Part 1. Overview Information

Key Dates

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.

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.

1. Use the NIH ASSIST system to prepare, submit and track your application online.
2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.
   
   
3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.



Table of Contents
Part 1. Overview Information
Key Dates
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

Purpose

The purpose of this notice of funding opportunity (NOFO) is to support planning and development, including pilot or feasibility research, in advance of a clinical trial testing interventions to improve health in Native American populations. Proposed research may address health promotion, disease prevention, treatment, recovery, or services research to inform intervention implementation and dissemination. Although the scientific literature or preliminary data may provide the rationale for conducting a clinical trial, investigators often lack critical information about the study population, recruitment challenges, intervention feasibility and acceptability, outcome measures, data and statistical challenges or operational risks necessary to finalize the trial protocol completely. Native American populations experience unique sociopolitical, historical, and environmental stressors and risks that may exacerbate health conditions and/or impact the effectiveness of existing solutions to address the conditions. They also possess unique strengths and resiliencies that can mitigate stressors and inform intervention strategies. Research with Native American populations requires engagement with tribal partners and communities to develop or adapt interventions and evaluate them with clinical trial protocols that are rigorous and culturally appropriate. Preparatory studies may fill information gaps, address unknowns, allow for strengthening of tribal partnerships, and pilot test the feasibility of the intervention and clinical trial design, thereby improving scientific rigor and cultural appropriateness of the future clinical trial. The inclusion of Native American investigators serving on the study team or as the PD(s)/PI(s) is strongly encouraged.

For the purposes of this NOFO, Native Americans include the following populations: Alaska Natives (AN), American Indians (AI); whose ancestral lands fall at least partially within the U.S. mainland border), and Native Hawaiians. The term Native Hawaiian means any individual any of whose ancestors were natives, prior to 1778, of the area which now comprises the State of Hawaii.

Background

Despite tremendous strengths, Native Americans have highly disparate rates of disease across many health outcomes such as chronic disease, substance use and addiction, cancer, mental illness, and sexually transmitted diseases. These disease outcomes in many cases can be traced to socio-structural factors and social and environmental determinants of health such as poverty, unemployment, pollution, and poor access to health care in combination with unique factors impacting Native people, such as historical trauma. In the face of these structural challenges, resiliencies and strengths within Native communities and individuals have been drawn upon to improve health outcomes.

A critical step towards ensuring scalable and sustainable interventions to reduce the health disparities impacting Native American communities is the development of scientifically rigorous and culturally appropriate clinical trials to test intervention efficacy, effectiveness, and implementation. Active and meaningful engagement of tribal communities and tribal leadership is essential to successful intervention development, adaptation, testing, implementation, and dissemination and to accelerate the translation of findings generated by the proposed research into practice. To this end, this R34 NOFO supports planning studies to strengthen community and tribal partnerships, develop and adapt interventions, collect intervention feasibility and acceptability data, test recruitment and retention strategies, and/or address clinical trial study design questions. Studies under this R34 planning grant are intended to address issues that will prepare the future clinical trial protocol for successful implementation and completion and facilitate rigorous full-scale testing of promising interventions to improve Native American health. Applicants must include specific milestones and/or study targets that, if met, will indicate readiness to conduct the planned future intervention efficacy, effectiveness, or implementation trial.

This NOFO is part of the Intervention Research to Improve Native American Health (IRINAH) initiative (see: https://cancercontrol.cancer.gov/native-american-intervention). The initiative also includes PAR-23-298, which uses the R01 Research Project Grant mechanism and PAR-23-299, which uses the R21 Exploratory/Developmental Grant mechanism. PAR-23-298 and PAR-23-299 have broader scope than this NOFO. Not all NIH Institutes and Centers (ICs) participate in all three NOFOs. Please speak with the Scientific Contact for the IC listed in Section VII below for the IC you wish to target to discuss which NOFO might be the best fit for your proposed project.

Scope

The activities proposed will depend on the stage of intervention development, the delivery setting, and the type of future trial proposed (e.g., efficacy, effectiveness, or implementation). Pilot tests of feasibility and acceptability of the intervention and/or future trial protocol are within scope of this NOFO.

Research should be designed in such a way that there is a high probability that interventions delivered can be scaled and sustained if the future trial finds the intervention to be effective. To ensure sustainability of intervention designs and service delivery strategies tested, applicants should, whenever possible, partner with tribes/communities and localities that use existing programming funds (e.g., funding from CDC, SAMHSA, Indian Health Services, Medicaid, Medicare and other insurance providers, and other program funding as appropriate) to support evidence-based programs and leverage those resources as the foundation for building infrastructure.

