Notice of Intent to Publish a Notice of Funding Opportunity for Open Measurement Coordinating Network for Non-Pharmacological Alzheimer's Disease (AD) and AD-Related Dementias (ADRD) Primary Prevention Trials (U24 Clinical Trial Not Allowed)

Key Dates

None.

National Institute on Aging (NIA)

The National Institute on Aging (NIA), part of the National Institutes of Health (NIH), intends to publish a Notice of Funding Opportunity (NOFO) to solicit applications that propose to establish a national Open Measurement Coordinating Network for Non-Pharmacological Alzheimer's Disease (AD) and AD-related Dementias (ADRD) Primary Prevention Trials. The Network will serve as a centralized hub for developing, validating, standardizing, and disseminating measures and measurement methods for AD/ADRD primary prevention trials. It will incorporate measures and measurement methods across neuropsychological, biomarker, and functional domains to meet the goal of primary prevention of AD/ADRD centered around brain health equity. Brain health equity is the fair distribution of brain health determinants, outcomes, and resources within and between segments of the population, regardless of social standing. Measures and methods of interest will test outcomes and mechanisms of action in settings customized for individuals with different needs and linked to real-world function.

Applications must explain how the platform will meet evolving community needs and partner with other NIA-funded programs. Applications must also describe activities that will achieve the following objectives:

1. Develop an organizational and governance structure to support the administration, innovation, and dissemination functions of the Network. Propose activities to establish a framework that will facilitate the development of innovative strategies for standardization and use of methods and measures across NIA-supported projects and support activities for the discovery and development of innovative and novel measures and data.
2. Disseminate Network resources and products to the broader AD/ADRD research community.
3. Ensure that all measures and methods development and validation occurs in a racially, ethnically, geographically, and diagnostically diverse set of participants, including members of NIH-defined Health Disparity Populations. This also includes establishing the acceptability and feasibility of using the proposed instruments in both cognitively normal individuals and persons living with cognitive impairment (PLWCI), including subjective cognitive decline.

NIA is particularly interested in proposals that advance equity for populations disproportionately impacted by AD/ADRD. For example, Black and Hispanic Americans have a higher prevalence of AD/ADRD compared to non-Hispanic White Americans. Resources, including measurement instruments, methods, algorithms, code, documentation, and normative data will enable other, future measures and methods development projects that support AD/ADRD primary prevention research needs.

This Notice is being provided to allow potential applicants sufficient time to develop meaningful collaborations and responsive projects.

The NOFO is expected to be published in early 2024 with an expected application due date in Spring/Summer 2024.

This NOFO will utilize the U24 activity code.

This Notice encourages investigators with expertise and insights into this area of prevention of AD/ADRD, especially the development, validation, and standardization of measures (neuropsychological, biomarker, functional) for outcomes and mechanisms of action, as well as moderators for midlife trials centered around brain health equity to begin to consider applying for the upcoming NOFO.

Recent clinical trials and observational studies suggest that targeting disease and modifiable risk factors in midlife or earlier can help prevent or delay significant cognitive and functional impairment in AD/ADRD. However, only 15% of AD/ADRD research studies include participants with a mean age of less than 60 years, and approximately 3% of AD/ADRD research studies include participants wit ha mean age of less than 50 years. AD/ADRD Milestone 8.D details the need for primary prevention trials for non-pharmacological interventions in midlife and describes successful trials as those that will provide evidence for potential therapeutic mechanisms and include the collection of biomarker data for future validation and longitudinal follow-up within the trial cohort. However, the evidence that would inform the design of such primary prevention trials in AD/ADRD, including leading therapeutic mechanisms, is mixed. A 2017 report from the National Academies of Sciences, Engineering, and Medicine (NASEM) suggested numerous ways to construct a stronger evidence base for the prevention of cognitive decline and AD/ADRD. This was followed by several meetings convened by NIA, which emphasized that targeting measurement needs was a critical first step for a successful AD/ADRD primary prevention approach.

