Assessing the Feasibility of Incorporating Mechanisms in Multi-site Clinical Trials of Mind and Body Interventions on Whole Person Health Restoration (R33 Clinical Trial Required) | PAR 28 091

Opportunity Information: Apply for PAR 28 091

The National Center for Complementary and Integrative Health (NCCIH), part of the National Institutes of Health (NIH), is offering support through a grant mechanism called an R33 (Clinical Trial Required) for teams that want to run early-phase, multi-site feasibility clinical trials of mind and body interventions. In this announcement, mind and body interventions refers to complementary and integrative health approaches that involve physical and/or psychological therapeutic inputs, and the central scientific emphasis is on emotional well-being (EWB) as a set of mechanisms that may help explain how these interventions contribute to whole person health restoration. The overall intent is not to fund a large definitive efficacy trial yet, but to build the practical and scientific groundwork needed for later, larger clinical trials that can credibly test outcomes and perform mechanistic mediation analyses.

A core feature of this opportunity is its focus on reproducibility and translation across multiple sites. Applicants are expected to use a multi-site design to show that an intervention can be delivered consistently (with fidelity) in different real-world research environments, and that the same hypothesized EWB mechanisms can be engaged in a rigorous and reproducible way at each site. This reflects NCCIHs interest in moving beyond single-site proof-of-concept studies toward designs that better anticipate the operational complexity and variability that show up in large-scale trials. In practice, this means the application should pay close attention to standardization of intervention delivery, training and certification procedures for interventionists, quality assurance monitoring, and harmonized protocols so that results are interpretable when data are pooled across sites.

The NOFO lays out several concrete feasibility targets that these early-phase trials should address. First, studies need to demonstrate cross-site intervention fidelity, meaning the intervention is delivered as intended and in a comparable way at every participating location. Second, they must test whether the proposed emotional well-being mechanisms are actually engaged by the intervention across sites, using measures and procedures that are strong enough to support later mechanistic testing. Third, projects should evaluate recruitment, retention, and randomization feasibility, since these operational factors often determine whether a later full-scale trial is realistic. Fourth, applicants should assess the feasibility of collecting both comprehensive clinical outcome data relevant to whole person health restoration and mechanistic EWB data across all sites, which implies harmonized assessment schedules, consistent data collection procedures, and workable data management plans. Fifth, while the trial is still considered feasibility-focused, investigators are encouraged to explore relationships between changes in mechanistic targets and changes in clinical outcomes using pooled data across sites, which helps generate evidence that the mechanism and the outcomes move together in the way the theory predicts.

In terms of scope, this program is essentially asking applicants to bridge two needs at once: operational readiness for multi-site research and scientifically credible measurement of mechanisms related to emotional well-being. Successful applications will typically make a clear case for why a specific mind and body intervention should influence specific EWB mechanisms, explain how those mechanisms are measured consistently, and show that the team can run a coordinated multi-site study with strong data quality. The longer-term payoff NCCIH is aiming for is a pipeline of well-prepared interventions and research teams that can go on to run large, rigorous clinical trials capable of testing whole person health outcomes and formally evaluating whether EWB mechanisms mediate those outcomes.

The funding opportunity is listed as PAR 28 091, uses a grant funding instrument, and falls under NIH health research activity areas (CFDA numbers 93.213 and 93.473). The posted award ceiling is $500,000, and the opportunity is open for submissions until an original closing date of 2029-11-16. Eligibility is broad within the United States and includes state and local governments, tribal governments and certain tribal organizations, public and private institutions of higher education, nonprofit organizations (with or without 501(c)(3) status), and for-profit organizations (including small businesses, though the listing specifies for-profits other than small businesses as well). As a strict limitation, non-U.S. organizations are not eligible to apply, non-U.S. components of U.S. organizations are not eligible, and foreign components are not allowed as defined by NIH policy. For details beyond the summary, applicants are directed to consult Section III of the NOFO for the complete eligibility requirements and any additional constraints.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Assessing the Feasibility of Incorporating Mechanisms in Multi-site Clinical Trials of Mind and Body Interventions on Whole Person Health Restoration (R33 Clinical Trial Required)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.213, 93.473.
• This funding opportunity was created on 2026-10-15.
• Applicants must submit their applications by 2029-11-16.
• Each selected applicant is eligible to receive up to $500,000.00 in funding.
• 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 PAR 28 091

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