Part 1. Overview Information

Key Dates

All applications are due by 5:00 PM local time of applicant organization.

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from NIH Guide for Grants and Contracts).

Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Background

Food allergy includes several immune-mediated conditions that have become serious health problems in the United States and other countries. Over the past 3 decades, the prevalence of food allergy in children has increased substantially.

IgE-mediated food allergy is associated with severe and sometimes life-threatening allergic reactions. Among certain cohorts of highly allergic children, accidental exposure results in approximately one reaction per person per year, and 11% of such reactions are severe. It is impossible to predict which individuals are at risk of severe reactions, and the gold-standard of diagnosis is to challenge the individual and observe a reaction. There is only one FDA-approved therapy for IgE-mediated food allergy, which is limited to peanut and designed only to make children "bite-safe" to accidental exposures; avoidance of food allergens and treatment of food allergy-induced systemic reactions with epinephrine remain the standard of care.

To address the concerns about the increasing incidence of food allergy and paucity of treatment options, NIAID established the Consortium for Food Allergy Research (CoFAR) in 2005. During three consecutive funding periods, CoFAR has conducted clinical trials and observational studies testing various forms of food allergen immunotherapy and examining the natural history of food allergy in children. CoFAR and other research groups have demonstrated that oral food allergen immunotherapy has promise as an approach that can allow most children with IgE-mediated food allergy to become desensitized and tolerate substantial amounts of the food to which they are allergic.

However, oral immunotherapy has limitations: it can cause allergic reactions, some patients are not able to tolerate it, and not all patients that are able to tolerate therapy achieve the ability to ingest an appreciable amount of the food allergen in question. Furthermore, there is a small risk for developing Eosinophilic Esophagitis (EoE) while on oral immunotherapy, and many patients are unable to stop therapy without rapidly regaining their food reactivity. Studies are needed to address these challenges and to optimize and test various immunotherapeutic approaches in food allergy. Importantly, determining optimal timing (best age to initiate treatment, duration of treatment) and optimal dosing of food allergen immunotherapy require careful evaluations. In addition, the immunologic changes that are necessary for a food-allergic patient to acquire durable food tolerance need exploration so that tolerance-focused therapies can be developed. Management of food allergy may benefit from the emergence of multiple immunomodulatory agents that target various aspects of Type 2 immunity. Some of these agents, including adjuvants, could theoretically be combined with allergen immunotherapy to induce therapeutic, antigen-specific immune regulation, deviation, or deletion of effector cells.

The LEAP study, conducted by the NIAID-funded Immune Tolerance Network, successfully established the concept of prevention of IgE-mediated peanut allergy by early dietary introduction in infancy. Since then, various studies have suggested that other IgE-mediated food allergies could be similarly prevented. Many questions remain as to the optimal age, dose, and frequency for early dietary introduction of allergenic foods. Also, additional concepts on the prevention of IgE-mediated food allergy have emerged that require more definitive testing. For example, does allergenic food consumption during pregnancy or lactation have preventive effects? What is the role of the intestinal microbiome in early infancy, how is it influenced by the mother's microbiome, and can alterations of early life gut microbiome improve immunologic tolerance and reduce food allergy? Other factors, potentially acting through epigenetic or other indirect mechanisms need to be explored.

The oral food challenge remains the gold standard in the diagnosis of IgE-mediated food allergy. This procedure is time-consuming and has risks; therefore, it cannot be conducted in large scale. This diminishes accuracy in the epidemiology and clinical diagnosis of food allergy. Results obtained from in vitro testing, particularly with component diagnostics and newer allergenic epitope methodologies, have yielded promising results and need to be rigorously tested in diverse populations alone or in combination with carefully developed questionnaires in order to create diagnostic algorithms of high positive and negative predictive values.

The spectrum of food-induced allergic conditions is wider than IgE-mediated food allergy and continues to expand. EoE was first reported in 1978 and only recognized as a distinct clinical entity in 1993. At first thought to be a rare disease, the current estimate is that it affects up to 1 in 1,000 people in the US and is the most common cause of food impaction. Food protein-induced enterocolitis syndrome (FPIES) also was first described in the 1970s and is a disease that causes acute and repetitive vomiting, sometimes accompanied by diarrhea, that can be severe enough to cause hypovolemic shock. Alpha-Gal Syndrome (AGS) was only recognized in 2008. It produces reactions that occur after ingesting mammalian meats but are delayed for several hours after exposure. Although, in recent years, significant knowledge has been acquired and therapeutic advances in EoE have been made, the fundamental pathophysiology of this condition remains unknown and additional therapeutic approaches need to be developed. The mechanism(s) of FPIES also are unknown, accurate identification of the offending food(s) and follow-up to assess resolution require oral food challenges with the above-described limitation of these procedures, and no specific therapeutics or therapeutic strategies are available. Similarly, although the culprit for AGS is probably allergic sensitization to galactose-?-1,3-galactose, the mechanism of allergic sensitization (currently assumed to be linked to tick bites) requires further examination, the reason why reactions are delayed are unclear, and therapies are not available.

