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)
Activity Code

R34 Planning Grant

Announcement Type
Reissue of PAR-18-417
Related Notices

None

Funding Opportunity Announcement (FOA) Number
PAR-21-240
Companion Funding Opportunity
PAR-21-241 , R01 Research Project
PAR-21-242 , U24 Resource-Related Research Project (Cooperative Agreements)
PAR-21-243 , UG3/ UH3 Phase 1 Exploratory/Developmental Cooperative Agreement/Exploratory/Developmental Cooperative Agreement Phase II
Assistance Listing Number(s)
93.213
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.

Key Dates

Posted Date
June 14, 2021
Open Date (Earliest Submission Date)
June 21, 2021
Letter of Intent Due Date(s)

Not Applicable

Application Due Dates Review and Award Cycles
New Renewal / Resubmission / Revision (as allowed) AIDS Scientific Merit Review Advisory Council Review Earliest Start Date
July 20, 2021 July 20, 2021 July 16, 2021 November 2021 January 2022 April 2022
October 20, 2021 October 20, 2021 November 15, 2021 March 2022 May 2022 July 2022
February 18, 2022 February 18, 2022 March 11, 2022 July 2022 October 2022 December 2022
June 20, 2022 June 20, 2022 July 22, 2022 November 2022 January 2023 April 2023
October 19, 2022 October 19, 2022 November 14, 2022 March 2023 May 2023 July 2023
February 21, 2023 February 21, 2023 March 10, 2023 July 2023 October 2023 December 2023
June 20, 2023 June 20, 2023 July 22, 2023 November 2023 January 2024 April 2024
October 20, 2023 October 20, 2023 November 14, 2023 March 2024 May 2024 July 2024
February 20, 2024 February 20, 2024 March 11, 2024 July 2024 October 2024 December 2024

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.

Expiration Date
March 12, 2024
Due Dates for E.O. 12372

Not Applicable

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.

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.

  1. Use the NIH ASSIST system to prepare, submit and track your application online.
  2. 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.

  3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.


  4. Table of Contents

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Background

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).

Overview of NCCIH Mind and Body Clinical Trials Research Funding Opportunities

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."

NCCIH has designed its Clinical Trials Program to support a range of investigator-initiated studies with funding mechanisms tailored to address different scientific questions and levels of study complexity from early stage discovery research through large-scale efficacy or effectiveness trials. For complementary and integrative health approaches with physical and/or psychological therapeutic inputs (often called mind and body approaches), this pipeline of research is supported under funding opportunities that include the following options:

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.

Timeline

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

As NCCIH's clinical research portfolio matures, 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 meet at least one element in each of the following criteria:

  • 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 settings1, or the inclusion of health disparity and vulnerable populations.2

1Examples of diverse settings include families, schools, Federally Qualified Health Centers, child welfare and juvenile justice systems, and homeless shelters).

2NIH-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-21-243and 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

Funding Instrument

Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.

Application Types Allowed
New
Resubmission

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.

Clinical Trial?

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.

Award Budget

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.

Award Project Period

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

1. Eligible Applicants

Eligible Organizations

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

  • Small Businesses
  • For-Profit Organizations (Other than Small Businesses)

Local Governments

  • State Governments
  • County Governments
  • City or Township Governments
  • Special District Governments
  • Indian/Native American Tribal Governments (Federally Recognized)
  • Indian/Native American Tribal Governments (Other than Federally Recognized)

Federal Governments

  • Eligible Agencies of the Federal Government
  • U.S. Territory or Possession

Other

  • 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
  • Regional Organizations
Foreign Institutions

Non-domestic (non-U.S.) Entities (Foreign Institutions) 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. 

Required Registrations

Applicant organizations

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.
  • 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.

2. Cost Sharing

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

3. Additional Information on Eligibility

Number of Applications

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.

Page Limitations

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

Instructions for Application Submission

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.

SF424(R&R) Cover

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.

R&R or Modular Budget

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).

R&R Subaward Budget

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.

PHS 398 Research Plan

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Research Strategy

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:

Significance: The significance 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 clinical significance and, when applicable, the biological relevance of the future fully powered clinical trial should be clearly stated. The importance of the proposed feasibility trial should be described and why it is necessary to plan the subsequent future trial. It is particularly important that there be discussion of how the proposed early-phase trial will test the primary hypothesis focused on feasibility and how the results of the trial (positive or negative) will guide decisions about whether a subsequent study is feasible or justified, 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.

Innovation: Explain how the application challenges and seeks to shift current research or clinical practice paradigms or guidelines.

Approach: The research approach section should include a description of the supporting data, clinical trial experience, the experimental approach.

