Mind and Body Interventions to Restore Whole Person Health via Emotional Well-Being Mechanisms (R61/R33 Clinical Trial Required) is sponsored by U.S. Department of Health and Human Services; National Institutes of Health. This grant supports mechanistic research on the impact of mind and body interventions on emotional well-being and whole person health.

It focuses on feasibility studies and multi-site clinical trials to inform future large-scale studies.

PAR-25-449: Mind and Body Interventions to Restore Whole Person Health via Emotional Well-Being Mechanisms (R61/R33 Clinical Trial Required) Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) Components of Participating Organizations National Center for Complementary and Integrative Health ( NCCIH ) Funding Opportunity Title Mind and Body Interventions to Restore Whole Person Health via Emotional Well-Being Mechanisms (R61/R33 Clinical Trial Required) R61 / R33 Exploratory/Developmental Phased Award April 4, 2024 - Overview of Grant Application and Review Changes for Due Dates on or after January 25, 2025.

See Notice NOT-OD-24-084 . August 31, 2022 - Implementation Changes for Genomic Data Sharing Plans Included with Applications Due on or after January 25, 2023. See Notice NOT-OD-22-198 .

August 5, 2022 - Implementation Details for the NIH Data Management and Sharing Policy. See Notice NOT-OD-22-189 . Funding Opportunity Number (FON) Companion Funding Opportunity See Part 2, Section III.

3. Additional Information on Eligibility.

Assistance Listing Number(s) Funding Opportunity Purpose The National Center for Complementary and Integrative Health (NCCIH) announces this Notice of Funding Opportunity (NOFO) to solicit applications for research on how mind and body interventions through psychological and/or physical practices (e.g., mindfulness meditation, yoga, acupuncture, massage, and other brain- and/or body-based interventions) impact mechanisms of emotional well-being (EWB) and their associations with whole person health (WPH), consistent with the NIH priority to address the health needs of the American people and improve their well-being.

The NOFO will support rigorous and well-powered human mechanistic research studies that are supported by strong preliminary data. The studies should examine the effects of mind and body interventions on innovative mechanisms of EWB (as the primary outcome), as well as the associated relationship with the Whole Person Health Index (WPHI, as a secondary outcome).

To enhance research safety, rigor, and efficiency of NIH-funded mechanistic clinical trials, this initiative will use a two-phased award funding mechanism (R61/R33). The funding will support an initial phase (R61) to establish feasibility benchmarks for a subsequent proposed second phase (R33) mechanistic clinical trial, which will be contingent upon successful achievement of R61 benchmarks ("Go/No-Go Criteria").

Applications should provide preliminary data that are comparable in quality and quantity to those expected for an R01 application. Funding Opportunity Goal(s) The National Center for Complementary and Integrative Health (NCCIH) provides funding for research into complementary and integrative health approaches.

Eligible entities (including, but not limited to: research and academic institutions, private companies) may submit research grant applications using the Grants. gov website. All applications undergo a rigorous two-stage peer review system, and funding decisions are made based on the review of applications that are most meritorious and responsive to the mission of NCCIH.

Open Date (Earliest Submission Date) Renewal / Resubmission / Revision (as allowed) AIDS - New/Renewal/Resubmission/Revision, as allowed All applications are due by 5:00 PM local time of applicant organization. Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

Required Application Instructions It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide , except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts ). Conformance to all requirements (both in the Application Guide and the NOFO) is required and strictly enforced.

Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

There are several options available to submit your application through Grants. gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

Use the NIH ASSIST system to prepare, submit and track your application online. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants. gov and eRA Commons to track your application.

Check with your institutional officials regarding availability. Workspace to prepare and submit your application and eRA Commons to track your application. Part 1.

Overview Information Part 2. Full Text of Announcement Section I. Notice of Funding Opportunity Description Section II.

Award Information Section III. Eligibility Information Section IV. Application and Submission Information Section V.

