ADRD registry resources that the Incubator Core could develop to serve the broader research community.
10. Plans to engage with, and integrate feedback from, communities that have been historically underrepresented in research.

In addition, applications must briefly describe how the Incubator Core will accomplish the following required features starting in Year 2 (unless otherwise specified) of the award:

1. Awarding Challenge prizes for developing digital and AI research tools for the Platform.
2. In consultation with incubator project awardees, developing KPIs and KRIs associated with each incubator project.
3. Holding a semi-annual national competition for AD/ADRD research projects using the Platform in innovative ways to address AD/ADRD research priorities identified in the NIH AD+ADRD Research Implementation Milestones database, and recommending funding of such studies to NIA/NINDS starting in Year 2. Individual studies may not exceed $200,000 in direct costs.
4. Holding a semi-annual national competition for AD/ADRD clinical trials using the Platform in innovative ways to address AD/ADRD research priorities identified in the NIH AD+ADRD Research Implementation Milestones database, and recommending funding of such trials to NIA/NINDS starting in Year 3. Individual trials may not exceed $500,000 in direct costs. These projects can support full trials or be designed to lead to (or inform) the design of larger scale AD/ADRD trials that leverage RWD.
5. Providing recruitment, design, and analysis support for human subjects research using the Platform.
6. In coordination with the Clinical Research Networks Core, expanding the number of partners and data sources within the Clinical Research Network.
7. Including high-value RWD, such as lab results.

It is understood that these features may be adapted in response to (1) responses to RFIs issued to seek input from the broader research and stakeholder communities, (2) input from the Steering Committee and EAP, and (3) input from NIA/NINDS program staff. Therefore, applicants are only expected to provide brief descriptions for the above features starting in Year 2 or later. Detailed research strategies are not requested and are not required for anticipated research activities to be carried out between Years 2 through 6, but a plan for a national competition must be included for Year 2 through Year 6.

In addition, applications must address how the Incubator Core will report the following required KPIs and KRIs to the Administrative Core:

• Utility and return of investment of individual Incubator Core projects, including the AD/ADRD registry
• Number of external projects funded
• Timeliness of annual competition

Applications are encouraged to provide additional KPIs/KRIs applicable to the Core.

Letters of Support: Only letters of support specific to "Incubator Core" should be attached to this section.

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 (Incubator 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.

Optional Investigator-Initiated Core 1

When preparing your application, use Component Type II Core 1.

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

SF424 (R&R) Cover (Optional Investigator-Initiated Core 1)

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 (Optional Investigator-Initiated Core 1)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Optional Investigator-Initiated Core 1)

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) (Optional Investigator-Initiated Core 1)

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 (Optional Investigator-Initiated Core 1)

In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project 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 (Optional Investigator-Initiated Core 1)

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

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 (Optional Investigator-Initiated Core 1)

Specific Aims: State the goals of the proposed Optional Investigator-Initiated Core 1 concisely and summarize the expected outcome(s), including the impact that the results of the proposed research will exert on the AD/ADRD and aging research field(s) involved. Succinctly list the specific objectives of the research proposed and state how it will benefit the Platform overall.

Research Strategy: This is an Optional Core proposed by the applicant. Applicants should specify how this Core will benefit the overall Platform, including the impact of the Core on the overall Platform.

In addition, applications must address how Optional Investigator-Initiated Core 1 will develop, track, monitor, and report relevant KPIs and KRIs to the Administrative Core.

Letters of Support: Only letters of support specific to "Optional Investigator-Initiated Core 1" should be attached to this section.

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 (Optional Investigator-Initiated Core 1)

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.

Optional Investigator-Initiated Core 2

When preparing your application, use Component Type II Core 2.

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

SF424 (R&R) Cover (Optional Investigator-Initiated Core 2)

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 (Optional Investigator-Initiated Core 2)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Optional Investigator-Initiated Core 2)

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) (Optional Investigator-Initiated Core 2)

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 (Optional Investigator-Initiated Core 2)

In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project 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 (Optional Investigator-Initiated Core 2)

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

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 (Optional Investigator-Initiated Core 2)

Specific Aims: State the goals of the proposed Optional Investigator-Initiated Core 2 concisely and summarize the expected outcome(s), including the impact that the results of the proposed research will exert on the AD/ADRD and aging research field(s) involved. Succinctly list the specific objectives of the research proposed and state how it will benefit the Platform overall.

Research Strategy: This is an Optional Core proposed by the applicant. Applicants should specify how this Core will benefit the overall Platform, including the impact of the Core on the overall Platform.

In addition, applications must address how the Optional Investigator-Initiated Core 2 will develop, track, monitor, and report relevant KPIs and KRIs to the Administrative Core.

Letters of Support: Only letters of support specific to "Optional Investigator-Initiated Core 2" should be attached to this section.

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 (Optional Investigator-Initiated Core 2)

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.

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 applications will be automatically assembled for review and funding consideration after submission, refer 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.

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.

In order to expedite review, applicants are requested to notify the NIA Referral Office by email at [email protected] when the application has been submitted. Please include the NOFO number and title, PD/PI name, and title of the application.

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.

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

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?

In addition, for applications involving clinical trials

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

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?

