Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	National Institute of Allergy and Infectious Diseases (NIAID)
Funding Opportunity Title	Pharmacological Approaches to Evaluating Drug Regimens to Address Antimicrobial Resistance (R01)
Activity Code	R01 Research Project Grant
Announcement Type	New
Related Notices	August 21, 2013: Removed reference to ASSIST in section IV.3, since ASSIST is currently only available for multi-project applications. May 1, 2013 - See Notice NOT-AI-13-042. Notice of Correction to Award Information.
Funding Opportunity Announcement (FOA) Number	RFA-AI-13-024
Companion Funding Opportunity	None
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.855, 93.856
Funding Opportunity Purpose	The purpose of this FOA is to support antimicrobial pharmacokinetic and pharmacodynamic (PK/PD) studies of drug combinations or sequentially administered (sequenced) antimicrobial agents in relevant in vitro and animal models to enhance understanding of the host, drug and microbial factors that contribute to the emergence of antimicrobial drug resistance in clinically relevant pathogens with a goal of minimizing the potential for development of resistance. A secondary objective is to establish partnerships among anti-microbial pharmacologists, microbiologists and animal modelers to bridge the gap between antimicrobial pharmacology and its application to fundamental and translational research for the clinical management of drug resistance.

Posted Date	April 18, 2013
Open Date (Earliest Submission Date)	June 30, 2013
Letter of Intent Due Date(s)	June 30, 2013
Application Due Date(s)	July 30, 2013, by 5:00 PM local time of applicant organization. Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.
AIDS Application Due Date(s)	Not Applicable
Scientific Merit Review	November, 2013
Advisory Council Review	January, 2014
Earliest Start Date	March, 2014
Expiration Date	July 31, 2013
Due Dates for E.O. 12372	Not Applicable

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 FOA is to support antimicrobial pharmacokinetic and pharmacodynamic (PK/PD) studies of drug combinations or sequentially administered (sequenced) antimicrobial agents in relevant in vitro and animal models to enhance understanding of the host, drug and microbial factors that contribute to the emergence of antimicrobial drug resistance in clinically relevant pathogens with a goal of minimizing the potential for development of resistance. Studies of an individual drug may be supported under this FOA if the drug to be studied is currently used clinically as a single drug therapy for a particular diagnosis and considered the standard of care for that diagnosis.

A secondary objective is to establish partnerships among antimicrobial pharmacologists, microbiologists and animal modelers to bridge the gap between antimicrobial pharmacology and its application to fundamental and translational research for the clinical management of drug resistance.

Resistance is a natural and inevitable event in microbial populations that are exposed to antimicrobial agents and is starting to limit the effectiveness of available drugs for the treatment of bacterial, viral fungal and parasitic infectious diseases. Since the introduction of antimicrobial agents as standard medical practice and in veterinary applications, indiscriminate use and incomplete therapies have resulted in a substantial increase in antimicrobial resistance in the U.S. and globally. Furthermore, already drug resistant strains of pathogens are being transmitted and are causing primary drug resistant disease.

Prevention and management of clinical antimicrobial drug resistance is an area of principal interest for NIH, and NIAID in particular, as well as a special concern for the microbial research and clinical communities. In January 2001, DHHS released an action plan to combat antimicrobial resistance (http://www.cdc.gov/drugresistance/actionplan/actionplan.html). Recognizing the urgent need to more effectively manage the development of resistance to anti-infective agents, NIAID has added antimicrobial resistance to the NIAID Category C list of Biodefense and Priority Pathogens (http://www3.niaid.nih.gov/Biodefense/Research/biotresearchagenda.htm) to promote research on the prevention, diagnosis and treatment of drug-resistant pathogens.

Frequently, resistant infections are treated empirically with drug combinations, many of which were established in the absence of controlled clinical data. Limited scientific studies have been conducted to apply the principles of antimicrobial pharmacology, pharmacokinetics (PK, the process by which a drug is absorbed, distributed, metabolized and eliminated by the body resulting in a characteristic drug exposure profile) and pharmacodynamics (PD, the study of the action or effects of drugs on living organisms) to characterize the effectiveness of combination antimicrobial agents against infectious agents. The unique aspect of PK/PD interactions for treatment of infectious diseases is that an antimicrobial drug does not target the human body but rather on a separate, infecting organism with its own response kinetics. Therefore, to design the most effective therapeutic combination regimens, it is critical to study not only concentrations of drugs individually and in combination, but also the kinetics of drug(s) action on the microbial pathogen.