Application Review Information Section VI. Award Administration Information Section VII. Agency Contacts Section VIII.

Other Information Part 2. Full Text of Announcement Section I.

Notice of Funding Opportunity Description The National Center for Complementary and Integrative Health (NCCIH) announces this Notice of Funding Opportunity (NOFO) to solicit applications for research on how mind and body interventions through psychological and/or physical practices (e.g., mindfulness meditation, yoga, acupuncture, massage, and other brain- and/or body-based interventions) impact mechanisms of emotional well-being (EWB) and their associations with whole person health (WPH), consistent with the NIH priority to address the health needs of the American people and improve their well-being.

The NOFO will support rigorous and well-powered human mechanistic research studies that are supported by strong preliminary data. The studies must examine the effects of mind and body interventions on innovative mechanisms of EWB (as the primary outcome), as well as the associated relationship with the Whole Person Health Index (WPHI, as a secondary outcome).

To enhance research safety, rigor, and efficiency of NIH-funded mechanistic clinical trials, this initiative will use a two-phased award funding mechanism (R61/R33). The funding will support an initial phase (R61) to establish feasibility benchmarks (“Go/No-Go Criteria”) for a subsequent proposed second phase (R33) mechanistic clinical trial(s), which will be contingent upon successful achievement of R61 benchmarks.

Applications should provide preliminary data that are comparable in quality and quantity to those expected for an R01 application. Chronic diseases are a health and economic burden. Approximately 60 percent of Americans have at least one chronic disease, such as high blood pressure, diabetes, and/or heart disease, and chronic diseases make up 8 of the 10 leading causes of death in the United States.

Ninety percent of the nation’s $4. 5 trillion in annual health care expenditures are for people with chronic and mental health conditions ( CDC 2024 ). Interventions to prevent and manage chronic disease could have significant health and economic benefits.

However, health and disease are not separate, disconnected states. Rather, they exist on a continuum, wherein a person can move toward or away from a state of health. The process by which individuals travel along this continuum from a less healthy state to a healthier state can be referred to as health restoration.

Health restoration is likely a complex and multifactorial process, involving multiple pathways, mechanisms, and the whole person. One way to assess health restoration is to explore potential positive changes in WPH. WPH involves looking at the whole person—not just separate organs or body systems—and considering factors that promote either health or disease.

Instead of just treating a specific disease, WPH focuses on restoring health and preventing diseases across the lifespan.

In collaboration with the Centers for Disease Control and Prevention, NCCIH has created the Whole Person Health Index (WPHI) Patient-Reported Measure that consists of nine domains asking individuals to rate their overall health, quality of life, social and family connections, physical activity, diet, stress management, sleep, sense of meaning and purpose, and health management.

Given the observation that health has been associated with EWB, one route to improved health may be through studying the impact of mind and body interventions on EWB. It is commonly believed that interventions that can prevent and manage chronic disease may also be able to promote whole person health. However, this concept has not been rigorously studied.

Data from the National Health Interview Survey found that over a third of U.S. adults use complementary and integrative health approaches, including mind and body interventions that involve psychological and/or physical inputs (e.g., yoga, meditation, acupuncture) ( Nahin et al. 2024 ). Mind and body interventions are often used for various health reasons including pain management ( Nahin et al.

2024 ), stress management ( Mandlik et al. 2024 ), and general health and well-being maintenance ( Rhee et al. 2018 ).

They are also used to improve EWB, a multidimensional composite that encompasses how positive an individual feels generally and about life overall ( Park et al. 2023 ) as defined by six research networks funded by a trans-NIH Emotional Well-Being Initiative led by NCCIH along with the National Institute on Aging (NIA) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).

Emotional well-being and positive emotions have often been associated with better health, including improved recovery and survival from physical illness. Preliminary evidence generated by the funded EWB research networks identified potentially innovative mechanisms of EWB, but whether they can be modified by mind and body interventions and are associated with restoring WPH are unknown.