Specific to this NOFO: How appropriate is the breadth of expertise and experience of the investigative team to develop and manage the Platform? How well does the application describe how the investigators will cooperate with the NIH in the development and design of research approaches, methods, processes, policies, and tools used in this program? To what extent does the investigative team have documented prior experience of working collaboratively in research consortia and other collaborative projects to accomplish shared goals? To what extent has the investigative team demonstrated an ongoing record of accomplishment in support of coordination, collaboration, and communication of large, national-level, inclusive Platforms, networks or consortia? To what extent does the application demonstrate how the planned collaboration will work among a team with potentially very different backgrounds? How appropriate are the proposed leadership approach, staffing, governance, and organizational structure? To what extent does the application articulate how the investigators will collaborate with the Research Project recipients and how the investigative team is up to date on the changing landscape of data science research and participant protection regulations?

Do the application's proposed PD(s)/PI(s) commit to sustaining at least 9 person-months of effort per year throughout the award? Alternatively, if a multi-PD/PI structure is proposed, do the applicant's proposed PIs commit to sustaining at least 6 person-months of effort per year throughout the award? Do the application's proposed Executive Director and Deputy Director commit to sustaining full-time effort throughout the award? Do the application's proposed Core Directors for each Core commit to sustaining at least 6 person-months of effort per year throughout the award? Alternatively, if a multi-Core Director structure is proposed for a Core, do those Core Directors commit to sustaining at least 4 person-months of effort per year throughout the award (except for the Platform Access, Data Quality, and Integration Core)? Do the application's proposed Core Director(s) for the Platform Access, Data Quality, and Integration Core commit to sustaining at least 6 person-months of effort per year across the award, regardless of whether a multi-Core Director structure is proposed for this Core?

In addition, for applications involving clinical trials

With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

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?

Specific to this NOFO: How well-described are the innovative elements, as appropriate, that enhance the Platform’s potential to advance scientific knowledge and clinical practice?

In addition, for applications involving clinical trials

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

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?

Specific to this NOFO: How well-described is the plan to accomplish the following goals while maintaining a patient-centered approach and mission: (1) improve applicability and generalizability of findings through larger datasets that include more diverse populations; (2) capture more complete information through linking a variety of data sources; (3) increase the speed at which scientific questions can be answered; and (4) improve researchers ability to answer questions that cannot be feasibly or readily answered via clinical trial? How well-articulated are plans for the Platform to engage nationally with others working in similar areas (including both NIH-funded projects and projects with other funding sources) to stay abreast of emerging experience, regulations, and technical advances that impact the ability for research to be conducted in health care settings?

How well-described is the plan for the Platform to provide tools, resources, and data that promote research studying health disparities in the AD/ADRD population and beyond? How well-articulated is the plan to mitigate the risk of the Platform perpetuating or exacerbating health disparities and to serve communities that have been historically underrepresented in research? How well-described is the plan to provide national leadership and engage stakeholders when developing and implementing the Platform, and when designing the Platform's plan to advance data access and integration for Platform users? Is the plan to translate findings resulting from the Platform into clinical practice and RWE that can impact the health of, and policy for, people living with AD/ADRD and their caregivers likely to lead to success?

Does the application adequately detail the centralized and/or federated systems proposed for the Platform as well as which data sources can be feasibly included in the Platform, and how these sources can include representative coverage of the U.S. population?

How well-described are the plan for the different components of the Platform to interact to help accomplish its aims, the way in which the approaches of the Core components complement each other or are interdependent, and the mechanisms to be used in assessing progress toward the Platform's goals?

Does the application adequately explain how the Platform will be made widely available and easily accessible to a wide range of researchers by Year 4 of the award? How well-described are the plans to challenge and seek to impact current data management and research implementation strategies by developing novel approaches and tools, and how these approaches and tools will be disseminated for broader use by Platform-users?

Are the plans to leverage RWD to enhance representative recruitment in research and clinical trials likely to lead to success?

Does the application provide an adequate Resource Sharing Plan and an adequate Data Management and Sharing Plan which allow for sharing of data and resources developed by the Platform?

In addition, for applications involving clinical trials

Does the application adequately address the following, if applicable

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

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?

In addition, for applications involving clinical trials

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

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.

Study Timeline

Specific to applications involving clinical trials

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

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 Animals 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

Not Applicable.

Renewals

Not Applicable.

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

Reviewers will comment on whether the Resource Sharing Plan(s) (e.g., 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.

Scored Review Criteria - Administrative Core

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

Significance

Does the proposed Core address the needs of the Platform that it will administer? Is the scope of activities proposed for the Core appropriate to meet those needs? Will successful completion of the aims bring unique advantages or capabilities to the Platform?

Investigator(s)

Are the PD(s)/PI(s) and other personnel well suited to their roles in the Core? Do they have appropriate experience and training, and have they demonstrated experience and an ongoing record of accomplishments in managing cross-institutional or cross-organizational research? Do the investigators demonstrate significant experience with coordinating collaborative clinical research? If the Core is multi-PD/PI, do the investigators have complementary and integrated expertise and skills; are their leadership approach, governance, plans for conflict resolution, and organizational structure appropriate for the Core? Does the applicant have experience overseeing selection and management of subawards, if needed?

Innovation

Does the application propose novel organizational concepts, management strategies, or instrumentation in coordinating the research projects, networks and resources the Core will serve? Are the concepts, strategies, or instrumentation novel to one type of research program or applicable in a broad sense? Is a refinement, improvement, or new application of organizational concepts, management strategies or instrumentation proposed?

Approach

Are the overall strategy, operational plan, and organizational structure well-reasoned and appropriate to accomplish the goals of the research projects, networks, and resources the Core will serve? Will the investigators promote strategies to ensure a robust and unbiased scientific approach across the projects, networks, and resources, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the Platform is in the early stages of operation, does the proposed strategy adequately establish feasibility and manage the risks associated with the activities of the Platform? Are an appropriate plan for work-flow and a well-established timeline proposed? Have the investigators presented adequate plans to ensure consideration of relevant biological variables, such as sex, for studies of vertebrate animals or human subjects?

