Feasibility Clinical Trials of Mind and Body Interventions for NCCIH High Priority Research Topics (R34 Clinical Trial Required) PAR-25-274 is sponsored by National Institutes of Health (NCCIH). Supports feasibility trials of complementary and integrative health mind-body interventions including massage therapy for high-priority topics like pain, anxiety, and whole person health.

Allows integration of technology like mHealth or AI for delivery or personalization.

PAR-25-274: Feasibility Clinical Trials of Mind and Body Interventions for NCCIH High Priority Research Topics (R34 Clinical Trial Required) This funding opportunity was updated to align with agency priorities. Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission. 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 Feasibility Clinical Trials of Mind and Body Interventions for NCCIH High Priority Research Topics (R34 Clinical Trial Required) Notices of Special Interest associated with this funding opportunity March 31, 2025 - This funding opportunity was updated to align with agency priorities.

Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission. 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 Phase 1 Exploratory/Developmental Cooperative Agreement/Exploratory/Developmental Cooperative Agreement Phase II Resource-Related Research Project (Cooperative Agreements) See Section III. 3.

Additional Information on Eligibility. Assistance Listing Number(s) Funding Opportunity Purpose The goal of this notice of funding opportunity (NOFO) is to support feasibility trials of complementary and integrative health approaches with physical and/or psychological therapeutic inputs (often called mind and body interventions) for conditions that have been identified by NCCIH as high-priority research topics.

This funding opportunity is intended to support feasibility clinical trials that provide new information that are scientifically necessary for the planning and conduct of a subsequent clinical efficacy or effectiveness study, pragmatic trial, or dissemination and implementation trial within NCCIH’s mission.

NCCIH expects that applications to this NOFO will describe the planned future clinical trial and in so doing demonstrate that the proposed (R34) research is scientifically necessary to design or plan the subsequent competitive full-scale clinical trial.

Under this R34, the data collected should be used to fill gaps in scientific knowledge necessary to develop a competitive full-scale clinical trial, including, but not limited to the following: examining feasibility and acceptability of interventions lacking published data; tailoring or adapting the content or structure of an intervention to a specific population, modality, or setting; refining the intervention to determine the most appropriate frequency or duration; determining feasibility of recruitment, retention, and data collection procedures; refining and assessing the feasibility of protocolized multi-component interventions; or examining acceptability and adherence of control conditions.

The subsequent full-scale clinical trial should have the potential to make a significant impact on public health. Prior to submitting to this NOFO, applicants are encouraged to contact the appropriate NCCIH Scientific/Research contact person for the science area of the planned application.

Funding Opportunity Goal(s) The National Center for Complementary and Integrative Health (NCCIH) provides funding for research into complementary and integrative health approaches. Research constituting a rigorous evidence base for complementary health approaches will be developed through a range of research strategies including basic and translational research, and clinical investigation.

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) is committed to the rigorous investigation of promising complementary and integrative health approaches with physical and/or psychological therapeutic inputs (often called mind and body interventions).

These mind and body interventions are widely used by the public, and they are increasingly recognized as a nonpharmacologic approach to symptom management (e.g., chronic pain, mild depression, anxiety). These approaches can be used by individuals to help prevent, treat, or self-manage various conditions, and they can be complementary to conventional health care.

There is a need for research to evaluate mind and body approaches as they are used and delivered to determine whether they are safe and efficacious or effective for given conditions or disorders. For clinical trials to address this need, they must be well designed and test hypotheses that will guide decisions about the inclusion of these interventions or approaches in health care for a given condition or disorder.

Investigators need to cite published literature or conduct a series of early-phase clinical trials to gather the multiple types of information to design subsequent large and rigorous efficacy or effectiveness studies. Although the scientific literature may provide the rationale for conducting an efficacy or effectiveness trial, investigators may lack critical information about key elements needed to plan and conduct such a trial.

Some key aspects that may need further investigation to plan the future clinical trial could include refining or adapting the intervention to specific populations, modalities, or settings; assessing the feasibility, acceptability, and adherence to protocolized multi-component interventions; and/or finalizing the intervention delivery method, appropriate outcome(s), or recruitment strategy.

Feasibility clinical trials can fill these information gaps. Overview of NCCIH Mind and Body Clinical Trials Research Funding Opportunities NCCIH has designed a framework for research to describe the broad spectrum of complementary and integrative health research it supports ( https://www. nccih.

nih. gov/grants/nccih-research-framework ). NCCIH supports investigators working on the continuum of the research framework, from basic science, and feasibility research, through high-impact clinical trials as well as research on dissemination and implementation ( https://www.

nccih. nih. gov/grants/funding/clinicaltrials ).

