Exploratory Clinical Trials of Mind and Body Interventions for NCCIH High Priority Research Topics (R34)

Exploratory Clinical Trials of Mind and Body Interventions for NCCIH High Priority Research Topics (R34) is sponsored by National Center for Complementary and Integrative Health (NCCIH). This opportunity supports mission-aligned projects and measurable outcomes.

Expired PAR-21-240: Feasibility Clinical Trials of Mind and Body Interventions for NCCIH High Priority Research Topics (R34 Clinical Trial Required) This notice has expired. Check the NIH Guide for active opportunities and notices. 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 December 21, 2023 - This PAR has been reissued as PAR-24-084 September 28, 2023 - Notice of Intent to Publish a Notice of Funding Opportunity for Feasibility Clinical Trials of Mind and Body Interventions for NCCIH High Priority Research Topics (R34 Clinical Trial Required).

See Notice NOT-AT-24-015 NOT-OD-23-012 Reminder: FORMS-H Grant Application Forms and Instructions Must be Used for Due Dates On or After January 25, 2023 - New Grant Application Instructions Now Available NOT-OD-22-190 - Adjustments to NIH and AHRQ Grant Application Due Dates Between September 22 and September 30, 2022 October 28, 2021 - Reminder: FORMS-G Grant Application Forms & Instructions Must be Used for Due Dates On or After January 25, 2022 - New Grant Application Instructions Now Available.

See Notice NOT-OD-22-018 . September 13, 2021 - Updates to the Non-Discrimination Legal Requirements for NIH Recipients. See Notice August 5, 2021 - New NIH "FORMS-G" Grant Application Forms and Instructions Coming for Due Dates on or after January 25, 2022.

August 5, 2021 - Update: Notification of Upcoming Change in Federal-wide Unique Entity Identifier Requirements. See Notice NOT-OD-21-170 April 20, 2021 - Expanding Requirement for eRA Commons IDs to All Senior/Key Personnel.

See Notice NOT-OD-21-109 Funding Opportunity Announcement (FOA) Number Companion Funding Opportunity Resource-Related Research Project (Cooperative Agreements) UG3 / UH3 Phase 1 Exploratory/Developmental Cooperative Agreement/Exploratory/Developmental Cooperative Agreement Phase II See Section III. 3. Additional Information on Eligibility .

Assistance Listing Number(s) Funding Opportunity Purpose The goal of this funding opportunity is to support early phase clinical 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, which will provide data that are critical for the planning and design of a subsequent clinical efficacy or effectiveness study, or a pragmatic trial.

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; adapting an intervention to a specific population; 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 multimodal interventions; or examining acceptability and adherence of control conditions.

This FOA will not support randomized clinical trials that test or determine efficacy or effectiveness; nor will this FOA support repetition of feasibility or acceptability research that has been previously conducted in the same or similar patient population with the same or similar intervention.

Applications that propose solely to write a protocol or manual of operations or to develop infrastructure for a clinical trial are not appropriate for this announcement. Applications must propose to conduct a feasibility clinical trial. The subsequent larger trial should have the potential to make a significant impact on public health.

Open Date (Earliest Submission Date) Letter of Intent Due Date(s) Renewal / Resubmission / Revision (as allowed) All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).

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.

New Date December 21, 2023 (Original Date: March 12, 2024) per issuance of PAR-24-084 Required Application Instructions It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide , except where instructed to do otherwise (in this FOA or in a Notice from NIH Guide for Grants and Contracts ).

Conformance to all requirements (both in the Application Guide and the FOA) 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. Part 1. Overview Information Part 2.

Full Text of Announcement Section I. 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. 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, as well as be complementary to treatment offered by 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 into the delivery of 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 preliminary data needed 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 design and implement such a trial.

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

Early phase clinical trials can fill this information gap, thereby improving study design and knowledge of trial feasibility.

Multi-site feasibility trials can provide information regarding whether the intervention and comparator condition can be delivered with fidelity by multiple providers across sites; demonstrate feasibility of recruitment, randomization, and retention procedures; and test methods for consistent collection of follow up data from sites to minimize missing data.

Preliminary data about the intervention and the research team's experience conducting clinical trials are important elements for successful conduct of fully powered efficacy, effectiveness, pragmatic, or implementation trials.