Specific to this NOFO:

How well does the application demonstrate the PD/PI's ability to establish effective collaborations? Are the processes for problem-solving, communicating, and prioritizing work logical and appropriate? How well does the application address each of the following required objectives and features of the Administrative Core:

1. Ensuring completion of stated milestones;
2. Providing a public website for communication and sharing of activities, events, trainings, publications, and program resources;
3. Hosting AD/ADRD RWD Grand Rounds;
4. Convening an annual meeting that includes Cores, Steering Committee members, EAP members, and NIA program staff;
5. Managing quarterly meetings with the Steering Committee, including by providing a meeting summary to NIA program staff;
6. Coordinating and collaborating with Core leaders to facilitate the alignment of tactical and strategic process goals;
7. Providing organizational and logistical support for Cores, Project Scientist(s), Steering Committee activities, and EAP activities;
8. Managing the Resource Sharing Plan;
9. Developing high-quality communication materials, including guidance documents, training materials, promotional materials, and presentations;
10. Producing quarterly (during Y1-Y3) and biannual (during Y4-Y6) progress reports for submission to NIA program staff;
11. Developing and tracking OKRs, KPIs, and KRIs applicable to each Core, and providing the resulting data monthly to NIA program staff;
12. Creating dashboards highlighting KPIs and KRIs associated with execution risk of the platform (e.g., risk associated with execution of data agreements, risk associated with data reviews, risk associated with using clinical research networks);
13. Providing NIA program staff an annual internal evaluation report that evaluates progress towards study goals, milestones, KPIs, and KRIs; and
14. Facilitating, creating, and supporting the development and execution of ALL material transfer agreements within 30 days of NIA notice?

To what extent will the strategies to address the required objectives and features as well as any proposed additional objectives and features lead to success in accomplishing the goals of the Administrative Core?

How well does the application address the required Administrative Core KPIs and KRIs, which will be tracked, monitored, and reported to NIA program staff by the Administrative Core?

Environment

Will the institutional environment in which the Core will operate contribute to the probability of success in facilitating the research projects, networks, and resources it serves? Are the institutional support, equipment and other physical resources available to the investigators adequate for the Core proposed? Will the Core benefit from unique features of the institutional environment, infrastructure, or personnel? Are resources available within the scientific environment to support electronic information handling?

Additional Review Criteria - Administrative Core

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.

Additional Review Considerations - Administrative Core

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).

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.

Scored Review Criteria - Clinical Research Networks Core

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

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?

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?

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?

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?

Specific to this NOFO:

How well does the application address each of the following the required objectives and features of the Clinical Research Networks Core:

1. Executing Platform partnerships to incorporate new health networks and nurture existing health network partnerships;
2. Establishing a virtual trial recruitment tool that is accessible to Platform users and will facilitate inclusive and diverse recruitment by the second year of the award;
3. Establishing three point of care networks, including national pharmacy chains, by the end of the sixth month of Y1;
4. In coordination with the Health Disparities Research and Recruitment Innovation Core and Trial Innovation Core, leveraging CRNs to support recruitment;
5. Integrating multiple CROs within the Platform for supporting human subjects studies;
6. Integrating appropriate sensor API and FHIR API with individual point of care networks;
7. In coordination with the Health Disparities Research and Recruitment Innovation Core, addressing overlap of sampling frames across health organizations so that prospective study participants are not contacted more than once; and
8. Providing support services for recruitment of studies funded by NIA by the second year of the award?

To what extent will the strategies to address the required objectives and features as well as any proposed additional objectives and features lead to success in accomplishing the goals of the Clinical Research Networks Core?

How well does the application address the required Clinical Research Networks Core KPIs and KRIs, which will be tracked, monitored, and reported to NIA program staff by the Administrative Core?

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?

Additional Review Criteria - Clinical Research Networks Core

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.

Additional Review Considerations - Clinical Research Networks Core

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).

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.

Scored Review Criteria - Business Case and Translation Core

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

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?

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?

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?

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?

Specific to this NOFO:

How well does the application address each of the following the required objectives and features of the Business Case and Translation Core:

1. Developing business cases that project the long-term financial viability of the Platform;
2. Handling financial, regulatory, and legal aspects of the Platform;
3. Developing regulatory, reimbursement and legal templates for Platform access and utilization;
4. Serving as the point of contact for public-private partnerships;
5. Developing and sharing use cases for partners;
6. Returning results to partners, as appropriate;
7. Developing reimbursement metrics for negotiating and paying partners within the CRNs for facilitating screening and recruitment; and
8. Developing business cases that track how Platform results generate RWE applicable to clinical practice and policy?

To what extent will the strategies to address the required objectives and features as well as any proposed additional objectives and features lead to success in accomplishing the goals of the Business Case and Translation Core?

How well does the application address the required Business Case and Translation Core KPIs and KRIs, which will be tracked, monitored, and reported to NIA program staff by the Administrative Core?

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?

Additional Review Criteria - Business Case and Translation Core

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.

Additional Review Considerations - Business Case and Translation Core

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).

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.

Scored Review Criteria - Community Engagement, Data Privacy, and Ethics Core

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

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?

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?

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?

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?

