Department of Health and Human Services

Part 1. Overview Information

Key Dates

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.

Table of Contents

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

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Background and Research Objectives

The objective of this FOA is to encourage research aimed at clarifying the cellular and molecular mechanisms underlying the presence and function of eosinophil leukocytes in eosinophilic associated rare diseases such as, but not limited to, Eosinophilic Gastrointestinal Disorders (EGIDs), Hypereosinophilic Syndrome (HES) and Eosinophilic Granulomatosis with Polyangiitis (EGPA), formerly known as Churg-Strauss Syndrome.

Eosinophil-associated disorders are a group of uncommon medical conditions in which the eosinophil is considered to have a primary or an important pathophysiologic role. Such disorders can affect the skin, upper and lower airways, cardiovascular system, connective tissues, gastrointestinal tract, the hematopoietic and immune systems, and other organs. However, despite the abundance of these cells, the pathophysiologic roles that eosinophils play in these disorders are not well understood. As a result, treatment options are limited and are associated with significant untoward problems. From a patient’s perspective, not only the limited treatment options, but also physicians limited knowledge of eosinophil-associated diseases can be detrimental to physical and psychological health and can result in substantial quality-of-life restrictions. This can also affect the emotional and social lives of the patients families.

On June 4, 2012, a workshop was convened in Bethesda, Maryland, by a consortium of several National Institutes of Health (NIH) Institutes and the Office for Disease Prevention with the purpose of defining, clarifying, and prioritizing the unmet research needs of eosinophil-associated diseases. The membership of this workshop published its findings in a September 2012 issue of the Journal of Allergy and Clinical Immunology (Bochner, B.S. et al. 2012. Workshop report from the National Institutes of Health Taskforce on the Research needs of Eosinophil-Associated Diseases (TREAD). J. Allergy Clin. Immunol. 130(3): 587-596.) This FOA builds on the recommendations of the workshop and on recent developments in the field.

Specific Areas of Research Interest

Areas of interest include, but are not limited to, the following topics:

Research on the fundamental immuno-biologic and mechanistic roles of human eosinophils in Eosinophil-Associated Disorders.

Eosinophils are bone marrow derived blood cells that normally migrate to specific tissues of healthy individuals such as the gut, mammary glands, uterus, and thymus. The cause of their abundance, persistence and function at tissue sites that are not normally infiltrated remains unknown. Their chronic presence and state of activation may be responsible for alterations in homeostatic tissue function which eventually leads to tissue damage. Understanding the eosinophil's basic immuno-biological and mechanistic roles in these unique conditions may be a key to the prevention and treatment of these disorders. Topics of interest include:

• Identification of unique factors responsible for the selective tissue recruitment and activation of eosinophils in these disorders
• Identification of best measures for detecting eosinophil presence and activity in tissues of eosinophil-associated disorders
• Testing whether targeting eosinophils in these disorders can result in unwanted immune consequences

Development of predictive biomarkers and clinical outcomes for Eosinophil-Associated Disorders

Reliable biomarkers of eosinophil involvement and of disease activity are largely lacking. Without this knowledge, the current approach toward disease management is imprecise and therefore, the development of new treatment modalities for these conditions is limited. Furthermore, specific clinical and surrogate outcomes to be used in clinical trials for these conditions are not available. Topics of interest include:

• Identification of biomarkers that evaluate both the various states of eosinophil activation and involvement in disease
• Testing whether eosinophil specific proteins or metabolomics serve as predictors of disease activity
• Development and validation of disease-specific clinical and surrogate outcomes that can be used in future clinical trials testing therapeutic modalities in these conditions

Development of novel therapeutic targets for use in Eosinophil-Associated Disorders

Eosinophil-Associated Disorders are considered orphan diseases and nearly all the current treatments for patients with these conditions are used off-label. New therapeutic targets that offer enhanced treatment selectivity and benefit for these conditions need to be identified and developed. Topics of interest include:

• Identification of unique factors for tissue recruitment and activation of eosinophils, which are shared across Eosinophil-Associated Disorders and can be targeted therapeutically
• Preclinical testing of potential therapeutic interventions (biologics, small molecules or other mechanisms)

Preclinical evaluation of existing therapeutic agents for use in Eosinophil-Associated Disorders

Nearly all current treatments are used off-label (e.g., alpha-interferon). Significant additional preclinical research is needed to clarify the utility of these and other potential licensed agents for use in treating patients with Eosinophil-Associated Disorders.

