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 number of older individuals living with HIV is rising. In 2005, 29% of Americans infected with HIV were age 50 years or older. By 2012, this proportion had risen to 42%. By 2020, it is projected that over half of HIV-infected Americans will be 50 years or older. These trends are mirrored globally. The rise in HIV infection among older individuals is due primarily to the successes of modern antiretroviral therapy, which has allowed individuals infected at a younger age to survive into older age. A smaller but growing fraction of the rising prevalence of HIV in older adults is attributed to new infections in later life.

In contrast to the pre-modern era of HIV treatment, where AIDS-related opportunistic infections and cancers were common, the most frequent morbidities and causes of death currently in treated HIV infection are similar to those seen in older non-infected adults. These conditions include cardiovascular disease, lung disease, infection-related and non-infection-related cancers, HIV-Associated Neurocognitive Disorders (HAND), neuropsychiatric disorders, osteopenia/osteoporosis, liver cirrhosis, and renal disease. In addition, individuals living with HIV infection may exhibit many of the clinical and socio-behavioral characteristics commonly observed in aging, such as multiple morbidities, polypharmacy, declining physical and cognitive function, alterations in body composition, social isolation, and increasing caregiver burden. People living with HIV also exhibit molecular changes associated with aging such as epigenetic alterations, mitochondrial impairment, and telomere shortening. Thus, accumulating evidence suggests that HIV and/or its treatment may lead, at least in part, to an accelerated aging phenotype. In addition, recent advances have led to greater adoption of pre- and post-exposure prophylaxis, but the impact of these measures on aging are unclear.

This FOA encourages applications at the intersection of HIV and aging by addressing two overarching objectives: 1) to improve understanding of biological, clinical, and socio-behavioral aspects of aging through the lens of HIV infection and its treatment; and 2) to improve approaches for testing, prevention, and treatment of HIV infection, and management of HIV-related comorbidities, co-infections, and complications in different populations and cultural settings by applying our current understanding of aging science. Applications appropriate to this FOA should be consistent with the scientific priorities outlined by the NIH Office of AIDS Research (OAR) as described in NOT-OD-15-137.

This FOA encourages applications with the following characteristics:

• Clinical orientation. HIV in aging involves complex interactions among multiple physiologic systems and a variety of human-level factors such as functional status, quality of life, health behaviors, and psychosocial issues; therefore, studying individual factors in isolation may be counter-productive. This FOA encourages animal models and in vitro studies where appropriate; however, inclusion of such approaches should be integrated with human studies or demonstrate direct relevance to clinical features of HIV/AIDS.
• Focus on aging or the aged. Applicants are strongly encouraged to enroll individuals across the range of older ages, especially individuals at the upper end of the age range (i.e., 70 years or older). Comparisons between younger and older HIV-infected populations or comparisons between older HIV-infected individuals and their age-matched non-HIV-infected counterparts are appropriate.
• Attention to geriatric outcomes. In addition to traditional important outcomes of HIV/AIDS research (e.g., viral load, survival), studies are encouraged to also include outcomes considered important in geriatric medicine and gerontology, such as physical and cognitive function, quality of life measures, and social support.
• Leveraging existing resources where possible. A variety of NIH-funded resources are available to study HIV in aging, such as longitudinal studies of HIV-infected individuals and/or their non-infected counterparts (observational or interventional), clinical networks, and research centers. Leveraging such resources through secondary analyses of available data, ancillary studies, or utilization of existing infrastructure are cost-effective approaches to testing hypotheses or generating relevant data for further studies.
• Selection of appropriate controls. Aging individuals with HIV present with varied and complex clinical pictures. Biological and psychological co-morbidities, treatment regimens, lifestyle and behavioral factors, socioeconomic factors, and social support may all impact on disease development, coping, and progression. This complexity presents a significant challenge to identifying appropriate control populations in observational studies of aging individuals with HIV. Such studies should include adequate justification for selection of the proposed control group(s).
• Characterization of phenotypes. Several biological or behavioral phenotypes of HIV in aging have been elucidated that may have markedly different disease courses, biological underpinnings, and treatment responses. Such phenotypes may be described by characteristics like frailty/disability, accelerated aging, successful aging, or other descriptors. Investigators are encouraged to maximize the homogeneity of subgroups by defining specific phenotypes in analyses.