Research Objectives and Requirements The NOFO will address the fundamental knowledge gaps by supporting rigorous, well-powered, and innovative mechanistic clinical trials with strong preliminary data to understand the impact of mind and body interventions on innovative mechanisms of EWB (primary outcome) as well as their associations with the Whole Person Health Index (secondary outcome).

The scientific priority of this NOFO is placed on the level of innovation for the proposed EWB mechanisms in the context of the proposed mind and body intervention. Examples of potentially innovative EWB-related mechanisms include, but are not limited to: Epigenetics, gene expression, and DNA repair Mechanisms of EWB will be the primary outcome to test if EWB is a path by which mind and body interventions are associated with WPH.

All studies are required to include the WPHI as a secondary outcome. Multidisciplinary collaborations are highly encouraged and may include experts such as mind and body researchers, clinicians, biologists, psychologists, neuroscientists, microbiologists, physiologists, and/or beyond. The proposed studies should foster innovation, academic freedom, and collaboration to advance the missions of both NIH and NCCIH.

Preliminary/Supporting Data Requirements Applications should be based on a clear scientific premise and compelling rationale for the proposed study, which should include empirical preliminary data based on previously published or unpublished data from animal or human clinical studies.

Preliminary data should provide evidence of a connection between the intervention to be used in the study (or similar intervention) and the proposed EWB-related mechanism, from either animal or human data. Evidence of a connection between the proposed intervention and at least one of the nine domains of the WPHI is also encouraged. The preliminary data supporting the hypotheses should be equivalent to an R01 application.

Examples of potentially relevant preliminary data include, but are not limited to: ?

Evidence from prior clinical studies, prior pilot mechanistic clinical trials, or animal model studies (including secondary outcome analyses) that the proposed mind-body intervention (e.g., yoga, mindfulness mediation), is associated with the proposed innovative mechanism (e.g., novel inflammatory markers, interoception-related neural networks, novel connectivity between affective brain regions)). ?

Evidence from prior clinical studies that the proposed mind-body intervention, or a related intervention (e.g., acupuncture or music-based intervention), is associated with improvements in one or more domains of the WPHI (e.g., ability to manage stress, social and family connections).

Study Design Considerations The mechanistic clinical trial design for the R33 phase should be equivalent to an R01 application, with the R61 phase demonstrating the feasibility of conducting the trial .

To ensure rigor of the proposed studies, applicants are expected to propose a well-powered, randomized, controlled mechanistic clinical trial that includes a mind and body intervention, at least one EWB mechanistic target as the primary outcome, and the association with the nine-item WPHI as a secondary outcome. Importantly, the proposed trial must not propose to evaluate efficacy or effectiveness of the mind and body intervention.

The selections of both the study population and the primary outcome are expected to be clearly justified. Both the mechanistic target and WPHI should be measured at baseline and following administration of the intervention, at a minimum. To assess long-term WPH restoration, the WPHI should also be evaluated at least 6 months after cessation of the intervention.

Applicants may also propose other mechanistic measures or associated clinically relevant health restoration outcomes as secondary outcomes, if appropriate. A control group for the proposed intervention or a comparator intervention is required for the proposed mechanistic trial.

The choice of the control group or comparator intervention should be justified by the needs to test the specific hypothesized mechanism(s) or process(es), with a strong scientific rationale provided.

A randomized study design is expected to be adequately powered to detect the effect of the mind and body intervention on the hypothesized EWB mechanism(s) or process(es) in comparison to the chosen justified control condition or comparator intervention. Statistical analyses should include sample size and power calculations, with a primary focus on between-group comparisons for the proposed primary mechanistic outcomes.

Masking (blinding) of study participants and the use of objective assessment methods with masked raters should be implemented whenever feasible. A detailed description of the intervention procedures is expected to be provided, including randomization, blinding, dosing, intensity, duration, frequency, and group assignment.

