Notice of Intent to Publish a Funding Opportunity Announcement for the National Institute on Aging (NIA) Alzheimer's Disease (AD) and Alzheimer's Disease-Related Dementias (ADRD) Real-World Data (RWD) Platform Initiative (U54 Clinical Trial Required)

Key Dates

NOT-AG-22-039 - Request for Information (RFI) for the National Institute on Aging (NIA) Alzheimer’s Disease (AD) and AD-Related Dementias (ADRD) Real-World Data (RWD) Platform

National Institute on Aging (NIA)

This Notice informs the research community that the National Institute on Aging (NIA) intends to issue a Funding Opportunity Announcement (FOA) inviting applications for the NIA Alzheimer’s Disease (AD) and Alzheimer’s Disease-Related Dementias (ADRD) Real-World Data (RWD) Platform. This platform will aim to transform the AD/ADRD research enterprise by serving as a central hub for NIA grantees to:

1. Improve applicability and generalizability of research findings through larger datasets that incorporate more inclusive and diverse populations;
2. Capture complete information through linking a variety of real-world data sources;
3. Increase the speed at which scientific questions can be answered by facilitating many objectives, from clinical trial/clinical research recruitment to the generation of real-world evidence (RWE); and
4. Improve researchers’ ability to answer questions that cannot be feasibly or readily answered with a clinical trial.

The FOA is expected to be published in January 2023 for fiscal year 2024 funding, with the goal of making an award no later than spring 2024. The award for this FOA will be a cooperative agreement mechanism that will include substantial scientific and programmatic involvement by NIH officials and oversight by External Advisory Panel (EAP) appointed by NIA.

This FOA will utilize the U54 activity code. Details of the planned FOA are provided below.

Background

Despite the passage of the National Alzheimer’s Project Act in 2011, there is still an incomplete understanding of the mechanisms causing Alzheimer’s disease (AD) and Alzheimer’s disease-related dementias (ADRD), and few FDA-approved treatments, including diagnostics. Furthermore, many of the studies and trials examining AD/ADRD are conducted on individuals who do not adequately represent the populations experiencing disproportionately high rates of AD/ADRD. 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 that (1) AD/ADRD poses unique ethical considerations; (2) there is insufficient understanding of whether and how AD/ADRD can be prevented and when prevention interventions must begin; and (3) AD/ADRD typically requires a long duration of care. A central platform for data access would help researchers evaluate therapeutic treatments and behavioral interventions more rapidly, and at lower cost.

Real-world data (RWD) are defined as "the data relating to patient health status and/or the delivery of health care routinely collected from a variety of sources,” and reflect real-world settings, 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 (Food and Drug Administration, Framework for FDA’s Real-World Evidence Program, 2018). Examples of RWD include electronic health records (EHR), claims and billing data, registry data, public health data, patient-generated data in home-use settings, data generated and collected from mobile devices and wearables, and data collected from digital health technologies (DHTs). Studies of RWD reflect the actual clinical setting in which therapeutic interventions are applied, including patient demographics, comorbidities, adherence, and concurrent treatments. Further advantages of using RWD for healthcare research include lower costs, lower participant burden, increased efficiency, and increased participation of diverse patient groups who have historically been excluded from healthcare research.

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 to improve health outcomes for older adults and persons living with dementia (PLWD). However, 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 slows the progress of healthcare research—including research on drug design, biologic and device trials, and trials of behavioral health interventions—that requires analysis of multimodal data sets.

Establishing a platform that increases data access for recruitment and analyses of longitudinal RWD from older populations is timely given that the number of people diagnosed with dementia is expected to triple in the next 30 years. With few promising AD/ADRD prevention interventions and therapies to treat or slow the progression of AD/ADRD in the pipeline, there is a pressing need to understand how AD/ADRD care is supplied by various professional providers and institutions, the burden AD/ADRD can have on the health care system, and AD/ADRD’s effects on PLWD and their caregivers. This RWD platform is particularly important for research involving PLWD because of AD/ADRD’s long duration of care, unique ethical considerations, and high economic burden. RWD can help researchers evaluate therapeutic treatments, as well as clinical and behavioral interventions, more rapidly and at lower cost. RWD can also support the development and evaluation of therapeutic treatments that cannot or should not be studied through traditional randomized controlled clinical trials.

