NIH’s new Application Submission System & Interface for Submission Tracking (ASSIST) is available for the electronic preparation and submission of multi-project applications through Grants.gov to NIH. Applications to this FOA must be submitted electronically; paper applications will not be accepted. ASSIST replaces the Grants.gov downloadable forms currently used with most NIH opportunities and provides many features to enable electronic multi-project application submission and improve data quality, including: pre-population of organization and PD/PI data, pre-submission validation of many agency business rules and the generation of data summaries in the application image used for review.

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) and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. 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

This FOA is seeking applications from single institutions, or consortia of institutions, proposing research to understand the role of allergen epitope-specific T-cell responses in the pathogenesis and treatment of allergic diseases including allergic rhinitis, asthma and food allergy, by utilizing allergen epitope-specific reagents. Identification, characterization and validation of new T-cell epitopes for allergens that have not been previously extensively examined (e.g. fungal allergens or food antigens such as milk), will also be supported under this FOA. Applicants are encouraged to submit multi-project research programs that propose to study immune responses to allergens at the level of epitope-specific T cell subsets, including comparative or interventional studies in humans. Applicants are also encouraged to capitalize on the availability of allergen T cell epitopes, including those available through the NIAID-funded Immune Epitope Database and Analysis Resource (IEDB).

The NIAID Division of Allergy, Immunology and Transplantation (DAIT) promotes and supports research to enhance the understanding of the mechanisms that lead to the development of immunologic diseases and to generate an expanded knowledge base that can be applied to the development of improved diagnosis, treatment, and prevention.

In allergic diseases, where IgE antibodies mediate most of the effector pathogenetic mechanisms, the role of allergen-specific T cells is not clear. It is widely accepted that T-cells orchestrate some of the early steps in allergic immune responses and play a significant role in sustaining type 2 polarization of the immune system, but the role of specific T-cell allergen epitopes in this process has not been delineated. More research is needed to identify the most common T-cell epitopes of all major aeroallergens and food allergens and to probe their role in allergic disease. The ultimate goal of this line of research is to utilize T-cell epitopes either as biomarkers predicting disease development and possibly severity or as therapeutic targets for immune tolerance.

In response to a 2005 workshop on allergen immunotherapy, DAIT developed an initiative entitled "Allergen & T Cell Reagent Resources for the Study of Allergic Diseases" that funded two 5-year awards in FY2007. The contracts were completed in 2012 with significant progress in the identification of T cell epitopes for various food and pollen allergens. Information about these epitopes and the assays used to validate them is available through the NIAID-supported Immune Epitope Database and Analysis Resource (IEDB).

Following the success of these contracts, DAIT awarded 2 cooperative agreements (U19) on the initiative entitled "Allergen Epitope Validation Resource" in FY2012. These awards have pursued the identification and validation of T-cell epitopes primarily of German cockroach allergens and the exploration of the therapeutic value of major cat allergen T-cell epitopes.

In addition to the important task of identifying major allergen T-cell epitopes, questions that remain unanswered for most common allergens include, but are not limited to:

• Does the presence of T-cells with particular epitope specificities differentiate allergic from non-allergic individuals?
• How stable is the epitope-specific T-cell repertoire over time and what are the clinical implications of natural alterations in the repertoire within individuals?
• In persons with allergy, do specific T-cell epitopes differentiate between various clinical phenotypes or between stages of disease severity?
• How important is the immunologic phenotype of epitope-specific T-cells as a marker of clinical presentation?
• Does allergen exposure or allergen immunotherapy influence a particular group of epitope-specific T-cells? If so, would these epitope-specific T-cells constitute best targets for new forms of immunotherapy aiming at inducing immune tolerance?

The goal of this FOA is to continue NIAID's support of multidisciplinary and collaborative research programs that focus on identifying, characterizing and validating allergen T cell epitopes during the development, progression, or immunotherapeutic management of allergic disease. For the purpose of this FOA, epitope validation is defined as the ability to track the numbers and functions of epitope-specific T cells during various clinical stages and to associate these parameters with careful phenotypic or endotypic characterization. These programs should include state of the art techniques to explore epitope-specific T-cell repertoires and to illuminate their phenotypes, their function and their contribution to allergen-specific T cell memory. New T cell epitope identification should be limited to allergens that have not been previously extensively examined and which are of importance in allergic diseases with high public health impact (e.g., milk, mouse and fungal antigens).

