HEAL INITIATIVE: Development and validation of remote or patient wearable device derived objective biosignatures or functional assessments to monitor pain for use as endpoints in clinical trials (UG3/UH3 - Clinical Trial Optional) | RFA NS 24 023

Opportunity Information: Apply for RFA NS 24 023

This funding opportunity, titled "HEAL INITIATIVE: Development and validation of remote or patient wearable device derived objective biosignatures or functional assessments to monitor pain for use as endpoints in clinical trials (UG3/UH3 - Clinical Trial Optional)" (RFA-NS-24-023), is a National Institutes of Health (NIH) cooperative agreement aimed at pushing pain research toward more objective, real-world measures that can be used in clinical studies. The core idea is to support projects that can develop and validate digital endpoints captured remotely, especially through wearable devices, to track how pain is experienced over time, how it changes as a condition progresses, and how it responds to interventions or treatments. A major motivation behind this is the long-standing challenge in pain research: pain is often measured primarily through self-report, which is important but can be variable and difficult to standardize across settings, populations, and trials. This initiative is meant to help create reliable, scalable measures that reflect meaningful aspects of pain and function in everyday life, rather than only in clinic visits.

In this announcement, "endpoints" refers to measures that can serve as outcomes in clinical trials, including trials evaluating therapeutics for pain. The opportunity emphasizes "remote digital endpoints," meaning the data are collected outside the clinic in real-world contexts, and "objective biosignatures," meaning patterns or combinations of signals derived from wearable sensors that reflect physiological and functional states relevant to pain. These biosignatures may come from functional assessments (such as mobility, gait characteristics, activity patterns, or performance on defined tasks that can be captured by sensors) and physiological assessments (such as heart rate and variability, sleep metrics, autonomic indicators, electrodermal activity, respiration-related measures, or other sensor-derived signals). The intent is not just to gather wearable data, but to translate those signals into validated measures that can credibly indicate pain experience, pain-related disability, recovery or deterioration, and treatment response, including impacts on quality of life.

Because this is a UG3/UH3 mechanism, the structure is typically milestone-driven and phased, supporting a progression from earlier-stage development work into a later-stage implementation and validation phase. While the source text does not detail the milestones, UG3/UH3 programs generally expect investigators to propose clear go/no-go criteria and a plan that reduces risk by demonstrating feasibility first (UG3) and then moving into more definitive validation activities (UH3) once initial benchmarks are met. The listing also notes "Clinical Trial Optional," which signals that applicants may propose a clinical trial if it is appropriate for validating the endpoint, but a clinical trial is not strictly required for all projects. The overall emphasis remains on producing endpoints that are credible for use in clinical trials of pain therapeutics, meaning they should be measurable, interpretable, and linked to clinically meaningful outcomes.

The opportunity is part of the HEAL (Helping to End Addiction Long-term) Initiative, reflecting a broader federal effort to improve pain management and develop better tools and treatments while addressing downstream harms associated with inadequate or risky pain treatment pathways. In practical terms, the program is trying to accelerate the field toward endpoints that can make trials more efficient and informative. If wearable-derived endpoints can reliably measure pain-related function and physiology in daily life, they can potentially improve trial sensitivity, reduce reliance on episodic clinic-based assessments, capture more representative patient experiences, and help determine whether a therapy produces real improvements that matter to patients.

Administrative details from the notice include that this is a discretionary funding opportunity using a cooperative agreement mechanism, indicating substantial NIH program involvement during the project period compared with a standard grant. The activity categories listed span education, health, income security, and social services, and the CFDA numbers provided (93.213, 93.273, 93.313, 93.393, 93.394, 93.395, 93.853, 93.865, 93.866) reflect the NIH program and institute components associated with the award. The opportunity was created on 2023-09-01, with an original closing date of 2024-10-05. The excerpt does not provide an award ceiling or expected number of awards, suggesting those details may be specified in the full funding announcement or depend on appropriations and program priorities.

Eligibility is broad and includes many types of domestic organizations and certain non-U.S. entities. Eligible applicants explicitly include state, county, city/township, and special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; federally recognized Native American tribal governments; Native American tribal organizations that are not federally recognized tribal governments; public housing authorities/Indian housing authorities; nonprofits (both 501(c)(3) and non-501(c)(3)); for-profit organizations (other than small businesses); small businesses; and other entities. The opportunity additionally highlights a wide set of organizations as eligible or encouraged to apply, including Alaska Native and Native Hawaiian Serving Institutions, AANAPISIs, Hispanic-serving Institutions, Historically Black Colleges and Universities, Tribally Controlled Colleges and Universities, faith-based or community-based organizations, regional organizations, U.S. territories or possessions, eligible federal agencies, and non-domestic (non-U.S.) entities/foreign organizations, as well as Indian/Native American tribal governments other than federally recognized. Taken together, this suggests NIH is seeking broad participation and potentially diverse patient populations and real-world settings, which is particularly relevant for pain research where experience and access to care can vary widely across communities.

At a high level, a competitive project under this RFA would likely focus on turning wearable sensor data into an endpoint that is demonstrably fit-for-purpose for pain trials. That typically implies careful attention to analytic validity (the sensor and processing pipeline accurately and reliably measure the signal), clinical validity (the derived endpoint relates to pain states, functional impairment, or treatment response in a meaningful way), and usability and feasibility in real-world use (participants can and will wear the device, data capture works outside controlled settings, and missing data and confounding factors like activity, comorbidities, and medication use are handled appropriately). The program description makes clear that the desired outputs are not just new gadgets or raw data streams, but validated biosignatures and functional/physiological assessments that can serve as trial endpoints to monitor pain and the effects of therapeutics.

• The National Institutes of Health in the education, health, income security and social services sector is offering a public funding opportunity titled "HEAL INITIATIVE: Development and validation of remote or patient wearable device derived objective biosignatures or functional assessments to monitor pain for use as endpoints in clinical trials (UG3/UH3 - Clinical Trial Optional)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.213, 93.273, 93.313, 93.393, 93.394, 93.395, 93.853, 93.865, 93.866.
• This funding opportunity was created on 2023-09-01.
• Applicants must submit their applications by 2024-10-05. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

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