Specific Objectives of the Platform

The platform will transform the AD/ADRD research enterprise by improving data accessibility, building investigator capacity, and supporting AD/ADRD research through the following features:

• Centralized data-warehouse for integrating EHR, health and pharmacy claims data, sensor data/Internet of Things (IoT), mortality and natality data, and more, starting in 2015, which—by the end of the grant period—will represent 70-90 percent of the United States population (which is estimated to yield up to 80 percent of the AD/ADRD patient population), a wide range of adult cohorts, and the racial-ethnic diversity of the United States.
• Partnerships across various health providers, including pharmacies, for recruitment of inclusive and diverse populations for NIA-funded studies.
• Defined goals and objectives for using RWD to address health disparities through recruitment innovation, community engagement, and improved capacity to conduct research on more inclusive and diverse populations to address health disparities in the United States.

These features will support researchers to:

1. Securely access (zero trust environment and/or ATO environment for data linked from federal sources) multimodal health data (e.g., EHR, claims, genetics, imaging data, mobile devices generated data, etc.) from private data providers, the federal government, and academic institutions to gain insight across the complete AD/ADRD disease trajectory;
2. Develop a platform for an AD/ADRD digital cohort that provides access to a more diverse pool of individuals for recruitment (i.e., Recruitment as a Service) for clinical trials/research;
3. Collaborate in partnerships with health care and community health providers to enable rapid drug trials (RDT) and other trials and observational studies for improving care for older adults with multimorbidity, including AD/ADRD; and
4. Facilitate secure analyses of RWD through secure cloud workspaces while protecting the privacy of the study participants (e.g., cell size limit disclosure, geographics restriction, privacy preserving linkages so personal identifiers are not available to researchers).

The platform will be responsive to concerns expressed by communities that have been historically marginalized and underrepresented in clinical research. Applicant organizations will be expected to take appropriate and thorough measures to inform community representatives of any plans to procure various data from third-parties’ real-world sources of de-identified clinical data used for indefinite purposes well in advance of conducting research. The platform will take appropriate measures to facilitate programmatic accountability in seeking community input on equitable and fair processes to inform the use of de-identified data for indefinite purposes.

Core Structure

This initiative will include required Cores, along with a maximum of two optional Cores specified by the applicant.

The required Cores may include:

Vision, Planning, and Administration 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.

Clinical Research Network 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.

Community Engagement, Data Privacy, and Ethics Core: Will engage with diverse and underrepresented 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.

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.

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.

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.

Data Quality, Integration, and Access 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 Centers for Medicare and Medicaid Services (CMS) claims data.

Incubator Core: Will hold national competitions to fund and facilitate research projects (e.g., generating RWE of a new AD/ADRD drug approved by the Food and Drug Administration (FDA), novel recruitment services, AD/ADRD registries, generating RWE on marketed devices that had been granted FDA Breakthrough Device designation, health surveillance, rapidly deploying clinical trials in real-world settings, expansion of clinical research networks).

Applicants may also include up to two optional Cores (e.g., Reproducibility Core, Community Outreach Core, Social Determinants of Health Core, etc.).

Applicants will be asked to supply details for all required Cores, interactions between cores, population estimates (without duplicates) for data coverage, information on how optional cores (if used) will support the initiative’s goals, and the vision and plan for interactions between Cores as part of one cohesive platform.

Data and Resource Sharing: Robust and comprehensive data and resource sharing will be required.

PD/PI/MPI/Core Lead/Executive Director Effort: This initiative will require 9-12 months of effort from key personnel.

Other related information: NIA issued a Request for Information related to this announcement and intends to incorporate feedback from the community (as appropriate and within the scope of the concept approved by the National Advisory Council on Aging) when issuing the FOA.

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)
Regional Organization

Applications are not being solicited at this time. 

Please direct all inquiries to:

Partha Bhattacharyya, Ph.D.
Office of Data Resources and Analytics (ODRA)
National Institute on Aging (NIA)
Phone: (301) 496-3131
Email: NIARWD@nih.gov