Required Application Instructions

It is critical that applicants follow the 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/AIDS has risen over the last decade. In 2010, 19% or 217,300 of the Americans living with HIV infection were older than 55 years of age. In 2011, more than one-quarter of HIV-infected Americans were aged 55 years or older (1). African-Americans and Hispanics are at greatest risk in the US, but the rise in HIV among older adults is a global trend. The rise in HIV prevalence among older Americans is attributed primarily to two factors. First, effective treatment with highly active antiretroviral therapy (HAART) has led to a marked increase in survival among individuals who were infected in their younger years. Second, new infections continue in older age.

While HAART has led to a marked reduction in the incidence of AIDS-defining illnesses, a variety of HIV-Associated Non-AIDS (HANA) conditions are becoming increasingly commonplace in individuals with long-standing HIV infection. 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.

While it is unclear whether HIV infection and/or its treatment lead directly to these conditions, which might suggest an "acceleration of aging," it is clear that individuals living with prolonged HIV infection exhibit many of the clinical characteristics commonly observed in aging, such as multiple co-morbidities, polypharmacy, physical and cognitive impairment, functional decline, alterations in body composition, and increased vulnerability to stressors.

Previous conferences involving NIH have identified important research directions at the intersection of HIV and aging. The proceedings of an early workshop by the Association of Specialty Professors with involvement from NIA, NIAID, the Infectious Diseases Society of America, and the HIV Medical Association, were published in Clinical Infectious Diseases 2008; 47:542-553. Later, a report from the NIH Office of AIDS Research Working Group on HIV and Aging was published in the Journal of Acquired Immune Deficiency Syndromes 2012; 60:S1-S18.

The goal of this announcement is to invite research grant applications studying HIV infection, HIV-associated conditions, HIV treatment, and/or biobehavioral or social factors associated with HIV/AIDS in the context of aging and/or in older adults. Research approaches of interest include clinical translational, observational, and intervention studies in domestic and international settings. General topic areas appropriate for this FOA include, but are not limited to, cellular and molecular mechanisms of HIV in aging, HANA conditions and comorbidities, biomarkers or clinical indices of HIV-associated pathology, HIV-associated neurocognitive disorders (HAND), frailty/vulnerability in HIV-infected individuals, and social, behavioral, and mental health studies. Applications submitted to this FOA should be exploratory and novel. These studies should break new ground or extend previous discoveries toward new directions or applications.

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 and/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 approaches.
• Attention to geriatric outcomes. In addition to traditional outcomes of HIV/AIDS research are important (e.g., viral load, survival), studies are encouraged to also include outcomes considered important in geriatric medicine and gerontology, such as physical function, cognitive status, 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 such characteristics as 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 (I/Cs) are summarized below. Applicants are encouraged to contact the Scientific/Research contact of the intended I/C to ensure that the aims of the proposed project are consistent with I/C mission.

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 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 genetic, molecular, and cellular changes with aging and HIV risk, infection, and pathogenesis
• Interactions among HIV, other diseases, social structural variables, and population aging in low-income countries, such as sub-Saharan Africa, to understand health, functional status, and social conditions, and their impact on 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,
• Interactions of HIV infection and treatment with other diseases, conditions, or syndromes prevalent in aging individuals 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 Heart, Lung, and Blood Institute (NHLBI)

NHLBI supports research on the prevention and treatment of heart, lung, blood, and sleep disorders. As the population of individuals living with HIV/AIDS ages, the interplay of the viral infection, antiretroviral therapies, and complicating chronic conditions becomes increasingly important. For this initiative, NHLBI is interested in clinical translational, observational, and interventional studies on topics such as, but not limited to:

• Elucidating the impact of accelerated senescence, HIV, and antiretroviral therapy on the pathogenesis of HIV associated cardiovascular (e.g., coronary artery disease) and lung diseases (e.g., chronic obstructive pulmonary disease (COPD), pulmonary hypertension, and pulmonary fibrosis)
• Understanding the changes in hematopoiesis that occur with HIV infection, including changes in the hematopoietic stem cells and the stem cell niche
• Developing stem cell strategies as a means to cure HIV infection.
• Understanding the impact of disordered sleep and sleep-disordered breathing on cardiovascular and pulmonary disease risks and exploring strategies to reduce these risks.
• Investigating interventions aimed at reducing HIV-related heart, lung, blood diseases by modifying or eliminating more traditional risk factors such as smoking, metabolic disturbances, hypertension, and coagulation abnormalities
• Developing strategies for novel biomarkers or other measures to detect subclinical HIV-related heart, lung, and blood diseases and strategies to mitigate the manifestation of clinical disease

National Institute of Allergy and Infectious Diseases (NIAID)

NIAID is interested in applications focused on HIV in the aging population when the primary focus is on the HIV virus or on behaviors that facilitate transmission of HIV; on basic research studies assessing the PK, PD, safety and efficacy of therapeutic and non-vaccine biomedical HIV prevention products in aging individuals; and on studies focused on HIV infection and related immune function, vaccine responses, and treatment-related co-morbidities in aging individuals.

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 autoimmune diseases of skin.
• 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 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)

Examination 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
• Characterize 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 Diverse Research Workforce

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 co-morbid conditions such as stroke, small vessel diseases and neurodegenerative processes;
• Determining the effects of HIV, aging, and HAART on blood brain barrier (BBB) integrity;
• Developing novel biomarkers for detecting HIV-associated CNS diseases in the older population.

National Center for Complementary and Integrative Health (NCCIH)

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

• Evaluation of "geriatric" complementary health interventions, such as movement-based interventions (e.g., tai chi).
• Development and evaluation of complementary health strategies to maintain or improve cognition in older adults with HIV.
• Comparative effectiveness studies of combined pharmacological/non-pharmacological (CAM) interventions, particularly incorporating patient and family preferences and evaluating cost effectiveness.
• 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.

(1) CDC Fact Sheet: HIV Among People Aged 50 and Older http://www.cdc.gov/hiv/risk/age/olderamericans/index.html?s_cid=drmermin-00340

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)

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).

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

It is critical that applicants follow the 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 Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.

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

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 I. Section III.1 for information regarding the requirements for obtaining a Dun and Bradstreet Universal Numbering System (DUNS) Number and for completing and maintaining an active System for Award Management (SAM) registration. Part I. Overview Information contains information about Key Dates. 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.

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. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

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.

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 our Post Submission Application Materials policy.

Important Update: See NOT-OD-16-006 and NOT-OD-16-011 for updated review language for applications for due dates on or after January 25, 2016.

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.

For this particular announcement, note the following:

The R21 exploratory/developmental grant supports investigation of novel scientific ideas or new model systems, tools, or technologies that have the potential for significant impact on biomedical or biobehavioral research. An R21 grant application need not have extensive background material or preliminary information. Accordingly, reviewers will 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, 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.

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? 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 New 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?

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? 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?

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 five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. 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

Not Applicable

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

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 Wide Association Studies (GWAS) /Genomic Data Sharing Plan.

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.

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.

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.

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: https://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 CenterTelephone: 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

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

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

Renee Wong, PhD
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-451-6808
Email: wongr2@nhlbi.nih.gov

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

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

Robin Huebner, PhD, MPH
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3216
Email: rhuebner@niaid.nih.gov

Carl C. Baker, MD, PhD
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-594-5032
Email: bakerc@mail.nih.gov

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

David M. Stoff, PhD
National Institute of Mental Health (NIMH)
Telephone: 240-627-3876
Email: dstoff@mail.nih.gov

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

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

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

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

Amy Connolly
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0169
Email: connolla@mail.nih.gov

Robin Laney
National Institute on Aging (NIA)
Telephone: 301-496-1473
Email: Robin.Laney@nih.gov

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

Ann Devine
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-402-5601
Email: adevine@niaid.nih.gov

Andy Jones
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-451-0610
Email: jonesan@mail.nih.gov

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

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

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