Examples of appropriate research activities include the following, but this list is not intended to be exhaustive:

• Activities to further develop and establish meaningful and trusted partnerships with Native communities.
• Develop culturally grounded study designs in collaboration with Native American community partners to ensure acceptability and feasibility in Native communities, including developing and/or selecting an intervention, defining the appropriate study population, outcome, study endpoint, and control or comparison group to use in the subsequent efficacy, effectiveness, or implementation trial.
• Determine the acceptability and feasibility of the intervention for study participants, Native American communities, and tribal partners, including standardization across sites and measures of intervention fidelity when appropriate.
• Adapt, standardize, and/or validate an intervention or assessment originally designed for non-Native populations for Native populations.
• Develop a novel intervention grounded in Indigenous Knowledge (see: https://www.whitehouse.gov/ostp/ostps-teams/climate-and-environment/indigenous-knowledge/), empirical and/or theoretical evidence, and/or adapt or standardize an intervention currently used in Native American communities to plan for a future efficacy or effectiveness trial.
• Develop inclusive and culturally appropriate recruitment and retention strategies that engage Native communities.
• Develop culturally informed study protocols, data and safety monitoring plans, analytical plans, and data management and sharing plans.
• Standardize and test the effectiveness of training tools for implementation of the intervention or clinical trial protocol.
• Employ qualitative methods, including talking circles, interviews, or focus groups as needed to address study aims and the development, testing and validation of quantitative survey tools. Qualitative or mixed methods research may also be helpful to assess community or tribal approval and commitment and to contextualize quantitative research findings as appropriate.
• Planning activities to assess the potential feasibility and acceptability of implementation strategies to be utilized in a future implementation research trial in Native American communities, including planning for hybrid effectiveness implementation studies.

This R34 NOFO will not support research testing intervention efficacy or effectiveness. Efficacy or effectiveness research could be submitted to the companion IRINAH NOFOs (PAR-23-298 and PAR-23-299).

Preliminary data are not required for this NOFO.

Non-responsive Applications

Applications with the following attributes will be deemed non-responsive and will not be reviewed:

• Applications that include exclusively mechanistic or etiological research, include only analysis of existing data and/or do not include an intervention or proposal to develop an intervention.
• Applications that do not include a Milestones and study targets section within the Research Strategy (see Section IV below)
• Applications that propose efficacy or effectiveness testing of an intervention
• Applications that only propose to write a protocol or manual
• Applications that propose research objectives that are not aligned with the mission of any of the participating ICs.
• Applications that do not propose community-engaged projects
• Applications that do not propose research with Native Americans

Additional Considerations for Proposed Research

Applicants are encouraged to consult American Indian and Alaska Native Research in the Health Sciences: Critical Considerations for the Review of Research Applications, which can be found at https://dpcpsi.nih.gov/sites/default/files/Critical_Considerations_for_Reviewing_AIAN_Research_508.pdf

Coordination across projects. Although the studies supported by the IRINAH initiative will not use a common study protocol, investigators are expected to meet regularly to participate in activities in support of advancing research on Native American Health. Such activities could include participating in cross-cutting interest groups, sharing and discussion of measures, and developing collaborative publications and products. An annual meeting will be held of all investigators with optional attendance by community partners who are funded by the IRINAH initiative; monthly or bi-monthly phone calls will also be held. Locations of the annual meeting will vary depending on sites funded through the initiative. Project budgets should include costs for one or more study team members to attend the annual meeting.

Conceptions of Health. While the absence of a particular disease is a critical outcome, the concept of health within many Native American communities embodies wellness and is broader than the absence of disease. All four elements of life physical, emotional, mental, and spiritual are intricately woven together and interact to support a strong and healthy person. In this holistic perspective, illness results from imbalance and wellness from balance in these elements. For Native people who identify strongly with tribal or indigenous culture, working with traditional healers or engaging in traditional cultural practices may be a core strategy to address disease or improve wellness. For this NOFO, investigators are encouraged to consider Native concepts of health and Native traditional practices as appropriate and approved by the community.

Community Engagement. The appropriate conduct of research with Native American populations has been widely documented; research must be conducted in a community-engaged manner, where the community has an equal voice as a research partner. The research should be consistent with community desires and informed by these at every step of the process. Community based participatory research (CBPR) approaches are one way to ensure appropriate engagement with communities in research and the cultural appropriateness of the intervention, study design and overall approach. Where communities desire to do so, researchers should incorporate a CBPR approach. Communities may choose to pursue approaches other than CBPR, and other forms of community-engaged research are acceptable for this NOFO. The community/tribe(s) should be appropriately involved in the study design and overall approach.

Culturally Appropriate Research and Preparatory Activities. Native communities and experts on Native American research have made clear the importance of culture in addressing health outcomes. Investigators are encouraged to consider culturally unique etiological factors or targets for intervention, relying on culturally relevant theories to frame research, considering culturally specific world views and Indigenous Knowledge as they relate to the research approach and design, culturally sensitive research processes, and culturally appropriate measurement strategies and processes.

Strength-Based Focus. Since many communities place a high value on the strengths and resilience of Native peoples, investigators are encouraged to incorporate community/cultural strengths and resilience. It is appropriate to consider community resilience in addition to the resilience of individuals.

Interventions. Interventions must be consistent with community cultural values, and be supported by theory or empirical knowledge, which can originate from Indigenous Knowledge or from culturally appropriate non-Native paradigms. Interventions may include traditional health, medical, and/or cultural practices independent of or in concert with practices that have been tested in research with non-Native populations. Intervention delivery should, whenever possible and scientifically or otherwise appropriate, employ individuals from the community. Such interventionists could include behavioral professionals, community health workers, counselors, nutritionists, nurse practitioners, physician assistants, or traditional healers.

Beyond the Individual Reflecting the importance of community and relations, researchers should consider proposing studies that address community, institutional, familial, peer network, or other factors that directly influence health outcomes or that impact individual's abilities to enact health preserving practices. This could include multi-level intervention approaches or addressing and reporting on changes in known contextual influences while intervening to create individual level change. However, the interventions should not be so intensive or time-consuming that they would exceed the resources of the participants/community to participate or affect sustainability. Please see the NIMHD Minority Health and Health Disparities Research Framework as one example (https://www.nimhd.nih.gov/about/overview/research-framework/).

