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

Persons with HIV are disproportionately affected by viral hepatitis. Because HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV) share common modes of transmission, approximately one-third of HIV-infected persons are co-infected with HBV or HCV. The progression of viral hepatitis is accelerated among persons with HIV; therefore, persons who are co-infected experience greater risk of viral persistence, advanced fibrosis, cirrhosis, end-stage liver disease, hepatocellular carcinoma, and liver-related death compared to persons without HIV.

Through a variety of immune evasion mechanisms these hepatitis pathogens establish long-term chronic viremia in their infected hosts, which leads to immune destruction and fibrosis, possibly progressing to cirrhosis, end-stage liver disease, and hepatocellular carcinoma (HCC). On the other hand, it is not clear why a significant proportion of persons infected with these viruses are able to spontaneously control these infections and avoid their complications. The mechanisms underlying control of HCV and HIV remain incompletely understood but have important implications for development of successful preventive or therapeutic approaches. In HIV/HBV co-infection, HIV can lead to higher rates of chronicity, decreased rates of anti-HBe and anti-HBs seroconversion, and increased viral replication.

The spectrum of HCV-associated complications goes beyond the liver, and HIV co-infection appears to magnify this effect in multiple organ systems. The pathogenesis of HIV and HCV-related chronic inflammation is complex and incompletely understood. To decrease the morbidity and mortality of viral hepatitis in HIV co-infection, information is needed about both the cause of this inflammation and ways of suppressing it. Information is also needed about the pathogenesis, diagnosis, and treatment of HIV/HCV-associated, non-liver-disease complications.

HIV/HCV co-infection could also have a major impact on the nervous system. For example, there is increasing evidence that co-infected individuals fare worse on neuropsychological measures than mono-infected individuals or healthy controls. There is research demonstrating neuroinvasiveness by HIV and HCV via the blood-brain barrier, and both viruses replicate in brain tissue. Increased inflammation and neurotoxicity likely contribute to enhanced neurocognitive dysfunction among individuals with dual infections. HCV may enhance the impact of HIV neurotoxic proteins in microglia and astrocytes leading to greater neuroimmune activation.

The HIV/HCV co-infection epidemic has been driven by people who inject drugs (PWID), although incident HCV is rising among HIV-infected men who have sex with men (MSM) in the absence of drug injection. HCV incidence is increasing among young adults (15 to 30 years of age) living in rural and suburban U.S. areas who are transitioning from oral prescription opiate abuse to opiate injection. Alcohol contributes to liver disease progression in the HIV/HCV co-infected host, and alcohol abuse has been reported in a high percentage of co-infected PWID. These co-infected populations are among the most likely to be affected by HCV but are the least likely to have access to treatment.

Cure of HCV infection is achievable through the use of new direct-acting antiviral (DAA) drugs, with response rates for HIV/HCV-co-infected individuals approaching that for HCV alone. However, many of the regimens using FDA-approved DAAs include interferon. A major barrier to successful treatment for a large number of HIV/HCV co-infected individuals has been the use of interferon, due to side effects or ineligibility for treatment. Recent data have demonstrated that a sustained virologic response can be achieved in different HCV patient populations with a variety of interferon-free regimens. While the clinical benefit of HCV eradication is increasingly recognized, data on the effectiveness of interferon-free HCV treatment in HIV/HCV-co-infected patients is needed.

While there have been considerable improvements in the treatment of HBV, the global burden of disease remains high. Research is needed to inform better ways to prevent, diagnose, and treat people with HIV/HBV co-infection, especially in high-prevalence settings in Asia and Africa.

In summary, HIV/hepatitis co-infection results in accelerated liver disease and cancer, driving morbidity and mortality. Understanding the pathogenesis of co-infections will lead to improved prevention and treatment in HIV-infected individuals.

Research should focus on HIV-infected adults, pregnant/postpartum women, adolescents, children, infants and sub-populations at highest risk for HBV or HCV co-infection. The R21 mechanism is intended to encourage new exploratory and developmental research projects. Applications for R21 awards should describe projects distinct from those supported through the traditional R01 mechanism. Applications submitted under this mechanism should be exploratory and novel. These studies should break new ground or extend previous discoveries toward new directions or applications.

Clinical trials and the establishment of new cohorts will not be supported. However, leveraging ongoing NIH- or non-NIH-supported clinical trials and cohorts to collect samples and data (or to use existing samples and data) to address areas of research interest is encouraged. Examples of NIH-supported programs include, but are not limited to, AIDS Clinical Trials Group (ACTG), AIDS Linked to the IntraVenous Experience (ALIVE), CNS HIV Antiretroviral Therapy Effects Research Resource (CHARTER as a Resource), HIV/HBV co-infected subjects in the NIDDK Hepatitis B Research Network, International Epidemiologic Databases to Evaluate AIDS (IeDEA), International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT), Multicenter AIDS Cohort Study (MACS), National NeuroAIDS Tissue Consortium (NNTC), Veterans Aging Cohort Study (VACS), and Women s Interagency HIV Study (WIHS).

