Part 1. Overview Information

Key Dates

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide,except where instructed to do otherwise (in this FOA or in a Notice from NIH Guide for Grants and Contracts ).

Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Purpose

The purpose of this funding opportunity announcement (FOA) is to support developmental/exploratory studies in preparation for health promotion, disease prevention, treatment, or treatment services research to improve health in Native American (NA) populations. Applications may include 1) etiologic research, where there is a significant gap in knowledge, that will directly inform intervention development or adaptations, 2) research to develop and pilot test new or adapted interventions for feasibility, acceptability, and scalability, 3) research to test the short-term efficacy of interventions, 4) where a sufficient body of knowledge on intervention efficacy exists, research on strategies to overcome barriers to the adoption, integration, scale-up, and sustainability of effective interventions. Native Americans have highly disparate rates of disease across many health outcomes such as chronic disease, substance abuse, mental illness and sexually transmitted diseases. These disease outcomes in many cases can be traced to socio-structural factors and social determinants of health such as poverty, unemployment, 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.

Research can aid in improving health conditions for NA communities and individuals by identifying malleable targets for intervention, testing the impact of new or existing theoretically grounded intervention approaches, and building knowledge around best practices for dissemination and implementation, including developing and testing strategies for overcoming barriers to the adoption, integration, scale-up, and sustainability of effective interventions. In the face of extreme health disparities, there remains a dearth of research to inform the most effective intervention approaches for NA communities. Dissemination and implementation research are also needed and will be supported through this FOA for existing, developed, or adapted effective interventions.

Projects proposed should 1. clearly identify a health or disease condition for which there is need for intervention and community support and engagement to address the problem, 2. articulate a process for ensuring cultural appropriateness and/or recognition of community strengths and resiliencies, and 3. advance knowledge toward addressing the health or disease condition through etiologic research, prevention research, treatment research or dissemination and implementation research. Interventions may address individual behaviors, social conditions, or environmental conditions related to a disease or disorder.

Participating NIH Institutes have identified priority research areas below; applicants are encouraged to speak with IC representatives for technical assistance. Applicant organizations with limited research experience are strongly encouraged to develop applications in collaboration with research organizations.

This FOA will utilize the Exploratory/Developmental Research Grant Award (R21) mechanism. Projects may include prevention research, treatment research, or etiology research to support the identification of prevention (including screening and early intervention) or treatment research. It is essential for applicants to provide a strong premise for the proposed research. However, for this announcement, pilot data collected from within the community (or communities) while encouraged are not required.

This FOA runs in parallel with an FOA of similar scientific scope, PAR-20-238, which utilizes the Research Project Grant (R01) mechanism.

Additional Considerations

Conceptions of Health. While the absence of a particular disease is a critical outcome, the concept of health within many NA 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 first step taken to address disease or improve wellness. For this announcement, investigators are encouraged to consider Native concepts of health and Native practices in the study of etiology, prevention, and treatment.

Community Engagement. The appropriate conduct of research with NA 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. Where communities desire to do so, researchers should incorporate a CBPR approach to develop, adapt, and test interventions. The community/tribe(s) should be appropriately involved in the study design and overall approach.

Culturally Appropriate Research. Native communities and experts on NA 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 as they relate to the research approach and design, culturally sensitive research processes, and culturally appropriate measurement strategies and processes.

Etiology Research. In describing research priorities, the National Congress of American Indians has stated that research must benefit Native people. This means that the research should have tangible benefits by informing strategies for increasing health equity or otherwise provide information that can be used by the community to make improvements. As such, the etiology research supported by this FOA should have clear implications for improving the ability to intervene. Etiology research should only be proposed when it is intended to discover a more basic understanding or add nuanced clarification which would be helpful in designing efficacious interventions.

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 resiliencies in the research or in the content and delivery of interventions. It is appropriate to consider community resilience in addition to the resilience of individuals.

Interventions. When studies involve prevention or treatment interventions, the interventions must be consistent with community values. Interventions should be supported by theory or empirical knowledge, which can originate from traditional Native or from culturally appropriate non-Native paradigms. Interventions studies may test traditional health, medical, and/or cultural practices independent of or in concert with practices that have been tested in research with non-Native populations.

Interventions that involve the delivery of prevention or treatment services should, whenever possible and scientifically or otherwise appropriate, employ individuals drawn from the community. Such interventionists could include behavioral professionals, community health workers, counselors, nutritionists, nurse practitioners, physician assistants, or traditional healers.