Future Clinical Trial Design Considerations: Investigators are encouraged to work with Tribal partners and communities to identify potential research designs that will provide robust evidence of intervention efficacy or effectiveness in the future clinical trial. Rigorous research designs are expected, but investigators are not required to conduct randomized controlled trials in the future trial. Applicants are strongly encouraged to consult the NIH Research Methods Resources page (https://researchmethodsresources.nih.gov/) and to ensure that they have appropriate statistical expertise on the study team to address any non-independence or other potential sources of bias in the study design.

If participants are assigned to study arms for the future trial, other potentially appropriate study designs with randomization include parallel group or cluster-randomized trials, individually randomized group-treatment trials, and stepped wedge group or cluster-randomized trials. When it is not possible to assign participants to study arms for the future trial, alternative rigorous research designs that provide robust evidence of intervention effectiveness include, but are not limited to, multiple baseline or repeated measures designs, interrupted time series studies, or stepped-wedge cluster randomized trials in which all subjects receive the intervention.

In these studies, special methods may be warranted for analysis and sample size estimation, particularly for small or hard to reach populations where traditional experimental randomization is not possible without impacts on bias or contamination. Planning activities proposed under this NOFO may include working to incorporate such methods into the clinical trial protocol and research design.

Research Objectives

Participating NIH ICs have identified priority research areas below. Applicants are encouraged to speak with IC representatives for technical assistance (see Agency Contacts in Section VII). Applicant organizations with limited research experience are strongly encouraged to develop applications in collaboration with research organizations.

Applicants should ensure that the IC they wish to target participates in the IRINAH NOFO to which they wish to submit. Applications that do not align with the missions of any of the participating ICs will be considered non-repsonsive.

National Institute on Drug Abuse (NIDA)

The National Institute on Drug Abuse (NIDA) is interested in culturally appropriate prevention, treatment, recovery, implementation, and dissemination research focused on substance use among Native adolescents and adults. NIDA is interested in a wide array of substances including but not limited to nicotine, psychostimulants/methamphetamines, opioids, cannabis, synthetic drugs, and psychoactive prescription drugs. Research at the intersection of HIV and substance use, including research that incorporates HIV prevention and/or care, also is welcome. Investigators are encouraged to propose research in urban, rural, and reservation settings and research that utilizes existing infrastructure, community resources, service systems (public and private), and health and wellness providers.

NIDA applicants are strongly encouraged to review the guidelines and adhere to the requirements applicable to their research listed in the Special Considerations for NIDA Funding Opportunities and Awards. Upon award, these considerations will be included in the Notice of Grant Award.

National Cancer Institute (NCI)

The National Cancer Institute (NCI) is not participating in this NOFO. Please do NOT submit R34 applications directed to NCI, as they will not be funded. However, NCI encourages applicants to incorporate aims that fit within the scope of this NOFO into their IRINAH R01 applications (submitted through PAR-23-298). For further clarification, potential applicants are encouraged to contact the NCI Scientific Staff listed in PAR-23-298.

National Institute on Alcoholism and Alcohol Abuse (NIAAA)

Although abstinence from alcohol is prevalent among Native American populations, there are also higher rates of alcohol use disorder (AUD) compared to other racial and ethnic groups in the United States. We need to engage communities and continue building a body of culturally appropriate empirically supported prevention, treatment, recovery, and health services research within Native American populations, and how they can be modified to better address societal and cultural needs and health disparities. The National Institute on Alcoholism and Alcohol Abuse (NIAAA) is interested in novel prevention and clinical interventions as well as research that seeks to understand processes of recovery and health services usage among Native American populations.

National Institute of Mental Health (NIMH)

The National Institute of Mental Health (NIMH) is interested in applications relevant to priorities described in this NOFO and that support the NIMH Strategic Plan for Research. NIMH is interested in applications relevant to preventive and treatment interventions in Native American, Alaska Native, and Native Hawaiian communities in both non-AIDS and AIDS research areas. NIMH is particularly interested in exploring the mechanisms by which policies and relevant interventions lead to better access/engagement and mental health outcomes.

Examples of specific areas of interest for NIMH are included below, but not limited to:

a) Non-AIDS-related Research Areas

• Based on empirical evidence of the need for tailored approaches, develop and test new preventive, treatment, and services interventions and/or strategies for implementing interventions with established effectiveness, to determine whether the engagement of novel targets improves clinical and/or implementation and sustainment outcomes;
• Optimize and test evidence-based interventions that preempt, prevent and treat mental disorders, including interventions to reduce suicide, consistent with research priorities noted by the National Action Alliance for Suicide Prevention's Research Prioritization Task Force;
• Empirically identify barriers and facilitators of engagement in mental health treatment and services that are unique to Native American, Native Hawaiian, and Alaska Native people and communities; develop interventions that address those factors; and test their effectiveness in increasing engagement and improving mental health outcomes;
• Test strategies to increase use of evidence-based mental health care for individuals in hard-to-reach communities, including mobile and IT interventions (see NIMH workgroup report for guidance on technology development research: https://www.nimh.nih.gov/about/advisory-boards-and-groups/namhc/namhc-workgroups/namhc-bssr-workgroup-charge.shtml);
• Initial development of a project to assess which factors promote resilience and prevent mental disorders to develop preventive intervention targets at individual or other levels;
• Test innovative, empirically guided strategies for implementing integrated primary health care and mental health care in settings predominantly serving American Indian, Native Hawaiian, and Alaska Native communities in order to improve access, engagement, and continuity, equity, and value of mental health services while simultaneously addressing commonly occurring medical comorbidities;
• Initial development of a project to assess whether and to what extent financing mechanisms, policies, regulations, and healthcare system rules optimize patient-level outcomes (including suicidal behavior and other mental health crises), and identify mutable factors and policy interventions that can improve mental health outcomes;
• Initial development of a project to identify malleable factors underlying the development and/or course of mental illness to serve as potential therapeutic targets and inform development of interventions tailored for Native American, Native Hawaiian, and Alaska Native populations;
• Examine responding to existing treatments in support of developing culturally informed study designs and conduct the initial development of a project to identify reasons for nonresponding; develop strategies to overcome these factors impeding treatment response to improve outcomes.