The scientific interests of participating Institutes and Centers (ICs) are summarized below. Applicants are encouraged to contact the Scientific/Research contact of the intended IC to ensure that the aims of the proposed project are consistent with IC mission and OAR's scientific priorities.

National Cancer Institute (NCI)

NCI as a participating institute seeks to foster research studies to help understand how aging in the presence of chronic HIV infection affects the risk, spectrum and biology of cancer (AIDS-defining and non-AIDS-defining cancers). Recent data indicates an increase in the non-AIDS-defining cancers that is driven to a large extent by the growth and aging of the HIV/AIDS population. Aging is by itself a key factor promoting the development of many cancers, and there is a lack of data on the interplay between aging, HIV, long-term exposure to antiretroviral drugs, and other factors promoting cancer development in the aging population. In addition, there is little understanding of the interplay between host factors and immune perturbations that occur in aging and how these interactions affect cancers that are mostly seen in older people (e.g., Kaposi’s sarcoma and Merkel cell carcinoma).

National Center for Complementary and Integrative Health (NCCIH)

NCCIH has an interest in examination of mind/body interventions including:

• Evaluation of "geriatric" complementary and integrative health interventions, such as movement-based interventions (e.g., tai chi);
• Development and evaluation of complementary and integrative health strategies to maintain or improve cognition in older adults with HIV;
• Comparative effectiveness studies of combined pharmacological/non-pharmacological (complementary and integrative health) interventions, particularly incorporating patient and family preferences and evaluating cost effectiveness; and
• Interventions to promote subjective well-being and resilience, and to reduce symptom burden in older adults with HIV, including examination of the impact of individual differences (e.g. personality, sense of control, self-efficacy) on their effectiveness.

National Institute on Aging (NIA)

NIA is interested in understanding how biological, clinical, and socio-behavioral processes affect older individuals with HIV and their caregivers, and the social, economic, and health consequences of HIV. Example topics include:

• Interactions among aging-related genetic, molecular, and cellular changes with HIV risk, infection, and pathogenesis;
• Interactions among HIV/AIDS, other diseases, social structural variables, and population aging (including in low-income areas such as sub-Saharan Africa) to understand how individual, interpersonal, social, structural, and other factors contribute to physical, psychological, and economic well-being;
• Interactions among HIV infection, treatment, and development or progression of cognitive decline, dementia, and other disabilities in older adults; and
• Interactions of HIV infection and treatment with other aging-related diseases, conditions, and syndromes and geriatric approaches to assessment and management of older adults with HIV.

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Patterns of alcohol use among HIV-infected individuals are associated with increased morbidity and mortality from multiple causes. Research priorities for NIAAA include the impact of alcohol use and its interaction with HIV and antiretroviral medications in both causing and adapting to accelerated disease progression. Alcohol may cause increased inflammation, and the accumulation of toxicities result in organ and tissue damage impacting the gut, liver, and brain. Research should address the development of interventions for health care providers to screen for early signs of these conditions, and preventive interventions should be developed, tested, and implemented to ameliorate the interaction of current or past, acute and chronic use of alcohol on patient frailty and associated health outcomes over the lifespan.

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

NIAMS is interested in studies that investigate the effects of HIV infection and/or antiretroviral therapy on musculoskeletal and skin tissues and diseases. Proposed research should focus on chronic diseases and conditions in older adults and/or arising in the context of long-term HIV infection and/or antiretroviral therapy. Mechanistic ancillary studies that leverage existing HIV/AIDS cohorts and clinical trials are encouraged. NIAMS does not support clinical trials through this FOA. Areas of interest include, but are not limited to:

• Mechanisms by which HIV infection and/or antiretroviral therapy contribute to bone loss and osteoporosis;
• Mechanisms by which HIV infection and/or antiretroviral therapy specifically and directly affect skeletal muscle leading to cachexia or weakness;
• Mechanisms by which HIV infection and/or antiretroviral therapy lead to lipoatrophy of the skin;
• Effects of HIV infection and/or antiretroviral therapy on the rheumatic diseases and on inflammatory and autoimmune diseases of skin; and
• Effects of HIV infection and/or antiretroviral therapy on the skin barrier, including both the physical barrier as well as regulation of the cutaneous innate and adaptive immune system, and subsequent changes in the skin microbiome that may affect the incidence and/or severity of skin diseases.