This FOA seeks applications with projects that are highly synergistic and relate to a central theme relevant to the goals described above. All projects in an application must focus on human disease and can involve subjects with allergic rhinitis, asthma, or food allergy who will be carefully phenotyped. In addition or alternatively, the application can utilize human specimens obtained from outside studies provided that these studies have conducted clinical phenotyping of high quality and that all this information is readily available to the applicant investigators. Applicants are encouraged to collaborate with funded clinical networks that can supply high quality clinical information and have the ability to prospectively follow large numbers of participants with various phenotypic characteristics. NIAID requires that all of the proposed research in each application meets the definition of NIH clinical (human subjects) research and clearly defines the central role of T cell epitope analyses in the study hypothesis, design, and mechanistic assays. For the NIH definition of clinical (human subjects) research, please refer to the NIH Office of Extramural Research Human Subjects website. Healthy non-allergic subjects may be included in the proposed clinical studies as controls. This FOA may also support new phase I and small-scale phase II clinical trials. If proposed, these clinical trials must focus on immune-based therapies and/or interventions involving experimental allergen exposure.

Projects that propose to use or develop novel sample sparing technologies that can enhance research in children and infants are encouraged.

Applications proposing the following studies will be considered non-responsive and will not be reviewed:

• Research conducted in animal models;
• Research on epitopes derived from allergens not relevant to human allergic diseases;
• Projects seeking to study only a single allergen T cell epitope;
• Research focused solely on allergen B cell epitopes;
• Research focused solely on non-peptide allergen T cell epitopes;
• Genome Wide Association Studies (GWAS);
• Research focused solely on sample sparing technologies;
• Phase III clinical trials in asthma and/or allergic diseases; and
• The continuation of ongoing (active) clinical trials
• Research on HIV/AIDS

For all clinical trials that will be conducted, NIAID will provide a Data and Safety Monitoring Board (DSMB) or a Safety Monitoring Committee (SMC).

Administrative Core: An administrative core must be proposed and is responsible for providing overall management, coordination and oversight for the Program. 

Research Projects: Each application must propose two, but no more than three highly synergistic research projects centering on the common theme of epitope validation.

Clinical Core, Data Management and Analysis Core or additional Scientific Core(s): Cores are optional and if proposed are responsible for providing common services to support the Program as a whole and two or more projects to maximize synergy and optimize resources.

See Section VIII. Other Information for award authorities and regulations.

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.

Only one application per institution (normally identified by having a unique DUNS number or NIH IPF number) is allowed.

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 can access 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.

Most applicants will use NIH’s ASSIST system to prepare and submit applications through Grants.gov to NIH. Applications prepared and submitted using applicant systems capable of submitting electronic multi-project applications to Grants.gov will also be accepted.

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 and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. 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:

B. Duane Price, PhD
Telephone: 240-669-5074
Email: pricebd@niaid.nih.gov

Component Types Available in ASSIST	Research Strategy/Program Plan Page Limits
Overall	12
Admin Core (use for Administrative Core)	6
Core (Use for Clinical Core, Data Management and Analysis Core or Scientific Cores)	12
Project (Use for Research Projects)	12

Additional page limits 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 a multi-component application.

The application should consist of the following components:

• Overall: required
• Administrative Core: required
• Clinical Core: optional, maximum 1
• Data Management and Analysis Core: optional, maximum 1
• Scientific Core(s): optional, no maximum
• Research Projects: 2 required, a maximum of 3 allowed

When preparing your application in ASSIST, use Component Type Overall .

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

Complete entire form.

Note: Human Embryonic Stem Cell lines from other components should be repeated in cell line table in Overall component.

Follow standard instructions.

Enter primary site only.

A summary of Project/Performance Sites in the Overall section of the assembled application image in eRA Commons compiled from data collected in the other components will be generated upon submission.

Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this FOA) for the entire application.

A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.

The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover.

A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.

Specific Aims: List in priority order, the broad, long-range objectives and goals of the proposed Program. Concisely describe the hypothesis or hypotheses to be tested.

Research Strategy: Summarize the overall research strategy for the multi-component application, describing the focus of the research program in this application. The multi-component application should be viewed as a confederation of interrelated research projects, each capable of standing on its own scientific merit, but complementary to one another. This is an important section for it provides the group of investigators an opportunity to give conceptual wholeness to the overall program by giving a statement of the general problem area and by laying out a broad strategy for attacking the problem. As the strategy develops, each project and core should be cited briefly as to its place in the overall scheme. Summarize the special features in the environment and/or resources that make this application strong or unique. To highlight program synergy, applicants should describe how the individual components will be coordinated and work together to address the overall goals and aims of the program including conflict resolution. Include a schematic overview of the interactions and collaborations among the components, and indicate collaborations among members and relevant publications co-authored by members of the program. Program synergy may also be addressed in other sections of the application, as appropriate.