Specific to this NOFO: How well does the application address each of the following the required objectives and features of the Community Engagement, Data Privacy, and Ethics Core:

1. Engaging with a wide range of stakeholders, including representatives from communities that have been historically underrepresented in research, and addressing data privacy and ethical issues such as algorithm bias, re-identification risk, and consenting for human subjects studies, in a collaborative manner;
2. Integrating stakeholder feedback to develop best practices and ethical guidelines for the Platform, and ensure the Platform is HIPAA compliant;
3. Providing a plan that incorporates input from the Steering Committee, EAP, and NIA program staff for when and how to, as appropriate, return results or information back to the patients providing the data;
4. Coordinating with the Administrative Core to recommend a governance structure for the Platform;
6. Producing best practices and ethical guidelines related to RWD usage on topics including: consent to linkage of administrative data; reproducibility standards; return of results to study participants; and regulatory structures that affect data access;
7. Collaborating with the Health Disparities Research and Recruitment Innovation Core to address challenges of algorithm bias;
8. Developing and integrating Platform consent practices adherent to the NIH Research Involving Individuals with Questionable Capacity to Consent: Points to Consider; and
9. Developing patient and caregiver-reported outcomes and instruments relevant to AD/ADRD research that can be captured in RWD sources?

To what extent will the strategies to address the required objectives and features as well as any proposed additional objectives and features lead to success in accomplishing the goals of the Community Engagement, Data Privacy, and Ethics Core?

How well does the application address the required Community Engagement, Data Privacy, and Ethics Core KPIs and KRIs, which will be tracked, monitored, and reported to NIA program staff by the Administrative Core?

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?

Additional Review Criteria - Community Engagement, Data Privacy, and Ethics Core

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.

Additional Review Considerations - Community Engagement, Data Privacy, and Ethics Core

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).

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.

Scored Review Criteria - Health Disparities Research and Recruitment Innovation Core

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

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?

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?

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?

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?

Specific to this NOFO: How well does the application address each of the following the required objectives and features of the Health Disparities Research and Recruitment Innovation Core:

1. Developing strategies and programs that leverage the Platform to facilitate inclusive and diverse recruitment for human subjects research studies;
2. Actively facilitating, supporting, and conducting research examining health disparities in AD/ADRD populations, and preparing reports that highlight the methods of, and use cases for, using the Platform to address the causes and consequences of disparate AD/ADRD care and outcomes across the U.S.;
3. Developing innovative methods to improve the diversity of research and clinical trial recruitment while adhering to ethical best practices;
4. Evaluating the diversity of the population captured by each data source included in the Platform;
5. Identifying potential study participants and providing recruitment services that support real-time or near real-time recruitment and expedite study enrollment;
6. Collaborating with the Platform Access, Data Quality and Integration Core to incorporate various data sources that capture information on the SDOH;
7. Collaborating with the Community Engagement, Data Privacy, and Ethics Core to address challenges of algorithm bias; and
8. Preparing an annual report describing how the Platform has addressed gaps in AD/ADRD health disparities starting in Year 3?

To what extent will the strategies to address the required objectives and features as well as any proposed additional objectives and features lead to success in accomplishing the goals of the Health Disparities Research and Recruitment Innovation Core?

How well does the application address the required Health Disparities Research and Recruitment Innovation Core KPIs and KRIs, which will be tracked, monitored, and reported to NIA program staff by the Administrative Core?

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?

Additional Review Criteria - Health Disparities Research and Recruitment Innovation Core

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.

Additional Review Considerations - Health Disparities Research and Recruitment Innovation Core

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).

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.

Scored Review Criteria - Trial Innovation Core

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

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?

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?

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?

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?

Specific to this NOFO: How well does the application address each of the following the required objectives and features of the Trial Innovation Core:

1. Advancing and incorporating cutting-edge informatics for recruitment in clinical trials;
2. Providing innovative methods for tracking patients and observing long-term follow up of clinical trial participants;
3. Developing and disseminating innovative methods for conducting clinical trials using RWD;
4. Developing and integrating electronic consent procedures;
5. Developing and integrating technology and artificial intelligence tools for clinical trials (e.g., protocol navigator; optimizing recruitment);
6. Developing digital tools that support the initiation of clinical trials;
7. Cultivating and preparing the clinical trial workforce;
8. Integrating RPA for protocol development/modification, as well as processes such as patient recruitment, onboarding, testing, data collection, scheduling, follow-ups, etc.;
9. Providing support services for clinical trials funded by NIA; and
10. Integrating with applications and services (e.g., rideshare companies, integrated electronic delivery of incentives) to improve the research participant experience?

To what extent will the strategies to address the required objectives and features as well as any proposed additional objectives and features lead to success in accomplishing the goals of the Trial Innovation Core?

How well does the application address the required Trial Innovation Core KPIs and KRIs, which will be tracked, monitored, and reported to NIA program staff by the Administrative Core?

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?

Additional Review Criteria - Trial Innovation Core

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.

Additional Review Considerations - Trial Innovation Core

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).

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.

Scored Review Criteria - Platform Access, Data Quality, and Integration Core

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

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?

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?

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?

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?

Specific to this NOFO: Are the plans to develop and manage the Platform's three locations for data access (1) centralized data warehouse that exists within the Platform and stores privately acquired datasets (e.g., pharmacy chain data, EHR vendor data), 2) federated environment that exists within the Platform and with linkage to health systems, clinical research networks,?and various studies, and 3) ATO enclave that exists outside the Platform for linkage of centralized (Location 1) and federated data (Location 2) to federal data sources such as Centers for Medicare & Medicaid (CMS) data) likely to be successful? Are the strategies for creating and providing access to Platform resources likely to provide a service to the research community?