Reflecting the importance of community, researchers should consider proposing studies that address community, institutional, familial, peer network, or other factors that directly influence health outcomes or that impact individuals abilities to enact health preserving practices. This could include testing 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.

Randomized controlled trials, which are often considered as the gold standard in intervention research, may be inappropriate in some NA communities because of belief systems that do not support the selection of only some community members to receive benefits. Still, it is imperative that research studies have sufficient rigor to ensure confidence in results. Investigators conducting clinical trials may select other research designs that will provide robust evidence, including quasi-experimental designs, such as an interrupted time series design, or stepped-wedge cluster randomized designs in which all subjects receive the intervention. Investigators should justify their research design selection and provide adequate details for their ability to execute a rigorous and appropriate analysis of study data.

Dissemination and Implementation Research: This effort also supports studies that identify, understand, and develop strategies for overcoming barriers to the adoption, adaptation, integration, scale-up, and sustainability of evidence-based interventions, tools, policies, and guidelines that support the health of Native populations. Given continued disparities in access, quality, and disease outcomes, additional efforts are needed to advance dissemination and implementation science.

Qualitative and Mixed Methods Research: Qualitative data (structured and semi-structured) can be particularly useful for understanding unique factors related to risk and resilience processes, for refining interventions and measures, for interpreting intervention research findings, and for understanding challenges in dissemination and implementation of effective strategies. Qualitative research is also helpful for assessing community or tribal-level approval and buy-in. As such, applicants may choose to incorporate a mixed-methods approach. This could include the use of talking circles, interviews, or focus groups, in addition to quantitative methods. When applicable, applicants should make clear how they will utilize qualitative and quantitative data to inform one another.

Standardization and Coordination. Although the studies supported by this initiative will not use a common study protocol, investigators are expected to meet regularly to participate in activities in support of advancing research on NA Health. Such activities could include participating in cross-cutting interest groups, sharing and discussion of measures, and developing of collaborative publications and products. An annual meeting will be held of all investigators funded by the initiative; monthly or bi-monthly phone calls will also be held. Locations of an annual meeting will vary depending on sites funded through the initiative. Project budgets should include costs for PI attendance at annual project meetings.

Investigators should collaborate and report in a standardized manner when they are measuring key common variables, such as social and environmental determinants of health, access to care, diet, physical activity, height and weight, oral disease status, and smoking status and rates. Investigators may use different methods of measuring similar outcome variables when justified. Investigators are also encouraged to collaborate in the development of formative assessment measures, such as survey instruments and focus group guides. In addition, investigators are encouraged to archive data for the use of other scientists and to select a single archive and archiving format in cooperation with community collaborators.

Specific Research Objectives and Scope

Each institute has specific areas of research interest.

National Institute on Drug Abuse (NIDA)

NIDA is interested in culturally appropriate etiology, prevention, treatment, 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, marijuana, and synthetic drugs, and psychoactive prescription drugs. Investigators are encouraged to propose research in urban, rural, and reservation settings and research that utilize existing infrastructure, community resources, service systems (public and private), and health and wellness providers. Specific areas of interest include, but are not limited to:

• Etiologic or intervention research that addresses substance use and incorporates comorbid conditions, including suicidal ideation and other mental health conditions
• Studies that examine SU prevention, treatment or relapse prevention targeting AI/AN adolescents and young adults
• Research that includes trauma (current and historical) and/or stigma, either as an etiological factor or considered in intervention development, implementation, or analysis
• Research pertaining to the prevention and treatment of opioid use disorder (OUD) among individuals and families who are affected, including risk and protective factors, integration of prevention and treatment with healthcare, increasing the availability of naloxone, intervening to improve the uptake of, medication assisted treatment (MAT) to treat opioid use disorder (OUD); interventions to reduce the risk of exposure to opioids among pregnant women
• Research to examine the impact of environmental, programmatic, and policy changes on initiation and/or escalation of drug use in youth and adolescents
• Research that uses innovative technologies to deliver or enhance prevention or treatment interventions
• Research on the essential components of treatment intervention (putative treatment targets) to focus on personalization and optimization
• Studies that include justice-involved AI/AN populations
• Studies that take a multi-generational perspective, for example research on personalization of prevention and/or treatment interventions for individuals who experienced childhood trauma or children of parents with a SUD

National Cancer Institute (NCI)

Cancer incidence and mortality among Native American populations varies by region of the country. For all areas combined, the five most common types of cancers among NA men were prostate, lung, colon and rectum, kidney, and urinary bladder. The five most common types of cancer among NA women were breast, lung, colon and rectum, uterus, and kidney. Native American populations overall have the lowest 5-year cancer survival rate of any subpopulation in the U.S. Poorer cancer survival rates have been attributed to many factors, among them inadequate access to health care, geographic isolation, later stage of detection, underutilization of treatment, poverty, and social and cultural barriers.

