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 purpose of this Funding Opportunity Announcement (FOA) is to solicit applications from single institutions, or consortia of institutions, to identify existing anti-HIV molecules, or discover new highly potent and selective anti-HIV small molecules, with the potential for development as sustained release products (SRP) with a dosing interval from once a week to three months or longer. Research supported by this FOA includes a development plan designed to achieve a SRP for an oral, implantable, injectable or transdermal delivery system; and studies to provide proof-of-concept validation of the proposed small molecules incorporated into a delivery system relevant to a selected dosing interval.

Clinical experience for HIV treatment has established that adherence is a significant factor in the success of HIV treatment regimens. Currently, effective treatment of HIV-infected individuals requires strict adherence to a multi-component regimen of antiretroviral agents that must be taken at least daily for the remainder of a patient's life. Non-adherence can lead to emergence of drug-resistance and loss of therapeutic effectiveness, which can be amplified by the unique challenges of treating HIV in vulnerable populations such as children, adolescents, pregnant women, intravenous drug users, individuals with mental health issues and when HIV disclosure is associated with risk of stigma and/or violence.

For the purposes of this Funding Opportunity Announcement (FOA), the term sustained release product (SRP) will be defined as a product for which a single dose provides for a minimum of 1 week of treatment. SRP have also been identified in the scientific literature as extended release, and long acting products. Thus, there is significant interest in the development of SRPs with 30 and 90 days of therapy from a single application or dose.

Common approaches to development of SRPs include physical modification (e.g. micronization) of poorly soluble Active Pharmaceutical Ingredients (APIs) to the nanoparticle size and their injections as suspension (release based on solubility at the injection site); and embedding APIs in a matrix of insoluble polymers and their injection as suspension, or their implantation as rods (release based on the rate of matrix degradation). Although formulation technologies have made significant advances in recent years, challenges remain. APIs in SRPs must be exceedingly potent (picomolar levels) to keep application volumes small; formulation chemists often have limited access to novel new compounds; FDA-approved APIs have limited potential as SRPs due to low potency; and chemical characteristics most favorable for SRPs are incompatible with those required for traditional oral formulations.

Two antiretroviral agents amenable to intramuscular or subcutaneous dosing are furthest along in clinical development: rilpivirine, a non-nucleoside reverse transcriptase inhibitor, and cabotegravir, a novel strand transfer inhibitor of HIV-1 integrase that is an analog of dolutegravir. Because treatment of HIV requires drug combinations to avoid drug resistance and because infected-individuals need to have treatment options, there is a need to expand the pipeline of new small molecule APIs for the potential use as slow release products.

The development of anti-HIV molecules for HIV treatment/therapy has a long history of development of novel small molecule drugs that target multiple HIV targets (coreceptor, entry (gp120/gp41), reverse transcriptase, integrase and protease and additional hypothetical targets). Chemistry, isolation and characterization/development efforts have created a diverse range of chemical types and series of analogs/prototypes for both licensed and unlicensed small molecules. Within these series of compounds are many highly potent candidates that were not developed because they lacked properties (e.g. bioavailability) conducive to daily oral dosing. These compounds, either directly or with minimal chemical modifications to facilitate micronization, encapsulation in nano- or macro-delivery devices, represent an untapped source of SRP candidates.

To assist investigators in developing SRP approaches to HIV therapy, the Division of AIDS (DAIDS) has created the "Long-Acting/Extended Release Antiretroviral Resource Program" (LEAP) (http://www.longactinghiv.org/) to provide access to scientific, pharmaceutical and regulatory expertise, as well as access to computer-based modeling and simulation services.

The goal of this FOA is to encourage and provide support to investigators to identify and study new or existing small molecules Active Pharmaceutical Ingredients (APIs) - for their ultimate potential as anti-HIV treatment SRPs with dosing intervals from once a week to three months, or even longer. APIs may be obtained through chemical synthesis or the repurposing of existing compounds. APIs must exhibit highly potent and selective anti-HIV in-vitro activity. Dosing formulations may be oral, injectable, implantable or transdermal in nature. Collaborations with formulation chemists are encouraged.

The development of SRPs requires incorporating in-vivo safety, efficacy and pharmacokinetic (PK) studies to support candidate selections, as well as consideration of the feasibility of chemical synthesis, scale-up and cost of production. In addition, advancements in formulation sciences have increased the options for extending the pharmacokinetic (PK) and enhancing the pharmacodynamic (PD) range of all types of therapeutics. Thus, pre-formulation studies are needed to facilitate the incorporation of highly potent APIs into SRPs.

Targeted product profile (TPP) and development of appropriate milestones and go/ no-go criteria are important tools to guide research leading to the selection of candidate APIs and drug delivery systems (DDS) for development as anti-HIV therapy SRPs.

Responsive Areas of Research

Examples of the types of studies that are considered responsive to this FOA include, but are not limited to:

• Discovery, through chemical synthesis, of new APIs that exhibit highly potent and selective in-vitro anti-HIV activity.
• Identification and further development of existing APIs with established antiviral activity and HIV resistance patterns. If applicable, in silico tools, i.e. computational absorbance distribution, absorption, distribution, metabolism, excretion (ADME), and PK modeling tools may be used in SRP/DDS design.
• Pre-formulation studies that include chemical and physical characterization of the selected API and DDS. This includes performance of U.S. Pharmacopeial Convention (USP) compliant stability and drug release testing.
• In-vitro and in-vivo studies designed to assess the potential toxicity and safety of selected APIs and DDSs.
• PK and PD studies designed to characterize in-vivo release of the SRP for its proposed dosing interval.
• Studies with proposed SRP to assess local tissue concentrations of the API and studies to document local cellular and tissue reactions.