Applicants are encouraged to contact the Scientific/Research Contacts listed in Section VII of this FOA to discuss areas of interest for particular Institutes. Examples of research that would fit within the scope of this FOA include, but are not limited to, those listed below:

National Institute of Allergy and Infectious Diseases (NIAID)

• To fill gaps in our understanding of the pathogenic interactions between HIV disease and HCV infection or HBV infection;
• Among HIV-co-infected individuals, to study host and risk factors and mechanisms associated with spontaneous clearance of HCV and sustained virologic response to HCV or HBV treatment;
• To identify host and risk factors and mechanisms associated with co-morbidity (e.g., more rapid liver disease progression);
• To study factors associated with acquisition of HBV or HCV in HIV-infected individuals or acquisition of HIV in HBV- or HCV-infected individuals;
• To identify predictors for HBV or HCV perinatal transmission in HIV-co-infection;
• To study effectiveness of interferon-free direct-acting antiviral drug regimens to treat HIV/HCV co-infection.

National Cancer Institute (NCI)

NCI seeks to support highly innovative research on the effects of HIV infection on HBV and/or HCV infection and its role in hepatocellular carcinoma (HCC) development throughout the clinical spectrum of infection and disease. Topics relevant to this funding opportunity include, but are not limited to:

• Characterization of viral processes of disease sequelae associated with development of HCC at the cellular and/or virus population level with an underlying HIV infection;
• Cellular mechanisms associated with HIV plus HBV and/or HCV;
• Co-infection that controls innate immune control (or loss thereof) of latent HBV or HCV infection in the context of HCC development;
• Host and pathogen-mediated mechanisms of HBV or HCV latency such as neutralization of host defenses, viral adaptations and development of tolerance and their effects on the development of HCC in HIV infection;
• Studies to understand the molecular pathogenesis of HIV plus HBV and/or HCV co-infection and how co-infection induces progression to HCC;
• Identification of genetic markers informative for diagnosis and therapy;
• Animal model development that will lead to enhancing this area of research;
• Elucidating the role of HIV in the development of HCC in persons co-infected with HIV plus HBV and/or HCV;
• Identification of the role of other factors, such as drug effects, in the development of HCC in patients co-infected with HIV plus HBV and/or HCV;
• Identification of factors that are predictive of the subsequent development of HCC in persons co-infected with HIV plus HBV and/or HCV;
• Examination of the genetic and epigenetic signatures of persons co-infected with HBV- and/or HCV-associated HCC using global molecular profiling tools such as proteomic and/or gene array technologies, to identify biomarkers for the early detection of HCC;
• Changes in the HBV or HCV viral genome associated with high risk and early detection of HCC.

National Institute of Alcohol Abuse and Alcoholism (NIAAA)

• To study the effectiveness of the latest FDA-approved antiviral drug regimens for treatment of HCV in HIV/HCV co-infected patients with varying levels of alcohol use disorders (including the secondary analyses of data from current clinical trials of these medications where alcohol use is adequately characterized);
• To study the effectiveness of the latest medications for treating HBV in HIV/HBV co-infection subjects with alcohol use disorders;
• To study the impact of pattern and amount of alcohol use on the pharmacokinetics/phamacodynamics of the latest medications against HCV and HBV, with human subjects or in animal models including transgenic HIV-infected animals;
• To study the mechanisms by which alcohol affects the mortality and morbidity of co-infected patients including, but not limited to, host antiviral (HIV, HCV, or HBV) immune response resulting in changes in organ/tissue damage, repair, and progression of disease;
• To study the role of alcohol use disorders on emerging patterns of frailty within the co-infection populations;
• To develop and test the reliability and validity of alcohol-related biomarkers for monitoring the adverse health effects of the levels of alcohol use and associated disorders in co-infected subjects.

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

• To further understand the molecular virologic and immunologic mechanisms of accelerated liver injury in the co-infection state;
• To study the effect of hepatic fibrosis stage in the treatment response rates of DAAs for hepatitis C in co-infected individuals;
• To develop noninvasive means of assessing liver disease stage and activity in co-infected persons;
• To define factors that lead to reactivation of HBV in co-infected persons.