Supporting Data: The major findings of the preclinical and clinical studies that led to the proposed clinical trial should be described. Justification for the study from preliminary data may be presented as results from previous clinical studies conducted by the investigative team or from the scientific literature. Pilot studies that show the need for the trial should also be discussed. Preliminary data to justify the choice of intervention for the indication being proposed for study should be discussed as well. 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 of the mind and body intervention to be tested including elements of the intervention, proposed methods of assessing fidelity of intervention delivery and intervention performance, time duration of delivery (for clinician provided interventions) or participant practice (in group or individual/home settings), and frequency of delivery or practice.
  • A description and justification for assessments, including clinical, laboratory, physiological, behavioral, patient-centered, or other outcomes. Use of patient reported outcomes, including those available through the Patient-Reported Outcomes Measurement Information System (PROMIS), NIH Toolbox, and Quality of Life in Neurological Disorders (NeuroQoL), as well as non-traditional data collection approaches (e.g., telephone, mobile devices, or web-based systems) need to be described. A description of the laboratory evaluations (as appropriate) and plans to implement and monitor Good Clinical Practices (GCP), Good Laboratory Practices (GLP) and Good Manufacturing Practices (GMP), as appropriate should be provided.
  • Discussion of potential challenges expected in implementing the trial and how these might be overcome.
  • A timeline, which could be provided as a table or graph, for reaching important study milestones such as: (a) obtaining regulatory approval of the final protocol; (b) establishing agreements with participating partners, if relevant; (c) finalizing the study procedures and training participating clinical site staff; and (d) starting enrollment and completing all subject follow-up and data collection activities.
  • Descriptions of the organization of the study and how the trial will be managed.
  • Future Clinical Trial: A concise summary of the subsequent proposed fully powered trial should be provided including the study design (efficacy, effectiveness, or pragmatic) and how the proposed feasibility study will inform the design of that trial.

Letters of Support:

Letters of support from clinicians or clinical department chairs whose support are necessary to the successful conduct of the trial should be provided. Applicants are also encouraged to include documentation of the commitment of any subcontractors and consultants, as well as service agreements for personnel or facilities. Letters of commitment must be co-signed by the business official of the collaborating center.

If parts of the costs of the trial are to be provided by sources other than NCCIH, provide Letter(s) of Support signed by an authorized representative.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.

Appendix:
Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
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 SF424 (R&R) 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 SF424 (R&R) Application Guide must be followed.

Section 2 - Study Population Characteristics

2.4 Inclusion of Women and Minorities

Describe strategies for outreach to minorities and women.

2.5 Recruitment and Retention Plan

Describe the following: 1) the planned remote recruitment methods, including use of contact lists, databases or other pre-screening resources, advertisements, outreach, media / social media and referral networks or groups; 2) if there are known participant or study-related barriers to accrual or participation (based on literature or prior experience), please list these barriers and describe plans to address them to optimize success; 3) contingency plans for participant accrual if enrollment significantly lags behind accrual benchmarks; 4) participant retention and adherence strategies; and 5) possible competition from other trials for study participants; Investigators are encouraged to review the NCCIH Study Accrual and Retention Plan (https://www.nccih.nih.gov/grants/policies/nccih-policy-study-accrual-and-retention-for-human-subject-research ).

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 diverse 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 (http://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). The data and safety monitoring plan must explicitly describe plans to remotely monitor participant safety with appropriate safeguards to minimize risk. The Independent Monitoring Committee (IMC) or Data and Safety Monitoring Board (DSMB) will have the responsibility to review interim and final data and to recommend whether the protocol should be modified, and, at each meeting, whether the study should be continued or terminated early. Thus, its ethical responsibilities, to the participants as well as to the integrity of the study, are of paramount importance to NCCIH. The IMC/DSMB will meet in person or by phone at least twice a year. Applicants should not appoint IMC/DSMB members in advance of the peer review, or even inquire about the interest of possible DSMB members, to avoid conflicts of interest in peer review.

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 botanical, herbal, dietary supplement, probiotic, vitamin, or mineral), or drug, this attachment should describe correspondence from the FDA indicating whether the proposed study will require an IND/IDE. Investigators should describe the process that will be used for attaining all necessary FDA or other applicable regulatory agency approvals necessary to the conduct of the trial and associated timeline. For trials using an FDA-regulated product that requires an IND/IDE application, the grant application must include evidence regarding the outcome of a pre-IND meeting, or other evidence of communication with FDA. If the protocol is conducted under a non-U.S. regulatory agency, the applicant should submit a plan for attaining those regulatory approvals. If the protocol is exempt from an IND/IDE, a copy of the exemption letter from the FDA should be provided as part of the PDF file attachment.

Section 5 - Other Clinical Trial-related Attachments

5.1 Other Clinical Trial-related Attachments

The following attachments must be included as a part of the cooperative agreement application. Attachments permit expansion of certain elements that cannot be appropriately described in the Research Strategy. All attachments listed below must be provided or the application will not be peer reviewed.

1. Clinical Trial Experience

Applicants must provide a detailed table listing the characteristics of trials that demonstrate Key Personnel experience in trial coordination in the last 5 years. One table must be provided for each study record with a unique filename for each study record as an attachment (e.g. "Clinical Trial Experience1.pdf" , "Clinical Trial Experience 2.pdf", etc) and the table must not exceed three pages.

The table columns should include:

  • clinical trial title
  • applicant's role in the trial
  • a brief description of the trial design
  • planned enrollment
  • actual enrollment
  • number of sites
  • whether the trial(s) were completed on schedule or not
  • publication reference(s)
Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

PHS Assignment Request Form

All instructions in the SF424 (R&R) Application Guide must be followed.

3. Unique Entity Identifier and System for Award Management (SAM)

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov.

4. Submission Dates and Times

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide.  Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

In order to expedite review, applicants are requested to notify the NCCIH Referral Office by email at schmidma@mail.nih.gov when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

In addition to the NIH policy allowed post-submission materials in NOT-OD-19-083, the follow post-submission materials are allowed:

  • Clinical Trial Experience Table (e.g., due to updated enrollment numbers, publication of trial results, or newly started clinical trials).

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process.  Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

Overall Impact

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Scored Review Criteria

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance

Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Specific to this FOA:Does the applicant describe how the results of the feasibility trial will lead to the development of a larger more definitive study? Does the applicant provide justification as to why it is important to perform the future larger clinical study in the context of the present knowledge on clinical research on complementary and integrative health approaches? Is the proposed feasibility trial essential to inform the design and implementation of subsequent steps in the evaluation of the intervention?

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Specific to this FOA:Does the investigative team have a track record of publishing the results of clinical trials following their completion? Based on the clinical experience attachment, has the investigative team successfully recruited a similar study population in previous clinical trials?

With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Specific to this FOA:Have the investigators sufficiently justified how the proposed clinical trial will inform the design of the future efficacy or effectiveness trial so that it can inform clinical practice or practice guidelines? Does the proposed research have the potential to advance the field even if the proposed study design, methods, and intervention are not innovative?

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Specific to this FOA: Does the applicant describe how the proposed study relates to a larger strategy for research and development of the intervention, and will the proposed study provide pilot and feasibility data needed to advance that strategy? Is the proposed design feasible and the timeline proposed appropriate? Does the application address appropriate regulatory requirements (IND, IRB)? Are adverse events appropriately captured and monitored?

Does the application adequately address the following, if applicable

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Specific to this FOA:Is there documentation of the commitment of any subcontractors and consultants, as well as service agreements for personnel and facilities?

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

Additional Review Criteria

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Study Timeline


Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

Protections for Human Subjects

For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Individuals Across the Lifespan

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewals

Not Applicable

Revisions

Not Applicable

Additional Review Considerations

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Applications from Foreign Organizations

Not Applicable

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3)  Genomic Data Sharing Plan (GDS).

Authentication of Key Biological and/or Chemical Resources:

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Budget and Period of Support

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NCCIH, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications will receive a written critique.

Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Council for Complementary or Integrative Health. The following will be considered in making funding decisions:

  • Scientific and technical merit of the proposed project as determined by scientific peer review.
  • Availability of funds.
  • Relevance of the proposed project to program priorities.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

Section VI. Award Administration Information

1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the recipient's business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website.  This includes any recent legislation and policy applicable to awards that is highlighted on this website.

NCCIH requires independent monitoring for research involving human subjects. Applicants should refer to the NCCIH Guidelines for Data and Safety Monitoring (http://nccih.nih.gov/grants/policies/data-safety-monitoring). The IMC or DSMB will have the responsibility to review interim data and final data, and recommend whether the protocol should be modified, and, at each meeting, whether the study should be continued or should be terminated early. Thus, its ethical responsibilities, to the participants as well as to the integrity of the study, are of paramount importance to the NCCIH. The IMC/DSMB will meet in person or by phone at least twice a year. Applicants should not appoint IMC/DSMB members in advance of the peer review, or even inquire about the interest of possible DSMB members, because anyone so contacted would not be eligible to serve as a member of the peer reviewer committee that will evaluate the applications for scientific merit.

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE) if required by the FDA.

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain “applicable clinical trials” on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex. This includes ensuring programs are accessible to persons with limited English proficiency. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html.

HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA.

Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

Not Applicable

3. Reporting

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later.  All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000.  See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period.  The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS).  This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313).  As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available.  Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 – Award Term and Conditions for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

Application Submission Contacts

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

Scientific/Research Contact(s)

Peter Murray, Ph.D.
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301-496-4054
Email: peter.murray@nih.gov

Peer Review Contact(s)

Martina Schmidt, Ph.D.
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301-594-3456
Email: SchmidMa@mail.nih.gov)

Financial/Grants Management Contact(s)

Shelley Headley
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301-594-3788
Email: carows@mail.nih.gov

Section VIII. Other Information

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Authority and Regulations

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.


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