In order to meet these goals, the field needs to develop, validate, and standardize measures for outcomes and mechanisms of action, as well as moderators for midlife trials. Specific needs include:

1. Measurement approaches to detect changes in function in early stages of AD/ADRD (e.g., before 65 years, before dementia diagnosis), which are slow, subtle, and variable
2. Earlier detection of small changes in midlife to allow maximally responsive preventative interventions
3. Incorporation of cognitive and non-cognitive, biomarker, behavioral, psychosocial, and functional measures
4. Measures that eliminate, minimize, or rigorously account for ethnocultural bias
5. Brief, valid measures that relate to clinically meaningful outcomes and real-world function
6. Efficient, flexible study designs (e.g., longitudinal, ecological momentary assessment) to optimize sensitivity, assessment across critical periods of change, and enable participant-centered research.

Network infrastructure should be open, transparent, extensible, customizable, and have a sustainable revenue model. The goal is to create infrastructure to support the coordination of measurement development, validation, and standardization customized for individuals with different needs and linked to real-world function. The lack of comparable measures in clinical trials has made it difficult to detect and understand longitudinal changes in function, but recent advances in measurement and digital technology offer the possibility of improving future trials (Landscape of Early Changes in AD/ADRD Project, 2023). This will address AD/ADRD Milestones 8D, 11B, and 11F.?

The Network will collaborate with other NIA-funded programs to ensure interoperability, promote diversity, equity, and inclusion, and ensure the methods and resources are widely adopted by researchers and stakeholders. An example deliverable is a core set of measures for AD/ADRD primary prevention trials. These core measures could be identified for testing and validation and disseminated to researchers conducting prevention studies in the initial phases of the program. Subsequent phases of the program would include evaluation of initial findings and refinement of measures. The proposed development cycle should be multidirectional with evaluation at a later stage informing measures modification and testing at an earlier stage. Final implementation and full operational infrastructure to support primary prevention trial measurement needs would be established by the end of the five-year program. It is anticipated that new intervention targets will be discovered, potentially requiring new measures and methods; therefore, development and testing will focus on modification, repurposing, and new measures creation throughout the project period. The Network will enhance the sustainability and impact of research software tools by enabling the use of best practices and design principles in software development and leverage advances in computing in a modern data ecosystem. A successful Network will include collaborations between scientists and software engineers to optimize the design, implementation, and cloud-readiness of research software and to advance the principles and practices of open science. This initiative is aligned with the NIH Strategic Plan for Data Science, which describes actions aimed at building a better data infrastructure and a modernized data ecosystem as well as NIA Strategic Goal G: support the infrastructure and resources needed to promote high-quality research.

Open principles and practices are central to this initiative. Network infrastructure will promote equity and innovation through an open-source model that emphasizes collaboration and transparency over traditional single-provider and proprietary models. Single-provider refers to a centralized system where all services and assessments are exclusively offered and controlled by one organization (e.g., academic institution, company). Open collaboration, including more inclusive and equitable research participation and practices, leads to more effective measurement development. When researchers from different fields, regions, and backgrounds collaborate, they can contribute unique insights and approaches to complex problems. Additionally, open collaboration facilitates transparency and improves the quality of research outcomes. Open software tools improve the quality and sustainability of research software in the face of ongoing technical enhancements and allow community development responsive to rapidly evolving needs. Open practices promote sharing of data, methods, and results, enabling other researchers to replicate and build upon existing work. Open practices include open measures and scoring algorithms, as well as open, but protected, data.

Funding Information

Public/State Controlled Institution of Higher Education
Private Institution of Higher Education
Nonprofit with 501(c)(3) IRS Status (Other than Institution of Higher Education)
Small Business
For-Profit Organization (Other than Small Business)
State Government
Indian/Native American Tribal Government (Federally Recognized)
County governments
Independent school districts
Public housing authorities/Indian housing authorities
Indian/Native American Tribally Designated Organization (Native American tribal organizations (other than Federally recognized tribal governments)
U.S. Territory or Possession
Indian/Native American Tribal Government (Other than Federally Recognized)
Non-domestic (non-U.S.) Entity (Foreign Organization)
Regional Organization
Eligible Agencies of the Federal Government

Applications are not being solicited at this time.

Inquiries

Please direct all inquiries to:

Luke Stoeckel, Ph.D. and/or Kristina McLinden, Ph.D.
National Institute on Aging (NIA)
Email: [email protected]