b) AIDS-related Research Areas

1. Develop and test interventions to address the HIV prevention, care, and treatment needs based on the mechanisms that are driving new infections and poor health outcomes among those living with HIV (e.g., factors like intersectional stigma, mental health, social/sexual networks, access to and quality of health care, experiences of trauma);
2. Conduct implementation science research to focus on barriers, facilitating factors, and outcomes of scaling-up HIV prevention and care interventions with known efficacy; and improve uptake and effectiveness of efficacious interventions, particularly for individuals in rural/remote Tribal communities;

All applications that propose clinical trials should follow the NIMH’s experimental therapeutics approach to intervention development and testing (see https://www.nimh.nih.gov/funding/opportunities-announcements/clinical-trials-foas/index.shtml). That is, the scope of work must include specification of targets/mechanisms and assessment of intervention induced changes in the presumed targets/mechanisms that are hypothesized to account for the intervention’s outcomes. In this manner, the results of the trial will advance knowledge regarding therapeutic change mechanisms and be informative regardless of trial outcomes (e.g., in the event of negative results, information about whether the intervention was successful at engaging its targets can facilitate interpretation).

Both non-AIDS and AIDS applications that propose adaptations to existing interventions should provide an empirical rationale for the need for and focus of the adaptation, consistent with NAMHC Workgroup Report recommendations on intervention adaptation (https://www.nimh.nih.gov/sites/default/files/documents/about/advisory-boards-and-groups/namhc/reports/fromdiscoverytocure.pdf).

NIMH encourages a deployment-focused model of intervention and services design and evaluation that takes into account the perspective of relevant stakeholders (e.g., service users, providers, administrators, payers) and the key characteristics of the settings (e.g., resources, including workforce capacity; existing clinical workflows) that are intended to implement optimized mental health interventions. This attention to end-user perspectives and characteristics of intended clinical and/or community practice settings is intended to ensure the resultant interventions and service delivery strategies are acceptable to consumers and providers, the approaches are feasible and scalable in the settings where individuals are served, and the research results will have utility for end users.

NIMH encourages research on potentially scalable preventive, therapeutic, and services interventions that focuses on practice-relevant questions. Accordingly, collaborations between academic researchers and clinical or community practice partners or networks are encouraged. When possible, studies should capitalize on existing infrastructure (e.g., practice-based research networks such as the NIMH-sponsored Mental Health Research Network (MHRN), electronic medical records, administrative databases, patient registries, institutions with Clinical and Translational Science Awards) to increase the efficiency of participant recruitment (i.e., more rapid identification and enrollment) and to facilitate the collection of moderator data (e.g., clinical characteristics, biomarkers), longer-term follow-up data, and broader, stakeholder-relevant outcomes (e.g., mental health and general health care utilization, value and efficiency of intervention approaches).

Potential applicants are strongly encouraged to consult with relevant Institute Scientific/Research Staff as far as possible in advance of any application to discuss the match to current Institute priorities.

National Institute of Environmental Health Sciences (NIEHS)

The mission of the National Institute of Environmental Health Sciences (NIEHS) is to discover how the environment affects people in order to promote healthier lives. The NIEHS is interested in applications that support the initial development of a culturally appropriate clinical trial or research project in preparation for health promotion or disease prevention interventions addressing the health impacts of environmental exposures that disproportionately impact Native American populations. Examples of activities NIEHS will support with this R34 include, but are not limited to:

• Developing inclusive research teams where Native American investigators and/or community members have significant leadership roles (e.g., key personnel, Multiple Principal Investigators);
• Activities to establish and sustain authentic, trusted partnerships with tribal communities;
• Activities to build capacities of academics and Native American partners to engage in collaborative research;
• Co-development of research designs that respect Native American cultural values, are inclusive of Tribal Ecological Knowledge/Indigenous Knowledge, and are feasible in Native American communities;
• Co-development of recruitment strategies, study protocols, data safety and data management and sharing plans, data analyses, and study milestones with Native American partners

National Institute of Dental and Craniofacial Research (NIDCR)

The prevalence of oral diseases in Native American communities is amongst the highest in the U.S. Oral diseases share common behavioral and physiologic risk and protective factors with many other diseases and conditions, while those impacting health disparities and inequities are also known to be influenced by a range of social determinants of health such as education, employment, housing and food security, and distance to health care facilities. The National Institute of Dental and Craniofacial Research (NIDCR) is interested in prognostic research to identify new upstream risk and protective factors of dental caries, periodontal disease, or oral and pharyngeal cancer, and their interactions with other common risk factors of comorbid conditions affecting Native American population; developmental/exploratory research to engage with Native American communities and design intervention strategies to address social determinants of health contributing to oral health disparities and inequities; pilot testing feasibility, acceptability, and scalability of evidence-based/community-informed intervention strategies to address oral health risk factors and overcome barriers for adaptation. These R34 projects should inform multi-disciplinary and community-based implementation research that will promote oral health and disease prevention across the lifespan in Native American populations through holistic and sustainable interventions.