For more information about NCCIH recommendations for the multi-staged process of developing and testing physical and/or psychological therapeutic inputs (mind and body interventions), see the NCCIH website ( https://www. nccih. nih.

gov/grants/funding/clinicaltrials ). NIH defines a clinical trial as "a research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes." i) Pre-clinical/animal studies (which may use Parent R21 or R01 FOAs).

ii) Mechanistic studies focused on the fundamental science of mind and body approaches (which may use Parent R21 or R01 FOAs).

iii) Human feasibility and intervention refinement studies to obtain preliminary data on novel interventions, new multicomponent interventions that need to be protocolized, or existing interventions requiring substantial adaptations; to assess the ability to recruit/randomize and accrue participants; to evaluate the fidelity of delivering the intervention; to assess participant adherence to the intervention and study procedures; to reliably collect outcomes data for follow-up durations; and to assess retention of participants (which may use this R34 PAR-21-240 ).

Feasibility studies are not needed when published literature or previous studies by the investigators demonstrate the feasibility of a similar interventional trial in a similar population.

iv) Multi-site feasibility clinical trials to demonstrate delivery of the intervention with fidelity across at least two geographically distinct sites; to assess adherence to the study protocol across sites; to evaluate the ability to recruit and retain participants consistently across sites; to perform minimal intervention adaptation when needed; and to collect data with consistency across sites (which may use R01 PAR-21-241 ).

Multi-site feasibility studies are not needed when published literature or previous studies demonstrate that a similar intervention in a similar population can be delivered with fidelity across sites, and the investigative team has experience conducting multi-site trials. v) Multi-site clinical trials to determine efficacy or effectiveness of an intervention in a fully powered clinical trial.

Trials must be conducted across at least three distinct geographic regions and adhere to NIH policy for enrollment of diverse populations in Phase III trials. An independent Data Coordinating Center is required for multi-site trials (which may use UG3/UH3 for Clinical Coordinating Center PAR-21-243 with companion U24 for Data Coordinating Center PAR-21-242 ).

vi) Remotely delivered and conducted clinical trials to determine efficacy or effectiveness of complementary and integrative health interventions in a representative sample (which may use R01 PAR-20-154 ).

vii) Dissemination and implementation science trials to support innovative approaches to identifying, understanding, and developing strategies for overcoming barriers to the adoption, adaptation, integration, scale-up and sustainability of evidence-based complementary and integrative health interventions, tools, policies, and guidelines.

Hybrid Type 1 and Type 2 effectiveness-implementation studies should use the multi-site clinical trial pathway described above in item v. Hybrid Type 3 effectiveness-implementation studies should use the NIH-wide FOAs (R21 PAR-19-275 or R01 PAR-19-274 ).

Research Objectives of the Mind and Body Feasibility Clinical Trial Phase (R34) The objective of this FOA is to develop the building blocks with which to design 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.

Important building blocks include refining the experimental protocols, including the assessment protocol, experimental intervention protocol, comparison intervention protocol, and randomization procedures (if appropriate); examining the feasibility of recruiting and retaining participants in the study conditions (including the experimental condition and the control/comparison condition, if relevant); and developing supportive materials and resources.

Investigators should keep in mind the future planned trial and then design the R34 to provide the necessary preliminary data to fill gaps in the literature to justify a future efficacy, effectiveness, or pragmatic trial. Accordingly, collection of preliminary data regarding feasibility, acceptability, safety, and target outcomes is appropriate.

If it is possible to reference successful demonstration of these benchmarks in the literature for the proposed or similar intervention and study population, further feasibility work is not needed.

Given the limited sample sizes that can be supported under this exploratory R34 grant mechanism, proposing to conduct fully powered tests of clinical outcomes (i.e., efficacy) or underpowered test of outcomes (i.e., "preliminary efficacy") or attempting to utilize the highly variable point estimate of an effect size for power calculations would not be appropriate or supported by this funding mechanism.

Subsequent larger studies should be based on an achievable, clinically meaningful improvement due to the intervention in the research population with appropriate power calculations. A comparison group is usually needed in exploratory studies, such as for determining the acceptability and feasibility of group assignment. 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 pilot studies.

The following are examples of the types of goals appropriate for feasibility clinical trials proposed for this FOA when the literature has not already demonstrated this evidence for the proposed or similar intervention and study population: Assessment of acceptability and adherence to dose, frequency and/or duration of the intervention for testing in a future large-scale, multi-site efficacy or effectiveness clinical trial.

Substantial intervention refinement to tailor or customize an intervention to a new patient population, such as adapting adult interventions for children or tailoring interventions to increase acceptability by participants with health disparities. Development and assessment of acceptability or adherence to a protocolized multi-modal intervention.

Iterative intervention refinement to address challenges with intervention fidelity, participant adherence, selection of appropriate outcomes, ability to capture outcome measures within designated time frames, and/or participant retention.