National Institute of Dental and Craniofacial Research (NIDCR)
NIDCR is interested in research that investigates the effects of HIV infection and treatment on dental, oral soft and hard tissues, and salivary glands. Specifically, changes in these tissues with relation to aging adults and premature aging of oral tissues in chronic and acute HIV infections are of high priority. NIDCR does not support clinical trials through this FOA. Studies may include, but are not limited to:

• Periodontal disease progression in the context of HIV infection and HAART;
• Mechanisms of dental caries development and progression in HIV/AIDS-affected individuals;
• Effects of HIV/AIDS and HAART on salivary gland infiltrates, fibrosis and xerostomia;
• Oral mucosal pathologies and composition changes in the context of HIV/AIDS; and
• HIV infection, HAART, and their influence on developing osteonecrosis of the jaw.

National Institute on Drug Abuse (NIDA)

NIDA strongly encourages new interdisciplinary collaborations on a wide range of issues focused on HIV in aging, high-risk, substance-abusing populations, including those with multiple infections (e.g., HIV and HCV).

National Institute of Mental Health (NIMH)

NIMH's overarching angle in HIV and aging is interdisciplinary, conceptually grounded HIV research studies in behavioral/clinical science research and basic/clinical neuroscience research of older adults.

Major NIMH/DAR Research Program Themes in HIV and Aging:

• Sociobehavioral Influences and Neuropsychiatric Comorbidities
• Characterization of some major aging phenotypes (e.g., accelerated aging, neurocognitive aging, successful aging)
• HIV care continuum research
• HIV CNS pathophysiology and neurotherapeutics
• Mentoring and training of a diverse research workforce

National Institute of Minority Health and Health Disparities (NIMHD)

NIMHD leads scientific research to improve minority health and reduce health disparities. HIV/AIDS disproportionately effects racial and ethnic minority populations in the US, particularly African Americans and Hispanics/Latinos, and is increasing fastest amongst minorities and women. NIMHD is interested in applications that address HIV in aging health disparity populations which include socioeconomically disadvantaged and underserved rural populations to better understand the biological, clinical, socio-behavioral and cultural aspects of aging with HIV. Areas of research interest include, but are not limited to:

• Effects of HIV-related stigma and discrimination on patient-clinician interactions and engagement with care among health disparity populations;
• Interactions of cultural attitudes and age-related beliefs of HIV-positive individuals that impact health-promoting behaviors (e.g., diet, exercise), help-seeking behaviors, and adherence to care within health disparity populations; and
• Quality of care and quality of life and/or daily functioning of HIV-positive older adults in ambulatory and hospital settings and in long-term care facilities.

National Institute of Neurological Disorders and Stroke (NINDS)

NINDS is interested in fostering innovative basic, translational and clinical research on the effects of chronic HIV infection, co-morbidities, and aging on the central nervous system (CNS). Research to define and elucidate novel mechanisms of pathogenesis that are driving neurocognitive decline at the intersection of HIV-associated neurodegenerative processes, aging-associated CNS diseases, chronic antiretroviral treatment effects, and host susceptibility factors are highly encouraged. Areas of research interest include, but not limited to:

• Investigating the effects of HIV infection and/or antiretroviral therapy on age-related, non-infectious neurodegenerative processes;
• Understanding the role and mechanisms of vascular contributions to cognitive impairment and dementia (VCID) in HIV-infected individuals. This includes, but is not limited to, vascular dementia, vascular cognitive impairment, post-stroke dementia and other cerebral vascular conditions such as stroke and small vessel diseases that can be co-morbid with HIV;
• Determining the effects of HIV, aging, and HAART on blood brain barrier (BBB) integrity; and
• Developing novel biomarkers for detecting HIV-associated CNS diseases in the older population.

Note: NINDS will not accept clinical trials in response to this FOA.

