It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

The purpose of this funding opportunity announcement (FOA) is to encourage exploratory developmental research to improve Native American health. Such research can include: conducting secondary analysis of existing data (such as databases that the Tribal Epidemiology Centers have collected); merge various sources of data to answer critical research questions; conduct pilot and feasibility studies; and/or assess and validate measures that are being developed and/or adapted for use in NA communities. Possible areas of interest would include the following:

• Piloting of potential treatment interventions, both adapted, evidence-based treatments and those that build upon screening and brief interventions often included in prevention interventions;
• Analyzing existing data to develop and test models that account for differential risk, morbidity, and mortality for NA in a variety of health domains;
• Examining patterns of health services utilization and best practices to reduce health disparities;
• Conducting analyses to understand where there are critical failures of health-care systems and public health systems to provide timely and readily available health services; ascertain where making even minor, cost-effective additions would have most impact on health outcomes (e.g., case management, community care workers, social support groups, etc.);
• Developing and demonstrating programs that encourage enhanced health screenings;
• Understanding how traditional practices, beliefs, and medicine can be linked with or integrated into medical and psychological interventions to improve health services and health outcomes.

Tribes, communities, and organizations that do not have research experience are strongly encouraged to develop collaborations with research organizations

An R21 grant application should not have extensive background material or preliminary information. Extensive preliminary data demonstrating feasibility is an indication that the project is beyond the scope of this FOA. Reviewers' determinations of merit will instead place emphasis on the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge, understanding or practice. Applicants can provide appropriate justification for the proposed work through literature citations, data from other sources, or analytical and computational models. The proposed research could involve considerable risk that the work may not be successful and applicants should clearly explain the significance of the work in order to allow the reviewers to determine whether the potential impact justifies these risks.

This FOA is similar in scientific scope to PAR-17-496, which utilizes the Research Project Grant (R01) mechanism.

For the purposes of this funding opportunity announcement, Native Americans include the following populations: Alaska Native (AN), American Indian (AI), and Native Hawaiian (NH). The term 'Native Hawaiian' means any individual any of whose ancestors were natives, prior to 1778, of the area which now comprises the State of Hawaii.

Investigators are encouraged to view the following website: Intervention Research to Improve Native American Health (IRINAH) and are encouraged to contact the relevant Scientific/Research Contact listed in Section VII. Agency Contacts before application submission. This website will have information related to Technical Assistance Workshops that are planned for this FOA.

Cultural Factors

NAs have a concept of health that is often broader than the definition of 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.

Visiting the health care system is often not the first recourse to those AI/ANs who identify strongly with their Tribal culture. They may initially go to a traditional healer or medicine man. Traditional native cultures often integrate several factors, such as an imbalance in the elements of life, as contributing to diseases such as cancer. AI/AN cultural norms regarding modesty, introversion, pragmatism, and fatalism can be barriers to screening and other secondary prevention programs, and treatment seeking. However, high levels of traditionalism are significantly associated with disease protective behaviors and are inversely associated with disease risk factors, such as smoking and obesity. To be effective, interventions must demonstrate the immediate and long-term value of prevention and treatment and its importance to the balance of health.

Individual Factors

Increasing rates of chronic conditions in AI/AN populations are likely the result of a combination of factors, as discussed above. Adopting unhealthy lifestyles at the expense of healthy, culturally appropriate lifestyles are possibly the most important.

Unhealthy diets have had a significant impact on the health and disease progression and survivorship among AI/ANs. The Federal government food commodities program, introduced about 60 years ago to combat starvation on reservations, had the unintended consequence of introducing some unhealthy dietary changes. For example, fry bread was one of the foods that resulted from the commodities given to reservation-residing NAs. Traditional diets, by contrast, are very healthy, based on seasonal foods, and consist largely of vegetables (corn, climbing beans, squash), lean game meats (bison, deer, turkey, fish), and gathered foods (wild rice, nuts, berries). The traditional life promoted active lifestyles, such as hunting, canoeing, athletics, and traditional dancing.