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

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

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

When preparing your application in ASSIST, use Component Type Admin Core.

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

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget forms appropriate for the specific component will be included in the application package.

Funding for the overall administrative efforts, including administrative salaries and services, publication expenses resulting from collaborative efforts, and communication expenses, should be requested in this core.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Specific Aims: List, in priority order, the broad long-range objectives and goals of the proposed Administrative Core.

Research Strategy: Provide an administrative plan that includes a description of the structure and roles of administrative staff, and the functions to be performed; how fiscal and other resources will be prioritized, allocated and managed; how communications will be facilitated; and how research-related travel and training will be budgeted.

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.

PHS Inclusion Enrollment Report (Administrative Core)

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

When preparing your application in ASSIST, use Component Type Core.

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

SF424 (R&R) Cover (Clinical Core)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Clinical Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Clinical Core)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Facilities & Other Resources: The Clinical Core should present a clear picture of what the facilities will provide. For Clinical Study Sites (if applicable) describe:

• Available access to relevant patient populations to ensure timely screening and enrollment of appropriate study participants;
• The availability of support personnel and clinical research facilities to execute clinical trial and observational study protocols;
• Capabilities to collect and process the required biologic samples.

Project /Performance Site Location(s) (Clinical Core)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Clinical Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• Describe in the Biosketch the experience of the core leader and other key persons in conducting clinical studies and trials in allergy.
• Describe in the Biosketch the experience of the core leader and other key persons with regulatory activities, including IND applications, recruitment and retention of study participants, medical monitoring, and safety oversight and reporting.

Budget (Clinical Core)

Budget forms appropriate for the specific component will be included in the application package.

Include the costs of all support for study design, protocol development, data collection, clinical site monitoring, medical monitoring, project management and quality assurance of the proposed clinical studies or trials. If applicable include all costs associated with data management and analysis.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Clinical Core)

Specific Aims: List in priority order, the broad, long-range objectives and goals of the proposed Core.

Research Strategy: For an application proposing to evaluate substantial numbers of human subjects for the clinical research or clinical trial(s) proposed by the Projects, applicants may consider proposing a Clinical Core. The Clinical Core should present a clear picture of the techniques, and skills that it will provide, but should not propose hypothesis generating research. The attributes of the Clinical Core should include but are not limited to:

• Description of source and quantity of biospecimens to be obtained
• Process and procedures for preparation of an IND/IDE application, if needed
• Plans and procedures for recruitment including access to the appropriate type and number of study participants
• Plans and anticipated problems for subject recruitment and retention, as well as proposed approaches to overcome or minimize such problems
• Study organization: a plan for the management of the clinical trial (if proposed) that includes a description of personnel other than the key personnel involved in conducting the trial and personnel involved in safety monitoring; the interactions between the clinical core and the data management and analysis core teams, if applicable, should be described.
• Describe procedures to ensure proper training of personnel including protocol specific training
• Describe how the core will develop protocol, informed consent, manual of procedures, case report forms, IRB applications and other relevant clinical documents.

The activities of the Clinical Core must not overlap with those of a proposed Research Project.

If a Data Management and Analysis Core is not proposed the Clinical Core may include data management functions such as database development and cleaning.

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.

PHS Inclusion Enrollment Report (Clinical Core)

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

When preparing your application in ASSIST, use Component Type Core.

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

SF424 (R&R) Cover (Data Management and Analysis Core)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Data Management and Analysis Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Data Management and Analysis Core)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Facilities & Other Resources: The Data Management and Analysis Core should present a clear picture of the facilities available.

Project /Performance Site Location(s) (Data Management and Analysis Core)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Data Management and Analysis Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Data Management and Analysis Core)

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Data Management and Analysis Core)

Specific Aims: List in priority order, the broad, long-range objectives and goals of the proposed Core.

Research Strategy: The Core should present and justify the techniques, and skills that will be provided. Describe how the statistical analysis methods, database resources, data entry and validation resources are appropriate to support the studies proposed in the application. The Core should include a plan for the management of the personnel involved in data entry and management and the statistical analysis of scientific and clinical trial (if proposed) data; the interactions between these teams should be described.

The activities of Data Management and Analysis Core must not overlap with those of a proposed Clinical Core (if applicable) or a proposed Research Project.

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.

PHS Inclusion Enrollment Report (Data Management and Analysis Core)

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

When preparing your application in ASSIST, use Component Type Core. The Scientific Core should be limited to providing standard assays, reagents, technologies, or other available services to the investigators, but should not be testing scientific hypotheses. Examples of Scientific Cores may include state-of-the-art technical (e.g. flow cytometry, multiplex cytokine assays, sequencing), bioinformatics, or other non-administrative activities that directly support the research programs.