The National Cancer Institute (NCI) is interested in applications that focus on both individual and community interventions relating to primary and secondary cancer prevention, treatment, and follow-up care. It is important that researchers consider the context in which people live (place, built environment, etc.) and develop feasible, acceptable, sustainable, and scalable interventions that can improve overall health and result in improved health outcomes as they relate to cancer health care delivery and cancer survivorship; improve treatment adherence and/or health-care systems in adopting standard of care treatment to improve overall quality of life.

National Institute on Alcoholism and Alcohol Abuse (NIAAA)

Although Native American/Alaska Natives have high rates of abstinence from alcohol use, they also have higher rates of alcohol use disorder (AUD) than other racial and ethnic groups. We need to continue to build a body of empirically supported prevention, treatment, recovery and health services research within Native American populations, and how they can be modified to address their societal and cultural needs. The National Institute on Alcoholism and Alcohol Abuse (NIAAA) is interested in prevention and clinical interventions as well as research that seeks to understand processes of recovery as well as health services usage among Native Americans. Such research can include, but is not limited to the following areas:

• Interventions to reduce high risk drinking and alcohol use;
• Interventions to promote moderate drinking or abstention;
• Interventions to postpone onset of drinking among youth; and
• Interventions to prevent any alcohol use among pregnant women;
• Test the relative effectiveness of comprehensive, multicomponent, community-based environmental interventions to reduce underage and binge drinking and related harmful behaviors among youth and young adults, in rural and urban areas;
• Research to culturally adapt existing behavioral treatments among Native Americans in order to reduce heavy and problematic drinking;
• Identify precipitants of relapse, and evaluate interventions to address these risk factors in the course of recovery;
• Develop and test interventions that integrate clients, families, communities and other local support institutions into the prevention, treatment and recovery process;
• Identify, develop, and test models and methods that can enhance the diffusion, implementation, and adoption of evidence-based alcohol-related treatment practices across the full spectrum of services for at-risk, harmful, and dependent Native American drinkers.
• Innovative health services research to understand and expand the availability and acceptability of existing alcohol services, including prevention and treatment interventions; along with research to increase uptake in both reservation and urban dwelling Native populations.

National Institute of Mental Health (NIMH)

The National Institute of Mental Health (NIMH) is interested in applications relevant to preventive and treatment interventions in Native American communities in both non-AIDS and AIDS research areas.

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 Tribal communities or geographic region; 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;
  • Explore 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

b) AIDS-related Research Areas

• • 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);
  • 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;

Applications that involve developing or testing preventive-, therapeutic-, or services- interventions are expected to comply with NIMH's mechanism-based, experimental therapeutics approach as outlined in NIMH's Clinical Trials Funding Opportunity Announcements. Under this approach, trials must be designed to explicitly test whether the intervention engages the proximal target(s)/mechanism(s) presumed to underlie the intervention effects. Both non-AIDS and AIDS, that applications 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 (http://www.nimh.nih.gov/about/advisory-boards-and-groups/namhc/reports/fromdiscoverytocure.pdf). 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 National Institute of Environmental Health Sciences (NIEHS) is interested in interventions aimed to reduce the impact of environmental exposures on diseases and disorders among NA populations. In addition to testing the efficacy of interventions on exposure reduction, applicants also are encouraged to examine the effects on interim preclinical markers of disease when possible. Applications may include, but are not limited to, projects focused on:

• Development and testing of culturally-appropriate health promotion strategies and interventions designed to educate tribal leaders and tribal members about historical and emerging environmental hazards;
• Evaluation of existing environmental risk messages for their efficacy at changing behavior or policies (Implementation Research);
• Development and testing of interventions that encourage behavior change to reduce or eliminate exposure;
• Development and testing of existing low cost, sustainable methods that address indoor air pollution; or that provide safe alternatives to contaminated drinking water and food and/or remediation of contaminated water, air and/or soil;
• Testing the impacts of policy-level decisions and interventions which are likely to influence environmental exposure levels and associated health outcomes.