• Conducting preclinical, mechanistic studies to provide evidence that currently approved treatments with no indication for Eosinophil-Associated Disorders may be promising candidates for treating those disorders

Identification and improvement of novel invasive and non-invasive techniques for the diagnosis and clinical monitoring of Eosinophil-Associated Disorders

In several eosinophil-associated disorders the precise pathogeneses are unknown, and determining the absence, presence, and number of eosinophils in biopsies are often of limited value. For example, in patients with eosinophil cardiovascular disorders, there are 3 stages, acute, chronic and fibrotic. During the acute stage, the duration of illness is short and is usually neither clinically recognized nor diagnosed because echocardiography and angiography detect no abnormalities. However, endocardiac tissue damage is observed during histopathological evaluation. Therefore, improvement of non-invasive and/or invasive techniques that allow physicians to be better able to monitor or identify patients with Eosinophil-Associated Disorders is needed. Topics of interest include:

• Development of clinically useful assays that better reflect relevant tissue damage
• Examination of metabolic products for predictive use in assessing eosinophil damage during tissue infiltration
• Standardization of histological techniques for assessments of eosinophil involvement in tissue samples, including the validation of immunohistology for detecting the deposition of eosinophil derived proteins

Improvement of diagnostic criteria that delineate differential phenotypes within Eosinophil-Associated Disorders

The International Classification of Diseases, Clinical Modification, based on the World Health Organization’s Ninth Revision (ICD-9 CM), includes diagnostic codes that are used for various Eosinophil-associated disorders. ICD-9 CM codes are critical for reporting and tracking information on the incidence and prevalence of specific disorders. However, several of the eosinophilic syndromes are grouped together and several conditions lack any coding. While transition to ICD-10 is anticipated in late 2015, improvement in the diagnostic criteria to separate and distinguish disease entities is needed. Topics of interest include:

• Assessing whether Eosinophilic Granulomatosis (EGPA) is a single or multiple entity
• Testing for additional genetic mutations, associated with tyrosine kinase activity, that may distinguish Hypereosinophilic Syndrome (HES) patients in terms of their responsiveness to kinase inhibitors
• Testing whether subsets of HES patients with associated eosinophil apoptosis defects exist

Development of novel animal models with improved predictive value for human Eosinophilic-Associated Disorders

Murine models have been valuable as both the starting point and as a confirmation of insights derived from studies of human tissues/cells. The availability of mice that congenitally lack eosinophils has helped in the definition of the immunoregulatory capacities of these cells and their role in TH2-driven allergic inflammation. However, while informative, the existing murine models do not recapitulate eosinophil-associated human diseases. Therefore, new animal model development that better predicts human disease, or response to therapy, is needed. This modeling could include:

• Development of humanized mouse models in which immuno-compromised mice are repopulated with human cells
• Development of preclinical models that exhibit spontaneous eosinophil-mediated specific tissue damage e.g., cardiac damage

NIAID Specific Areas of Research Interests

The National Institute of Allergy and Infectious Diseases (NIAID) is interested in applications on all of the research topics described above with particular interest on those eosinophil-associated disorders that affect the upper and lower airways, cardiovascular system, skin, gastrointestinal tract, and the hematopoietic and immune systems. Eosinophilic-associated diseases of interest to the NIAID include but are not limited to: Chronic Eosinophilic Leukemia, Hypereosinophilic Syndrome (HES), Eosinophilic Gastrointestinal Disorders (EGIDs), Acute and Chronic Eosinophilic Pneumonia, and Eosinophilic Granulomatosis with Polyangiitis (EGPA), formerly known as Churg-Strauss Syndrome.