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

SF424 (R&R) Cover (Scientific Core)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Scientific Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Scientific Core)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Facilities & Other Resources: The Scientific Core should present a clear picture of what the facilities will provide.

Project /Performance Site Location(s) (Scientific Core)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Scientific Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Scientific Core)

Budget forms appropriate for the specific component will be included in the application package.

Include the apportionment of dollars or percentage of dollars that will be required to support each component research project that will utilize each scientific core.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Scientific Core)

Specific Aims: List in priority order, the broad, long-range objectives and goals of the proposed Core.

Research Strategy: The application should present a clear picture of the techniques and skills that the core will provide and should justify the proposed services.

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.

PHS Inclusion Enrollment Report (Scientific Core)

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

When preparing your application in ASSIST, use Component Type Project.

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

SF424 (R&R) Cover (Research Project)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Research Project)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Research Project)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Facilities and Other Resources: If not proposing a Clinical Core please address the Clinical Study Sites in this section.

For the Clinical Studies Sites (if applicable) describe:

• Available access to relevant patient populations to ensure timely screening and enrollment of appropriate study participants;
• The availability of support personnel and clinical research facilities to execute clinical trial and study protocols;
• Capabilities to collect and process the required biologic samples

Project /Performance Site Location(s) (Research Project)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Research Project)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• Describe in the Biosketch the project leader's and other key persons' experience in designing and conducting clinical studies and trials in allergy.

Budget (Research Project)

Budget forms appropriate for the specific component will be included in the application package.

For the conduct of human subject research, include the costs of all support for study design, protocol development, data collection, data analysis and management, clinical site monitoring, medical monitoring, project management and quality assurance.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Research Project)

Specific Aims: List, in priority order, the broad long-range objectives and goals of the proposed Research Project. Concisely describe the hypothesis or hypotheses to be tested.  In addition, state the individual Research Project’s relationship to the overall goals of the multi-component application. Applicants should also describe how individual projects relate to other Research Projects or Cores in the application.

Research Strategy: Use this section to describe how the proposed research will contribute to meeting the Center’s goals and objectives and explain the rationale for selecting the methods to accomplish the specific aims. In addition to stating the biological significance of the research, indicate the project's relevance to the primary theme of the application. Describe the experimental approaches to be used that characterize the phenotype and function of epitope specific T cell subsets and the approaches that validate the clinical importance of these subsets.

If the project is proposing to further characterize and clinically validate an existing allergen T cell epitope(s), provide preliminary or published data demonstrating that these epitopes meet two or more of the following criteria:

• The epitopes are peptides identified from clinically-important protein allergens;
• Peptides consisting of, or containing, the epitopes activate allergen-specific primary human T cells in vitro;
• Allergen-specific human T cell lines and clones derived from these allergen-specific primary human T cells are capable of activation by these peptides in vitro;
• The epitopes are capable of direct peptide binding to human allergen-specific T cells, with measurable binding affinities and binding specificities for one or more MHC class I or class II molecules; and
• The phenotype and function (i.e. effector and/or regulatory [immunosuppressive]) of human allergen-specific T cell subsets activated by these peptides are known.

If the project is proposing to characterize and validate new T-cell epitopes, provide evidence that these epitopes derive from allergens relevant to an allergic disease of high public impact including food allergy, allergic rhinitis and asthma and that epitopes from these allergens are not already well characterized.

Describe the research design, conceptual procedures, and analyses to be used to accomplish the specific aims of the project. Describe any new and novel methodology and its advantage over existing methodologies. Discuss associations with clinical project(s). Discuss the potential difficulties and limitations of the proposed procedures and alternative approaches to achieve the aims. As part of this section, provide a tentative sequence or timetable for the project.

The activities of the Research Project must not overlap with those of a proposed Clinical Core, Data Management and Analysis Core and Scientific Core if applicable.

Clinical trials:

For applications proposing a clinical trial, do not submit a detailed, final clinical protocol; following an award, the final clinical protocol will be developed collaboratively with input from NIAID-Medical Officers or Project Scientist.