National Institute on Minority Health and Health Disparities (NIMHD)

NIMHD leads scientific research to improve minority health and reduce health disparities, to realize an America in which all populations will have an equal opportunity to live long, healthy, and productive lives. To accomplish this, NIMHD raises national awareness about the prevalence and impact of health disparities and disseminates effective individual-, community-, and population-level interventions to reduce and encourage elimination of health disparities. NIMHD is interested in projects including, but not limited to, the following:

• Interventions derived from local culture in strategies, process, implementation, and evaluation.
• Projects that directly address methodological issues inherent in research in small populations such as those in many native communities.
• Culturally-leveraged community based interventions focused on existing practices that support strengths and resilience factors that may be applicable and useful in other communities.
• Projects that document efficacy and monetize traditional healing interventions for coverage by insurance.
• Projects that develop innovative approaches to the provision of non-stigmatizing and resilience supportive prevention and treatment interventions.

National Institute of Nursing Research (NINR)

The National Institute of Nursing Research (NINR) supports clinical, basic, and translational research to build the scientific foundation for clinical practice, prevent disease and disability, manage and eliminate symptoms caused by illness, and enhance palliative and end-of-life care. In doing so, NINR promotes and improves the health of individuals, families, and communities across the lifespan, in a variety of clinical settings and within diverse populations. NINR’s goal is to enhance nursing science and health care by integrating the biological and behavioral sciences, applying new technologies, promoting health equity, and developing scientists of the future.

Research projects considered for funding should be aligned with NINR’s scientific programs in the area(s) of:

• Symptom Science: Promoting Personalized Health Strategies
• Wellness: Promoting Health and Preventing Disease
• Self-Management: Improving Quality of Life for Individuals with Chronic Illness
• End-of-Life and Palliative Care: The Science of Compassion

Applicants are encouraged to contact the NINR Scientific/Research contact prior to submission to discuss the proposed project risk level and alignment with NINR’s mission and strategic plan.

National Library of Medicine (NLM)

For this FOA, NLM is interested in innovative research and development in biomedical informatics and data science to improve health in Native American (NA) populations through interventions.

The National Library of Medicine seeks applications for novel informatics and data science approaches that can help NA populations gather, manage and use data and information about their personal health. To bring the benefits of big data research to NA populations, new biomedical informatics and data science approaches are needed, shaped to meet the needs of NA populations, whose health literacy, language skills, technical sophistication, education and cultural traditions affect how they find, understand and use personal health information. Novel data science approaches are needed to help NA populations at every step, from harvesting to storing to using data and information in a personal health library.

Applicants must base their proposed work on an informed profile of the intended users among NA populations, and, the work should be developed through interaction with the users. The strongest projects will provide approaches that incorporate health data and information from more than one source, such as diagnostic images and links to full-text articles or genome sequence data linked to a family health history. An application should be centered on the problem area being addressed and the intended audience among NA populations, propose a possible solution that employs novel data science or informatics, and undertake a pilot that will result in evidence of the degree of success and/or needed next steps. Applicants should expect to involve the intended users in their work.

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases. In the context of this FOA, the NIAMS is interested in applications relevant to preventive and treatment interventions on both individual and community level in Native American populations, to reduce and encourage elimination of health disparities in the NIAMS mission relevant diseases. Research areas include rheumatology, orthopaedics, dermatology, metabolic bone diseases, heritable disorders of bone and cartilage, inherited and inflammatory muscle diseases, and sports and rehabilitation medicine.Note that different from the other participating Institutes, NIAMS will not support clinical trial applications in response to this FOA. NIAMS only supports clinical trial applications when they are in response to NIAMS clinical trial specific FOAs. A current list of active NIAMS clinical trials FOAs is available at https://www.niams.nih.gov/grants-funding/conducting-clinical-research/grants. Applicants are encouraged to discuss potential applications with the appropriate NIAMS program director.

National Institute of Dental and Craniofacial Research (NIDCR)

The National Institute of Dental and Craniofacial Research (NIDCR) is interested in research that examines social-ecological factors (including, but not limited to, individual, cultural, community, policy, and the health care system) that influence oral health in Native American communities. The prevalence of oral diseases in Native American populations is amongst the highest in the U.S.