Tobacco is a sacred plant in many native cultures, and tobacco is used in prayer and in other customs. Mass-produced cigarettes, along with the introduction of habitual use of tobacco, have led to the current permissive attitudes towards smoking among AI/AN populations. This contrasts with traditional Native American cultures in which smoking cigarettes is called abusing tobacco, and is considered taboo.

Developing Culturally Appropriate Studies

The research plan should be consistent with community attitudes. The following describes elements of the research and experimental approaches that are being sought to achieve the following Specific Research Objectives:

1. Community-based Participatory Research (CBPR). Given the long history and deep involvement of the family and the tribe in individual decisions on health and ultimately disease outcomes, projects to serve the NA communities should incorporate a community-based participatory research (CBPR) approach, where applicable

2. Interventions. Pilot interventions should be designed to engage the participants and be of sufficient intensity to affect change, because sustained behavior change is needed to reduce risk of disease, morbidity, and mortality. Moreover, despite the efficacy of some treatments, such as combination HIV-related therapies, many people living with HIV in the U.S. and worldwide do not benefit from treatment because they are poorly engaged in medical care, and research is needed to promote factors contributing to engagement. Interventions should be directed both at the individual and familial/institutional/structural levels simultaneously. The proposed intervention in addition to behavior change should also incorporate familial/community/institutional changes so that these interventions can be sustained over time. However, the interventions should not be so intensive or time-consuming that they would exceed the resources of the participants/community to participate.

The pilot interventions to be tested must be consistent with community values and may include traditional health, medical, and/or cultural practices. Proposed interventions should account for community resilience in the health promotion and disease prevention projects. The term community resilience is often defined as the sustained ability to utilize available resources to respond to, cope, withstand and recover from with unexpected shocks or adverse situations. Resilient communities are those with a particular capacity to cope and respond to these adverse conditions. As a result, if ethics are not consciously considered at the inception of community-driven data projects, steps taken to increase community resilience and eliminate health inequities could in fact create more vulnerability and thus do harm.

3. Standardization and Coordination. Although the studies supported by this initiative will not use a common study protocol, whenever possible, investigators are expected to meet after the awards are made and should, to the extent possible, 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 also use different methods of measuring similar outcome variables when justified. Investigators may also collaborate in the development of formative assessment measures, such as survey instruments and focus group guidelines.

Investigators are encouraged to collaborate for data archiving, such as selecting a single archive and archiving format, if that is acceptable to community collaborators. Locations of semi-annual meetings will vary depending on sites funded through the initiative. The meetings will provide a venue for presenting scientific findings from each of the funded studies and are intended to facilitate synergistic interactions among the projects within the evolving community of scientists. The investigators may form committees that would meet periodically by conference calls as needed. PDs/PIs will be expected to participate in these conference calls for planning purposes at monthly or other appropriate intervals. Other investigators should set time aside as needed to participate in cross-cutting "research interest groups" and other collaborative activities as a way of advancing transdisciplinary science in NA communities.

4. Outcome Measures. Potential outcome measures include, but are not limited to:

• Increased availability of healthy foods;
• Increased development of community-based programs, such as community physical activity programs;
• Improved clinical practices that are culturally relevant and appropriate;
• Verified screening rates;
• Biochemical verification for smoking status;
• Nutrient biomarkers as measures of dietary intake (e.g., urinary sodium as a measure of dietary sodium intake, urinary potassium as a measure of fruit and vegetable intake);
• Body mass index or body weight for diet and physical activity;
• Delayed initiation of drug and alcohol use or decreased frequency of use;
• Reduction in high risk drinking and alcohol use;
• Reduction in alcohol and drug use among women of childbearing age;
• Improvement in HIV-related biological markers (CD4, VL);
• Reduction in HIV-related risk behaviors and in AIDS-associated co-morbidities;
• Increase in pro-social behaviors;
• Reductions in deaths due to suicide and/or number of persons who report a major depressive episode;
• Increased use of mental health services;
• Increased access to specialized mental health services through mobile devices, or telemedicine;
• Decreased body burden of key environmental agents of interest;
• Improved access to and use of sustainable preventive, telehealth and self-care strategies for oral health.

