Investigator-initiated Clinical Trials of Complementary Health Approaches Delivered Remotely or via mHealth Devices (R01 Clinical Trial Required) PAR-25-268 is sponsored by National Institutes of Health (NCCIH). Funds clinical trials of complementary health interventions (e. g.

, massage, yoga) delivered via apps, wearables, or remote tech, ideal for AI-driven personalized massage therapy protocols.

PAR-25-268: Investigator Initiated Clinical Trials of Complementary and Integrative Interventions Delivered Remotely or via mHealth (R01 Clinical Trial Required) This funding opportunity was updated to align with agency priorities. Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission. Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) Components of Participating Organizations National Center for Complementary and Integrative Health ( NCCIH ) Funding Opportunity Title Investigator Initiated Clinical Trials of Complementary and Integrative Interventions Delivered Remotely or via mHealth (R01 Clinical Trial Required) R01 Research Project Grant Notices of Special Interest associated with this funding opportunity September 9, 2025 - Notice of Correction to Key Date(s) for PAR-25-268 "Investigator Initiated Clinical Trials of Complementary and Integrative Interventions Delivered Remotely or via mHealth (R01 Clinical Trial Required)".

See Notice NOT-AT-25-008 . March 31, 2025 - This funding opportunity was updated to align with agency priorities. Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission.

April 4, 2024 - Overview of Grant Application and Review Changes for Due Dates on or after January 25, 2025. See Notice NOT-OD-24-084 . August 31, 2022 - Implementation Changes for Genomic Data Sharing Plans Included with Applications Due on or after January 25, 2023.

See Notice NOT-OD-22-198 . August 5, 2022 - Implementation Details for the NIH Data Management and Sharing Policy. See Notice NOT-OD-22-189 .

Funding Opportunity Number (FON) Companion Funding Opportunity Phase 1 Exploratory/Developmental Cooperative Agreement/Exploratory/Developmental Cooperative Agreement Phase II Resource-Related Research Project (Cooperative Agreements) See Section III. 3. Additional Information on Eligibility.

Assistance Listing Number(s) Funding Opportunity Purpose This Notice of Funding Opportunity (NOFO) encourages applications for investigator-initiated fully remotely delivered and conducted clinical trials to assess the efficacy or effectiveness of complementary and integrative health interventions in NCCIH- designated areas of high research priority.

Applications submitted under this NOFO are expected to propose a remotely delivered and conducted fully powered clinical trial with no in-person contact between research staff and study participants and may utilize mHealth tools or technologies.

Applicants must provide justification for the remotely delivered approach and provide preliminary data on the feasibility and safety of the approach, along with evidence that the intervention has promise of clinical benefit. Applicants are encouraged to contact the appropriate NCCIH Scientific/Research contact for the area of science for which they are planning to develop an application prior to submitting to this NOFO.

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

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

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

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

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

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

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

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

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

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

Other Information Part 2. Full Text of Announcement Section I. Notice of Funding Opportunity Description The National Center for Complementary and Integrative Health (NCCIH) is committed to rigorous investigation of promising complementary and integrative health interventions with physical and/or psychological inputs (often called mind and body approaches), and nutritional approaches, including natural products.

For the purposes of this notice of funding opportunity (NOFO), nutritional approaches include botanicals, probiotics, and products marketed as dietary supplements; mind and body approaches include meditation approaches (e.g., mindfulness), hypnosis or guided imagery, meditative movement approaches (e.g., yoga, tai chi, qi gong), body-based approaches (e.g., progressive muscle relaxation, acupressure), music or art-based therapy; or a combination of these approaches (e.g., mindfulness-based stress reduction).

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

Overview of NCCIH Mind and Body Clinical Trials Research Funding Opportunities: NCCIH has designed a framework for research to describe the broad spectrum of complementary and integrative health research it supports ( https://www. nccih. nih.

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

nih. gov/grants/funding/clinicaltrials ). We encourage investigators to examine the full suite of notices of funding opportunities (NOFOs) to determine which one best aligns with the proposed stage of intervention development and testing.

NCCIH has an oversight process to provide stewardship and maintain excellence, integrity, and rigor in our supported clinical studies ( https://www. nccih. nih.

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

nih. gov/research/nccih-clinical-terms-of-award-for-human-subjects-research ) to learn more about NCCIH's requirements. Prior to submitting an application, NCCIH strongly encourages consultation with the NCCIH Scientific/Research contacts relevant to the area of science for which they are planning to develop an application.

Early contact provides an opportunity for NCCIH staff to discuss the scope and goals, and to provide information and guidance. Overview of Remotely Delivered Interventions: Increasingly, researchers are incorporating mobile health (mHealth) technologies to remotely deliver interventions, including complementary and integrative health interventions.

These remotely delivered interventions may utilize phone delivery, app-based approaches, video delivery, web-based platforms, wearable devices, and/or new technologies. The rapid expansion of mHealth technologies makes it possible to digitally transmit participant data from remote areas to centrally based researchers and interventionists, deliver feedback, and capture all interactions in a database.

Additionally, these mHealth technologies have the potential to improve and increase access to complementary and integrative health approaches to address existing health disparities. Many commercially available mHealth complementary and integrative health approaches already exist.

However, rigorously designed research is needed to test the usefulness and safety of remotely delivered complementary and integrative interventions for given conditions/disorders and/or for health promotion. For clinical trials to address this need, they must be well-designed and appropriately powered to test clinically relevant hypotheses.

To that end, before proposing an efficacy or effectiveness clinical trial, it is necessary to conduct early-phase clinical trials to collect the multiple types of preliminary feasibility data needed to rigorously design a definitive clinical trial.

Applications submitted under this NOFO would be appropriate when there is a clear and compelling rationale, a rigorous empirical basis, strong feasibility and safety data, and scientific premise to conduct a fully powered remotely delivered efficacy, effectiveness, or pragmatic clinical trial.

Research Objectives of Remotely Delivered mHealth Complementary and Integrative Health Interventions (R01): This NOFO supports remotely delivered clinical trials (e.g., efficacy, effectiveness or pragmatic trials) to study the effects of complementary and integrative health interventions in NCCIH-designated areas of high research priority.

Proposed clinical trials may utilize a design anywhere along the continuum between explanatory and pragmatic. For this NOFO, pragmatic trials are considered those that test an intervention under the usual conditions in which it will be applied in the ‘real world' while explanatory trials do so under more idealized circumstances.

For example, pragmatic trials may employ interventions that would not require research staff to interact directly with participants, such as clinician decision support tools embedded in the electronic health record, system changes within the health care system, or when complementary interventions are implemented and delivered within the health care setting. The trial design should be appropriate for the study question.

Study Design Considerations: For this NOFO, the proposed trial must study an intervention that can be delivered in a fully remote manner, and all data collected remotely (i.e., no in-person contact between research staff and study participants).

The application should propose to recruit a representative sample for the population and condition of interest, and to conduct all study activities, including recruitment, intervention delivery, and data collection, remotely. The proposed remotely delivered clinical trial should utilize methods that allow for the participation of geographically distributed participants (e.g., not limited to a single city or location).

Applications to this NOFO should be based on a strong rationale for the need of a fully remotely delivered design as opposed to a multi-site in-person clinical trial. Trials supported under this NOFO are expected to contribute to research topics relevant to the mission of NCCIH and be designed with a minimum of 90-percent power to test the primary hypothesis.

The choice of study design (e.g., standard efficacy, effectiveness, and/or pragmatic randomized control trial) should be justified scientifically. In all cases, there should be strong rationale for the proposed comparator condition(s) (e.g., time and attention control, usual care, standard of care, sham condition, and/or active comparator(s)) based on the research question you plan to address.

Due to lack of rigor and potential expectancy effects, NCCIH will not support studies proposing a waitlist comparator condition.

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

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

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

In traditional randomized clinical trials (RCTs), individual participants are randomized to receive an intervention that is delivered individually (e.g., a specific natural product, individually delivered hypnosis, massage). When an intervention can be delivered in a group, there are several methods of randomizing participants.

The first option is an individually randomized group treatment trial (IRGT, where individual participants are randomized to one of the interventions, but the intervention is delivered in small groups (e.g., Mindfulness based Stress Reduction or tai chi classes).

The second option is a group-randomized trial (GRT), also called a cluster randomized trial (cRCT), 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 the entire randomized group.

The study biostatistician will need to consider how the chosen study design led to the proposed data analyses and sample size estimations. The justification should include discussion of the positive intraclass correlation expected in data obtained from participants in the same groups or clusters (IRGT, GRT, or cRCT).

In general, these types of studies need to consider how the data analyses and sample size addressed the extra variation in the data and degrees of freedom available to estimate that extra variation. Failure to account for this variable in sample size calculations can result in underpowered studies.