National Institute of Nursing Research (NINR)

The National Institute of Nursing Research (NINR) supports research to solve pressing health challenges and inform practice and policy - optimizing health and advancing health equity into the future. NINR discovers solutions to health challenges through the lenses of health equity, social determinants of health, population and community health, prevention and health promotion, and systems and models of care. Drawing on the strengths of nursing’s holistic, contextualized perspective, core values, and broad reach, NINR funds multilevel and cross-sectoral research that examines the factors that impact health across the many settings in which nurses practice, including homes, schools, workplaces, clinics, justice settings, and the community. Observational, intervention, and implementation research are of interest.

National Center for Complementary and Integrative Health (NCCIH)

The mission of the National Center for Complementary and Integrative Health (NCCIH) is to define, through rigorous scientific investigation, the usefulness and safety of complementary and integrative health interventions and their roles in improving health and health care. In the context of this NOFO, NCCIH is particularly interested in encouraging applications that develop and conduct pilot feasibility trials of culturally appropriate mind and body or natural product approaches for symptom management (e.g. pain, stress, anxiety, depression) or for health promotion and well-being in Native American populations. 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). NCCIH is also interested in investigating the use of natural products, including botanicals, dietary supplements, and probiotics in AI/AN populations. NCCIH will also support research on Traditional Medicine approaches, which may include mind and body and/or natural product approaches.

NCCIH will not fund research proposing efficacy or effectiveness clinical trials through this NOFO (please see NCCIH Clinical Trial Funding Opportunities instead). Investigators are strongly encouraged to discuss their research plans with NCCIH program staff prior to submitting their application.

The Office of Research on Women’s Health (ORWH)

The Office of Research on Women’s Health (ORWH) is part of the Office of the Director, NIH, and works with the 27 NIH ICs to advance rigorous research of relevance to the health of women. ORWH does not award grants but co-funds women’s health-related applications and research projects that have received an award from one of the participating NIH Cs listed in the announcement. Applications seeking ORWH co-funding, in response to this NOFO, should ensure that the proposed work is aligned with at least one goal and objective outlined in the Trans-NIH Strategic Plan for Women’s Health Research (https://www.nih.gov/women/strategicplan).

For this announcement, ORWH is interested in research projects that address health disparities in American Indian/Alaskan Native (AI/AN) and Native Hawaiian (NH) women and support culturally appropriate prevention and treatment interventions across the lifespan. These projects should also, when possible, leverage indigenous knowledge and expertise in the research questions being explored, and consider tribal input in implementation strategies, intervention methods, and evaluation processes. Interdisciplinary partnerships to advance maternal health research, reduce preventable causes of maternal morbidity, and propose clinical interventions to improve pregnancy outcomes within populations of AI/AN and NH women are of particular interest. Projects that build the capacity of AI/AN and NH investigators to conduct this research are also encouraged.

The Office of Disease Prevention (ODP)

The ODP is the lead office at the NIH responsible for assessing, facilitating, and stimulating research in disease prevention. In partnership with the 27 NIH ICs, the ODP strives to increase the scope, quality, dissemination, and impact of NIH-supported prevention research. For additional information about ODP, please refer to the ODP Strategic Plan for Fiscal Years 2019 2023.

The ODP provides co-funding for, but does not award, grants. ODP only accepts co-funding requests from NIH ICs. Therefore, applications likely to receive co-funding must be relevant to the objectives of at least one of the participating NIH Institutes and Centers (IC) listed in this announcement. Please contact the relevant IC Scientific/Research Contact(s) listed for questions regarding the IC’s research priorities and funding.

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

Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs.

Section II. Award Information

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

1. Eligible Applicants

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

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

Local Governments

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

Federal Government

• 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) 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

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 Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• 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 registration; 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.

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. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019.

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.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed only when the ancestral catchment area(s) of tribe(s) cross(es) U.S. national boundary.

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per NIH Grants Policy Statement Section 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NIH Grants Policy Statement 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

All page limitations described in the 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 NOFO.

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.

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

R&R or Modular Budget

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

The combined budget for direct costs for the project period may not exceed $450,000. No more than $225,000 in direct costs may be requested in a single year. Budgets should include domestic travel funds for one or more study team members to attend the annual IRINAH investigators meeting.

R&R Subaward Budget

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 describe the significance of the proposed research in the context of the future efficacy, effectiveness, or implementation trial it is meant to inform. Applicants must provide evidence that the research question addressed is relevant to and prioritized by the Native American community partners for the study and that the project, if completed successfully, can improve the health of one or more Native American communities. Applicants should clearly articulate how their research builds fundamental knowledge relevant to Native American health. NIH’s mission is to seek fundamental knowledge about the nature and behavior of living systems and to use that knowledge to enhance health, lengthen life, and reduce illness and disability. Through this initiative, fundamental knowledge includes findings that may be specific to a Native American community or group of communities, even if the outcomes may not generalize broadly. Fundamental knowledge may also be defined as principles for community engaged research, or methodological innovations.