Non-Responsive Areas of Research

Applications proposing research in the following areas will be considered non-responsive to this FOA and will not be reviewed:

• Clinical trials.
• Activities intended for enabling/facilitating clinical studies conducted with other funds. This includes activities that support the administrative preparation/submission of a an Investigational New Drug (IND), Investigational Device Evaluation (IDE) and/or New Device Exception (NDE) application to the FDA or other regulatory bodies, or to produce clinical supplies for future trials.
• Random or bulk screening of chemical or natural product libraries or collections to "discover" SRP candidates, including development of an uncharacterized natural product consisting of a complex mixture of potentially active and inactive ingredients.
• Development of intravaginal rings (IVR) and/or products to be delivered exclusively by topical delivery to the male or female genital or GI tracts.
• Development or use of genetically modified organisms or use of bacterial, fungal or viral vectors to delivery SRP candidates.
• Applications proposing broadly generalized global assessments of the impact of SRP in animal or in-vitro models using genomic, proteomic, scriptomic, and/or microbiome analysis technologies to characterize safety and/or markers for safety or efficacy of SRPs are discouraged. Limited studies of this type may be included if justified based on predicted safety issues and/or known/suspected characteristics of the API or DDS.
• Further development/testing of the following compounds as single SRPs: Rilpivirine (TMC-278), Cabotegravir (GSK-744, GSK/S 1265744), Tenofovir (TFV, PMPA, (R)-9-(2-Phosphonoylmethoxypropyl) adenine), Tenofovir Disoproxil Fumarate (TDF or Viread ) or Tenofovir Alafenamide fumarate (TAF). Combination development of Rilpivirine and Cabotegravir as an oral SRP. Antiretrovirals that are currently licensed for HIV treatment maybe developed as SRP products, however the applicant is cautioned that these antiretrovirals have been developed for daily oral delivery, and thus may not have the chemical properties or potency required for incorporation into a sustained release DDS.
• Development of broadly neutralizing antibodies or non-neutralizing antibodies as a SRP.

 

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 obtain 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.

Collaborations with formulation chemists are encouraged.

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

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

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

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Research Strategy: As relevant to the proposed research, provide a brief overview of your research plan, sufficient background information to support the feasibility of the approach, and describe how its success provides an advancement in a useful therapeutic application.

• Indicate the proposed Active Pharmaceutical Ingredient (API), its source and timing for availability for research; indicate the proposed Drug Delivery System (DDS).
• Indicate the molecular target of the proposed API and discuss the rationale for choosing it as a candidate to be developed as a sustained-release formulation; describe how this work differs from previous approaches and provide the unique features of the proposed work.
• Include a targeted product profile (TPP), milestones and go/no-go criteria as tools to guide research leading to the selection of the candidate APIs for development as anti-HIV therapy SRPs. Because of the potential complexity of a proposed SRP development plan, applicants are asked to include at the end of the research approach a summary Gantt chart to help understand the flow of the proposed specific aims and interrelatedness of the components of the proposed development plan.
• Describe all phases of the proposed API development plan as part of a proposed SRP. Include planned methods, proposed evaluations, and criteria to define success. Applicants may use animal models (e.g. humanized mice and/or nonhuman primates) for PK, safety and/or efficacy determinations of the SRP candidates. Applicants should consider the following in proposed animal studies:
• Superiority assessments of the drug product(s)/DDS being tested should be used and include appropriate positive control and placebo arms.
• Sufficient numbers of animals should be included in all groups to allow for endpoint statistical analysis.
• Wherever possible, formulated products characterized for API stability and release should be used. If unformulated products and vehicle admixtures are proposed without some level of drug stability and release, then clearly explain why this mode has been chosen over other possibilities.
• Where appropriate, the inclusion of laboratory safety measurements (e.g. liver, and kidney function, hematological assessment) is encouraged.
• When animal studies are used to assess PK parameters, sufficient time points should be collected to derive critical standard PK parameters for the device , e.g. area under the curve (AUC), and concentration minimums and maximums (Cmin or Cmax, respectively). PK modeling may be used to support spare sampling approaches.
• Provide a cost forecast for large scale production of the API (>100 grams), and discuss the expected practical feasibility of a finished product (e.g. number of steps in the manufacturing process).

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

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

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

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

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 are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.

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 R01-based Identification of Small Molecules for Sustained-Release Anti-HIV Products FOA is intended to support high-risk and high-innovative research that can lead to the identification and development of an API as SRP for anti-HIV therapy. Accordingly, evaluation of the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge and understanding of SRP development will be critical to achieving the goals of this FOA. Although preliminary data with a specific API and DDS can play a significant role in providing a justification or rationale for research on the proposed API and DDS, the high level of innovation and risk that could be associated with these applications may not be supported by extensive specific preliminary data, but may be embodied in the experience of the investigators with sustained release systems used for other therapeutic indications, i.e. cancer, Alzheimer's, Parkinson's disease, Diabetes etc. Thus, judgments regarding potential success for the proposed research may require reliance upon relational and/or inferential data to establish the potential for success rather than substantial experimental data directly supporting the proposed API/SRP/DDS.

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 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? 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?

Is the proposed development plan likely to support the identification of a new SRP? Does the proposed cost and scale-up discussion support the proposed development plan of a new SRP candidate?

If a TPP is proposed, are the indicated parameters appropriate for the proposed SRP development? Do the proposed milestones and Go/ No-Go criteria support the TPP?

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.

Not Applicable

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 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.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Allergy and Infectious Diseases Council. 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.

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: 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 CenterTelephone: 800-518-4726

Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: support@grants.gov

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

Telephone: 301-710-0267

Daniella Livnat
National Institute of allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3087
Email: dlivnat@niaid.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@niaid.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.