NIDCR welcomes culturally-appropriate studies that examine oral health in the context of general health. The overall goal of the studies should be to establish factors for future interventions to improve oral health. Specific areas of interest include, but are not limited to:

• Studies that examine oral health in the context of general health
• Research that utilizes mixed methods in order to better understand barriers, enablers, and determinants of oral health in Native American communities
• Research that analyses existing datasets to better understand barriers, enablers, and determinants of oral health in Native American communities
• Studies that take a multi-generational perspective to address family factors influencing the oral health of all family members

National Institute of Biomedical Imaging and Bioengineering (NIBIB)

The mission of the National Institute of Biomedical Imaging and Bioengineering (NIBIB) is to improve health by leading the development and accelerating the application of biomedical imaging and bioengineering tools, methods, devices, and technologies for the prevention, detection, quantification, treatment, and monitoring of disease. The technology may focus on translation of methods, devices, and tools for pre-clinical research, pediatrics, and retrospective data analysis.

For applications submitted to this FOA that propose clinical trials, NIBIB will only support applications proposing early stage clinical trials through Phase I, first-in-human, safety, feasibility, or other small clinical trials that inform the early stage technology development in the submitted application. NIBIB will not support applications proposing Phase II, III, IV or pivotal clinical trials, or trials in which the primary outcome is efficacy, effectiveness, or a post-market concern.

National Center for Complementary and Integrative Health (NCCIH)

The mission on 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 FOA, NCCIH is particularly interested in encouraging applications that develop culturally appropriate mind and body or natural product approaches for symptom management (e.g. pain, stress, anxiety, depression) or for health promotion and wellbeing in AI/AN 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. Applications may include, but are not limited to, projects focused on:

• Secondary data analyses of existing data sources to examine associations between Traditional Medicine approaches, mind and body approaches, and/or natural products and health outcomes in Native American communities;
• Observational and/or qualitative research to understand how traditional practices, beliefs, and medicine can be linked with or integrated into medical and psychological interventions to improve health outcomes;
• Mixed methods research to adapt existing complementary and integrative health interventions to Native American communities.

NCCIH will not fund research proposing efficacy or effectiveness clinical trials through this FOA (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 National Center for Advancing Translational Sciences (NCATS)

NCATS strives to develop innovations to reduce, remove, or bypass costly and time-consuming bottlenecks in the translational research pipeline in an effort to speed the delivery of new drugs, diagnostics and medical devices to patients. NCATS is interested in clinical and translational research that address the significant burden of conditions that disproportionately affect Native American populations.

Specific areas of interest include, but are not limited to:

• Translation of effective, evidence-based prevention strategies to Native American populations in a culturally and linguistically sensitive and participatory manner.
• Innovative strategies to accelerate detection of treatable diseases which disproportionately affect Native American populations and for which early diagnosis improves outcome.
• Dissemination and implementation science projects that enhance access to health care and improve disease prevention and health promotion through community-driven and community-engaged translational science research.
• Innovative strategies to accelerate or improve diagnosis of rare diseases that disproportionately affect Native American populations.

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

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 FOA.

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)

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

• 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 Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

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

3. Additional Information on Eligibility

Number of Applications

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101)

Section IV. Application and Submission Information

1. Requesting an Application Package

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

2. Content and Form of Application Submission

Letter of Intent

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to: [email protected].

Applicants are encouraged to send the letter of intent by email to the email address above but as an alternative the letter may also be sent to:

Office of Extramural Policy and Review
National Institute on Drug Abuse
DER/OEPR
3WFN 9^th Floor, MSC 6021
301 North Stonestreet Ave
Bethesda, MD 20892

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

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

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

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

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.

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: Applicants should address the following topics as they pertain to the research project proposed:

1. Pilot Data: Given that prior research within NA communities is often limited, it is not a requirement to provide pilot data from the community under study. However, PD/PI(s) and collaborator(s) are encouraged to provide such data if they are available. If not, applicant(s) are encouraged to provide data on similar interventions that have been conducted in comparable (sub) populations or settings. Sources reflecting local knowledge that are not peer-reviewed or that are unpublished are acceptable when justified.
2. Generalizability: 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 etiology, prevention, or treatment findings specific to a tribal community or group of communities, even if the outcomes may not generalize broadly. Fundamental knowledge may also be defined as etiologic principles, principles for community engaged research, or methodological innovations. Applicants should clearly articulate how their research builds fundamental knowledge.
3. Evidence of Capacity to Recruit Participants and Conduct the Research: Applicants must provide evidence of community support and of their ability to recruit participants in each community involved in the study, to implement measurement and intervention protocols in the target population, to provide appropriate oversight, and to maintain high rates of retention throughout the intervention and follow-up period.