Objectives and Scope

CoFAR is a clinical network consisting of two distinct entities, the CoFAR Leadership Center (LC) and the CoFAR Clinical Research Centers (CRCs). The two entities will work collaboratively to conduct network-wide, ground-breaking clinical research projects in the areas of prevention, therapy, and understanding of the mechanisms of food allergy. The CoFAR-LC will provide leadership, overall strategy, and support for the network-wide clinical research projects. The CoFAR-CRCs will execute all network-wide clinical research projects.

It is expected that CoFAR will conduct at least two network-wide clinical research projects. At least one of these projects will be a therapeutic or preventive clinical trial. Both the CoFAR-LC and the CoFAR-CRCs will propose network-wide clinical research projects. Once CoFAR is formed, these proposals will be considered by the CoFAR Steering Committee and those to be executed will be chosen by the CoFAR-LC PD(s)/PI(s). The network-wide clinical research projects that the CoFAR will conduct will require approval by NIAID, which will consider programmatic priorities in its decision.

Each CoFAR-CRC will propose one network-wide clinical trial or observational study. In addition, each CoFAR-CRC will conduct one or two center-specific research projects.

The scope of the network-wide, multi-center clinical trial or observational study the CoFAR-CRC will propose includes but is not limited to:

• Therapeutic or preventive trials of
  
  
  • Early allergenic food introduction for the prevention of IgE-mediated food allergy
  • Direct or indirect manipulation of the microbiome
  • Food allergen immunotherapy
  • Drugs, biologics, adjuvants, or devices for the management of food allergy conditions
  • Combinations of the above
    
    
• Studies to improve the diagnosis of food allergy aiming at replacing oral food challenges
• Studies to accurately assess the incidence and prevalence of food allergy conditions in diverse populations, in the US
• Studies examining the interactions between immunologic, microbial, environmental, and genetic or epigenetic factors underlying the development of food allergy conditions
• Studies of molecular mechanisms associated with the development and clinical presentation of food allergy conditions or response to therapy (targeted and/or unbiased approaches)
• Studies on the mechanisms underlying severe allergic reactions

The center-specific research projects the CoFAR-CRCs will conduct can be a non-therapeutic observational study, a clinical mechanistic study, or a laboratory study utilizing new or existing human biosamples. The center-specific project should involve junior faculty investigators in key roles whenever possible. Clinical trials per the NIH definition (https://grants.nih.gov/policy/clinical-trials/definition.htm) are not allowed to be proposed for center-specific research projects. One of the goals of the center-specific research projects is to provide pilot data to inform potential larger, future CoFAR network-wide projects and to assess various aspects of the presentation of food allergy in diverse populations.

The scope of center-specific research projects includes, but is not limited to:

• Small scale investigations of mechanisms related to response to oral food challenges
• Development of biomarkers for the diagnosis of a particular food allergy condition or for predicting severity of food reactions
• Analysis of samples obtained prospectively from protocols funded by other sources or clinical samples obtained under IRB approval
• Analysis of existing data sets or samples available to the site
• Electronic Health Record research on food allergy conditions
• Development of a new laboratory methodology with direct clinical implications
• Qualitative assessments to investigate practices/ perceptions/ behaviors as they pertain to various food allergy conditions

Applicants may submit to both the CoFAR Leadership Center (RFA-AI-22-077) and the CoFAR Clinical Research Centers. However, an applicant must propose different network-wide clinical trials in each of the two applications.

Applications that propose the following topics will be considered non-responsive and will not be reviewed

• Research conducted in animals or animal cells (including humanized mice)
• Center-specific projects involving more than one clinical site
• Center-specific clinical trials
• Research on immunologic or non-immunologic food-related diseases other than IgE-mediated food allergy, FPIES, AGS, or EoE, such as celiac disease, irritable bowel syndrome, or food intolerances
• Research on HIV/AIDS

Note: Foreign Components may only provide services in support of clinical study or clinical trial activities (e.g., conduct of laboratory assays). Foreign Components must not conduct clinical trials or clinical studies.

Resources provided by NIAID to the CoFAR Clinical Research Network

The following resources will be provided by NIAID to the CoFAR for network-wide projects:

NIAID-DAIT funds resources (Centers) that provide a broad range of clinical research services including support for the design and organization of clinical study protocols, data management, biosample repository and management, clinical site monitoring, safety monitoring and reporting, data analysis and manuscript development.