The NIH defines a clinical trial as a research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes (https://grants.nih.gov/grants/glossary.htm#ClinicalTrial). Research with human subjects to develop or evaluate clinical laboratory tests (imaging or molecular diagnostic tests) might be considered as a clinical trial if the test will be used for medical decision-making, or if the test itself imposes more than minimal risk for subjects. In the spirit of the above definition, any study that involves interventions aiming at understanding mechanisms of disease (e.g. allergen challenges, experimental exposure of humans to an inflammatory mediator or to a rhinovirus), or any study that involves an intervention for which the FDA will require an IND/IDE application will be considered a clinical trial. The rationale and design of a clinical trial should be presented. The Approach section of a Project that contains a clinical trial should address the following aspects of the trial(s)

• Study Title
• Study objectives (primary and secondary)
• Study population(s)
• Proposed clinical study site(s)
• Intervention and comparators (if any)
• Investigational drugs and/or devices
• Study design:
• Inclusion/exclusion criteria
• Randomization/stratification plan
• Number of subjects
• Anticipated duration of recruitment
• Total study duration and timeline
• Primary endpoints/outcomes
• Secondary endpoints/outcomes
• Study visit schedule and primary evaluations, including laboratory evaluations
• Description of source and quantity of biospecimens to be obtained
• Sample size justification
• Statistical analyses and data analyses plans and management
• Study feasibility:
• Experience and ability of the investigator’s team to prepare an IND/IDE application for this trial, if needed
• Availability of and access to the appropriate type and number of study participants
• Experience and expertise of each proposed clinical trial site in executing the proposed clinical trial and its procedures
• Plans and anticipated problems for subject recruitment and retention, as well as proposed approaches to overcome or minimize such problems
• Study organization: a plan for the management of the clinical trial that includes description of personnel involved in conducting the trial, personnel involved in data entry and management, personnel involved in statistical analysis and personnel involved in safety monitoring; the interactions between these teams should be described.

Clinical studies:
For applications proposing one or more clinical studies (observational studies with no-interventions and involving only minimal risk procedures), planned or ongoing, the rationale and design of the study should be presented. The Approach section of a Project that contains a clinical study should address the following aspects:

• Study title
• Primary hypothesis to be tested
• Study objectives (primary and secondary)
• Study population(s)
• Proposed clinical study sites
• Key design features, including inclusion/exclusion criteria, primary and secondary endpoints, comparison/control groups, study duration and timeline
• Description of source and quantity of biospecimens to be obtained
• Sample size justification and statistical analyses plans
• Study feasibility:
• Availability of and access to the appropriate type and number of study participants
• Experience and expertise of each proposed clinical site in executing the proposed clinical study and its procedures (including the ability to obtain the samples required for the proposed study)
• Plans, anticipated problems, and proposed approaches to overcome or minimize such problems, for subject recruitment and retention (for planned or ongoing studies)

Project obtaining human biospecimens from clinical studies or trials not proposed by this application: For a project that plans to obtain human biospecimens derived from clinical studies or clinical trials that are planned, ongoing or completed and are not funded by this FOA, the information in the Approach section should include the following:

• Study title
• Study objectives (primary and secondary)
• Study population(s) with clear description of clinical phenotypes
• Key design features, including primary and secondary endpoints, comparison/control groups
• Sample size calculations and statistical analyses plans as they pertain to the questions posed by the proposed Project that will utilize the parent study/trial samples
• Study duration and timeline (if a planned or an ongoing study)

Protection of Human Subjects:

Clinical Trials: For all clinical trials (but not for clinical studies) the following additional information is required:

• Listing of all interventional agents (FDA approved or not) and of all procedures to be used in the trial with anticipated adverse experiences and risks
• Plan for independent clinical monitoring of the trial (including site monitoring visit schedule and content)

Clinical Studies: For all clinical studies, the following additional information is required:

• List of all procedures to be used in the study with anticipated risks
• Methods for adverse event identification, recording and reporting (including serious adverse events and unexpected events)
• Individual subject and study stopping rules

Letters of Support: Include documentation of the ability to acquire human biospecimens, including written agreements between the PD(s)/PI(s), the applicant institution, the clinical study/trial sponsor(s), including drug companies, if applicable, and the IND/IDE sponsor (if not one of the above) to be used in the studies proposed by the application.

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.

PHS Inclusion Enrollment Report (Research Project)

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

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

See Part 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) using ASSIST or other electronic submission systems. 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.

For information on how your application will be automatically assembled for review and funding consideration after submission go to: https://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.

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) and component Project Leads 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.

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 (SAM). 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 our Post Submission Application Materials policy.

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 consider each of the review criteria below in the determination of scientific and technical merit, and in providing an overall impact score, but will not give separate scores for the individual items.