How well does the application address each of the following required objectives and features of the Platform Access, Data Quality, and Integration Core:

1. Acting as the central hub for multimodal data access for research recruitment and analysis;
2. Developing tools that ensure consistency in research protocols and solutions to address data quality, including through addressing the impact of missing data;
3. Securely procuring data (including from Tribal Health Centers and Federally Designated Health Centers) and securing administrative data use agreements to facilitate reuse and transfer of data within the 3 specified locations, (1) centralized within Platform, (2) federated within Platform, and (3) ATO enclave outside the Platform;
4. Securely de-identifying (e.g., privacy preserving linkages, encryption of PII, or tokenization), curating, and creating longitudinal files across multiple RWD data sources with CDE in the centralized data warehouse (Location 1) and the ATO enclave (Location 3);
5. For Platform Locations 1 and 2, obtaining either (1) an ATO from a federal agency for facilitating data access through a DaaS environment to Platform users, or (2) a FedRAMP authorization with high impact level for security controls that incorporates zero trust principles/architecture;
6. Procuring public and private SDOH data, consumption data, contextual data at various levels (e.g., geographic data), individual and household level behavioral and economic measures (e.g., income, employment, consumption, etc.), and private data sources for inclusion in Location 1;
7. Providing the ability to link federated data sources to data in Locations 1 or 3, as appropriate;
8. Performing a quarterly review of types of data accessible, data leakages, access protocol violations (based on tiered access), and open vulnerabilities to ensure high accessibility while complying with federal regulations and maintaining high ethical standards and security;
9. Addressing data interoperability across data sources;
10. Working closely with the Clinical Research Network Core to integrate appropriate API (for sensor and/or data) and FHIR API with individual point of care networks to facilitate recruitment;
11. Promoting the efficacious use of Platform data by providing trainings, tools, and support that take into account underlying biases and inaccuracies inherent to certain data sources;
12. Assessing the impact of various data sources on cohort size and representativeness;
13. Acquiring private RWD data sources as needed to have national representation while maintaining data quality and completeness;
14. Maintaining data codebooks, metadata, and other data documentation, and creating a cross-walk between these resources and their respective datasets;
15. Using a common data model, such as OMOP;
16. Enhancing and incorporating data from other NIH data resources/programs or other national sources (when applicable) (e.g., N3C, RECOVER, PCORNET etc.);
17. Incorporating a suite of software to allow for in situ analyses of data that cannot be linked or pooled across data sources (e.g., data from multiple health systems used for recruitment);
18. Incorporating input from Platform users during the development, integration, and update of various Platform user interfaces;
19. Performing data harmonization and implementing quality assurance procedures;
20. Linking longitudinal data as appropriate (with IRB-reviewed protocols) within a federated data environment (Location 2) to Platform user studies (e.g., clinical research networks; cross-sectional and longitudinal studies; and/or clinical trials);
21. Facilitating linkages of CMS data through the currently supported NIA contract with Acumen, LLC, a new contractor (upon expiration of the current contract with Acumen, LLC), and/or CMS directly (upon expiration of the current contract with Acumen, LLC);
22. Evaluating the quality of data sources, particularly for novel data sources; and
23. In collaboration with Health Disparities Research and Recruitment Innovation and Trial Innovation Cores, developing a tool to help clinical trials incorporate nudges?

To what extent will the strategies to address the required objectives and features as well as any proposed additional objectives and features lead to success in accomplishing the goals of the Platform Access, Data Quality, and Integration Core?

How well-described are the following Platform Access, Data Quality, and Integration Core functions that serve to facilitate Platform access to the research community:

1. In coordination with the Administration Core, Clinical Research Networks Core, Health Disparities Research and Recruitment Innovation Core, and Trial Innovation Core, providing an application (accessible via smartphone and other devices) that provides and supports easily accessible user support services, including data visualization tools, recruitment services, and AI tools that can improve the Platform’s accessibility to a broad range of researchers and research fields;
2. Optimizing access to data by utilizing data warehousing techniques and methods (e.g., data lakes);
3. Making analytical tools available for research projects (e.g., statistical software);
4. Cloud-based repository and project management tools for Platform users;
5. Facilitating large-scale data processing for batch and streaming workloads to reduce costs traditionally associated with processing large datasets;
6. Optimizing use of APIs (including FHIR API) for data transfer and connectivity;
7. Supporting standards and mechanisms to publicly share data, resources, and codes developed through use of the Platform;
8. Providing design and analysis support for AD/ADRD observational research using RWD;
9. Instituting a Data Access Committee, and monitoring and providing clearance for data requests based on research needs (i.e., Platform users will be provided with the minimum data necessary for their individual study with IRB approval);
10. Managing the full lifecycle of data requests from Platform users, including but not limited to initial data or recruitment request, issuance of data, and termination of data request; and
11. Responding to technical queries and providing support to Platform users?

How well does the application address the required Platform Access, Data Quality, and Integration Core KPIs and KRIs, which will be tracked, monitored, and reported to NIA program staff by the Administrative Core?

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?

Additional Review Criteria - Platform Access, Data Quality, and Integration Core

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 theGuidelines 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 theGuidelines 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 theWorksheet 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.

Additional Review Considerations - Platform Access, Data Quality, and Integration Core

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).

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.

Scored Review Criteria - Incubator Core

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

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?

In addition, for applications involving clinical trials

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

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?

In addition, for applications involving clinical trials

With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

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?

In addition, for applications involving clinical trials

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

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?

Are there adequate institutional plans and procedures to assure compliance with applicable federal regulations and NIH policies for the protection of human research participants, including the evaluation of risks and protections in project proposals, appropriate ethical oversight of funded projects, and plans for monitoring data and safety in clinical research projects?