Procedures for masking and blinding are expected to be clearly specified for all relevant parties, including study participants/patients, instructors/practitioners, outcome assessors, data analysts/statisticians, and principal investigators. To enhance research safety, rigor, and efficiency of NIH-funded mechanistic clinical trials, this initiative will utilize a two-phased award funding mechanism (R61/R33).

The initial R61 phase will support the establishment of feasibility for conducting the proposed mechanistic clinical trial, with an emphasis on demonstrating the ability to meet study participant recruitment and retention benchmarks. The subsequent R33 phase will support completion of the full-scale trial(s), contingent upon successful achievement of R61 benchmarks (“Go/No-Go Criteria”).

R61 Phase: Feasibility Phase (1–2 years) The goal of the R61 phase is to demonstrate the feasibility of conducting the proposed hypothesis-driven mechanistic clinical trial. Key benchmarks for a successful demonstration of feasibility must include both recruitment and retention goals. NCCIH may, as appropriate, negotiate “Go/No-Go” transition criteria prior to award.

There will be no negotiations regarding benchmarks or milestones prior to the submission of applications for this NOFO. All applications are expected to clearly articulate the transition feasibility criteria. Applicants must provide justification of the chosen feasibility criteria.

Unblinding and data analysis are not permitted at the end of the R61 phase. Key evidence in the feasibility “ Go/No-Go Criteria ” should be included as part of the R61 Phase description. Recruitment numbers for the R61 phase (1-2 years) should be prorated as part of the overall 5-year recruitment total.

Criteria must include the following (with information in bold italics to be modified as appropriate for the proposed study): Demonstrate the ability to recruit and retain participants in the clinical trial, with a pre-planned timeline for reaching the randomization target, and ensuring the estimated drop-out rate is not exceeded. For example: To demonstrate the ability to recruit participants.

For example, we will enroll 40 participants into 2 arms of the proposed mechanistic clinical trial by Month 12 of the study. To demonstrate the ability to retain participants in the clinical trial. For example, we will retain at least 80 percent of randomized participants through the end of their data collection of the R61 phase of the study, e.g., by the end of the first year .

To demonstrate that the intervention can be delivered with sufficient adherence to the intervention. For example, we expect that 80 percent of subjects will participate in at least 75 percent of the sessions. Demonstrate the ability to collect the primary EWB mechanistic outcome measure.

R33 Phase: Mechanistic Study (2–4 years, maximum total award period of 5 years) Funding for the R33 phase is contingent on demonstrating the ability to successfully recruit and retain participants, and collect the proposed mechanistic measure according to the proposed study design. The R33 phase will continue participant recruitment, conduct, and assessment to complete the mechanistic clinical trial.

No changes to the interventions or design are permitted in the R33 phase. A clear study timeline for completion of the proposed mechanistic trial during the R33 phase must be included. R61/R33 Transition Process R33 transition requests will undergo an administrative review by NCCIH to determine whether the Go/No-Go Criteria for the feasibility criteria have been met before an R33 award is made.

Funding for, and transition to, the R33 phase is contingent on the following: Submission of an “R33 Transition Request Application” 2 months prior to the end of the R61 Meeting the Go/No-Go Criteria articulated in the R61 phase The availability of funds Meeting the Go/No-Go Criteria is the minimum requirement to transition to the R33 phase. It is expected that not all R61 awardees will transition to the R33 even if milestones are met.

Definitions and restrictions for this NOFO: Clinical trials are research studies in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control(s)) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes.

The following type of clinical trial is within scope of this NOFO: Mechanistic trial —defined as studies designed to understand a biological or behavioral process, the pathophysiology of a disease, or the mechanism of action of an intervention (i.e., how an intervention works, but not if it works or is safe).