NIAMS Specific Areas of Research Interests

The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) is interested in applications on the research topics described above, and that are specifically focused on skin, connective tissues and musculoskeletal rare diseases including but not limited to: Bullous pemphigoid and other immune-mediated blistering skin diseases, Eosinophilic cellulitis (Wells syndrome), Eosinophilic pustular folliculitis, Eosinophilic vasculitis (EV), Drug Reaction with Eosinophilia and Systemic Symptoms, Kimura disease, Prurigo nodularis, Eosinophilic fasciitis, and Omenn syndrome.

NIDDK Specific Areas of Research Interests

The National Institute of Diabetes, Digestive, and Kidney Diseases (NIDDK) is interested in preclinical, clinical and epidemiological research studies of eosinophilic esophagitis and other eosinophilic digestive disorders to facilitate the translation of promising and relevant new developments into the clinical setting. The NIDDK is particularly interested in supporting research targeted to identifying noninvasive approaches to diagnose eosinophilic gastrointestinal diseases. Studies focused on identifying factors which may play a role in the pathophysiology of eosinophilic esophagitis, such as aerodigestive reflexes, patterns of esophageal clearance, and neuromuscular abnormalities are encouraged. Additionally, the development of alternative approaches in the management and treatment of eosinophilic disorders are encouraged.

Clinical trials will not be supported by this FOA. Clinical trials are defined by a prospective study of human subjects designed to answer questions about biomedical or behavioral interventions, e.g., investigational drugs or investigational medical devices, or new ways of using known treatments.

HIV/AIDS Studies will not be supported by this FOA.

Section II. Award Information

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.

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

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)

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.

Required Registrations

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.

Eligible Individuals (Program Director/Principal Investigator)

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.

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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.

Section IV. Application and Submission Information

1. Requesting an Application Package

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.

2. Content and Form of Application Submission

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.

Page Limitations

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

Instructions for Application Submission

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.

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

SF424(R&R) Senior/Key Person Profile

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

R&R or Modular Budget

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

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

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

• All applications submitted for the January 25, 2015 due date or after are expected to comply with the NIH Genomic Data Sharing Policy as detailed in NOT-OD-14-111, as applicable.
• 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.

Planned Enrollment Report

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

PHS 398 Cumulative Inclusion Enrollment Report

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

Foreign Institutions

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.

3. Submission Dates and Times

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.

4. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

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.

6. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review, NIH. Applications that are incomplete or non-compliant will not be reviewed.

Requests of $500,000 or more for direct costs in any year

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

Post Submission Materials

Applicants are required to follow our Post Submission Application Materials policy.

Section V. Application Review Information

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.

1. Criteria

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.

Overall Impact

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).

Scored Review Criteria

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 those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

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?

Additional Review Criteria

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

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

Revisions

For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

Additional Review Considerations

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

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.

2. Review and Selection Process

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.

3. Anticipated Announcement and Award Dates

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.

Section VI. Award Administration Information

1. Award Notices

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.

2. Administrative and National Policy Requirements

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

3. Reporting

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.

Section VII. Agency Contacts

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

Application Submission Contacts

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
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
Email: GrantsInfo@nih.gov

Scientific/Research Contact(s)

Patricia Noel, Ph.D.
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0202
Email: noelp@nhlbi.nih.gov

Michael Minnicozzi, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3532
Email: minnicozzim@niaid.nih.gov

Ricardo Cibotti, Ph.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-594-5032
Email: ricardo.cibotti@nih.gov

Frank Hamilton, M.D., M.P.H.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-8877
Email: hamiltonf@mail.nih.gov

Peer Review Contact(s)

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Financial/Grants Management Contact(s)

Howard Moore
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-5081
Email: mooreh@nhlbi.nih.gov

Donna Sullivan
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-2979
Email: dsullivan@mail.nih.gov

Melinda Nelson
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Phone: 301-435-5278
Email: nelsonm@exchange.nih.gov

Helen Cox
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-402-9285
Email: coxhh@mail.nih.gov

Section VIII. Other Information

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.

Authority and Regulations

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.