The following Centers will be supporting CoFAR:

• NIAID Clinical Data and Safety Management Center (CDSMC)
• Allergy and Asthma Statistical and Clinical Coordinating Center (AA-SCCC)
• NIAID Clinical Site Monitoring Center (CSMC)

Study Drug Distribution Center: NIAID-DAIT funds a study drug distribution center which will store, label, and distribute study drug used for some or all network-wide CoFAR trials.

Clinical Trial Sponsorship: NIAID will be the Sponsor for all network-wide clinical trials.

NIAID-appointed Asthma and Allergy Data and Safety Monitoring Board (DSMB): All CoFAR network-wide clinical trials will be reviewed by the DSMB provided by NIAID. After study initiation, the DSMB will conduct periodic safety reviews.

Public Access to CoFAR Network-Wide Data: All network-wide clinical trial, clinical study, biomarker, and mechanistic data produced by the CoFAR will be made publicly available by NIAID through the CDSMC and the AA-SCCC either via ImmPort or another NIAID-approved resource.

The services outlined above will NOT be provided for center-specific projects. For center-specific projects, the AA-SCCC will validate the biostatistical work conducted by the CoFAR-CRC prior to final manuscript submission.

CoFAR Committees

• The CoFAR Steering Committee will be the forum for CoFAR to discuss network-wide studies and to advise the CoFAR-LC PD(s)/PI(s) on scientific and organizational aspects of the network's activities. The Steering Committee also will receive information and discuss the progress of individual CoFAR-CRC center-specific research projects, but it will not be involved in the development or implementation of these projects.
• The CoFAR Protocol Working Group(s): Responsible for development, review, and management of the progress of CoFAR network-wide projects including both clinical trials and studies.
• The CoFAR Publications Committee: Responsible for reviewing manuscript proposals, abstracts, posters, and final manuscripts.

Structure and Requirements of the CoFAR Clinical Research Centers

The CoFAR-CRCs will conduct network-wide and center-specific projects. To accomplish this goal, each CoFAR-CRC should have the ability to support Clinical Research Functions and propose Research Projects as follows:

• Clinical Research Functions: Each CoFAR-CRC must be able to ensure that there are personnel and facilities capable of conducting network-wide and CoFAR-CRC center-specific projects, including trained clinical staff, capabilities of recruiting participants with a variety of food allergic conditions, clinical research facilities, investigational pharmacy services, and laboratory facilities capable of processing, storing, and shipping human biosamples. For center-specific research, additional requirements include local biostatistical support, a conditionally IRB-approved protocol that can be activated immediately upon award, a data management facility with established data management, quality assurance and control plans, and capability to upload data into the NIAID designated repositories.
• CRC-specific Research Projects: Each CRC application will propose 1) a single network-wide clinical trial or observational study and 2) 1 or 2 center-specific clinical research project(s).

CoFAR network-wide protocol funds:

The CoFAR-CRC award will provide funds for 12 person-months of clinical coordinator time and 1 month of PI time that will specifically support some of the work that will be required for the CRC to conduct CoFAR network-wide projects and to participate in other network-wide activities. Additional protocol-specific funds will be disbursed by the CoFAR-LC to CoFAR-CRCs participating in a network-wide project. The magnitude of funds will depend on the specifics of the project.

Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs.

For more information see the NIAID Research Funding site "Questions and Answers for RFA-AI-22-076" found at the following: FAQs link

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

Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs.

Section II. Award Information

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.

Section III. Eligibility Information

1. Eligible Applicants

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)

Local 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)

Federal Government

• 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

Foreign Components may only provide services in support of clinical study or clinical trial activities (e.g., conduct of laboratory assays). Foreign Components must not conduct clinical trials or clinical studies.

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not 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.

• System for Award Management (SAM) 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.
  • Unique Entity Identifier (UEI)- A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registration; all registrations must be in place by time of submission. 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 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 diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per 2.3.7.4 Submission of Resubmission Application. 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 2.3.9.4 Similar, Essentially Identical, or Identical Applications)

Applicants may submit to both the CoFAR-LC and CoFAR-CRC funding opportunities. However, different clinical research projects must be proposed in each of the two applications.

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Letter of Intent

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:

Poonam Tewary, Ph.D.
Telephone: 301-761-7219
Email: [email protected]

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

For this specific FOA, the Research Strategy section is limited to 30 pages.

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages.

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

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

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

Facilities & Other Resources:

• Clinical Sites: Describe the clinical research facilities available to conduct single-center and multi-site clinical trials and clinical studies under the CoFAR umbrella.
• Laboratory Facilities: Describe the laboratory facilities capable of processing, storing, and shipping human biosamples including peripheral blood, stool samples, and microbial samples.
• Pharmacy: Describe the investigational pharmacy services available and their capabilities to store, mask, dispense, and maintain product accountability in multi-site clinical trials.
• Data Management: Describe the data management facility and the statistical services available to conduct center-specific clinical research projects including the capacity to carry out data management and quality control with reference to Federal regulations and ICH E6 (R2) guidelines.