Applicants must demonstrate innovation in their proposed research. Some examples of the types of innovations that may be included are the use of Indigenous Knowledge (https://www.whitehouse.gov/ostp/ostps-teams/climate-and-environment/indigenous-knowledge/), research capacity development, novel research design and analysis, novel approaches to community engagement and/or participant recruitment, research to address the cultural appropriateness of standard measures or develop new measures, determination of culturally/clinically meaningful effect sizes for a future efficacy or effectiveness trial, or through the development or adaptation of interventions or implementation strategies.

Investigators

Investigators, both those from research institutions and those who work with or in the community, must show relevant proficiency to conduct the proposed research, including proficiency for working with Native American partners and communities. Indications of proficiency might include research publications, efforts to build relationships and trust with communities, dissemination of information to Native American communities, personal engagement in community events, provision of training to communities, knowledge of community systems and settings, and leadership roles in the community. Productivity of community-based investigators may rely on a description of their proficiency in working within the community.

Partnerships and collaborations

The community-researcher partnership must be documented in the Research Strategy section to describe the community's support for and involvement in development, design, testing, and dissemination of the study, including establishing a Community Advisory Board. If using CBPR research methods, these must be appropriately documented. The description of the community-research organization partnership must describe the scientific, logistic, and organizational responsibilities of each of the collaborators for each aspect of the proposed project. If building upon existing partnerships, the application should also describe the history of the partners in collaborating on prior research projects, or other mutually beneficial activities, the mutual understanding and cooperation among the partners, procedures for resolving disagreements, and the relative contributions to the previous and current projects.

Approach

Preliminary data: Applications to this NOFO are not required to present preliminary/pilot data in support of the proposed approaches, hypotheses and aims; rather, a well-defined theory of change, logic model, or cultural source and associated hypotheses are expected.

Specific justification must be provided for the necessity of all planning and intervention development activities proposed, including cultural adaptation of interventions or measures that have been used or validated with other populations. Research questions that have been addressed for other populations may still need to be specifically addressed for Native Americans if there is reason to believe that processes might operate differently for a Native American community or Native Americans more broadly. Appropriate justifications of scientific gaps areas must be provided in the applications. Justifications for the premise of the research can be established based on documentation from scientific and/or cultural sources.

Whenever possible, evidence should be included of the feasibility of planning and research activities proposed, including prior collaborations between the investigators and between the research team and study partners, prior experience working with the study population, and prior experience with the measures and methods to be used or tested in the research.

When the research involves intervention development, adaptation, or acceptability and feasibility testing, the intervention (or the process of its initial development) must be described, including the theoretical and empirical evidence informing the intervention, the proposed mechanisms of action of the intervention, the health outcomes the intervention is meant to impact, and any relevant protective factors or risk factors that the intervention acts on or through for its hypothesized effects. When appropriate, the study should include plans for assessing fidelity of intervention and/or protocol implementation and/or plans for manualization or other standardization practices.The application must describe how the approach taken will support the future sustainability of the intervention, and any implications for implementing or disseminating the intervention if it is found to be effective in the future trial.

The pilot studies proposed under this NOFO may or may not require a comparison condition. If included, the application should describe and justify the nature of any comparison/control group (e.g., whether the comparison group will receive information only, minimal treatment, or delayed intervention or some other design). Applicants should consult with collaborating communities to discuss the appropriateness of the selected approach to the comparison group, as tribal leaders and community members may believe that comparison group members should receive something more than usual care.

Milestones and study targets

Because this R34 mechanism is intended to provide planning time for a future clinical trial, the Research Strategy section must include a section with the subheading Milestones and study targets that describes the decision points that would justify moving to a full trial. Such targets might include agreements reached with community and tribal partners, success metrics for recruitment strategies, measure validation metrics, thresholds for measures of intervention and/or protocol acceptability and feasibility, or any other appropriate milestone or target. These decision points should be specific, well justified and, when appropriate, should be quantified. Milestones and study targets should not be a restatement of the study aims. The justification for the milestones and study targets should be discussed in the context of the goal of the future trial (e.g., testing intervention efficacy, effectiveness, or implementation) and include the specific ways that reaching these targets will indicate readiness for a future trial of the intervention.

Letters of Support

Provide all appropriate letters of support, including any letters necessary to demonstrate the support of community partners, collaborators, partners/experts (e.g., end users), and others. Letters of support should describe the scientific, logistic, and organizational responsibilities of each of the collaborators for each aspect of the proposed project. The letter(s) of support should also describe the history of the partners in collaborating on prior research projects, or other mutually beneficial activities, the mutual understanding and cooperation among the partners, and the relative contributions to the previous projects.