4. Data Ownership and Sharing: Collaborators should address issues of ownership, control, and storage of data and biological samples in the application. The NIH recognizes that communities may wish to retain ownership or control of data and biological samples. Applicable Federal, Tribal, state, ad local laws, regulations, statutes, guidance and institutional policies will also dictate how research involving human participants should be conducted and how the scientific data derived from human participants should be used. As projects submitted through this initiative will be subject to NIH data sharing requirements, PD/PIs are encouraged to develop a full understanding of the tribal and community requirements and needs with regard to data sharing and data ownership and provide a justification for the stated approach to data sharing and ownership and sharing, including requests for exceptions. The NH recognizes that certain factors (e.g., legal, ethical, technical) may limit the ability to preserve and share data. Plans should include consideration of these factors, when applicable. Full data sharing and ownership agreements can be negotiated and submitted after award if necessary, but the application should include a clear plan for establishing these agreements.
5. Research Design and Approach: The investigators should select a research design that will provide convincing evidence regarding the research questions. If a study design to test intervention efficacy other than a randomized control trial is chosen due to community preferences, the selection of alternate design should be well documented as the rigor of the research design will be a consideration in review. Applications should address concerns related to the quality of the research, such as outcome variables, psychometrics for planned measures, appropriateness of the measures for the planned study sample, expected attrition, power analysis, statistical analyses planned. Power estimation should consider power not just for main effects but also for any mediated analyses. Applicants are advised to consult with a methodologist and/or statistician when proposing a design with regard to level of rigor, handling of missing data, the data points needed for the planned analyses, and, for intervention research, the appropriateness for testing the proposed intervention.
6. Applicants should provide a justification for the measurement strategies used in their project. While many research measures have not been validated for Native people, they may be the only measures validated to assess constructs and thus may be an appropriate tool. Research projects may use existing measures or develop new measures that reflect culturally relevant constructs in the course of their project

Applicants pilot testing interventions should describe and justify the nature of any comparison/control group; that is, whether the comparison group will receive, e.g., usual care, information only, minimal treatment, or delayed intervention. 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. The application should provide sufficient description of the intervention approach and its implementation for reviewers to assess its significance, innovation, and potential for public health impact.

Investigators should demonstrate innovation in their application. Examples of innovations that may be included are the use of indigenous theory and cultural constructs, research capacity development, research design and analysis, community engagement, participant recruitment, measurement to strengthen cultural appropriateness of standard measures or develop new measures, or through the development or adaptation of interventions.

6. Collaborations: Applications that represent collaborations between a tribe or community and a research organization should describe the scientific, logistic, and organizational responsibilities of each of the collaborators for each aspect of the proposed project. 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.
7. Community Engaged Research: The community-researcher partnership should 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 Community Based Participatory Research (CBPR) research methods, these must be appropriately documented
8. Research Topic and Premise: Research questions that have been addressed for other populations may still remain a research gap area for Native Americans if there is reason to believe that processes might operate different 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.
9. 6. Investigators: Investigators, both those from research institutions and those who work with the community, must show relevant proficiency to conduct the proposed research. Indications of proficiency might vary across settings. Productivity might include research publications, but due to the unique nature of conducting research with Native American communities, it may also include, for example, 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.

Letters of Support: If the applicant(s) is working with tribes/Tribal governments then Tribal/community resolutions of support, or equivalent documents, should accompany the application.

• • Applications that represent a partnership between a tribe or community and a research organization should include a resolution from the 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.
  • Applications that include more than one tribe or community should include a resolution of support, or equivalent document from each participating tribe and community.
  • 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.
  • Applicants including participants from an extant study must submit, prior to the review, a letter from the PD/PI or steering committee of the parent study approving their participation.
  • 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.
  • Each NA organization that participates in the project should also submit such a letter of support.
  • If tribes seek ownership or control of all data and all biological samples, then universities and other partners should be prepared to negotiate data sharing and biological sample sharing agreements as appropriate and provide letters of agreement/partnership.
  • 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.
  • Because the application represents collaboration(s) between tribe(s)/community(ies) and research organization(s), the letters of support should also 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.