We encourage investigators to examine the full suite of available clinical trial notices of funding opportunities (NOFOs) to determine which one best aligns with the proposed stage of intervention development and testing. NCCIH has an oversight process to provide stewardship and maintain excellence, integrity, and rigor in our supported clinical studies ( https://www. nccih.

nih. gov/grants/toolbox ). Investigators are encouraged to review the NCCIH Clinical Terms of Award for Human Subjects Research ( https://www.

nccih. nih. gov/research/nccih-clinical-terms-of-award-for-human-subjects-research ) to learn more about NCCIH's requirements for clinical research.

Prior to submitting a grant application, NCCIH strongly encourages consulting with NCCIH Scientific/Research extramural program contacts relevant to the area of science for which they are planning to develop an application. Early contact provides an opportunity for NCCIH staff to discuss the scope and goals, and to provide information and guidance.

Research Objectives of the Mind and Body Feasibility Clinical Trial Phase (R34) The objective of this NOFO is to support the development of building blocks to plan and conduct novel, high priority clinical trials of complementary and integrative health approaches with physical and/or psychological therapeutic inputs (often called mind and body interventions) to enhance the probability of reaching more definitive outcomes in a future clinical trial.

Important building blocks that could be supported under this NOFO include refining the experimental protocols, including the assessment protocol, experimental intervention protocol, comparison intervention protocol, and randomization procedures; examining the feasibility of recruiting and retaining participants in the study; and developing supportive materials and resources.

Investigators should design the R34 to provide the necessary preliminary data to fill gaps in the literature to justify a future efficacy, effectiveness, pragmatic, or dissemination and implementation trial. Applications should describe and justify the need for feasibility data and ensure that no other published or completed pilot studies have been performed with a similar population and similar intervention.

If it is possible to reference successful demonstration of these benchmarks in completed trials or trials currently underway using the proposed or similar intervention and study population, further single-site feasibility work is not needed. Applications proposing such iterative or duplicative studies will be considered of low programmatic relevance, which will decrease likelihood of funding.

The following are examples of the types of aims appropriate for feasibility clinical trials proposed under this NOFO: Assessment of acceptability and adherence to dose, frequency, and/or duration of the intervention. Substantial intervention refinement to tailor, adapt, or customize an intervention to a new population, modality, or setting.

The need for adaptation/tailoring should be based upon a strong scientific rationale for the proposed adaptation. Comparisons on feasibility outcomes between the adapted intervention to the original intervention are strongly encouraged. Development and assessment of acceptability or adherence to a protocolized multi-component intervention.

Iterative intervention refinement via several small cohorts to address challenges with intervention fidelity, participant adherence, or selection of appropriate outcomes. Assessment of feasibility to measure outcomes within designated time frames; train interventionists to deliver the intervention with fidelity; and/or recruit, randomize, and retain participants in the intervention or comparison condition.

Development and feasibility testing of the strategies for integrating a mind and body approach into a health care system or delivery, to inform design of future pragmatic or implementation science trials. Assessment of acceptability or feasibility of randomization or other aspects of trial design. Development and feasibility testing of an appropriate control/comparison intervention for a future larger study.

Demonstration of feasibility of an intervention to be delivered remotely (e.g., tailoring of an algorithm for use in an mHealth intervention or smartphone application). Investigators should propose a randomized controlled trial design with at least one intervention arm and one comparator arm.

There should be strong rationale for the comparator condition (e.g., time and attention control, usual care, standard of care, sham condition, and/or active comparator(s)) based on the research question you plan to address in the future powered trial. Due to lack of rigor and potential expectancy effects, NCCIH will not support studies proposing a waitlist comparator condition.

Pilot or feasibility studies are carried out in preparation for future large-scale, adequately powered studies and, therefore, should address key feasibility issues such as participant recruitment and retention; burden and adherence to the intervention; provider fidelity to the intervention; and data collection methods.

Given the limited sample sizes that can be supported under this R34 grant mechanism, proposing to conduct fully powered tests of clinical outcomes (i.e., efficacy) or underpowered tests of outcomes (i.e., "preliminary efficacy") or attempting to utilize the highly variable point estimate of an effect size for power calculations would be non-responsive as noted below.

As pilot and feasibility studies are not designed (or powered) to address efficacy or effectiveness of an approach or intervention, statistical methods should be mainly descriptive. Applicants should define feasibility/acceptability with quantitative benchmarks corresponding to each assessment category.

Scientific and/or statistical justification should be provided to demonstrate how the sample size is sufficient to make a feasibility/acceptability determination in accordance with benchmarks. Sample sizes used in pilot studies are not powered for testing pre-specified hypotheses as expected for confirmatory studies.