• Each Native American organization that participates in the project should submit a letter of support.
• Applications that represent a partnership between a research organization and one or more tribes or communities should include a resolution from each tribal or community government or equivalent document, specifying that the community or tribe agrees to participate as a partner in the project and will strongly support the project for its entire duration.
• If the application includes a consortium of tribes or communities, applicants should provide a resolution of support from each tribe or community of the consortium.
• If the applicant is a tribally sanctioned non-profit tribal organization, specific tribal resolution(s) of support will not be required if the current tribal resolution(s) under which the organization operates encompasses activities proposed in the application. A copy of the current operational resolution(s) must be submitted with the application.
• In recognizing that Tribal governments are legal sovereign nations, potential partners should be informed that tribes may seek ownership or control of all data and all biological samples; therefore, universities and other partners should be prepared to negotiate data sharing and biological sample sharing agreements with tribes/Tribal government(s) as appropriate. If such an agreement is in place the applicant(s) should provide the letter of such an agreement with the application. Letters of Support should also explicitly stipulate that Tribes agree to respond expeditiously to requests for approval of the protocol, protocol modifications, approval of abstracts for presentation to scientific meetings, and approval of manuscripts for submission for publication in scientific journals. The time required for approving each of these (protocol, abstracts, manuscripts): 1) must be proposed and stated within the resolution of support, 2) may differ for each of these activities, 3) may be modified by study investigators only in consultation with the tribal/community leadership, and 4) should identify an individual or entity within the tribe or community to whom a request for waiver of the time requirement can be directed if circumstances arise. PD/PI(s) and tribes/communities are expected to publish scientific papers, present at scientific conferences/associations/meetings; and may also be expected to develop fact sheets/materials for dissemination to the tribe/community.

If the applicant is working with communities, tribes, or tribal governments then community/tribal resolutions of support, or equivalent documents, should accompany the application whenever possible. However, tribal resolutions and letters of support from community collaborators may be submitted as post-submission material up to 30 days before the study section meeting. Note that this flexibility is NOT extended to letters of support from Key Personnel and consultants with academic or research organization affiliations. Letters of support from personnel with academic or research organization affiliations must be submitted with the application (on either October due date for non-AIDs applications or the January due date for AIDs applications listed in the Key Dates table above).

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.

Other Plan(s):

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

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

• All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.
• Applicants should refer to the NIH Considerations for Researchers Working with AI/AN Communities page and NOT-OD-22-214 Supplemental Information to the NIH Policy for Data Management and Sharing: Responsible Management and Sharing of American Indian/Alaska Native Participant Data.

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

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

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

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

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

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 Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

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.

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

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

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

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile form. 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 NOFO for information on registration requirements.

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

See more tips for avoiding common errors.

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

Applicants are required to follow the instructions for post-submission materials, as described in the policy

Specific to this NOFO:

Letters of Support/Tribal Resolutions sent as post submission materials must be submitted as PDFs by the Authorized Organization Representative (AOR) of the applicant organization. Although the post-submission materials may originate from the PD/PI, Contact PD/PI, or organizational officials, the AOR must send the materials directly to the SRO or must send his/her concurrence to the PD/PI who will forward the materials and concurrence to the SRO. A communication from the PD/PI only or with a "cc" to the AOR will not be accepted. Please see Part 2. Section IV PHS Research Plan instructions for which letters of support are permissable as post submission materials.

Each Letter of Support submitted as post submission materials should contain the following:

• Principal Investigator(s) name(s)
• Principal Investigator(s) email(s)
• Principal Investigator(s) phone number(s)
• Title of the project
• Grant number (if available)

Section V. Application Review Information

1. Criteria

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

For this particular NOFO, note the following:

• Reviewers are encouraged to consult American Indian and Alaska Native Research in the Health Sciences: Critical Considerations for the Review of Research Applications. This document was commissioned by the NIH Tribal Health Research Office and a working group of NIH staff in order to assist reviewers in understanding the unique context of applications proposing research with American Indian and Alaska Native communities so that they can provide the most informed reviews.
• Reviewers are also asked to carefully review Part 2. Section I and Part 2. Section IV of this NOFO for important additional context for the applications.

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

Overall Impact

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

Scored Review Criteria

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

Significance

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

In addition, for applications involving clinical trials

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

Specific to this NOFO:

• To what extent will the project address research questions that are relevant to and prioritized by the Native American community partners for the study?
• To what extent will the project, if completed successfully, improve the health of one or more Native American communities?

Investigator(s)

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

In addition, for applications involving clinical trials

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

Specific to this NOFO:

• To what extent does the application provide evidence of the PD(s)/PI(s)’s proficiency to conduct the proposed research, including proficiency for working with Native American partners and communities (see Section IV above for examples, including those for community members serving as an investigator)?

Innovation

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

In addition, for applications involving clinical trials

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 NOFO:

• To what extent does the project innovate in its approach to Native American health, by incorporating Indigenous Knowledge, addressing the cultural appropriateness of new or standard measures, developing or adapting interventions, or in other ways as appropriate (see Section IV above for further examples)?

Approach

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

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

In addition, for applications involving clinical trials

Does the application adequately address the following, if applicable

Study Design

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

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

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

Data Management and Statistical Analysis

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

Specific to this NOFO:

• To what extent does the application provide evidence of the community-research organization partnership and mutual understanding of the responsibilities of each of the collaborators for the proposed project?
• How adequately are the planning and intervention development/adaptation activities scientifically justified?
• How adequately described is the intervention, including its proposed mechanisms of action, taking into account whether a novel intervention is being developed or a current intervention adapted in some way?
• To what extent does the project address issues related to the future sustainability and/or implications for implementing and/or disseminating the intervention, if successful, to other Native American communities/tribes?
• To what extent are the milestones and study targets specific, well justified, and, when appropriate, quantified?
• To what extent would achieving the milestone and study targets support a decision to conduct a future efficacy, effectiveness, or implementation trial of the intervention?