National Institute of Nursing Research (NINR)

NINR is interested in supporting basic, clinical, and intervention research related to aging with HIV infection. Topics appropriate for this FOA include, but are not limited to, the following:

• Identification of unique symptom clusters in the intersection of HIV infection, ARV therapy, aging and associated comorbidities;
• Innovative strategies to ensure proper identification of symptoms and symptom clusters among HIV-infected patients presenting with complex conditions;
• Development of innovative interventions that leverage community and other social and cultural resources to improve self-management and support meaningful activities among those aging with HIV;
• Interventions aimed at increasing functional capacity and resilience and interrupting progression towards age-related symptoms of frailty among people with prolonged HIV infection; and
• Interventions that delineate and address the impact of decreased functional capacity on caregivers of people living with HIV/AIDS (PLWHA) and identify/replicate unique solutions of caregivers of persons aging with HIV infection.

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:

o Hispanic-serving Institutions

o Historically Black Colleges and Universities (HBCUs)

o Tribally Controlled Colleges and Universities (TCCUs)

o Alaska Native and Native Hawaiian Serving Institutions

o Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

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

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations
• Non-domestic (non-U.S.) Entities (Foreign Institutions)

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

Applicant Organizations

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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:

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.

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 conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

Form only available in FORMS-E application packages for use with due dates on or after January 25, 2018.

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.

Delayed Onset Study: All instructions in the SF424 (R&R) Application Guide must be followed.

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

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

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 and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact a Scientific/ Research Contact at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF424 (R&R) Application Guide.

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

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.

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

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

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

Are the 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?

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?

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

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

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?

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.

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.

For Renewals, the committee will consider the progress made in the last funding period.

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.

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

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

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

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

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

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

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

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications . Following initial peer review, recommended applications will receive a second level of review by the 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.

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 http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.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 http://www.hhs.gov/ocr/civilrights/understanding/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 http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.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 progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

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

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

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573

Geraldina Dominguez, Ph.D.
National Cancer Institute (NCI)
Telephone: 301-496-3204
Email: domingug@mail.nih.gov

Dave Clark, DrPH.
National Center for Complementary & Integrative Health (NCCIH)
Telephone: 301-827-1916
Email: dave.clark@mail.nih.gov

Basil Eldadah, MD, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-496-6761
Email: eldadahb@nia.nih.gov

Kendall J. Bryant, Ph.D.
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-402-0332
Email: NIAAA-HIV-Initiatives@mail.nih.gov

Faye H Chen, Ph.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-594-5055
Email: chenf1@mail.nih.gov

Jag Khalsa, Ph.D.
National Institute on Drug Abuse (NIDA)
Telephone: 301-443-2159
Email: jkhalsa@nida.nih.gov

Gallya Gannot, DMD, Ph.D.
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-451-5096
Email: gallya.gannot@nih.gov

Pim Brouwers, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 204-627-3863
Email: pb56u@nih.gov

Rick Berzon, DrPH, PA
National Institute on Minority Health and Health Disparities (NIMHD)
Telephone: 301-594-8949
Email: rick.berzon@nih.gov

May Wong, Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-1431
Email: wongm@ninds.nih.gov

Rebecca Henry, Ph.D., BSN, RN
National Institute on Nursing Research (NINR)
Telephone: 301-594-5976
Email: Rebecca.Henry@nih.gov

Robert Freund, Ph.D.
Center for Scientific Review (CSR)
Telephone: 301-435-1050
Email: freundr@mail.nih.gov

Shane Woodward
National Cancer Institute (NCI)
Telephone: 301-496-8791
Email: woodwars@mail.nih.gov

Shelley Carow
National Center for Complementary & Integrative Health (NCCIH)
Telephone: 301-594-3788
Email: CarowS@mail.nih.gov

Johnny Bladen
National Institute on Aging (NIA)
Telephone: 301-402-7730
Email: bladenj@mail.nih.gov

Judy Fox
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-443-4704
Email: jfox@mail.nih.gov

Andy Jones
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-435-0610
Email: jonesan@mail.nih.gov

Carol Alderson
National Institute on Drug Abuse (NIDA)
Telephone: 301-933-6196
Email: aldersoc@nida.nih.gov

Diana Rutberg, MBA
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-594-4798
Email: rutbergd@mail.nih.gov

Rita Sisco
National Institute of Mental Health (NIMH)
Telephone: 301-443-2805
Email: siscor@mail.nih.gov

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

Tijuanna DeCoster, MPA
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9231
Email: decostert@ninds.nih.gov

Kelli Oster
National Institute of Nursing Research (NINR)
Telephone: 301-594-2177
Email: osterk@mail.nih.gov

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.