Adherence to recommendations, such as engaging in physical activity, diet, smoking cessation, moderate drinking, screening, oral disease preventive self-care, as well as improved quality of life, are of interest as indicators of success of the program(s). In addition to specifying the primary outcome, applicants should propose and justify secondary outcomes and measures. Although an extensive cost analysis is beyond the scope of this initiative, applicants should collect and consider limited analyses of cost data.

Each institute has specific areas of research interest.

National Cancer Institute (NCI)

Native American populations have the lowest 5-year cancer survival rate in the United States. This subpopulation also has the highest percentage of disseminated and ill-defined cancers. Poorer cancer survival rates have been attributed to many factors, including inadequate access to health care; geographic isolation; later stage of detection; underutilization of screening, vaccination, and treatment; poverty; and social, cultural, and environmental barriers. Significant behavioral factors at the individual-level may also include tobacco exposure/use, obesity/diet, sedentary behavior/physical activity, and alcohol use, among others.

The National Cancer Institute (NCI) is interested in applications that focus on both individual and community interventions that relate to primary and secondary cancer prevention and treatment. NCI is also interested in applications related to communication, attitudes, and knowledge of cancer risk factors (such as tobacco exposure, energy imbalance, and alcohol use). It is important that researchers consider the context in which people live (place, built environment, social norms, etc.) and develop interventions that can result in overall improved health outcomes as they relate to health behaviors (e.g., tobacco exposure/use, obesity/diet, sedentary behavior/physical activity, and alcohol use), healthcare delivery (e.g., screening, vaccination, treatment), disease outcomes, and cancer survivorship.

National Institute on Alcoholism and Alcohol Abuse (NIAAA)

According to the CDC, from 2001 to 2005, alcohol attributed deaths accounted for 11.7% of Native American deaths. At present, little is known about how empirically-supported alcohol prevention, intervention and clinical treatment interventions operate within Native American populations, and how they can be modified to address their societal and cultural needs. Additionally, little is known about how Native Americans may utilize already existing recovery-based support systems. Given this background, 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 among Native Americans.

• Intervention research of interest is as follows, but 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.

National Institute on Drug Abuse (NIDA)

NIDA is interested in culturally appropriate applications focused on substance use among Native adolescents and adults. Applications may use a range of approaches to assess substance abuse and related factors, including but not limited to piloting or testing novel prevention, screening, and treatment interventions; harmonizing and analyzing existing datasets to address intervention or etiological questions. Applications may also focus on a range of topics such as etiological factors; intervention; examining patterns of health service utilization; examining treatment work force factors; and studying adaptation, implementation, and dissemination of existing evidence-based prevention or treatment interventions to increase uptake. Specific areas of interest include, but are not limited to:

• Research pertaining to any aspect of opiate use disorder (OUD), including data on the nature of the problem and related factors on and/or off reservations; examining the efficacy of prevention and treatment interventions (including models that integrate treatment with healthcare); examining the impacts of increased availability of naloxone and approaches to disseminate naloxone widely; utilization of, and/or identification of factors associated with uptake of, medication assisted treatment (MAT) to treat opiate use disorder (OUD); characterization of workforce and/or community factors and barriers related to the treatment of OUD; a focus on pregnant women and exposure to opioids
• Research to test interventions developed through theory-based approaches to support healing, resilience, and substance abuse in Native youth with risk factors for drug use, such as suicidal ideation and other mental health conditions
• Research to test evidence-based prevention or treatment intervention approaches developed for a specific Native or non-Native population across multiple tribes, reservations, or regions
• Studies that examine SU prevention and treatment targeting AI/AN adolescents and young adults
• Development, implementation, or analysis of trauma-informed interventions to address SUD
• Research to examine the impact of environmental, programmatic, and policy changes on initiation and/or escalation of drug use in youth and adolescents
• Therapist/provider training and fidelity interventions to ensure faithful administration of treatment interventions
• Research that uses innovative technologies to develop or improve treatment interventions
• Research on the essential components of treatment intervention (putative treatment targets) to focus on personalization and optimization
• Research that addresses prescription drug abuse or effective pain management in AI/AN populations
• Studies that include justice-involved AI/AN populations. Data from SAMHSA's Treatment Episode Data Set (TEDS) show that nearly half of all substance abuse treatment referrals in AI/AN populations come from the criminal justice system.
• Studies that take a multi-generational perspective, for example addressing maternal-child effects of OUD