All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

The following modifications also apply:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

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.

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.

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

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

4. Submission Dates and Times

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

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

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

7. Other Submission Requirements and Information

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

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

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

Section V. Application Review Information

1. Criteria

Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) as part of the Resource Sharing Plan will not be evaluated at time of review.

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 announcement, note the following:

The R21 exploratory/developmental grant supports investigation of novel scientific ideas or new model systems, tools, or technologies that have the potential for significant impact on biomedical or biobehavioral research. An R21 grant application need not have extensive background material or preliminary information. Accordingly, reviewers will emphasize the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Preliminary data are not required for R21 applications; however, they may be included if available.

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

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

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

Significance

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

Specific to this FOA:

Does the project address issues that are critical to one or more Native American communities/tribes? Will the project advance the science and improve the lives for Native American communities/tribes?

Will the study develop and apply knowledge to enhance health, lengthen life, and reduce illness and disability for a Native community or Native people.? Reviewers should note that research results need not generalize to other samples or populations.

Does the project address issues related to sustainability and/or implications for implementing and/or disseminating the intervention, if successful, to other Native American communities/tribes? Will the study develop and apply knowledge to enhance health, lengthen life, and reduce illness and disability for a Native community or Native people? Reviewers should note that research results may not generalize to other samples or populations. Does the study address research questions relevant for the community partner? Reviewers should note that while research questions may have been addressed for other populations, they remain significant if advancing knowledge specifically for a Native community or for Native people more broadly.

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?

Investigator(s)

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

Specific to this FOA:

Does the application provide evidence of proficiency of working in the community for both the academic and community investigators? Does the application provide evidence of investigator productivity? Because of the unique nature of conducting research in NA populations, such productivity may not be reflected by research publications but can include efforts to build relationships and trust with community leaders, disseminate information to tribal communities, personally engage in community organized events, provide trainings to the community, or have other expertise in the community. Does the application provide evidence that the investigators are experts in the area of science proposed or have expertise by virtue of experience and/or relationships with a tribal community?

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?

Innovation

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

Specific to this FOA:

Does the application provide novel or innovative insights into improving the health of one or more Native American communities/tribe? Is the project innovative in its approach to Native research? Innovation may be demonstrated in the use of indigenous theory and cultural constructs, research capacity development, research design and analysis, community engagement, participant recruitment, measurement to strengthen cultural appropriateness of standard measures or develop new measures, or through the development or adaptation of interventions.

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?

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?

Specific to this FOA:

Is there evidence that the Native American community/tribe(s) have been appropriately involved in the study design and overall approach for the research proposed?

Does the research use a community engaged approach or cultural constructs that reflect the desires of the community? Are measures appropriate for the study? Reviewers should note that while many research measures have not been validated for Native people, they may be the only measures available to assess constructs and thus must be used. Research projects may use existing measures or develop new measures that reflect culturally relevant constructs in the course of their project.

Is the design appropriate for the study and does it reflect community preferences?

If qualitative and quantitative data are being used, is it clear how they will work in tandem and how the qualitative data will inform the quantitative?

Research premise can be established based on documentation from a variety of cultural and scientific sources.

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?

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?

Environment

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

Specific to this FOA:

Does the project provide evidence of Native American community/tribal support, as appropriate?

When research sites and study personnel are in different geographic locations, does the application have a plan for communication between project staff (e.g., videoconferencing) and data management? The study team may be at a distance from each other, given the location of Native communities and research institutions.

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?

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 Animal Section.

Biohazards

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

Resubmissions

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

Renewals

Not Applicable

Revisions

For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

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

Applications from Foreign Organizations

Not applicable

Select Agent Research

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

Resource Sharing Plans

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

Authentication of Key Biological and/or Chemical Resources:

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

Budget and Period of Support

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

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by 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.

• 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

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

Section VI. Award Administration Information

1. Award Notices

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

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

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

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: Grantee institutions must ensure that all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols. Data and Safety

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

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

2. Administrative and National Policy Requirements

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

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

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

• Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. HHS provides guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at https://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

• Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html.