• Is the administrative and organizational structure appropriate and adequate to the attainment of the objective(s) of the proposed program? 
• Are the overall program goals significant and focused on studies that meet the overall objectives of the FOA?
• Are there coordination and synergy of the individual research projects and cores towards the achievement of the central objectives of the program?
• Do(es) the PD(s)/PI(s) have the leadership and scientific ability to develop an integrated and focused research program?
• Will the PD(s)/PI(s) and other Project/Core Leaders devote adequate time and effort to the program?  
• For applications with multiple PDs/PIs, is there an adequate and appropriate leadership plan to ensure that there will be sufficient coordination and communication among the PDs/PIs?
• Is there adequate evidence of sufficient institutional support for the PD(s)/PI(s) in terms of laboratory space, equipment and other resources?
• Are the plans for coordination, communications, problem identification and resolution, appropriate?
• How well does each Project fit in the overall goals of the entire application and how much synergism is there among the Research Projects proposed by the application?

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? 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 allergens proposed for study significant to human allergic diseases and not adequately studied?

Does the Project assess an important problem or a critical barrier to progress in the allergen T-cell epitope field?

If the aims of the Project are achieved, how will scientific knowledge in the allergen T-cell epitope field be improved and how likely is it for the findings to become applicable for clinical diagnosis and for therapeutic approaches in allergic diseases?

Investigator(s)

Are the Project Leads, 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-project lead, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Do the Project Leader and the proposed project team propose to commit adequate effort to successfully fulfill the proposed Project’s needs?

Is there adequate scientific, clinical and technical expertise to design, conduct, and monitor clinical trials and interpret the outcomes if applicable? Are the clinical staff and study coordinator(s) sufficiently experienced in the execution of clinical trials of the nature and size proposed, if applicable?

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? 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?

If the Project proposes the conduct of a clinical study or trial, are they well developed? Are the applicant’s plans for managing the proposed study or trial sound and feasible?

Are there sufficient preliminary data to support the proposed research projects?

Are the source and procedures for the collection of clinical samples clearly described and are logistics and feasibility issues adequately addressed? Are the plans and resources for data collection and management adequate for the proposed studies? If the project involves a clinical trial, is the study design, including the selection of the study population, appropriate? Does the study design adequately address the safety of participants to the proposed intervention? Are the timeline for protocol development and implementation, plans for preparation of an Investigational New Drug application, and plans for recruitment and retention of study participants appropriate? Is the phenotypic characterization of the patients/participants sufficiently well-defined to maximize the translational potential of the results?

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?

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for each core 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 core proposed).

Reviewers will consider each of the review criteria below, as appropriate for the individual core, in the determination of scientific merit and provide an overall impact score for each Core, but will not give separate scores for these items.

Administrative Core

• Is the administrative and organizational structure appropriate and adequate to the attainment of the objective(s) of the proposed program?
• Is the management plan for fiscal accountability and communication within the program appropriate?
• Are the plans for coordination, problem identification and resolution, and the establishment of a strong collaborative environment for the program appropriate?
• Are the experience, level of commitment, and availability of the Administrative Core Leader and the administrative staff adequate to manage the program?
• Are plans for communication among the members of the U19 adequate to facilitate collaborative activities?
• Are the administrative plans for the management of projects, including plans for resolving conflicts, appropriate?
• Are the plans for resource allocation within the program adequate and appropriate?

Clinical, Data Management and Analysis, and Scientific Cores

• Does each of the proposed Cores provide services to two or more projects and are the resources and services proposed critical, justified, and related to the central focus of the overall program?
• Are the relevant facilities and services provided, including procedures, techniques, and quality control, appropriate for the needs of the Research Projects?
• Are the qualifications, competence and commitment of the Scientific Core Leader(s) and key personnel appropriate? If applicable, are the scientific methodologies and procedures proposed by each Scientific Core state-of-the art and appropriate for the needs of the Research Projects?
• If applicable, does the Clinical Core Leader have both the expertise/capabilities and demonstrated experience to support the clinical research and/or clinical trial activities proposed in the application? Does the Clinical Core have the capability and expertise to support the development and preparation of documentation required for clinical research and/or clinical trials, as well as experience with regulatory activities (including IND applications), recruitment and retention of study participants, medical monitoring, and safety oversight and reporting?
• If applicable, does the Data Management and Analysis Core Leader have both the expertise/capabilities and the demonstrated experience to support the data management and analysis activities proposed in the application? Are the statistical analysis methods, database resources, data entry and validation resources appropriate to support the studies proposed in the application?

As applicable for the core or 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 .

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 NIAID 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

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

Promoting rapid public access to research center supported data, NIAID expects that all investigators will share their data publicly through ImmPort or other public portals designated by NIAID. The privacy of participants will be safeguarded and confidential and proprietary information will be protected. After award and prior to data collection, data set definitions and schedules for data sharing will be negotiated between each awardee and NIAID, as will plans for other resource sharing. If further schedule changes are needed throughout the funding period, they will be negotiated with NIAID.  Sharing plans represent a commitment by the applicant institution (and its subcontractors, if any) to support and abide by the plan.  The PD(s)/PI(s) will establish procedures within the center to ensure that all members of that center conform to the data-sharing and other resource-sharing plans.  