National Institute on 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

• Develop and test new preventive and treatment strategies and novel implementation approaches to support sustained use of science-based interventions;
• Optimize and test science-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;
• Develop empirically informed culturally appropriate interventions for increasing engagement in mental health services and linkage to care across Tribes and geographical regions;
• Test strategies to increase use of evidence-based mental health care for individuals in hard-to-reach communities, including mobile and IT interventions;
• Explore which factors promote resilience and prevent mental disorders in at the individual level to develop preventive intervention targets;
• Test innovative, empirically guided strategies for integrated primary health care and mental health care 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 prevention, care, and treatment needs for sexual and gender minorities, two spirit people, and other individuals vulnerable to HIV from indigenous communities;
• Develop and test interventions based on the mechanisms that are driving new infections and poor health outcomes among those living with HIV (e.g., factors like stigma, mental health, social/sexual networks, access to and quality of health care, experiences of trauma);
• Develop novel multilevel preventive interventions, combination biomedical-behavioral approaches, and/or interventions targeting comorbidities to advance HIV prevention and care within those Tribal communities most impacted by HIV;
• Explore operations 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 hard-to-reach remote 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 Program Staff as far as possible in advance of any application to discuss the match to current Institute priorities.

National Institute of Nursing Research (NINR)

The National Institute on Nursing Research (NINR) is interested in research across the lifespan targeting wellness, management of illness related symptoms, enhancement of palliative and end-of-life care interventions, with an emphasis on individuals, families, communities, underserved, hard-to-reach, and vulnerable populations. Additional information on NINR's research interests can be found at http://www.ninr.nih.gov/AboutNINR/NINRMissionandStrategicPlan.

Specific topics of interest to the NINR include, but are not limited to:

• Develop innovative behavioral interventions that promote health and prevent illness across the lifespan in diverse and underserved populations, (e.g., families with special needs, parents, or caregivers of persons with chronic illness, serious advanced illness, or developmental disabilities);
• Elucidate mechanisms underlying health disparities and design interventions to eliminate them with particular attention to geographic and environmental issues, minority status, and persons whose chronic or temporary disabilities limit their access to care;
• Assess behavioral, biological, and genomic mechanisms (e.g., neurohumoral markers for differential responses to behavioral interventions);
• Improve quality of life by promoting personalized health strategies (e.g., promoting healthy lifestyles, prevention of obesity; prevention of HIV/AIDS transmission);
• Improve understanding of the complex issues and choices underlying palliative and end-of-life care (e.g., alleviating the burdens of caregiving; understanding the sociocultural and spiritual needs of seriously ill individuals and their families and communities; enhancing culturally sensitive communication regarding advanced care planning) in underserved populations.

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.

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

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

Higher Education Institutions

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

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

• 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

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed only when the ancestral catchment area(s) of tribe(s) cross(es) U.S. national boundary

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

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

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

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

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

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

Involvement of Native American researchers and other appropriate professionals is encouraged.

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

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

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

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

Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

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

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:

Shobha Srinivasan, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-6936
Fax: 240-276-7908
Email: ss688k@nih.gov

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

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

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

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

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

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.

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:

A. Pilot Data: Given that many NA communities are small and many members are dispersed across the US, 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. Or else applicant(s) are encouraged to provide data on similar interventions that have been conducted in comparable (sub) populations or settings. Some of the sources or citations may not published. Similarly, it may not be possible to generalize results from these studies to other (sub) populations. However, applicant(s) should discuss the above factors in the application.