National Institute on Drug Abuse (NIDA)

This FOA offers the opportunity to conduct clinical and basic research focused on prevention and treatment of HIV/HCV, with emphasis on at-risk populations including PWID, MSM, and others. This FOA supports, but is not limited to, research on the following issues:

• Impact of substance abuse on pathogenesis/disease progression and associated morbidity in HIV/HCV-infected populations;
• Strategies to maximize access to and engagement of at-risk populations in HCV/HIV treatment, including strategies to optimize treatment adherence, particularly with newer antiviral or antiretroviral regimens;
• Impact of drug abuse on treatment effectiveness of newer antiviral or antiretroviral regimens for HIV, HCV or HIV/HCV co-infections;
• Drug-drug interactions between antiretroviral, antiviral (e.g., direct-acting antiviral [DAA] agents), drugs of abuse, and medications used to treat substance dependence, and the best practices for managing them.

National Institute of Mental Health (NIMH)

• To study mechanisms of interactions between HIV and HCV in the pathophysiology of neurocognitive disorders in co-infected individuals;
• To assess the potentiation of inflammatory events such as enhanced cytokine production and resultant neurotoxicity in the brain in the setting of dual infection;
• To study the impact of HCV infection on trafficking of HIV through the blood-brain barrier and impact on central nervous system (CNS) seeding and establishment of latent reservoirs;
• To identify viral and host genetic factors impacting CNS disease susceptibility and progression in co-infected individuals;
• To discover and validate clinical biomarkers for CNS disease progression or recovery with interferon-free DAA drug regimens in co-infected individuals;
• To examine the clinical impact of interferon-free DAA drug regimens used to treat HIV/HCV co-infection on neurocognitive and neuropsychological outcome measures.

This FOA will NOT support:

• Applications that focus on basic molecular studies on HBV and HCV replication or HBV and HCV protein expression, or their regulation in the absence of HIV infection;
• Drug discovery or development;
• Clinical trials;
• Establishment of new cohorts;
• Studies of hepatitis in HIV other than HBV or HCV.

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).

In addition, the NIH will not accept a resubmission (A1) application that is submitted later than 37 months after submission of the new (A0) application that it follows. The NIH will accept submission:

• To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;
• Of an investigator-initiated application that was originally submitted to an RFA but not paid; or
• Of an application with a changed grant activity code.

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, 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 forms package associated with this FOA includes all applicable components, required and optional. Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate optional components.

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, with the following additional instructions:

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) 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.

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.

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 by the Center for Scientific Review, NIH. Applications that are incomplete 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.

Significance

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?

Investigator(s)

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?

Innovation

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

Approach

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?

Environment

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

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.

Protections for Human Subjects

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.

Inclusion of Women, Minorities, and Children

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.

Vertebrate Animals

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.

Biohazards

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

Resubmissions

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

Renewals

Not Applicable

Revisions

Not Applicable

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

Applications from Foreign Organizations

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.

Select Agent Research

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

Resource Sharing Plans

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

Budget and Period of Support

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

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 the DUNS, SAM Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants 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 annual Non-Competing Progress Report (PHS 2590 or RPPR) 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)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
Finding Help Online: https://grants.nih.gov/support/index.html
TTY: 301-451-5939
Email: commons@od.nih.gov

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)
Telephone: 301-945-7573
TTY 301-451-5936
Email: GrantsInfo@nih.gov

Christine Chiou, M.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: (240) 292-4181
Email: chiou@niaid.nih.gov

Elizabeth Read-Connole, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-6226
Email: bconnole@mail.nih.gov

H. Joe Wang, Ph.D. (for basic biological-immunologic studies and organ tissue injury)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-451-0747
Email: wangh4@mail.nih.gov

Kendall Bryant, Ph.D. (for epidemiological and clinical studies)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-402-9389
Email: kbryant@mail.nih.gov

Edward Doo, M.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-451-4524
Email: dooe@niddk.nih.gov

Jag Khalsa, Ph.D.
National Institute on Drug Abuse (NIDA)
Telephone: 301-443-2159
Email: jk98p@nih.gov

Jeymohan Joseph, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-443-6100
Email: jjeymoha@mail.nih.gov

Vaurice Starks (for epidemiological studies)
National Cancer Institute (NCI)
Telephone: 301-624-1299
Email: starksv@mail.nih.gov

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

Ann Devine
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-2988
Email: adevine@mail.nih.gov

Sean Hine
National Cancer Institute (NCI)
Telephone: 240-276-6291
Email: hines@mail.nih.gov

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

Florence Danshes
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-8861
Email: danshesf@extra.niddk.nih.gov

Diana Haikalis
National Institute on Drug Abuse (NIDA)
Telephone: 301-435-1373
Email: dhaikali@nida.nih.gov

Rita Sisco
National Institute of Mental Health (NIMH)
Telephone: 301-443-2805
Email: siscor@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 Parts 74 and 92.