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. These trials are expected to achieve the Phase III trial requirements of NIH (see https://grants. nih.

gov/policy/clinical-trials/glossary-ct. htm and https://grants. nih.

gov/policy/inclusion/women-and-minorities. htm ). For applications that propose the use of a dietary supplement, drug, or device as part of the intervention, the applicants must contact the U.S. Food and Drug Administration (FDA) prior to applying to determine whether an Investigational New Drug (IND) or an Investigational Device Exemption (IDE) application is necessary for the proposed clinical research.

This NOFO will not support trials of natural products that are regulated by the Drug Enforcement Agency (DEA) as a controlled substance. For applications that propose the use of an app or clinical decision support software, applicants must consult with their institutional review board (IRB) to determine whether the approach may qualify as a medical device.

If so, applicants must contact the FDA prior to applying to determine whether an IDE application is necessary for the proposed clinical research ( https://www. fda. gov/medical-devices/software-medical-device-samd/your-clinical-decision-support-software-it-medical-device ).

There are often questions about whether efficacy, effectiveness, or pragmatic trials should include any mechanistic aims to evaluate how interventions work. Mechanistic outcomes could be included in trials submitted to this NOFO, if a strong rationale is provided such as the need to assess whether the effect of the intervention is mediated via the measured mechanism.

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

Preliminary Data Requirement Preliminary Data About the Intervention: This NOFO is appropriate when there is a clear and compelling rationale, a rigorous empirical basis, and a scientific premise to conduct a remotely delivered efficacy, effectiveness, or pragmatic clinical trial.

The following preliminary data from previous human studies (from published literature or the team’s previous research) on a similar intervention and in a similar patient population and age group as proposed in the current application are required: Demonstration that an intervention similar to the one proposed in the trial is well tolerated (does not produce frequent severe adverse events) in pilot human studies.

Pilot feasibility data on a similar intervention in a clinical population similar to the one that will be studied in the proposed trial (e.g., a proposed study to examine vinyasa yoga in adults with anxiety may cite pilot work on hatha yoga in a population of adults with depression and anxiety) Demonstrated adherence and fidelity (e.g., cite a pilot study of a similar duration with sufficient adherence and fidelity to the intervention across sites/instructors).

Demonstrated retention of participants for a similar study duration (e.g., cite a pilot study that retained a sufficient percentage of participants at the primary outcome time point). Demonstrated remote recruitment methods that meet data security standards for collecting and accessing individual-level data. Demonstration that the primary outcome is a valid measure for the proposed condition and population.

Information to justify the selection of how the intervention is delivered (e.g., format of remote delivery, duration of individual intervention, frequency of delivery, and timeline of intervention delivery to achieve clinical benefit) in the study. For example, the intervention could be delivered as a single 30-minute session once a week for 8 weeks, or as self-paced 5-minute modules over 10 weeks.

Preliminary data should demonstrate that the selected doses are feasible and likely to have the greatest impact on clinical outcome and minimize the risk of adverse events. Demonstration from pilot studies that potential adverse events can be monitored and addressed remotely.

Preliminary Data about the Team: In addition, all of the following preliminary data demonstrating the team’s collective experience conducting clinical trials are required: Delivered a similar intervention via the same delivery mode in a clinical trial with fidelity using remote methods. Successfully recruited and accrued similar participants using remote methods.

Successfully randomized participants to similar intervention and control conditions using remote methods. Achieved adherence to a similar intervention study protocol by research staff using remote methods. Retained participants for a similar study duration using remote methods.

Completed collection of follow-up data with consistency and minimal missing data using remote methods. Published results from previous completed trials using remote methods.

Natural Products Preliminary Data: In addition, for applications utilizing a natural product, the following preliminary data from human studies (published and citable data from the peer-reviewed literature) on the same product and specific formulation as proposed in the current application are required: Demonstration that the natural product can produce a clinically meaningful and measurable change in target engagement (e.g., mechanism of action) in the human population of interest.

There must also be evidence that the change in target engagement has been replicated in a separate human study with the same natural product to be used in the proposed project, unless it is impossible or impractical to do so or when a mechanism of action has been clearly established . Evidence that the specific natural product is bioavailable in humans.

Note that for prebiotics or probiotics this may be demonstrated by documenting short-term retention in the gastrointestinal tract. Information to justify the selection of the dose(s) of the product proposed to be used in the study. Data should demonstrate that the selected doses are likely to have the greatest impact on target engagement and minimize the risk of adverse events.