B. Recruitment of Individuals and Communities: Applicants can propose to include one or more NA communities to achieve the necessary sample size or otherwise enhance the scientific value of the study sample. 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.

Individuals recruited as part of a pre-existing non-intervention study may be proposed for inclusion in the proposed study. However, applicants must provide evidence that recruitment from an existing cohort will not unduly interfere with the goals of the existing study or that the cohort is no longer being studied. In addition, the application should include a justification for including such participants for the proposed protocol.

C. Study Design: Applicants should choose rigorous study designs to test the effectiveness or efficacy of the proposed intervention. While randomized designs are ideal for reducing threats to internal validity, other research designs will be given consideration. The research approach is an important review criterion and investigators are encouraged to select a research design that will provide convincing evidence regarding the research questions. Thus applications must address concerns related to the quality of the research such as outcome variables and anticipated magnitude of change, psychometrics for planned measures, expected attrition, power estimation, and statistical analyses planned. Applicants should also provide plans for assessing fidelity of implementation and other relevant process measures. Applicants are advised to consult with a methodologist and/or statistician when proposing a design with regard to its appropriateness for testing the proposed intervention, level of rigor, handling of missing data, and with regard to the data points needed for the planned analyses.

It is imperative that applicants describe and justify the nature of any comparison/control group, that is, whether the comparison group will receive, for example, 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.

Awardees will have primary responsibility for collecting, editing, storing, and analyzing their data. Awardees should oversee testing of their interventions and adherence to their protocols, and assure that appropriate quality control procedures are in place. Each awardee will be responsible for training and certification of personnel.

D. Collaborations: Collaborators should address issues of ownership, control, and storage of data and biological samples in the application. However, NIH recognizes that communities may wish to retain ownership or control of data and biological samples. After award, partners should negotiate a formal and written data and biological sample agreement. This written agreement, once signed by all parties, should be submitted to NIH after award.

E. Community-based Participatory Research (CBPR): The community-researcher partnership should be documented in the grant application under Research Strategy to demonstrate the community's involvement in development, design, testing, and dissemination of the study, including establishing a Community Advisory Board. If this approach is used, 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.

F. Community Support: Applications are expected to include evidence of: 1) strong scientific capabilities; and 2) community involvement and support.

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 projects.

G. Standardization and Coordination: When applicable, Investigators should indicate in their application their willingness to collaborate on the development and use of standardized measurement protocols, and coordination of formative assessment and possibly of intervention approaches.

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

• Applications that represent a partnership between a tribe or community and a research organization must 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 must 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 must 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 must 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.

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

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

Appendix:

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

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

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

Protection of Human Subjects: A Data and Safety Monitoring Plan (DSMP) may be required or projects that are proposing to pilot test interventions. If a DSMP is needed, the PD(s)/PI(s) of each study will establish a DSMP to monitor data and oversee participant safety in each study supported by this initiative.

Applicants should not appoint DSMP members in advance of the peer review, or even inquire about the interest of possible DSMP members, to facilitate peer review.

Delayed Onset Study

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

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

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

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

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

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

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

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

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

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

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

An R21 grant application need not have extensive background material or preliminary information. Accordingly, reviewers will focus their evaluation on 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 (including unpublished sources), 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. The purpose of this funding opportunity announcement (FOA) is to conduct secondary analysis of existing data (such as databases that the Tribal Epidemiology Centers have collected); merge various sources of data to answer some critical questions; conduct pilot and feasibility studies; and assess and validate measures that are being developed and/or adapted for use in NA communities.

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

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

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

In addition, for applications proposing clinical trials

For all CT FOAs, add the following questions, after the standard questions for the Significance criterion.

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

Specific to this FOA: Does the project address issues that are critical to Native American communities? Will the project advance the science and improve the lives for Native American communities/tribes?

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

In addition, for applications proposing clinical trials

For all CT FOAs, add the following questions, after the standard questions for the Investigator(s) review criterion.