• HHS funded health and education programs must be administered in an environment free of sexual harassment. Please see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html; https://www2.ed.gov/about/offices/list/ocr/docs/shguide.html; and https://www.eeoc.gov/eeoc/publications/upload/fs-sex.pdf. 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.

• Recipients of FFA must also administer their programs in compliance with applicable federal religious nondiscrimination laws and applicable federal conscience protection and associated anti-discrimination laws. Collectively, these laws prohibit exclusion, adverse treatment, coercion, or other discrimination against persons or entities on the basis of their consciences, religious beliefs, or moral convictions. Please 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 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

Not Applicable

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.

3. Reporting

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

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

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

Section VII. Agency Contacts

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

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

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

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-637-3015

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

Melissa C. Green Parker, PhD
Office of Disease Prevention (ODP)
Telephone: 301-480-1161
Email: [email protected]

Kathy Etz, Ph.D.
National Institute on Drug Abuse (NIDA)
Telephone: 301-402-1749
Email: [email protected]

Aria Crump, Sc.D.
National Institute on Drug Abuse (NIDA)
Telephone: 301-435-0881
Email:[email protected]

Shobha Srinivasan, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-6938
Email: [email protected]

Judith A. Arroyo, Ph.D.
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-402-0717
Email: [email protected]

Dawn Morales Ph.D.
National Institutes of Mental Health (NIMH)
Telephone: 301-82709668
Email:[email protected]

Lindsey Ann Martin, PhD
National Institute of Environmental Health Sciences (NIEHS)
Telephone: (984) 287-4036
Email: [email protected]

Dorothy Castille, Ph.D.
National Institute on Minority Health and Health Disparities (NIMHD)
Telephone: 301-594-9411
Email: [email protected]

Lynn Adams, Ph.D.
National Institute of Nursing Research (NINR)
Telephone: 301-594-8911
Email: [email protected]

Hua-Chuan Sim, M.D.
National Library of Medicine (NLM)
Telephone: 301-594-4822
Email:[email protected]

Xincheng Zheng (Ted), M.D., Ph.D..
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-594-4953
Email: [email protected]

Hiroko Iida, DDS, MPH
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-594-7404
Email: [email protected]

Randy King, Ph.D.
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Telephone: 301-451-0707
Email: [email protected]

Lanay Mudd, Ph.D.
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301.594.9346
Email: [email protected]

Xinzhi Zhang, MD, PhD
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-827-9205
Email: [email protected]

Michael Spittel, PhD
Office of Behavioral and Social Sciences Research (OBSSR)
Telephone: 301-451-4286
Email: [email protected]

Damiya E. Whitaker, Psy.D., M.A.
Office of Research on Women's Health (ORWH)
Telephone: 301-451-8206
Email: [email protected]

The Office of Behavioral and Social Sciences (OBSSR) does not accept assignment of applications or manage awards that are funded. Please contact one of the ICs listed for inquiries regarding the suitability of the proposed project for the FOA and the IC’s research portfolio.

Delia Olufokunbi Sam, PhD
Center for Scientific Review (CSR)
Telephone: 301-613-6206
Email: [email protected].

Penny Greene
National Institute on Drug Abuse (NIDA)
Telephone: 301-827-6845
Email:[email protected]

Carol Perry
National Cancer Institute (NCI)
Telephone: 240-276-6282
Email: [email protected]

Judy S. Fox
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 302-443-4704
Email: [email protected]

Rebecca Claycamp, M.S., CRA
National Institute of Mental Health (NIMH)
Telephone: 301-443-2811
Email: [email protected]

Jenny Greer
National Institute of Environmental Health Sciences (NIEHS)
Telephone: 84-287-3332
Email: [email protected]

Priscilla Grant, J.D.
National Institute on Minority Health and Health Disparities (NIMHD)
Telephone: 301-594-8412
Email: [email protected]

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

Samantha Tempchin
National Library of Medicine (NLM)
Telephone: 301-496-4221
Email: [email protected]

Erik Edgerton
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-594-7760
Email: [email protected]

April L. Harrison
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-827-4628
Email: [email protected]

Angela Eldridge
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Telephone: 301-451-4793
Email: [email protected]

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

Brian Quillin
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-443-4295
Email: [email protected]

Elena Gorodetsky, M.D., Ph.D.
Office of Research on Women's Health (ORWH)
Telephone: 301-594-9004
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.