The choice of appropriate combination drug regimens to suppress and/or eliminate infectious pathogens is frequently based on empiricism rather than rational selection of drugs with appropriately matched pharmacokinetic and pharmacodynamic parameters and mechanisms of action. Many drug regimens continue to be based on the goal of achieving the maximum time for drug exposure above the minimum inhibitory concentration that the host can tolerate in the absence of adverse events.

While the effectiveness of a drug is defined by several components:

i) an anti-infective agent that is capable of acting on the pathogen;

ii) the administration of drug quantities that result in drug concentrations sufficient to be active against the pathogen;

iii) and administration of the therapeutic for a sufficient number of days to result in clearance of the infectious agent, combinations of anti-infective agents present a different level of complexity and make it difficult to understand the relative contribution of each drug. Furthermore, as is the case for chronic infectious diseases that require longer durations of treatment, for example tuberculosis, bacterial populations are hypothesized to change during the course of treatment and respond differently to combination drug approaches. In these instances, appropriate sequencing of drug combinations may be required to elicit the maximum therapeutic benefit.

In 2007, NIAID issued an FOA (RFA-AI-07-025, Pharmacological Approaches to Combating Antimicrobial Resistance (R01)) to expand the science base underlying anti-infective pharmacology to help prevent and treat drug resistant infections. This FOA builds on the successes of that previous FOA with an expanded focus on combination drug treatments as a current and contemporary issue in the management of drug resistant infectious diseases.

In the absence of a robust pipeline of new drugs, existing drugs and regimens have to be re-evaluated to determine whether novel combinations or a different sequence of administration are able to provide treatment options for patients with drug resistant infections. However, limited approaches/data for the systematic evaluation of the complex pharmacokinetic and pharmacodynamic interactions of combination drug treatment are currently available.

The objective of this FOA is to apply the discipline of antimicrobial pharmacology and PK/PD interactions to fundamental research studies to improve understanding of the factors underlying the effectiveness of combination drug regimens and/or sequentially applied drug regimens used against infectious diseases. While studies on combination drug regimens are the primary focus of this initiative, applications focused on an individual drug are responsive to this FOA in those instances where the drug to be studied is currently used clinically as single drug therapy for a particular diagnosis.

Projects are expected to contribute to and complement on-going NIAID-funded efforts in antimicrobial research for bacterial, fungal, viral and parasitic pathogens, and exclude studies in HIV/AIDS (http://www3.niaid.nih.gov/research/topics/antimicrobial/introduction.htm http://www.niaid.nih.gov/factsheets/antimicro.htm). To meet this expectation, applications must address infectious diseases for which drug resistance poses a significant patient care issue, and for which combination regimens or sequentially administered drugs are currently employed, and must be focused on currently approved drugs and regimens, or drugs and regimens that are currently under clinical evaluation.

Proposed studies should include collaborative approaches designed to investigate the interactions between host, drug, and pathogen in affected tissues or the interactions (synergistic or antagonistic) of combinations of drugs. Novel approaches using existing antimicrobial agents and regimens in in vitro and animal models based on human pharmacokinetics, are encouraged.

Research questions responsive to this FOA include, but are not limited to:

• How do specific drug combinations or sequences and their exposure/time profile contribute to the maximum effect on pathogen growth and treatment/prevention of resistance?
• Can the effect of the combination or drug sequence on the pathogen be negatively affected through variations in exposure profiles likely encountered in patient populations (including pediatrics)?
• Is the location of the pathogen, as it is relevant to disease, known and are the drug concentrations at the site of infection sufficient to effectively inhibit pathogen growth or viability?
• Are the interactions (additive/neutral) of the drugs used in combinations beneficial to derive maximum effectiveness?
• Do resistant or metabolically diverse microbial sub-populations respond equally well to drug combinations and what is the impact of the effectiveness of a regimen when sensitivity against individual drugs is lost?