Clinical Trials Not Responsive to this NOFO The following types of clinical trials are not responsive to this NOFO, and applications proposing such activities will be deemed non-responsive and not reviewed: Studies proposing to analyze data from a feasibility trial to assess efficacy/effectiveness of an intervention or estimate effect size ( https://www. nccih. nih.

gov/grants/pilot-studies-common-uses-and-misuses ). Applications that do not include an aim in the R61 phase to assess the feasibility of recruitment and retention, and adherence to the intervention. Studies that do not include a mind and body intervention.

Studies that do not propose an EWB mechanism as the primary outcome. Studies that do not include the WPHI as a secondary outcome. Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs.

See Section VIII. Other Information for award authorities and regulations. Section II.

Award Information Grant: A financial assistance mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity. Application Types Allowed The OER Glossary and the How to Apply Application Guide provide details on these application types. Only those application types listed here are allowed for this NOFO.

Required: Only accepting applications that propose clinical trial(s). Need help determining whether you are doing a clinical trial? Funds Available and Anticipated Number of Awards NCCIH intends to commit $2,000,000 in FY 2026 to fund three awards.

Support for subsequent submissions is contingent upon the availability of funds and appropriations. Application budgets need to reflect the actual needs of the proposed project. Application budgets may not exceed $475,000 per year in direct costs.

The scope of the project should determine the project period for each phase. The maximum period of the combined R61 and R33 phases is 5 years, with up to 2 years for the R61 phase and up to 4 years for the R33 phase. NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this NOFO.

Section III.

Eligibility Information Higher Education Institutions - Includes all types Public/State Controlled Institutions of Higher Education Private Institutions of Higher Education Nonprofits Other Than Institutions of Higher Education Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education) Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education) For-Profit Organizations (Other than Small Businesses) City or Township Governments Special District Governments Indian/Native American Tribal Governments (Federally Recognized) Indian/Native American Tribal Governments (Other than Federally Recognized).

Eligible Agencies of the Federal Government U.S. Territory or Possession Independent School Districts Public Housing Authorities/Indian Housing Authorities Native American Tribal Organizations (other than Federally recognized tribal governments) Faith-based or Community-based Organizations Non-domestic (non-U.S.) Entities (Foreign Organizations) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply. Foreign components, as defined in the NIH Grants Policy Statement , are not allowed. Applicant organizations must complete and maintain the following registrations as described in the How to Apply- Application Guide to be eligible to apply for or receive an award.

All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference the NIH Grants Policy Statement Section 2.

3. 9. 2 Electronically Submitted Applications for additional information.

System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually . The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.

NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM. Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM. gov registration process.

The same UEI must be used for all registrations, as well as on the grant application. eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants. gov registrations; all registrations must be in place by time of submission.

eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application. Grants. gov – Applicants must have an active SAM registration in order to complete the Grants.

gov registration. Program Directors/Principal Investigators (PD(s)/PI(s)) All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons.

If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Eligible Individuals (Program Director/Principal Investigator) Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the How to Apply-Application Guide. This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1. 2 Definition of Terms .

3. Additional Information on Eligibility Applicant organizations may submit more than one application, provided that each application is scientifically distinct. The NIH will not accept duplicate or highly overlapping applications under review at the same time, per NIH Grants Policy Statement Section 2.

3. 7. 4 Submission of Resubmission Application .

This means that the NIH will not accept: A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application. A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.

An application that has substantial overlap with another application pending appeal of initial peer review (see NIH Grants Policy Statement 2. 3. 9.

4 Similar, Essentially Identical, or Identical Applications ). Section IV. Application and Submission Information 1.

Requesting an Application Package The application forms package specific to this opportunity must be accessed through ASSIST, Grants. gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.

gov Workspace are available in Part 1 of this NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution. 2.

Content and Form of Application Submission It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced.

Applications that are out of compliance with these instructions may be delayed or not accepted for review. All page limitations described in the How to Apply- Application Guide and the Table of Page Limits must be followed. Instructions for Application Submission The following section supplements the instructions found in the How to Apply- Application Guide and should be used for preparing an application to this NOFO.