Development and feasibility testing of the strategies for integrating of 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.

Preliminary Data Requirements Preliminary data are not required for this FOA. However, there should be a clear and compelling rationale for the selected intervention's proposed impact on the outcome of interest. It is important that clinical trials have a realistic timeline that explicitly addresses how long it will take from time of award to first participant accrual.

NCCIH has an oversight process in place for clinical trials that may require revising and submitting a detailed study protocol, data and safety monitoring plan, case report forms, study accrual and retention plan for NCCIH, and IRB approvals. Investigators are encouraged to review the NCCIH Study Accrual and Retention Policy ( https://www. nccih.

nih. gov/grants/policies/nccih-policy-study-accrual-and-retention-for-human-subject-research ). Continuation of the award is conditional upon satisfactory progress and subject to availability of funds.

If, at any time, recruitment falls significantly below the projected recruitment, NCCIH will consider ending support and negotiating an orderly phase-out of the award and retain the option of periodic external peer review of progress. NCCIH staff will closely monitor progress at all stages, including milestones, accrual, retention, and safety.

Information to guide investigators for preparation of clinical trial implementation can be obtained from the NCCIH Program staff. NCCIH clinical research policy and guidance information and NCCIH templates for the protocol, study accrual and retention plan, and data and safety monitoring plan are available at the following website: https://www. nccih.

nih. gov/research/nccih-clinical-terms-of-award-for-human-subjects-research . Investigators are encouraged to review the NCCIH Clinical Research Toolbox ( https://www.

nccih. nih. gov/grants/toolbox ) to learn more about NCCIH's requirements for clinical research.

Clinical trials supported by this FOA will have to adhere to the NIH Policy on Good Clinical Practice Training ( https://grants. nih. gov/grants/guide/notice-files/NOT-OD-16-148.

html ).

NCCIH Priorities for Clinical Trials of Mind and Body Interventions 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: specific approaches such as spinal manipulation or mobilization, massage, tai chi, qi gong, yoga, acupuncture,* hypnosis, guided imagery, breathing exercises, progressive relaxation, meditation, biofeedback, mindfulness techniques, or music or art therapies; multicomponent interventions such a naturopathic medicine, traditional Chinese medicine, Ayurvedic medicine, chiropractic care, or a combination of two or more of the specific complementary health approaches; or integrated approaches to care in which a complementary health approach is used in combination with standard care (e.g., cognitive behavioral therapy combined with mindfulness or yoga).

In addition, proposed projects should study a mind and body or integrated approach for one of the following high priority topic areas and should include at least one outcome measuring the topic: promotion of whole person health, health restoration, emotional well-being, or resilience; prevention or treatment of symptoms including sleep disorders or disturbances, depression, anxiety, post-traumatic stress (disorder), obesity, and pain conditions; improving minority health and eliminating disparities in priority health conditions; the role of social and structural determinants of health; enhancement of adherence to medications or prescribed behavioral approaches (e.g., physical activity and healthy eating); reduction of inappropriate use of medications or substances (e.g., substance use disorder or medications that are contraindicated in specific patient populations); or symptom management among individuals living with HIV/AIDS.

NCCIH strongly encourages applications to this FOA that conduct studies in diverse settings 1 , or the inclusion of health disparity and vulnerable populations. 2 1 Examples of diverse settings include families, schools, Federally Qualified Health Centers, child welfare and juvenile justice systems, and homeless shelters).

2 NIH-designated health disparity populations include racial and ethnic minorities (African Americans/Blacks, Hispanics/Latinos, American Indians/Alaska Natives, Asian Americans, Native Hawaiians, and Other Pacific Islanders), sexual and gender minorities, socioeconomically disadvantaged populations, and under-served rural populations.

Other vulnerable populations include high-risk pregnant women; homeless youth, children with disabilities; children who have experienced abuse, older adults; veterans, military members and military families) *Applicants proposing acupuncture as an intervention should consult the NCCIH website ( https://www. nccih. nih.

gov/grants/acupuncture-research-areas-of-high-and-low-programmatic-priorities) to determine whether the proposed study is aligned with NCCIH's updated priorities for acupuncture research Applications proposing research topics not identified above as high programmatic priority can be submitted but are likely to be considered of lesser or low programmatic priority, which will significantly influence programmatic relevance and 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, or conducted, or published by other groups are likely to be lower programmatic priority.