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?

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

In addition, for applications proposing clinical trials

For all CT FOAs, add the following questions, after the standard questions for the Innovation review criterion.

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

Specific for this FOA: Are the issues addressed in the application of priority and importance to the Native American community/tribe? If the application is combining data sets, does it provide novel insights to understand and address the underlying challenges to improve the health of Native American communities/tribes?

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

In addition, for applications proposing clinical trials

For all CT FOAs, add the following questions, after the standard questions for the Approach review criterion.

Does the application adequately address the following, if applicable:

Study Design

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

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

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

Data Management and Statistical Analysis

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

Specific to this 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?

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

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

In addition, for applications proposing clinical trials

For all CT FOAs, add the following questions, after the standard questions for the Environment review criterion.

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

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

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

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

Specific to this FOA: Does the project provide evidence of Native American community/tribal support, as appropriate?

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

Study Timeline

Specific to applications proposing 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)?

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

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

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

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

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

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

Not applicable.

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.

Not Applicable.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Additionally, ICs may specify any special reporting requirements for the proposed clinical trial to be included under IC-specific terms and conditions in the NoA. For example: If the proposed clinical trial has elevated risks, ICs may require closer programmatic monitoring and it may be necessary to require the awardee to provide more frequent information and data as a term of the award (e.g., to clarify issues, address and evaluate concerns, provide documentation). All additional communications and information related to programmatic monitoring must be documented and incorporated into the official project file. Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA. ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain "applicable clinical trials" on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration of all trials whether required under the law or not. For more information, see http://grants.nih.gov/ClinicalTrials_fdaaa/

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that the application as well as all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols. Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

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

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

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person's race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator's scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

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

Cooperative Agreement Terms and Conditions of Award

Not Applicable

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

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

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

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

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
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GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
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Telephone: 301-945-7573

Shobha Srinivasan, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-6938
Email: ss688k@nih.gov

Judith A. Arroyo, Ph.D.
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-402-0717
Email: Jarroyo@mail.nih.gov

Aria Davis Crump, Sc.D.
National Institute on Drug Abuse (NIDA)
Telephone: 301-443-6504
Email: acrump@nida.nih.gov

Andrea Horvath Marques, M.D., Ph.D., M.P.H.
National Institutes of Mental Health (NIMH)
Telephone: 301-443-2847
Email: andrea.horvathmarques@nih.gov

Lindsey Ann Martin, PhD
National Institute of Environmental Health Sciences (NIEHS)
Phone: (984) 287-4036
Email: Lindsey.Martin@nih.gov

Dorothy Castille, Ph.D.
National Institute on Minority Health and Health Disparities (NIMHD)
Telephone: 301.594.9411
Email: dorothy.castille@nih.gov

Darien Weatherspoon, D.D.S., M.P.H.
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-594-5394
Email: darien.weatherspoon@nih.gov

Martha L. Hare, Ph.D.
Center for Scientific Review (CSR)
Telephone: 301-451-8504
Email: harem@mail.nih.gov

Carol Perry
National Cancer Institute (NCI)
Telephone: 240-276-6282
Email: carol.perry@nih.gov

Judy S. Fox
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 302-443-4704
Email: jfox@mail.nih.gov

Maryellen Connell
National Institute on Drug Abuse (NIDA)
Telephone: 301-774-3803
Email: mconnell@nida.nih.gov

Terri Jarosik
National Institute of Mental Health (NIMH)
Telephone: 301-443-3858
Email: tjarosik@mail.nih.gov

Molly Puente, Ph.D.
National Institute of Environmental Health Sciences (NIEHS)
Telephone: 919-541-1373
Email: puentem@mail.nih.gov

Priscilla Grant, J.D.
National Institute on Minority Health and Health Disparities (NIMHD)
Telephone: 301-594-8412
Email: grantp@mail.nih.gov

April L. Harrison
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-827-4628
Email: arrisona@mail.nih.gov

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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.