Specific to this NOFO: How well-described are the plans to develop an AD/ADRD registry by Year 2 Month 9 of the award and fund innovative research projects and clinical trials? Is the timeline for the integration of Incubator Core activities within the larger Platform logical and appropriate?

How well does the application address each of the following required features of the Incubator Core:

1. Plans and a research strategy for building an AD/ADRD registry, making reference to the "Registries for Evaluating Patient Outcomes: A User's Guide," fourth edition;
2. How the registry will incorporate feedback from various stakeholders/communities;
3. How the registry will integrate RWD data that can provide insight into an individual’s health before they are diagnosed with AD/ADRD;
4. How registries can support drug development, regulatory approval, and the translation of research into clinical practice;
5. Which data sources will be incorporated;
6. How the registry will be linked with CMS data;
7. How the registry will serve key stakeholders, including patients, caregivers, and underserved populations;
8. Development plans and objectives for the Incubator Core to track from Year 2 to Year 6 of the award;
9. AD/ADRD registry resources that the Incubator Core could develop to serve the broader research community; and
10. Plans to engage with, and integrate feedback from, communities that have been historically underrepresented in research?

How well does the application address each of the following required features starting in Year 2 (unless otherwise specified) of the award:

1. Awarding Challenge prizes for developing digital and AI research tools for the Platform;
2. In consultation with incubator project awardees, developing KPIs and KRIs associated with each incubator project;
3. Holding a semi-annual national competition for AD/ADRD research projects using the Platform in innovative ways, and recommending funding of such studies to NIA starting in Year 2; with individual studies not exceeding $200,000 in direct costs;
4. Holding a semi-annual national competition for AD/ADRD clinical trials using the Platform in innovative ways, and recommending funding of such trials to NIA starting in Year 3, with individual trials not exceeding $500,000 in direct costs and with projects supporting full trials or being designed to lead to (or inform) the design of larger scale AD/ADRD trials that leverage RWD;
5. Providing recruitment, design, and analysis support for human subjects research using the Platform;
6. In coordination with the Clinical Research Networks Core, expanding the number of partners and data sources within the Clinical Research Network; and
7. Including high-value RWD, such as lab results?

To what extent will the strategies to address the required features lead to success in accomplishing the goals of the Incubator Core?

How well does the application address the required Incubator Core KPIs and KRIs, which will be tracked, monitored, and reported to NIA program staff by the Administrative Core?

In addition, for applications involving clinical trials

Does the application adequately address the following, if applicable

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

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?

In addition, for applications involving clinical trials

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

Additional Review Criteria - Incubator Core

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.

Study Timeline

Specific to applications involving clinical trials

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

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.

Additional Review Considerations - Incubator Core

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).

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.

Scored Review Criteria - Optional Investigator-Initiated Core 1 and Optional Investigator-Initiated Core 2

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

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?

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?

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?

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?

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?

Additional Review Criteria - Optional Investigator-Initiated Core 1 and Optional Investigator-Initiated Core 2

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.

Additional Review Considerations - Optional Investigator-Initiated Core 1 and Optional Investigator-Initiated Core 2

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).

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.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the National Institute on Aging, 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 NOFO.

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 NOFO. 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.

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 NOFO 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.

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain applicable clinical trials on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that all 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.

Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

Prior Approval of Pilot Projects

Recipient-selected projects that involve {clinical trials or 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:

• Federal wide 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 condition of receiving the grant, to administer 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. 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 NOFO.

• 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.htmlandhttps://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 https://www.hhs.gov/civil-rights/for-individuals/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.

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 74 and 92 [Part 92 is applicable when State and local Governments are eligible to apply] and 2 CFR Part 200, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the recipients is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and the NIH as defined below.

Recipients will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies. If requested by program staff, a material transfer agreement must be executed within thirty days to facilitate materials sharing. Recipients will also facilitate, create, and support the development of material transfer agreements for transfer of data to the new recipient (if applicable) after the end of the project period if directed by NIA.

The PD(s) PI(s) will have the primary responsibility for:

• Ensuring completion of NOFO specified milestones, KPIs, and KRIs.
• Determining approaches, designing, and setting (1) PD/PI-specified additional project milestones, (2) KPIs, (3) KRIs and implementing the project plan for the Platform.
• Cooperating in sharing knowledge and experience with various tools and approaches utilized in conducting research in health care settings, including their strengths and weaknesses.
• Cooperating in sharing issues related to data quality, data management, data biases and errors, query quality and sampling challenges, and pitfalls in utilization of health care data for research.
• Cooperating with each incubator project recipient in the development and facilitation of Platform resources.
• Collaborating with Platform users in the harmonization and sharing of tools, methods, and approaches within and across the Platform.
• Cooperating with other researchers in the sharing of study designs, methods, protocols, tools, and strategies.
• Participating in group activities, including program-wide Work Group(s) and Steering Committee meetings.
• Facilitating collaboration across Platform cores while minimizing overlap of activities.
• Providing integrative, organizational, and logistical support for the entire program, including tracking, scheduling, and facilitating meetings and conference calls, and preparing minutes or summaries of meetings for distribution.
• Cooperating with Platform users in the publication and dissemination of program results and RWE and the eventual release to the scientific and healthcare communities of methods, tools, results, and other resources.
• Providing high-quality documentation, particularly of protocols or approaches that have broad applicability across the program, that will be sufficient for outside users to understand and apply to their research projects with minimal assistance.
• Providing expertise and leadership in addressing issues of broad applicability, such as informed consent, ethical standards, data sharing standards, analysis methodology, and dissemination.
• Sharing resources, data, and software as appropriate and consistent with achieving the goals of the Platform program and approved plans.
• Planning and hosting the face-to-face meetings of the Work Groups, Steering Committee, and any subcommittees.
• Alongside NIA program staff, attending and hosting External Advisory Panel (EAP) meetings.
• Agreeing to accept close coordination, cooperation, and management of the project with NIH, including those outlined under NIH Responsibilities .
• Producing quarterly progress reports during Year 1-Year 3 and biannually thereafter for submission to NIA through AOR.
• Retaining custody and having primary rights to the data and software at the recipient institution developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies and goals of this program. All research, data (it is expected the Platform will have a Data Sharing plan which will protect human subjects), and resources generated are expected to have broad availability through a public-facing website in order to facilitate collaboration, reuse, and replication, as appropriate and consistent with achieving the goals of the program.
• Managing the Platform Steering Committee of at least 7 independent experts in addition to Platform leadership, PDs/PIs, and the NIH Project Scientist(s) that is established to address issues that span across all projects, provide input towards the policies and processes of the Platform, and assist in dissemination of policies and processes that enable research in partnership with data vendors--public and private. The Steering Committee must be established by month three of Year 1, and must meet quarterly. All members are expected to participate actively in all Steering Committee activities. Action items and notes from each Steering Committee meeting must be produced and provided to NIA program staff.
• Engaging the parent institution and having one designated Authorized Organizational Representative (AOR) and dedicated email address designated to the AOR for communication with NIA.
• Engaging the parent institution and having one designated legal representative who will be responsible for executing legal agreements with the PD/PI and have signatory authority for facilitating, creating, and supporting the development and execution of ALL material and data transfer agreements within 30 days of NIA notice.
• Coordinating third party security audits of the platform and submitting findings to NIA.

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

• NIA and NINDS/NIH Project Scientist(s) will work with the PI/PD and the Steering Committee to ensure that the objectives of the program are being met. The dominant role and prime responsibility for the program resides with the recipient, although specific tasks and activities will be shared among the awardee and NIA/NIH Project Scientist(s).
• NIA/NIH Project Scientist(s) will provide technical assistance, advice, and coordination; however, the role of NIH staff will be to facilitate and not to direct activities. It is anticipated that decisions in all activities will be reached by consensus of the Platform and NIH staff will be given the opportunity to offer input to this process.
• NIA/NIH Project Scientist(s) serves as the contact point for addressing the program objectives with the recipient.
• NIA/NIH Project Scientists(s) will serve as liaison between the Steering Committee and NIH EAP.
• Additional NIA/NIH staff (e.g., additional projects scientists) may participate in all work groups, implementation teams, and committees, including the Steering Committee, as appropriate. Participation by staff from other federal agencies may also be appropriate and advantageous to facilitate the activities of the program.
• NIA/NIH staff may assist in development, design, and coordination of activities and projects.
• NIA/NIH staff may attend EAP meetings and receive a copy of the recommendations.
• An agency program official(s) will be responsible for the normal scientific (project scientist) and programmatic stewardship (program officer) of the award and will be named in the award notice.

In order to ensure that the Platform achieves NIA assistance objectives under the cooperative agreement, NIA will establish and appoint members to an EAP comprised of NIA and NINDS staff, study investigators, representatives from relevant federal agencies, and independent scientific experts in areas appropriate for the Platform’s multidimensional content. Experts, including but not limited to the Principal Investigator(s), co-Investigators, NIA and NINDS staff, and invited independent experts, will make presentations to the EAP on scientific and administrative issues regarding the development and implementation of study aims. NIA Program Officials and the PIs may request the EAP’s recommendations on specific issues, including progress towards Platform milestones (referenced in Section I.3). The NIA Program Official and the investigators will consider the recommendations of the EAP regarding implementation of study aims as well as additions or changes to content and methods during the execution of the cooperative agreement(s). The EAP will report to NIA and communicate specific recommendations regarding funding priorities via executive sessions in EAP meetings. The EAP will also, where appropriate, provide recommendations to the Principal Investigator(s) and Steering Committee; these recommendations are not binding on the Principal Investigator(s) who retain primary responsibility for scientific direction and implementation.

Areas of Joint Responsibility include:

• Incubator Core recipients will work with the Platform and the NIH, through all phases of their projects, including the implementation and close out phase, to assure all resources, materials, protocols, data, best practices, and lessons learned, as well as software or sets of code, are disseminated broadly through the Platform.
• The recipeint and the NIH will cooperate to ensure the timely and broad dissemination of all Platform developed and endorsed policies/practices and lessons learned in the program to inform researchers and health care systems engaged in AD/ADRD research.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual recipient. This special dispute resolution procedure does not alter the recipient's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

Additional Terms for Termination:

Dispute resolution will not be applicable if a recipient is unable to reach milestones (as specified in Part 7, Section I of this NOFO); unable to maintain clinical research networks; unable to maintain partnerships with RWD vendors; and/or fails to integrate private RWD with CMS claims data. The cooperative agreement may be terminated by the NIH/NIA if milestones (as specified in Part 2, Section I of this NOFO) are not reached. That is, the recipient institution and the NIH/NIA will not engage in dispute resolution.

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. If additional Data Management and Sharing requirements need to be added, please insert what requirements are desired.