Evidence that evaluates the pilot study data for strength of correlation between the impact on target engagement and changes in the clinical outcomes that will be studied in the proposed clinical trial. Pharmacokinetic data on the specific natural product and formulation to be used in the proposed trial to justify the dosing frequency in the proposed trial and demonstrate initial safety of the product.

PK studies are not required for natural products that do not require absorption for their intended effect (e.g. prebiotics and probiotics). Evidence that the natural product does not produce frequent or severe adverse events in human pilot trials.

For applications that include a mind and body approach as part of a multi-component intervention, the application must provide published data that the mind and body intervention proposed has demonstrated efficacy for the condition being studied from at least one fully powered controlled trial.

For the purposes of this NOFO, it is preferred that there be an established, measurable, reproducible, well-characterized target engagement measure for a given natural product in human subjects. However, NCCIH acknowledges that for some conditions, it may be impossible or impractical to directly measure the target engagement on a natural product.

In these circumstances the study should be justified by: (1) a clear rationale for why studying target engagement in human participants is impossible or impractical; (2) potentially proposing other objective, reproducible measures, that may be proxy to, or indicative of target engagement of the natural product; and (3) strong compelling preliminary data to warrant further study of a natural product in clinical studies.

In other cases, a fundamental understanding of a given natural product’s biologic target, or mechanism of action has been clearly established (e.g., compound’s affinity for a specific receptor is well established). In these situations, investigators are also encouraged to contact NCCIH Scientific/Research staff to determine whether this NOFO is the appropriate funding opportunity for the proposed clinical trial.

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

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

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

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

ninr. nih.

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

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

pdf ) NCCIH Priorities for Clinical Trials of Natural Products NCCIH has identified targeted areas of high program priority for clinical trials on natural products. Focus is on management of conditions for which natural products are used by the public and where there is evidence of postulated mechanism of action.

For this NOFO, NCCIH considers the following topic areas to have high program priority: Symptom management, particularly the use of natural products for sleep disorder/disturbance, management of pain conditions, common gastrointestinal disorders, post-acute sequelae SARS-CoV-2 infection (PASC), or mental health conditions such as those commonly managed in primary care (e.g., chronic stress, depression, anxiety disorders, or post-traumatic stress).

Studies to examine the effects of prebiotics/probiotics and other natural products on gut microbiome-brain interactions. Of particular interest are studies of prebiotics/probiotics for depression, anxiety disorders, irritable bowel syndrome (IBS), or chronic pain. Studies to reduce disparities in conditions noted above.

Studies to examine the effects of natural products to address comorbidities, coinfections and/or complications from HIV ( https://abs2. od. nih.

gov/Docs/NIH_StrategicPlan_FY2021-2025. pdf ) When evidence justifies, NCCIH encourages applications to conduct studies in a way that assesses the impact of integrating interventions into relevant settings (e.g., health care systems, schools, Federally Qualified Health Centers, military or veteran health care delivery organizations, community organizations, justice systems, or homeless shelters).

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

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

gov/grants/guide/notice-files/NOT-OD-18-116. html ). Applications proposing research topics not identified above as high programmatic priority can be submitted but 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, conducted, or published by other groups are likely to be lower programmatic priority.

Clinical Trials Not Responsive to this NOFO: The following types of clinical trials are not responsive to this NOFO and applications proposing such activities will be deemed non-responsive and not reviewed: Clinical trials with any in-person contact of research staff with research participants. Studies that do not have a primary aim to assess efficacy or effectiveness of the intervention.

Clinical trials proposing to deliver an intervention to participants outside the United States or Canada. Studies that are geographically limited (e.g., recruiting from one city or region). Studies that propose a waitlist control.

Trials that include a natural product that is regulated by the DEA as a controlled substance. Trials that propose to assess efficacy or effectiveness of interventions for the treatment or prevention of cancer. (Investigators interested in cancer treatment or prevention trials should contact the National Cancer Institute.)

Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs. See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information Grant: A financial assistance mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity. Application Types Allowed The OER Glossary and the How to Apply Application Guide provide details on these application types.

Only those application types listed here are allowed for this NOFO. Required: Only accepting applications that propose clinical trial(s). Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications. Application budgets are not limited but need to reflect the actual needs of the proposed project. The scope of the proposed project should determine the project period.

The maximum project period is 5 years. NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this NOFO. Section III.

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

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

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

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

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

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

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

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

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

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

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

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

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

3.