The PD(s)/PI(s) is/are responsible for ensuring that, in accordance with NIH clinical research policy and the NIAID Clinical Terms of Award, all clinical trials performed with the support of this award are conducted in accordance with the International Conference on Harmonization (ICH) Good Clinical Practices and applicable Federal regulations. The PD(s)/PI(s) will ensure that all individuals involved in clinical research projects provide current GCP certification prior to project initiation.

Protocol Development, Review and Approval

• Protocol Development. After awards are made, PD(s)/PI(s) will fully develop the clinical research protocols for projects supported by this FOA with the participation of the NIAID Division of Allergy, Immunology, and Transplantation (DAIT) staff. Study protocols will utilize the protocol templates provided by NIAID.
• Protocol Review and Approval. The PD(s)/PI(s) will provide all clinical research protocols to NIAID for review and will not implement the protocol until all NIAID approvals are obtained.
• Monitoring Boards. For clinical trials, the PD(s)/PI(s) will cooperate with and will abide by the decisions of the NIAID Data and Safety Monitoring Board (DSMB) or any other monitoring body that the NIAID will assign to the study.

Investigational New Drug Applications (IND)

It is the responsibility of the PD(s)/PI(s) to contact Regulatory Authorities and obtain guidance as to the need for an IND or IDE (Investigational Device Exemptions) for interventions (whether to be used for therapeutic or mechanistic purposes) that are planned to be employed in any clinical study or trial, if these interventions are not approved for the specific indication (including medical condition, age range, dose range) for which they will be used in the research project. In most cases of clinical trials under the FOA where an IND/IDE is required, either an awardee or the organization supplying the investigational agent or device will serve as the IND/IDE sponsor. The sponsor of an IND/IDE is responsible for the development, assembly, and submission of all required regulatory documents, and will provide NIAID all required information following NIH clinical research guidance. This includes but is not limited to all communications with the FDA (or other regulatory authority) and the IRB. In rare cases, NIAID retains the right to become the IND/IDE sponsor. If NIAID is the IND/IDE sponsor, then the NIAID is responsible for the development, assembly, and submission of all required regulatory documents, unless this responsibility is otherwise delegated by the NIAID. If NIAID is the sponsor, the PD(s)/PI(s) is responsible for providing all information to NIAID that is needed for compliance with FDA regulations.

Clinical Trial Monitoring

In all clinical trials and studies, the PD(s)/PI(s) of the Center has the financial and organizational responsibilities for data and safety site monitoring and medical monitoring. These include monitoring compliance with good clinical research practices, regulatory compliance, accurate protocol implementation, internal quality assurance, and test agent accountability at the clinical research sites.  Additional responsibilities to regulatory authorities that arise as a result of the PD(s)/PI(s) or another scientist being the IND/IDE sponsor of clinical trials supported by this FOA also belong to the PD(s)/PI(s) of the Center.

For all clinical trials and some clinical studies (to be identified by NIAID post-award), the PI is responsible for ensuring independent monitoring through a clinical monitoring plan and for obtaining NIAID approval of the plan. This plan should include site monitoring by experienced professionals who are independent from the Center PD(s)/PI(s) or the trial or study investigators.  In addition, in all clinical trials and in some clinical studies (to be identified by NIAID post-award), the PD(s)/PI(s) is responsible for including an Independent Safety Monitor (ISM) in the clinical monitoring plan. The ISM is a licensed physician with clinical research experience, administratively independent from the PD(s)/PI(s) team. The ISM will conduct safety monitoring by reviewing all serious adverse events, protocol deviations, individual and study stopping rules.  In some studies (to be identified by NIAID post-award), the ISM may also be required to conduct pre-study initiation protocol and consent document review, as well as periodic post-initiation safety and data review. 

Safety Reports 

If the PD(s)/PI(s) is the IND/IDE sponsor in any clinical trial supported by this FOA she/he is responsible for submitting complete safety reports to the FDA, per FDA regulations.  The PD(s)/PI(s) will submit these reports to NIAID for review prior to submission to the FDA.  For all clinical trials that are under a DSMB (or any other monitoring body) review, even if no IND/IDE is involved, the PD(s)/PI(s) has the responsibility for preparing and presenting annual safety reports.

Access to Data

The PD(s)/PI(s) is responsible for making data available for external checking against the original source documentation as required by federal regulations.

Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies. However, awardees must be committed to making the biological samples, diagnostic products, and other research tools, methods, data, and materials that they develop under these awards available to the research community. Informed consent/assent forms utilized in these NIAID-supported clinical trials or studies should reflect this commitment.

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

NIAID will assign a Project Scientist to an award. The Project Scientist will provide guidance and support in the design of research activities, will serve as a resource for protocol design and development, will provide scientific/programmatic support during the accomplishment of the research by participating in the design of the activities, will advise in the selection of sources or resources, and will advise in management and technical performance.  In projects that include clinical trials and in, some cases, clinical studies, the NIAID-assigned Project Scientist will be a Medical Officer. The role of the NIAID Project Scientist will be to facilitate and not direct activities. It is anticipated that decisions in all activities will be reached by consensus and that the NIAID Project Scientist will participate in this process.

Clinical Research Oversight

• Protocol Development, Review and Approval 
  NIAID staff will participate with the PD(s)/PI(s) in the development, review, and approval (as mentioned above) of all clinical trial and some non-trial, clinical study protocols for projects supported by this FOA. All clinical research protocols will be reviewed by NIAID and, depending on their level of complexity and risk, will be further reviewed by the NIAID DAIT Clinical Research Committee and by the NIAID DAIT Data and Safety Monitoring Board (DSMB) or another monitoring body. Prior to initiation, all clinical research protocols must be approved by an assigned NIAID Medical Officer.
• IND/IDE 
  For clinical trials under this FOA where NIAID is not the IND/IDE sponsor, NIAID will provide guidance on the development and submission of all required regulatory documents, e.g., those regarding the use of investigational drugs, to the FDA or other applicable health authorities. NIAID retains the right to have NIAID serve as the IND/IDE sponsor.
• Clinical Trial Monitoring 
  If NIAID holds the IND/IDE for a clinical trial supported by this FOA, NIAID will be responsible for monitoring compliance with good clinical research practices, regulatory compliance, accurate protocol implementation, internal quality assurance, and test agent accountability at the clinical research sites. In studies where NIAID does not serve as the IND/IDE sponsor, NIAID will review and approve the clinical monitoring plan, review the recruitment status of the trial on an ongoing basis, review the results of clinical trials, and provide oversight of data and safety monitoring.
• Safety Reports 
  NIAID will convene an independent NIAID Data and Safety Monitoring Board (DSMB) or another monitoring body to review and monitor any protocols deemed to possess more than minimal risks.

If NIAID holds the IND/IDE for clinical trials supported by this FOA, NIAID will be responsible for reporting safety information in accordance with FDA requirements. An NIAID Medical Officer or NIAID designated contractor will monitor the clinical trials and serve as the Medical Monitor.

• Study Termination
  NIAID reserves the right to terminate or curtail a clinical study for any of the following reasons:
• risk to subject safety;
• the scientific question is no longer relevant or the objectives will not be met;
• failure to comply with Good Clinical Practices, federal regulations, or Terms and Conditions of Award;
• occurrence of unforeseen drug safety issues or data from preclinical studies indicate a presence of unanticipated toxicity;
• risks that cannot be adequately quantified;
• failure to remedy deficiencies identified through site monitoring;
• substandard data;
• inadequate progress in fulfilling the research agenda;
• slow accrual; or
• reaching a major study endpoint substantially before schedule with persuasive statistical significance.
• Access to Data 
  The NIAID Project Scientist or designees will have access to all data generated under this cooperative agreement, and may review the data as recorded on the case report forms or in a database. Data must be available for external checking against the original source documentation. NIAID staff may use information obtained from the data for the preparation of internal reports on the activities of the study.

The Program Official will negotiate data deposition timelines with each awardees post award, and facilitate data deposition to either ImmPort or to another NIAID resource.

• Performance Monitoring 
  The NIH Project Scientist will review the performance of each participating awardee through consideration of annual reports, site visits, and compliance with NIH procedures.

Scientific and Programmatic Oversight

An NIAID Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. This stewardship includes monitoring program progress, approving changes and concurring in proceeding into study implementation stage. Release of each yearly funding increment for any/all U19s will be based on a review of progress.

Areas of Joint Responsibility include:

None; all responsibilities are divided between awardees and NIH staff as described above.

Dispute Resolution:
Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. The members will include a designee of the award recipient, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: https://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 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: 301-945-7573

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

B. Duane Price, PhD
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-5074
Email: pricebd@niaid.nih.gov

Jorge E. Machuca
National Institute of Allergy and Infection Disease (NIAID)
Telephone: 240-669-2981
Email: Jorge.Machuca@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.