All instructions in the How to Apply - Application Guide must be followed. SF424(R&R) Project/Performance Site Locations All instructions in the How to Apply- Application Guide must be followed. SF424(R&R) Other Project Information All instructions in the How to Apply- Application Guide must be followed.

SF424(R&R) Senior/Key Person Profile All instructions in the How to Apply- Application Guide must be followed. All instructions in the How to Apply- Application Guide must be followed. All instructions in the How to Apply-Application Guide must be followed.

PHS 398 Cover Page Supplement All instructions in the How to Apply- Application Guide must be followed.

All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions: The specific aims page should include the following information: Brief background information to describe the proposed mind and body intervention, Brief justification for the selection of the proposed EWB mechanism and study population, Brief outline of the knowledge gap relevant to the proposed mechanistic clinical trial, Brief rationale for the proposed hypotheses, including summary of the preliminary evidence to support the proposed hypotheses, Brief description of the specific aims that will test the proposed overall hypothesis, Brief description of the proposed study design, including study population, number of participants, intervention groups, primary EWB mechanistic measure(s), secondary WPHI measure, associated clinical or functional outcome(s), and alternative interpretations or strategies for each aim in the project, The investigators should also have at least one statement about innovation of the proposed hypothesis and the general impact of the proposed study, This page must include a header titled R61/R33 Specific Aims with brief descriptions of key hypotheses.

In the Research Strategy section, contents should adhere to the following order. (Please refer to details in Section I for the information to be included for each topic.) Background and Research Objectives The primary outcome and hypothesis must involve the proposed EWB mechanism(s).

The secondary outcome must be the WPH Index and secondary analyses should include the association of the changes in EWB mechanism(s) with the WPH Index.

Preliminary/Supporting Data Study Design details for the proposed mechanistic clinical trial R61 Feasibility Phase, including a brief synopsis of the recruitment and retention strategies, benchmarks, and the Go/No-Go Transition Criteria Quality Control During Both Phases: Methods for monitoring quality and intervention adherence.

Subsequent studies beyond the R61/R33: a brief summary of the subsequent studies, either with clinical efficacy as the primary goal or with further mechanistic investigation as the primary goal. Resource Sharing Plan : Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply- Application Guide.

All instructions in the How to Apply-Application Guide must be followed, with the following additional instructions: All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan.

All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan. Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the How to Apply- Application Guide.

No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

PHS Human Subjects and Clinical Trials Information When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the How to Apply- Application Guide, with the following additional instructions: If you answered “Yes” to the question “Are Human Subjects Involved?

” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record. Study Record: PHS Human Subjects and Clinical Trials Information All instructions in the How to Apply- Application Guide must be followed. Section 2 - Study Population Characteristics 2.

5 Recruitment and Retention Plan Applicants must provide strong evidence of the availability of appropriate institutional resources and suitable patient populations. Documentation of the availability of eligible participants must be provided. The application must provide relevant information that addresses the feasibility of recruiting a robust sample of eligible participants.

Section 3 - Protection and Monitoring Plans 3. 3 Data and Safety Monitoring Plan In addition to the NIH application requirements for data and safety monitoring for clinical trials, NCCIH requires independent monitoring for research involving human subjects. Applicants should refer to NIH’s policy on data and safety monitoring ( https://grants.

nih. gov/grants/guide/notice-files/not-od-00-038. html ), as well as the NCCIH guidelines for data and safety monitoring ( https://www.

nccih. nih. gov/grants/policies/data-and-safety-monitoring-of-nccihfunded-clinical-research ).

Section 4 - Protocol Synopsis 4. 5. Will the study use an FDA-regulated intervention?

4. 5. a.

If yes, describe the availability of Investigational Product (IP) and Investigational New Drug (IND)/Investigational Device Exemption (IDE) status If the proposed clinical trial will use a device, natural product (such as botanicals, probiotics, and products marketed as dietary supplements), or drug, this attachment should describe correspondence from the FDA indicating whether