Environment

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

In addition, for applications involving clinical trials

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 NOFO:

• To what extent does the application provide evidence of Native American community/tribal support?

Additional Review Criteria

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

Study Timeline

Specific to applications involving clinical trials

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

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

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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

Vertebrate Animals

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

Biohazards

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

Resubmissions

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

Renewals

Not Applicable

Revisions

Not Applicable

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

Applications from Foreign Organizations

Not Applicable.

Select Agent Research

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

Resource Sharing Plans

Reviewers will comment on whether the Resource Sharing Plan(s) (i.e., Sharing Model Organisms) or the rationale for not sharing the resources, is reasonable.

Authentication of Key Biological and/or Chemical Resources:

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

Budget and Period of Support

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

2. Review and Selection Process

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

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

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

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

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

3. Anticipated Announcement and Award Dates

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

Information regarding the disposition of applications is available in the NIH Grants Policy Statement Section 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

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

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

Recipients must comply with any funding restrictions described in Section IV.6. 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 NOFO 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.

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

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

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

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

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

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:

• Federal-wide Standard Terms and Conditions for Research Grants
• Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
• Acknowledgment of Federal Funding

If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS will be required to complete an HHS Assurance of Compliance form (HHS Assurance of Compliance form (HHS 690) in which the recipient agrees, as a condition of receiving the grant, to administer programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, age, sex and disability, and agreeing to comply with federal conscience laws, where applicable. This includes ensuring that entities take meaningful steps to provide meaningful access to persons with limited English proficiency; and ensuring effective communication with persons with disabilities. Where applicable, Title XI and Section 1557 prohibit discrimination on the basis of sexual orientation, and gender identity, The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. See https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html.

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

• For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov.

• For information on an institution’s specific legal obligations for serving qualified individuals with disabilities, including providing program access, reasonable modifications, and to provide effective communication, see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html.

• HHS funded health and education programs must be administered in an environment free of sexual harassment, see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.

• For guidance on administering programs in compliance with applicable federal religious nondiscrimination laws and applicable federal conscience protection and associated anti-discrimination laws see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/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.

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 and 2 CFR Part 200.206 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

Not Applicable

3. Data Management and Sharing

Note: The NIH Policy for Data Management and Sharing is effective for due dates on or after January 25, 2023.

Consistent with the NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

4. Reporting

When multiple years are involved, recipients 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. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.

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

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

Section VII. Agency Contacts

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

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

Finding Help Online: https://www.era.nih.gov/need-help (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-480-7075

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

Erin R. Harrell, Ph.D., PMP
Division of Behavioral and Social Research (DBSR)
National Institute on Aging (NIA)
Email: [email protected]

Frank Bandiera, Ph.D.
Division of Behavioral and Social Research (DBSR)
National Institute on Aging (NIA)
Email: [email protected]

Alexa Romberg, Ph.D.
National Institute on Drug Abuse (NIDA)
Phone: 301-435-0264
Email: [email protected]

Dawn Morales Ph.D.
National Institutes of Mental Health (NIMH)
Telephone: 301-827-9668
Email: [email protected]

Elena K Gorodetsky, MD, PhD
ORWH - Office of Research on Women's Health
Phone: (301) 594-9004
E-mail: [email protected]

Damiya Eve Whitaker PsyD, MA
ORWH - Office of Research on Women's Health
Phone: (301)-451-8206
E-mail: [email protected]

Tatiana Balachova, Ph.D.
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-443-5726
Email: [email protected]

Hiroko Iida, DDS, MPH
NIDCR - NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH
Phone: 301-594-7404
E-mail: [email protected]

Lindsey Ann Martin, PhD
NIEHS - NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
Phone: 984-287-4036
E-mail: [email protected]

Melissa C. Green Parker, Ph.D.
Office of Disease Prevention (ODP)
Phone: 301-480-1161
E-mail: [email protected]

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

Karen Marie McNamara, PhD
National Institute of Nursing Research (NINR)
Telephone: 301-337-1372
Email: [email protected]

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

Sarah Vidal, Ph.D. National Institute on Drug Abuse (NIDA)
Phone: 301-827-5529
Email: [email protected]

Juanita J. Chinn, PhD
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-827-4901
Email: [email protected]

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Kwesi Wright
National Institute on Drug Abuse (NIDA)
Phone: 301-451-0617
Email: [email protected]

Ryan Blakeney
National Institute on Aging (NIA)
Telephone: 301-451-9802
Email: [email protected]

Tamara Kees
National Institute of Mental Health (NIMH)
Telephone: 301-443-8811
Email: [email protected]

Judy Fox
NIAAA - NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
Phone: (301) 443-4704
E-mail: [email protected]

Gabriel Hidalgo, MBA
NIDCR - NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH
Phone: 301-827-4630
E-mail: [email protected]

Jenny L Greer
NIEHS - NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
Phone: 984.287.3332
E-mail: [email protected]

Debbie Chen
National Center for Complementary and Integrative Health (NCCIH)
Phone: 301-594-3788
Email: [email protected]

Randi Freundlich
National Institute of Nursing Research (NINR)
Telephone: 301-594-5974
Email: [email protected]

Debbie Chen
National Center for Complementary and Integrative Health (NCCIH)
Phone: 301-594-3788
Email: [email protected]

Margaret Young
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-642-4552
Email: [email protected]

Section VIII. Other Information

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

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 and 2 CFR Part 200.