Clinical Trials Not Responsive to this FOA The following types of clinical trials are not responsive to this FOA and applications proposing such activities will be deemed non-responsive and not reviewed: Studies proposing small trials with the sole purpose of estimating an effect size for a future trial. Mechanistic studies on the fundamental science of mind and body approaches. (Such studies should use the Parent R01 or R21 FOA.)

Studies to determine biological signature or psychological process (mechanism) of a complementary or integrative health approach and that do not include a primary outcome to assess the feasibility or acceptability of the intervention. Multi-site feasibility trials involving minor changes to interventions when there is existing literature on the intervention’s feasibility and acceptability in the same or similar patient population.

(Such studies should use R01 PAR-21-241 ). Fully remotely delivered clinical trials powered to evaluate efficacy or effectiveness (such studies should use the R01 PAR-20-154 ) Single or multi-site, Phase III trials of efficacy or effectiveness. (Multi-site studies should use UG3/UH3 FOA, PAR-21-243 and companion U24 FOA, PAR-21-242 .)

Natural product, pharmacologic, or device safety trials. Natural product or pharmacologic clinical trials that do not include a mind and body element to the intervention or comparison group. Single or multi-site observational studies that do not meet the NIH definition of a clinical trial.

(Such studies should use the Parent R21 or R01 FOAs.) Trials that propose to test interventions for the treatment or prevention of cancer. (Investigators interested in cancer treatment or prevention trials should contact the National Cancer Institute.)

Design, Analysis, and Sample Size for Studies to Evaluate Group-Based Interventions: 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.

Such studies may propose a parallel group- or cluster-randomized trial, an individually randomized group-treatment trial, a stepped-wedge design, or a quasi-experimental version of one of these designs. In these studies, special methods may be warranted for analysis and sample size estimation. 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/ .

For this FOA, investigators should consider their proposed study design when justifying proposed sample sizes to assess feasibility and acceptability metrics. See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information Grant: A support 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 SF424 (R&R) Application Guide provide details on these application types.

Only those application types listed here are allowed for this FOA. 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 FOA. Section III.

Eligibility Information Higher Education Institutions Public/State Controlled Institutions of Higher Education Private Institutions of Higher Education The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education: Hispanic-serving Institutions Historically Black Colleges and Universities (HBCUs) Tribally Controlled Colleges and Universities (TCCUs) Alaska Native and Native Hawaiian Serving Institutions Asian American Native American Pacific Islander Serving Institutions (AANAPISIs) 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 Institutions) are 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 SF 424 (R&R) 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. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.

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. eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.

gov registration, but 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 DUNS number and 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 his/her organization to develop an application for support.

Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH 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 SF424 (R&R) Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement. 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. 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 NOT-OD-11-101 ). 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 FOA. 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 SF424 (R&R) Application Guide except where instructed in this funding opportunity announcement 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 SF424 Application Guide and the Table of Page Limits must be followed.

Instructions for Application Submission Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing (DMS) Plan will be attached in the Other Plan(s) attachment in FORMS-H and subsequent application forms packages.

For due dates on or before January 24, 2023, the Data Sharing Plan and Genomic Data Sharing Plan GDS) will continue to be attached in the Resource Sharing Plan attachment in FORMS-G application forms packages. The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA. All instructions in the SF424 (R&R) Application Guide must be followed.

SF424(R&R) Project/Performance Site Locations All instructions in the SF424 (R&R) Application Guide must be followed. SF424(R&R) Other Project Information All instructions in the SF424 (R&R) Application Guide must be followed. SF424(R&R) Senior/Key Person Profile All instructions in the SF424 (R&R) Application Guide must be followed.

Biographical Sketches:Document the Program Director s/Principal Investigator’s experience in leading clinical trials and expertise in the content area of the trial (intervention, study population, and research methods).

Even feasibility clinical trials will require a multidisciplinary team (clinician, biostatistician, data manager, study coordinator, etc.) and the application should reflect their hands-on involvement in the design and implementation of the study protocol.

Applicants are encouraged to provide strong evidence of the study team's qualifications and ability to conduct the proposed as well as future research, experienced investigative team members, and previous investigative experience in related clinical trials. 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; see https://www.

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

All instructions in the SF424 (R&R) Application Guide must be followed. PHS 398 Cover Page Supplement All instructions in the SF424 (R&R) Application Guide must be followed. Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H and subsequent application forms packages.

For due dates on or before January 24, 2023, the Data Sharing Plan and Genomic Data Sharing Plan GDS) will continue to be attached in the Resource Sharing Plan attachment in FORMS-G application forms packages. 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. All instructions in the SF424 (R&R) 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