HEAL Initiative: Discovery of Biomarkers and Biomarker Signatures to Facilitate Clinical Trials for Pain Therapeutics (UG3/UH3 Clinical Trial Optional) | RFA NS 22 050

Opportunity Information: Apply for RFA NS 22 050

The HEAL Initiative FOA "Discovery of Biomarkers and Biomarker Signatures to Facilitate Clinical Trials for Pain Therapeutics (UG3/UH3 Clinical Trial Optional)" (RFA-NS-22-050) is an NIH cooperative agreement opportunity designed to speed up the development of non-opioid pain treatments by improving how Phase II clinical trials are run and interpreted. The central goal is to discover and refine strong candidate pain biomarkers, or multi-measure biomarker signatures (biosignatures), that can either predict who is likely to respond to a therapy and/or monitor whether a therapy is working during a trial. In practical terms, NIH is looking for clinical research programs that generate objective, trial-ready biological or physiological indicators of treatment response, so that future mid-stage trials can enroll the right participants, detect meaningful signals earlier, and make better go/no-go decisions.

The FOA emphasizes that the biomarker work must be grounded in clinical research focused specifically on therapeutic response. That means the proposed biomarker or biosignature is not just a general marker of pain severity, diagnosis, or risk; it is expected to be tied to how people respond to a pain therapeutic, especially non-opioid candidates being evaluated in Phase II settings. The biomarkers can be developed for a single pain condition, or they can be designed to generalize across multiple pain conditions that share underlying mechanisms or pathophysiology. NIH is explicitly open to either approach, but it sets different team expectations depending on whether the project spans one condition or several.

For applications that aim to create biomarkers or biosignatures that work across several related pain conditions, NIH expects a Multiple Principal Investigator (MPI) structure that includes leadership representing each pain condition and the relevant clinical networks. A key requirement is harmonization: the MPI team is expected to agree on one common set of measures or biomarker modalities that will make up the biosignature across all the pain conditions included. The FOA gives examples of modalities that could be combined, such as omics approaches, quantitative sensory testing (QST), actigraphy, EEG, and digital measures, among others. The intent is to avoid a patchwork where each condition uses a different toolbox; instead, the same core measures should be collected in a consistent way so that cross-condition comparisons and shared algorithms are realistic.

Whether the project targets one condition or multiple, applications are expected to include centralized resource groups that provide coordination and standardization. These centralized components are meant to support consistent trial operations and uniform data generation, including standardized sample and data collection methods, technology development where needed, statistical analysis, and algorithm development. In other words, NIH is encouraging a structure that looks like a coordinated network rather than a set of loosely connected sites. Even for a single-condition biomarker program, NIH still expects an MPI-led team with cross-functional expertise (for example, clinical pain expertise, biomarker science, data science/biostatistics, and related technical domains), plus the same kind of centralized infrastructure to keep procedures, data quality, and analytic approaches consistent.

Administratively, this is a discretionary NIH funding opportunity using a cooperative agreement mechanism, meaning NIH is likely to have substantial programmatic involvement compared with a standard investigator-initiated grant. The funding instrument is listed as UG3/UH3, which generally signals a phased, milestone-driven structure (often a start-up or planning/optimization phase followed by an implementation/expansion phase), and the announcement notes "Clinical Trial Optional." The originating agency is the National Institutes of Health, and the opportunity was created on 2022-02-08 with an original closing date of 2023-02-23. The FOA lists multiple CFDA numbers associated with NIH institutes and centers participating under the broader HEAL Initiative.

Eligibility is broad and includes many typical NIH-eligible organizations: state, county, and local governments; special district governments; independent school districts; public and private institutions of higher education; federally recognized Native American tribal governments and certain tribal organizations; public housing authorities/Indian housing authorities; nonprofits (both 501(c)(3) and non-501(c)(3)); for-profit organizations (other than small businesses); and small businesses. The FOA also calls out additional eligible applicants such as Alaska Native and Native Hawaiian Serving Institutions, AANAPISIs, Hispanic-serving institutions, HBCUs, Tribally Controlled Colleges and Universities, faith-based or community-based organizations, regional organizations, and U.S. territories or possessions. International participation is allowed in specific forms: non-U.S. entities (foreign organizations and foreign institutions) may apply, and non-U.S. components of U.S. organizations may participate. However, "foreign components" as defined by the NIH Grants Policy Statement are not allowed, which is an important distinction for teams considering overseas collaborations and how those collaborations are structured within the application.

Overall, the opportunity is aimed at building clinically meaningful, standardized, and scalable biomarker solutions that can make non-opioid pain therapeutic trials more efficient and informative. NIH is signaling that successful projects will look like well-integrated clinical research programs with strong coordination, agreed-upon measurement strategies, and robust analytic plans for turning multi-modal data into usable predictors or monitors of treatment response.

• The National Institutes of Health in the education, health, income security and social services sector is offering a public funding opportunity titled "HEAL Initiative: Discovery of Biomarkers and Biomarker Signatures to Facilitate Clinical Trials for Pain Therapeutics (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): 93.121, 93.213, 93.233, 93.242, 93.279, 93.313, 93.393, 93.395, 93.837, 93.838, 93.839, 93.840, 93.846, 93.853, 93.865, 93.866, 93.867.
• This funding opportunity was created on 2022-02-08.
• Applicants must submit their applications by 2023-02-23. (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.

Apply for RFA NS 22 050

[Watch] Creating a grant proposal using the step-by-step wizard inside the applicant portal: