It is critical that applicants follow 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 the 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 the 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

Background

The National Center for Complementary and Integrative Health (NCCIH) is committed to the rigorous investigation of promising mind and body interventions. These mind and body approaches are widely used by the public, and they are increasingly recognized to provide a non-pharmacological approach to symptom management (e.g., chronic pain, mild depression, anxiety, etc.). These approaches can be utilized by individuals to help prevent, treat, or self-manage various conditions (e.g., chronic pain, headache, anxiety, promote wellness), as well as being complementary to treatment offered by conventional health care. For the purposes of the current funding opportunity announcement (FOA), mind and body interventions include various meditation approaches (e.g., mindfulness), hypnosis or guided imagery, meditative movement approaches (e.g., yoga, tai chi, qi-gong), body-based approaches (e.g., spinal manipulation, massage, mobilization, acupuncture), or a combination of these approaches (e.g., meditation and yoga, or mindfulness-based stress reduction MBSR).

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/effective for given conditions/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/approaches into the delivery of health care for a given condition or disorder. It is typically necessary to 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 often 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 intervention refinement, finalizing the intervention delivery method, the outcome(s), or recruitment strategy necessary to design and conduct an efficacy or effectiveness trial. Early phase clinical trials can fill this information gap, thereby improving study design and knowledge of trial feasibility. Later phase trials can go further by assessing whether the intervention can be delivered with fidelity across sites in preparation for a future multi-site trial; determining the optimal duration or frequency of the intervention to be used in the future multi-site trial; optimizing an intervention to have a greater impact on the potential mechanism of action; or exploring, developing, and testing adaptive interventions.

For more information about what NCCIH recommends for the multi-staged process for mind and body intervention development and testing, see the NCCIH website (https://nccih.nih.gov/research/blog/clinical-mind-body; https://nccih.nih.gov/grants/funding/clinicaltrials).

Considerations for Selection of Study Design

For mind and body interventions that either are or can be delivered in groups, investigators must have a strong rationale for the choice among trial design options. The selection of study design should be guided by decisions about how best to deliver the intervention and by concerns regarding contamination and logistics.

In traditional randomized clinical trials (RCTs), individual participants are randomized to receive an intervention that is delivered individually (e.g. spinal manipulation, acupuncture, or individually delivered hypnosis). When an intervention can be delivered in a group format there are several methods of randomizing participants to the intervention. The first option is an individually randomized group treatment trial (IRGTs), where individual participants are randomized to one of the interventions but the intervention is delivered in small groups (e.g. yoga, Mindfulness Based Stress Reduction, or tai chi classes). The second option is a group-randomized trial (GRTs), also called cluster-randomized trial (cRCTs), where groups of participants are randomized to study conditions, often defined by their workplace, school, primary care provider, or community. In cRCTs, the intervention provided to the randomized groups can be delivered individually, in small groups, or to the entire group.

Feasibility pilot studies can help investigators develop methods for successfully implementing IRGTs, GRTs or cRCTs. For example, the pilot study may help investigators determine whether they can recruit eligible participants within a specific time-frame to enable an IRGT design; acceptable timeframes for group meetings to which participants will adhere; procedures to limit group contamination; appropriate group sizes; and other methods related to implementing an IRGT, GRT or cRCT design.

The study team biostatistician will need to consider how the chosen study design will impact the proposed data analysis and sample size estimates for the larger efficacy study. The justification should include consideration of the positive intraclass correlation expected in data obtained from participants in the same groups, or clusters (IRGT, cRCT, or GRT). In general, these types of studies need to consider how the data analysis and sample size address the extra variation expected in the data and the degrees of freedom available to estimate that extra variation. Failure to account for this variable in the sample size calculation can result in underpowered studies.

Overview of NCCIH Mind and Body Clinical Trials Research Funding Opportunities

A clinical trial is defined by NIH 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 Mind and Body 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. 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 NCCIH Clinical Trial Optional R21 or R01 FOAs);

iii) Human mechanistic studies to determine and verify the biological mechanisms or social behavioral process of a given mind and body approach and optimize the impact of the intervention (phased innovation awards using R61/R33);

iv) Human feasibility studies to ascertain preliminary data on ability to recruit/randomize and accrue participants; fidelity of delivering the intervention; participant adherence; determining appropriate outcomes and follow-up; and retention of participants (the current R34);

v) Clinical trials to determine or optimize "dosing;" develop and test adaptive intervention strategies; demonstrate fidelity of the intervention across sites and/or further ascertain clinical effects of the intervention in a given patient population with a given condition (U01);

vi) Multi-site clinical trials to determine efficacy/effectiveness (UG3/UH3 with companion U24).

Fundamental Science (R01, PA-18-323; R21, PA-18-322)

Fundamental research on mind and body approaches can address three key aspects. The first is the approach itself: What components impact the biological system or subjective experience? The second is the biological system potentially targeted by the approach: What cellular systems or hormonal, genetic, or neural mediators, for example, are influenced by the intervention? The third is the mechanisms: What are the key processes (i.e., biological and/or behavioral) by which the approach exerts its effects? Applications to these FOAs should propose fundamental science research projects that address at least one of these three aspects. These FOAs may support clinical trials of mind and body interventions in which the primary outcomes are mechanistic. However, they should not be used for clinical trials of mind and body approaches in which the primary outcomes are clinical endpoints (e.g., clinical pain assessments), although clinical endpoints may be measured as secondary outcomes. Applications submitted should not include any specific aims that propose to measure efficacy or effectiveness of any intervention. Investigators who wish to conduct studies with clinical endpoints as the primary outcomes should consider other NCCIH-issued FOAs described here.

Clinical Trial Planning Phase - Exploratory Clinical Trials (current FOA)

To maximize the impact of Mind and Body clinical trials, it is necessary to first refine the intervention to enhance its clinical benefit, improve adherence, and/or verify feasibility of the trial. Research supported under the R34 should generally precede submission of a fully powered efficacy, effectiveness or pragmatic trial, although this is not a requirement if such data are available or can be obtained through other means. Although the scientific literature may provide the rationale for conducting a clinical trial, investigators often lack critical information about the intervention, the outcome, or recruitment strategy necessary to design an efficacy or effectiveness trial. The R34 provides a funding opportunity to elucidate the optimal research strategy by conducting studies to adapt the intervention to a specific patient population; refine the intervention to determine the appropriate duration or frequency of treatment; and/or determine the appropriate outcome measure(s). The R34-funded study should have collected the preliminary data that would enhance the probability of reaching more definitive outcomes in a subsequent larger trial. This developmental work could include refining the assessment protocol, experimental intervention protocol, as well as the comparison intervention protocol and randomization procedures (if appropriate); examining the feasibility of recruiting and retaining participants into the study conditions (including the experimental condition and the comparison condition, if relevant); and developing supportive materials and resources.

Determining Biopsychosocial Mechanisms (R61/R33, PAR-18-114)

A key phase in developing a mind and body intervention can be determining and validating its biological signature or psychological process for the condition(s) of interest in a given human population. Research supported under the R61/R33 may precede submission of a fully powered efficacy, effectiveness, or pragmatic trial, although this is not a requirement if such data is already available or can be obtained in other ways. The Phased Innovation Award for Mechanistic Studies to Optimize Mind and Body Interventions in NCCIH High Priority Research Topics (R61/R33) supports two-phased research applications to: (1) discover the underlying biological, neurological, physiological, and/or behavioral mechanisms or processes relevant to mind and body interventions and then, (2) to utilize the results from the initial phase to improve, refine, enhance, or strengthen the identified mechanisms or processes through either rigorous validation and refinement of the intervention, or using combined approaches that, together, will modulate the underlying mechanism or process. This second phase should also be able to provide preliminary evidence that the mechanism or process modulated by the intervention is associated with a functional outcome or clinical benefit for a specific clinical condition or disorder.

The data collection in the R34 or R61/R33 should be finished and the data analysis completed before a U01 or UG3/UH3 is submitted. If these research funding mechanisms are used, it is expected that the information obtained will guide activities proposed under the U01 or UG3/UH3 grant application.

Clinical Trial Cooperative Agreement (U01, PAR-18-118)

The NCCIH Mind and Body Clinical Trial Cooperative Agreement (U01) award is for investigators who have typically completed either a relevant R34 or R61/R33 study, or have obtained analogous data by other means. The objective of the NCCIH U01 FOA is to increase the evidence base on which high priority mind and body clinical trials are based. The U01 will support non-efficacy/effectiveness clinical trials assessing key aspects of a clinical trial that could include but are not limited to the following: develop and test adaptive interventions using sequential, multiple assignment, randomized trials (SMARTs) design to determine the treatment options at decision points, possible tailoring variables, or a sequence of decision rules; optimize the intervention by evaluating which elements of a complex intervention are impactful using a multiphase optimization strategy (MOST) design; assess the relative fidelity of an intervention across sites for a future multi-site, randomized, clinical trial; or large scale, "dosing studies" for definitive determination of optimal "dose" which could include studying the frequency and duration for an intervention, among other variables, to be used in a future multi-site, randomized clinical trial.

Multi-Site Investigator-Initiated Clinical Trials Cooperative Agreement (UG3/UH3, PAR-17-175; with companion U24, PAR-17-173)

The UG3/UH3 FOA will support applications to implement a multi-site clinical trial of a mind and body intervention (Phase III and beyond). Under this phased award the UG3 phase supports the planning and development of resources necessary to perform the trial. If the UG3 phase successfully meets all planning milestones, the UH3 phase is awarded to implement the clinical trial. The UG3/UH3 award is used to implement a Clinical Coordinating Center (CCC) for an investigator-initiated multi-site clinical trial of mind and body interventions (efficacy, effectiveness, and pragmatic trials). In addition, multi-site clinical trials require a companion Data Coordinating Center (DCC) application (U24) be submitted with, and linked to the CCC application. Both applications undergo peer review simultaneously. Multi-site clinical trials are defined as trials that enroll from two or more recruitment sites. Multiple sites are necessary to increase generalizability of findings and enhance recruitment efficiency as well as representativeness of the participants. Multi-Site clinical trials are expected to contribute to the evidence base for important health matters of relevance to the research mission of NCCIH. In addition to scientific relevance and excellence, these clinical trials are expected to be conducted with a high degree of efficiency, with streamlined administrative procedures wherever possible. The Clinical Coordinating Center for Multi-Site Trials FOA runs in parallel with a companion FOA that solicits applications for the companion DCC. Multi-site trials will be expected to achieve the required phase III trial requirements of NIH (see:https://humansubjects.nih.gov/glossary and http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm

The objective of this FOA is to develop the building blocks with which to design high priority mind and body clinical trials to enhance the probability of reaching more definitive outcomes. Important building blocks include working out the details of the experimental protocols, including the assessment protocol, the experimental intervention protocol, as well as the comparison intervention protocol and randomization procedures (if appropriate); examining the feasibility of recruiting and retaining participants into the study conditions (including the experimental condition and the 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 for a future efficacy, effectiveness, or pragmatic trial; or controlled cohort or case-control study.

Accordingly, collection of preliminary data regarding feasibility, acceptability, safety, and target outcomes is appropriate. Given the limited sample sizes that can be supported under this exploratory R34 grant mechanism, proposing the use of a comparison group for conducting fully powered tests of outcomes (i.e., efficacy), 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. Power calculations for subsequent larger studies should be based on an achievable, clinically meaningful improvement due to the intervention in the research population. A comparison group could be proposed for some aspects of the exploratory study, such as for determining the acceptability and feasibility of group assignment. Investigators should consult the NCCIH website (https://nccih.nih.gov/grants/whatnccihfunds/pilot_studies) for more information on the uses and misuses of pilot studies.

The following are examples of the types of clinical trials appropriate for this FOA:

• Mind and body intervention refinement to assess acceptability and adherence to dose, frequency and/or duration for testing in a future clinical trial.
• Iterative intervention refinement to address challenges with intervention fidelity, participant adherence, or participant retention.
• Development and feasibility testing of the integration of a mind and body approach into a health care system or delivery, to inform design of future pragmatic trials.
• Assess acceptability or feasibility of randomization or other aspects of trial design.
• Develop an appropriate control/comparison intervention for a future larger study.

Information to guide investigators for preparation of clinical trial implementation can be obtained from the NCCIH Scientific/Research staff. NCCIH clinical research policy and guidance information as well as NCCIH templates for the manual of operating procedures, and data and safety monitoring are available at the following website: https://nccih.nih.gov/grants/toolbox.

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. This FOA is not appropriate for de novo intervention development.

Implementation 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, and accrual plan for NCCIH and IRB approvals, a site initiation visit by NCCIH to verify that the site is ready to begin participant recruitment and any subsequent remediation efforts. Investigators are encouraged to review the NCCIH Study Accrual and Retention Policy (https://nccih.nih.gov/grants/policies/SARP).

NCCIH Priorities for Clinical Trials of Mind and Body Interventions

As NCCIH's mind and body clinical research portfolio matures, NCCIH has identified targeted areas of investigation. For this funding opportunity, applications will be considered of high programmatic priority if they meet the following two criteria:

• Includes one or more of the following high priority mind and body or integrated approaches: spinal manipulation, mobilization, massage, tai chi, qi gong, yoga, acupuncture*, hypnosis, guided imagery, progressive relaxation, meditation, biofeedback, mindfulness techniques, or complex approaches like music and art-based therapies. To be considered an integrated approach to care for this FOA, the intervention must combine one or more of these complementary health approaches added to standard care or other interventions such as a natural product, pharmacological approach, and/or another conventional behavioral approach (e.g. health coaching, physical activity or nutritional recommendations).
• Proposes to study a mind and body or integrated approach for one of the following high priority topic areas: symptom management - particularly for chronic pain syndromes; reduction of prescription drug (opioid) use or abuse in patients with chronic pain; enhancement of medication adherence; treatment or prevention of post-traumatic stress (disorder), traumatic brain injury, sleep disorders or disturbances, anxiety, depression, obesity, and smoking; promotion of psychological resilience or wellbeing; and promotion of healthy eating and physical activity.

*Applicants proposing acupuncture as an intervention should consult the NCCIH website (http://nccih.nih.gov/grants/acupuncture/priorities) to determine whether the proposed study is aligned with NCCIH's updated priorities for acupuncture research.

NCCIH encourages applications to this FOA that meet the above criteria and also address health disparities; symptom management in patients with HIV/AIDS; or utilize special populations such as older adults, children, under-represented minorities, individuals in the military, or veterans.

Applications proposing research topics not identified above as high programmatic priority can be submitted, but will be considered of lesser or low programmatic priority.

Types of Clinical Trials Not Supported by this FOA

The following types of clinical trials will not be supported by this FOA and applications proposing such clinical trials will not be considered for funding:

• 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 R01 FOA, PAR-18-323; or R21 FOA, PAR-18-322)
• Studies to determine biological signature or psychological process (mechanism) of a mind and body approach (such studies should use R61/R33 FOA, PAR-17-149)
• Multi-site, phase III trials of efficacy/effectiveness (such studies should use UG3/UH3 FOA, PAR-17- 175 and companion U24 FOA, PAR-17-173)
• Natural product or pharmacological clinical trials that do not include a mind and body element to the intervention or comparison group (such studies should use NCCIH FOAs for natural products: https://nccih.nih.gov/grants/funding/clinicaltrials#natural)
• 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 mind and body approaches for the treatment or prevention of cancer (Investigators interested in cancer treatment or prevention trials should contact the National Cancer Institute)

Optional Administrative Period

In view of the preliminary work required to initiate research activity for exploratory clinical testing of mind and body interventions, this FOA can provide support for an early administrative period of the award, prior to implementation of the preliminary clinical trial. This early administrative period of the award can be up to 12 months in length and could include support for, but is not limited to, developing tools for data management and clinical safety oversight (including the Data and Safety Monitoring Plan [DSMP]), finalizing the clinical protocol and informed consent documents, developing the manual of operations/procedures, and obtaining appropriate regulatory approvals (e.g., IRB, FDA). Investigators are encouraged to review the NCCIH Clinical Research Toolbox (http://nccih.nih.gov/grants/toolbox) to learn more about NCCAM's requirements for clinical trials. Successful achievement during the early administrative period will be a requirement for initiating clinical testing and continued support of the project. The optional administrative period is included within the budget and project period limits specified in Section II. No human subjects activities are allowed during the administrative period.

Specific Areas of Research Interest

Applicants are strongly encouraged to consult with the NCCIH Scientific/Research contacts for the area of science for which they are planning to develop an application prior to submitting to this FOA. Early contact (12 weeks prior to submission is strongly encouraged) provides an opportunity for NCCIH staff to discuss the scope and goals, and to provide information and guidance.

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

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.

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:

o Hispanic-serving Institutions

o Historically Black Colleges and Universities (HBCUs)

o Tribally Controlled Colleges and Universities (TCCUs)

o Alaska Native and Native Hawaiian Serving Institutions

o 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)

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

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

In general, the National Center for Complementary and Integrative Health (NCCIH) support of investigator-initiated clinical trials that study an intervention delivered to human subjects will be limited to studies carried out within the United States and Canada, except in special settings (https://nccih.nih.gov/grants/internationalclinicaltrials).

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) (formerly CCR) 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 and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. 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.

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.

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).

Buttons to access the online ASSIST system or to download application forms 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.

It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions 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.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

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

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.

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

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

Facilities and Other Resources: Applicants are encouraged to provide strong evidence of the availability of appropriate institutional resources, and suitable patient populations. Documentation of availability of eligible subjects at clinic sites, presented in tabular format should be provided. The application should include relevant information that addresses the feasibility of recruiting participants who are eligible for the clinical trial. Specifically, applicants must provide evidence that each recruiting center in the trial has access to a sufficient number of study participants who meet the eligibility criteria as defined in the submitted protocol. For multi-site applications, information must be provided for each site participating in the trial.

Other Attachments:

The following attachments must be included as a part of the 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 experience of key personnel in trial conduct and/or coordination in the last 5 years. The table must be provided as an attachment called "Clinical Trial Experience.pdf" and must not exceed 3 pages.

The table columns should include:

Column A: clinical trial title

Column B: applicant's role in the trial

Column C: a brief description of the trial design

Column D: planned enrollment

Column E: actual enrollment

Column F: number of sites

Column G: whether the trial(s) were completed on schedule or not

Column H: publication reference(s

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 exploratory 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.

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 http://nccih.nih.gov/grants/policies/data-safety-monitoring).

Applicants may request up to $100,000 in direct costs for the optional initial administrative period (up to 12 months) of the award. The time and cost of the optional administrative period are included within the overall budget and time period restrictions of this mechanism.

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

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

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: Applicants should provide a clear and compelling rationale for pursuing the proposed early-phase clinical trial and development of the intervention, as well as for other critical aspects of the research design (e.g., frequency or schedule of intervention, duration of treatment, choice of endpoints of interest, feasibility and acceptability of the intervention, retention and adherence estimation, fidelity of the intervention etc.). There should be a strong rationale as to why the specific intervention proposed is likely to be beneficial for the clinical condition under study.

The clinical significance and, when applicable, the biological relevance of the future clinical trial should be clearly stated. The importance of the proposed exploratory 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 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 consideration 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, and the feasibility of, the trial should also be discussed. 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 exploratory trial protocol should be presented in the Research strategy and should include the items listed below.

• A rationale for the choice of the study design.
• Preliminary data to justify the choice of intervention for the indication being proposed for study. 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), frequency of delivery or practice.
• 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 rationale for assessments, including clinical, laboratory, physiological, behavioral, patient-centered, or other outcomes. Use of patient reported outcomes, including those available through PROMIS, NIH Toolbox, and 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 the challenges expected in implementing the trial and how these might be overcome.
• A timeline for reaching important study milestones such as: (a) obtaining regulatory approval of the final protocol; (b) establishing agreements with participating industry partners, if indicated; (c) finalizing the study procedures and training participating clinical site staff; and (e) 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.
• If an administrative period is proposed, a timeline and milestones during this period should be provided.
• Future Clinical Trial: A concise summary of the subsequent proposed trial should be provided including the study design (efficacy, effectiveness, or pragmatic).

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, with the following modification:

• Generally, Resource Sharing Plans are expected, but they are not applicable for this FOA.

Appendix:

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

Use only for applications with due dates on or after January 25, 2018. When involving NIH-defined human subjects research, clinical research, and/or 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 with the following additional instructions:

Delayed Onset Study

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

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

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions.

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

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.

This initiative is not subject to intergovernmental review.

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.

Funding will be restricted or the award may not be made until the necessary regulatory approvals, including FDA approval if applicable, are in place for the conduct of the proposed clinical trial.

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 Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. 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, NIH. Applications that are incomplete or non-compliant will not be reviewed.

In order to expedite review, applicants are requested to notify the NCCIH Referral Office by email at {[email protected]} when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

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.

Important Update: See NOT-OD-18-228 for updated review language for due dates on or after January 25, 2019.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research 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.

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).

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.

Does the project address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? 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?

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?

Specific to this FOA: Does the applicant describe how the results of the pilot and feasibility studies 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 mind and body therapies? Is the proposed feasibility trial essential to inform the design and implementation of subsequent steps in the evaluation of the intervention?

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?

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?

Specific to this FOA: Does the investigative team have a track record of publishing the results of clinical trials previously completed? Has the investigative team successfully recruited the study population in previous clinical trials?

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?

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?

Specific to this FOA: How will the proposed clinical trial inform the design of the future efficacy trial so that it can change 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? Will the results of the trial indicate whether further clinical trials of the intervention is unwarranted?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the 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 children, justified in terms of the scientific goals and research strategy proposed?

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 designed 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?

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

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?

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?

Specific to this FOA: Does the application document the availability of the requisite eligible subject pool in proposed clinical site(s)? Is there documentation of the commitment of any subcontractors and consultants, as well as service agreements for personnel and facilities?

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)?

For research that involves human subjects but does not involve one of the six 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 six 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.

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 children 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.

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.

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.

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.

Not Applicable.

Not Applicable.

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.

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

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).

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).

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.

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

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:

• 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.
• Will receive a written critique.

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 and 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.

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.

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 grantee'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.

Additionally, ICs may specify any special reporting requirements for the proposed clinical trial to be included under IC-specific terms and conditions in the NoA. For example: If the proposed clinical trial has elevated risks, ICs may require closer programmatic monitoring and it may be necessary to require the awardee to provide more frequent information and data as a term of the award (e.g., to clarify issues, address and evaluate concerns, provide documentation). All additional communications and information related to programmatic monitoring must be documented and incorporated into the official project file. 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 of all trials whether required under the law or not. For more information, see http://grants.nih.gov/ClinicalTrials_fdaaa/

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that the application as well as 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).

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).

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, Grantees, 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 law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person's race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. 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. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. 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. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

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

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.

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, 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)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

Lanay M. Mudd, Ph.D.
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301-594-9346
Email: [email protected]

Martina Schmidt, Ph.D.
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301-594-3456
Email: [email protected]

Shelley Carow
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301-594-3788
Email: [email protected]

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.

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.