Sample sizes for subsequent fully powered studies should be based on determining a clinically meaningful improvement due to the intervention in the appropriate research population. Investigators should consult the NCCIH website ( https://www. nccih.

nih. gov/grants/pilot-studies-common-uses-and-misuses ) for more information on the uses and misuses of feasibility studies.

Group-Based Interventions: In some cases, investigators who wish to evaluate the effect of an intervention on a health-related biomedical or behavioral outcome may propose a study in which (1) groups or clusters are assigned to study arms and individual observations are analyzed to evaluate the effect of the intervention, or (2) participants are assigned individually to study arms but receive at least some of their intervention in a real or virtual group or through a shared facilitator.

Investigators should provide a strong rationale for the choice among trial design options. The selection of study design should be guided by decisions about how best to deliver the intervention and by concerns regarding contamination and logistics. Applicants should show that their methods are appropriate given their plans for assignment of participants and delivery of interventions.

Additional information is available at https://researchmethodsresources. nih. gov/ .

There are often questions about whether feasibility trials should include mechanistic aims to evaluate how interventions work. Trials submitted under this NOFO should not include aims to assess the impact/efficacy of an intervention on a mechanism of action or evaluate mediation effects.

Mechanistic measures may be included in feasibility trials for the purpose of determining if collecting the mechanistic measure is feasible, which can inform whether mediation or moderation aims should be included in a future, large-scale efficacy or effectiveness trial. Applications would need to justify why the mechanistic outcome(s) should be included in the future efficacy or effectiveness trial.

The inclusion of mechanistic measures should not introduce significant burden for participants or utilize a significant portion of the budget. NCCIH has other funding mechanisms to support basic, mechanistic and translational research ( NOT-AT-21-006 ).

Preliminary Data Requirements Preliminary data are not required for this NOFO unless the application involves a natural product (i.e. botanicals, probiotics, and products marketed as dietary supplements) as part of a multi-component intervention. However, there should be a clear and compelling scientific rationale for the need for a feasibility study or intervention adaptation.

For applications studying the feasibility or acceptability of including a natural product as part of a multi-component intervention, the application must provide published data that the formulation of the proposed natural product has demonstrated efficacy for the condition being studied from at least one fully powered placebo-controlled trial.

Trials including natural products will have to adhere to the NCCIH Policy on Natural Product Integrity ( http://NCCIH. nih. gov/research/policies/naturalproduct.

htm) . Investigators should propose a realistic timeline for the startup and completion of the clinical trial and provide contingency plans to proactively confront potential delays or disturbances to the planned trial. NCCIH Priorities for Clinical Trials of Mind and Body Interventions NCCIH has identified targeted areas of investigation to align with the NCCIH Strategic Plan ( https://www.

nccih. nih. gov/about/strategic-plans-and-reports ).

For this funding opportunity, applications will be considered high programmatic priority if they address one of following criteria related to the intervention of study: The complementary or integrative approaches with physical and/or psychological therapeutic inputs (often called mind and body interventions) should include one or more of the following: Physical approaches such as spinal manipulation or mobilization, massage, tai chi, qi gong, yoga, acupuncture; or Psychological approaches such as hypnosis, guided imagery, breathing exercises, progressive relaxation, meditation, biofeedback, mindfulness techniques, music or other art-based therapies Multi-component interventions such as naturopathic medicine, traditional Chinese medicine, Ayurvedic medicine, chiropractic care, or a combination of two or more of the specific complementary health approaches (e.g., massage and biofeedback, or natural product and mindfulness); or integrated approaches to care in which a complementary health approach is used in combination with standard care (e.g., mindfulness or yoga as augmentation to conventional medications); or Multilevel intervention level (patient, caregivers of patient, clinicians, and health care system) where at least one level of intervention includes a mind and body intervention.

In addition, proposed projects could include an outcome measure(s) that relates to at least one of the following high-priority topic areas: Promotion of health behaviors, health restoration, emotional well-being, or resilience; Prevention or treatment of symptoms such as sleep disorders or disturbances, depression, anxiety, chronic stress, post-traumatic stress (disorder), obesity, and acute and chronic pain conditions; Whole person health outcomes including multisystem or multilevel outcomes; Minority health and reduction of disparities in areas such as pain, obesity, mental and emotional behavioral health, and maternal health; Social and structural determinants of health ( https://www.

ninr. nih.

gov/researchandfunding/nih-sdohrcc ); Enhancement of adherence to medications or prescribed behavioral approaches (e.g., physical activity and healthy eating); Reduction or deprescribing of inappropriate use of medications or other substances (e.g., drugs of abuse or medications that are contraindicated in specific patient populations); or Reduction in risk for/incidence of HIV, or comorbidities, coinfections and complications from HIV ( https://abs2.

od. nih. gov/Docs/NIH_StrategicPlan_FY2021-2025.

pdf ) When evidence justifies, NCCIH encourages applications to conduct studies in a way that assesses the impact of integrating interventions into relevant settings (e.g., health care systems, schools, Federally Qualified Health Centers, military or Veteran health care delivery organizations, community organizations, justice systems, or homeless shelters).