To answer these research questions, it is anticipated that in vitro models such as hollow fiber systems will be combined with mathematical modeling and animal models that have already been shown to mimic relevant aspects of human infectious disease. Furthermore, animal models are expected to use drug exposure/time profiles that are equivalent to those reached in humans, or that can be translated to human studies. In addition, singly drug resistant pathogens may be utilized to characterize the impact of loss of efficacy of individual drugs when used in combination regimens or sequences. It is expected that collaborations between antimicrobial pharmacologists, microbiologists and animal modelers will be established to facilitate cross-disciplinary projects to address these gap areas.

Examples of experimental approaches include, but are not limited to:

• Novel approaches using existing antimicrobial agents and combination drug regimens in vitro and in animal models, based on human pharmacokinetics.
• Studies analyzing specimens from treated patients.
• Refinement of animal models.
• In vitro PK/PD hollow fiber models.
• In silico modeling based on animal and in vitro data.

Studies supported through this FOA will lead to a better understanding of the contribution of PK/PD correlates to the effectiveness of combination/sequenced regimens and their potential to treat and avoid drug resistance. These studies are also expected to result in improved animal models of infection and drug treatments and are expected to inform the discovery and development process for new drug candidates and regimens. Once validated in human clinical trials, PK/PD optimized drug therapies should have the potential to extend the clinical utility of antimicrobial agents as part of regimens and sequences against drug resistant infections.

Note: This FOA will NOT support:

• efforts aimed at identifying new drug targets;
• development of new models of infectious disease;
• development of new antimicrobial agents;
• research on HIV/AIDS;
• clinical trials;
• studies of diagnostic tests for drug resistance; or
• studies aimed solely at the impact of anti-infective agents on the natural commensal flora

Applications proposing research in these areas are non-responsive and will not be reviewed.

Funding Instrument	Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.
Application Types Allowed	New The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	NIAID intends to commit $5.5 million in FY 2014. Future year amounts may vary depending on annual appropriations.
Award Budget	Application budgets are not limited, but need to reflect the actual needs of the proposed project.
Award Project Period	The scope of the proposed project should determine the project period. The maximum project period is 5 years.

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 and should work with their organizational officials to either create a new account or to affiliate an existing account with the applicant organization’s eRA Commons account. 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.

NIH will not accept any application that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for 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.

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Frank S. De Silva, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases (NIAID)
Room 3144, MSC-7616
6700B Rockledge Drive
Bethesda, MD 20892-7616
Phone: 301-594-1009
FAX: 301-480-2408
Email: [email protected]

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.

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 (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide, with the following modifications:

• 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.

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

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.

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

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

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

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? Will the proposed collaborative studies increase the knowledge base of combination PK/PD approaches in drug resistance research? Does the proposed research have the potential to extend the clinical utility of antimicrobial agents against drug resistant infections? Does the proposed research adequately address infectious diseases for which drug resistance poses significant patient care issues?

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? Are appropriate collaborations between antimicrobial pharmacologists and microbial researchers proposed?

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? Does the project have the potential to generate new approaches for research on drug combinations directed against drug resistant infectious diseases? If the study is focused on an individual drug, is that drug currently used clinically as a single drug therapy for a particular diagnosis and considered the standard of care for that diagnosis?

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? Does the project involve appropriate/adequate multi-disciplinary approaches that allow critical issues in infectious disease and microbial pharmacology to be addressed?

If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion 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 Human Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children

When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

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

Not Applicable

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 National Institute of Allergy and Infectious Diseases, 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. l 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 Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)

Web ticketing system: https://public.era.nih.gov/commonshelp
TTY: 301-451-5939
Email: [email protected]

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

Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-710-0267
TTY 301-451-5936
Email: [email protected]

Dr. Christine Sizemore
Division of Microbiology and Infectious Diseases
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-435-2857
Email: [email protected]

Frank De Silva, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-594-1009
Email: [email protected]

Victoria P. Connors
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-402-5065
Email: [email protected]

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 .