Principles of Data and Resource Sharing for the RWD Platform

• This NOFO REQUIRES the sharing of ALL resources with a broad availability of policies, practices, materials, and tools to facilitate collaboration, reuse, and replication, as appropriate and consistent with achieving the goals of the program unless they are prohibited by Bayh-Dole Regulations.
• It is imperative that any data collection performed or data purchased under the purview of this cooperative agreement must have permission/consents set up in such a manner with respondents and institutions that will allow broad use of data and resource sharing (i.e., not limited to researchers conducting the study).
• This NOFO requires sharing of all tools, software and codes that are developed or modified to accomplish the aims of this platform unless they are prohibited by Bayh-Dole Regulations.
• This NOFO requires sharing of all tools, software, codes, research protocols and other resources created via support from incubator core to be broadly shared unless they are prohibited by Bayh-Dole Regulations.
• This NOFO requires adoption of Findable, Accessible, Interoperable, and Re-usable (FAIR) data principles when addressing each application component and encourages PD/PIs to consider obtaining a Core Trust Seal by the third year of the award, including a separate Core Trust Seal approval for AD/ADRD registry.

Applications must address the following items:

• Describe any transformations to the RWD data (e.g., application of algorithms and/or tools) that will be applied to the data before it is shared and how codes associated with the transformation will be shared.
• Indicate the user access to RWD platform where data will be located and have a clear plan and capacity to share from their own site(s).
• Describe OMOP and other data transformations and release relevant codes used for data cleaning and aggregation.
• Describe and justify the timetable to release the data or other resources. Generally, data release by the Platform must meet NIA-defined milestones. Investigators should justify exceptions to that timing.
• The data, analytical codes and referenced resource generated by Platform users from a publication should be made available by the on-line publication date unless NIH policy specifies an earlier date
• Identify any restrictions on sharing and justify them. Restrictions might include, for example, no commercial use of the data or resource, only qualified users may access the material, or, no attempt to reveal personal or private information may be made. Investigators may also set different levels of access, for example, for expert users and novice users.
• Describe how all materials (e.g., individual sources of data, tools and software developed, and all resources generated from this NOFO) will be transferred to a new entity at the end of the project period to enable long-term maintenance of the RWD Platform
• For studies involving human participants, describe how the investigators will mitigate deidentification risk with the data, whether that procedure is one following HIPAA, IRB, or other Institutional guidance, and generally how they will secure the personal and private information of the participants; this includes a condition on the end-user certifying that no attempts to identify participants from the de-identified data will be made and specified cell sizes; and review of outputs.
• Address considerations of privacy-preserving linkages and how such keys will be transferred to various parties (e.g., pharmacy chains and NIA contractor; pharmacy chain and RWD vendors) preserving PII for future follow-up.
• Address timely (i.e., within 30 days of NIA notice) execution of the material transfer agreement within and across the consortia members, and with third parties if directed by NIA. The material transfer agreement includes, but is not limited to, transfer of RWD to NIA contractor for CMS linkage, providing access to users, and all derived data from RWD sources and resources generated by the cooperative agreement.
• Describe the risk to respondent and/or clinical trials study participants and how such risk and confidentiality will be mitigated.
• Explain how the complete collection of metadata (data about the data) will be provided.
• Explain how the complete variable metadata (variable and value labels) will be provided either directly in the data file(s) or in supporting syntax file(s) with searchable and dynamic view (i.e., not a PDF).
• Explain how documentation (e.g., codebook, questionnaire, and user guide) will be provided and how the data will be made searchable within Platform.
• Describe the process for ensuring that variable names for longitudinal data are consistent across time or follow a consistent pattern across waves so it is clear to secondary data users that those data were measured at each time point (for instance, T1_NUMBER_OF COMORBIDITIES; T2_NUMBER_OF COMORBIDITIES, etc.).
• Describe how user-friendly files will be created for research use and training which will be provided.
• Described how data will be released under minimum data necessary principles for research purposed (i.e., additional data should not be released in not needed for research purpose)
• If applicable, specify how data will be provided via tiered access (e.g., data access to registry vs enrolling study participants from the clinical research network by a via enclave) based on identification risk.
• Present milestones for various releases of data resulting from this NOFO (e.g., AD/ADRD registry and frequency of updates).
• Present a plan for programmatic evaluation of timeliness of data use agreement and platform access requests.

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 NOFOs 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 75.113 and 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 75 and 2 CFR Part 200 Award Term and Condition for Recipient Integrity and Performance Matters.

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]

Partha Bhattacharyya, Ph.D.
Division of Behavioral and Social Research (DBSR)
National Institute on Aging (NIA)

Stacy Carrington-Lawrence, Ph.D.
Division of Aging Biology (DAB)
National Institute on Aging (NIA)

Patricia Jones, DrPH, MPH, MS, MBA
Office of Special Populations (OSP)
National Institute on Aging (NIA)

Lisa Onken, Ph.D.
Division of Behavioral and Social Research (DBSR)
National Institute on Aging (NIA)

Marcel Salive MD, MPH
Division of Geriatrics and Clinical Gerontology (DGCG)
National Institute on Aging (NIA)

Nina Silverberg, Ph.D.
Division of Neuroscience (DN)
National Institute on Aging (NIA)

Nadezda Radoja, Ph.D.
Division of Neuroscience (DN)
National Institute on Aging (NIA)

M. Carolina Mendoza-Puccini, MD
Division of Clinical Research (DCR)
National Institute of Neurological Disorders and Stroke (NINDS)

Email address for all inquiries: [email protected]

Ramesh Vemuri, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-402-7700
Email: [email protected]

Megan Hancock
National Institute on Aging (NIA)
Telephone: 301-451-9802
Email: [email protected]

Chief Grants Management Officer
National Institute of Neurological Disorders and Stroke (NINDS)
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.