All National Institutes of Health (NIH)-funded research must adhere to the Code of Federal Regulations, which outlines specific requirements to enhance protections for pregnant women, human fetuses, and neonates; children; and prisoners ( https://grants. nih. gov/policy/humansubjects/policies-and-regulations/vulnerable-populations.

htm ). The Inclusion Across the Lifespan policy requires that individuals of all ages, including children (i.e. individuals under the age of 18) and older adults, must be included in all human subjects research, conducted or supported by NIH, unless there are scientific or ethical reasons not to include them ( https://grants. nih.

gov/grants/guide/notice-files/NOT-OD-18-116. html ). Applications proposing research topics not identified above as high programmatic priority can be submitted but may be considered lower programmatic priority, which may reduce the likelihood of funding.

Applications proposing research studies using an intervention and patient population that are the same as or very similar to those used in studies already in progress, conducted, or published by other groups are likely to be lower programmatic priority.

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 ). Trials that do not include an aim to assess the feasibility, acceptability, fidelity, and/or adherence to the intervention. Studies that do not include a mind and body intervention.

Studies that propose a waitlist control. Trials that propose to assess feasibility of interventions for the treatment or prevention of cancer. (Investigators interested in cancer treatment or prevention trials should contact the National Cancer Institute.)

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 The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications. This R34 is limited to direct costs requests of up to $450,000 over the entire project period. Although variations from year to year are permissible, in no case may any year be more than $225,000 in direct costs.

The maximum project period is 3 years. 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 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 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 ). Applications with Foreign components are encouraged to read NCCIH International Health Research page . Foreign components can include foreign collaborators or consultants, but should not include foreign sites outside of the U.S. or Canada, according to NCCIH’s policy.

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.

We strongly encourage that all clinical trials include a biostatistician as part of the key personnel, and the application should reflect their hands-on involvement in the design and implementation of the study protocol. All instructions in the How to Apply- Application Guide must be followed. All instructions in the SF424 (R&R) Application Guide must be followed.

The budget for the first year of the grant should reflect the support needed for trial startup. If parts of the costs of the trial are to be provided by sources other than NIH, these contributions must be presented in detail in the budget justification. Include budget support for the publication and dissemination of findings.

Applicants should budget for the services of appropriate safety monitoring (e.g., Medical Safety Monitor, Independent Medical Monitor, or Safety Monitoring Committee), as indicated; https://www. nccih. nih.

gov/grants/policies/data-and-safety-monitoring-of-nccihfunded-clinical-research. 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 research strategy should be organized in a manner that will facilitate peer review.

The body of the application should present a concise overview of the state of the science; current status and relevance of the trial; a discussion of the specific protocol; and the approach to data collection, analysis, and dissemination. The following criteria should be addressed: Importance of Research : The significance and innovation of the proposed clinical trial and importance of the question must be clearly stated.

It is particularly important that there be a discussion of how the trial will test the proposed hypotheses and how or why there is clinical equipoise. The application should make clear the need for and timeliness of the study, with emphasis on how the results will address an evidence gap and therefore advance our knowledge of theory and practice in this area.

A discussion of the costs and benefits of the study should be included for evaluation of the trial’s significance. The importance of the proposed feasibility trial and why it is scientifically necessary to plan the subsequent future trial should be described.

Discuss how the proposed trial will test the feasibility hypotheses and how the results of the trial (positive or negative) will guide decisions about whether a subsequent study is feasible, and/or evidence that additional studies must be completed before proceeding to a full-scale trial. Applications should address the reasons for selection of the intervention.

This may include public health impact if subsequent efficacy trials are conducted and positive, ethical dimensions, and patient perspectives on acceptability of the proposed intervention.

Characteristics of any preliminary research results provided in support of the proposed project, whether conducted by the applicant or others, should be described in the application so that peer reviewers may evaluate the strength of the supporting evidence. The applicant should also discuss the limitations of those data.

Explain how the application challenges and seeks to shift current research or clinical practice paradigms or guidelines. Rigor and Feasibility : The research approach section should include a description of the supporting data and the experimental approach. Supporting Data: Justification for the study may be presented as results from previous clinical studies conducted by the investigative team or from the scientific literature.

Study conceptualization and planning must be at a stage sufficient to allow for an assessment of the likelihood of trial success. Experimental Approach: A summary of the proposed feasibility trial protocol should be presented in the Research Strategy and should include the items listed below.

A description of why the target population is an appropriate group to address the proposed hypotheses and how or if results will generalize to a broader population. A description