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

• The PD(s)/PI(s) and key personnel should include in their biosketches their experience in conducting large single-center and multi-site clinical trials and clinical studies.
• The bio sketches should also include cGCP training status, and experience in preparing IND/IDE applications and, if applicable, reference relevant recent clinical studies conducted, highlighting recruitment target and recruitment and retention success.

R&R or Modular Budget

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

Include funds with justification for the following:

• For single PD/PI applications, the PD/PI must commit 1 person-month for CoFAR network-wide projects in addition to a minimum of 1 person-month for CoFAR-CRC site-specific projects. For multi-PD(s)/PI(s) applications, one of the PD(s)/PI(s) must commit 1 person-month for CoFAR network-wide projects, in addition to a minimum of 1 person-month for CoFAR-CRC site-specific projects.
• Include costs for at least 12 person-months of clinical coordinator effort for the CoFAR network-wide projects.
• Include funds for travel and other expenses for CoFAR-CRC Senior/Key Personnel to attend two (2) one and a half (1.5) day CoFAR Steering Committee meetings per year in the Rockville, Maryland area.
• For the CoFAR-CRC center-specific research project(s), include the costs for the proposed center-specific project(s), including all support for additional personnel, materials and equipment, participant recruitment, retention and compensation, statistical design, data collection, analysis and management, data deposition into ImmPort or other public portals designated by NIAID, as well as costs for project management, adverse event collection, safety reporting, and quality assurance as applicable.
• Do not include costs for the CoFAR network-wide project proposed in this application. Other than the personnel costs specified above (12 person months for clinical coordinator and 1 person month for a PD(s)/PI(s)), protocol funds for all the CoFAR network-wide projects will be disbursed by the CoFAR-LC to the CoFAR-CRCs participating in each network-wide clinical research project and will not be determined until after all CoFAR awards are issued and the projects to be undertaken are determined.

R&R Subaward Budget

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

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

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

Specific Aims: List the Specific Aims of the application.

Research Strategy:

The Research Strategy must include 3 clearly marked Subsections: A) CRC-Clinical Research Functions, B) Network-wide Clinical Research Project, and C) CRC-Specific Research Project(s).

Subsection A: CRC-Clinical Research Functions

• Discuss the capacity and readiness of the CoFAR-CRC to conduct center-specific and network-wide CoFAR clinical research projects under the direction of the CoFAR-LC, including the processes and flexibilities in place to expeditiously expand efforts, including staffing, to accommodate the needs of network-wide CoFAR clinical research projects.
• Describe the structure and range of services available at the site to support CoFAR studies.
• Discuss previous experience and any unique characteristics that the CoFAR-CRC will contribute to the CoFAR network.
• Describe recruitment capabilities and approaches for participants for CoFAR network-wide and center-specific research studies. Indicate the number of relevant patients seen per year in clinics within the applicant's institution. Include unique site characteristics and recruitment capabilities for both pediatric and adult patients.
• Describe the plans, process, and communication strategies required to work with a single IRB (in this case whichever IRB is chosen by the CoFAR-LC) in a multi-center study and any additional oversight or coordination that may be required by the CRC’s local IRB.
• Describe the professional development in clinical research that the staff of the CRC will be receiving and how this ensures in-depth knowledge of GCP, Federal regulatory requirements, and ICH guidelines.
• Demonstrate staff experience in the field of food allergy and in performing collaborative multi-center clinical trials.

Subsection B: Network-wide Clinical Research Project

Describe one cutting edge multi-center clinical research project (trial or study) in food allergy, considering the objectives and scope of CoFAR. Discuss the clinical and biological significance of the proposed project for the field of food allergy. Include preliminary and supporting data as appropriate.

For the proposed clinical research project:

• Discuss the rationale for the proposed project, the significance of the problem being studied, and the potential impact of the proposed work. For a clinical trial, indicate how the trial will improve the clinical outcome of patients with a specific food allergy condition.
• Describe earlier studies that led to the proposed project and provide information or data from preliminary studies that support the need for the project and its feasibility.
• Outline the hypothesis, objectives, and how the proposed outcomes will address the hypothesis.
• Concisely describe the design of the proposed project and include the process for the selection of the participant population, duration, and schedule of events.
• Discuss each project's feasibility, difficulties that may be encountered, and offer alternative approaches to be implemented, if needed. Provide information on any competing clinical research projects underway in the community, conducted either by the PD/PI(s) or other investigators, and their potential influence on recruitment. Discuss any investigational agents with similar mechanism of action currently under development and their potential influence on the proposed clinical trial.
• Include general concepts for sample size determinations and statistical methodologies but, particularly for clinical trials, provide study-specific details in the PHS Human Subjects and Clinical Trial Information Forms. Note: Specific details for trials and studies will be captured using the PHS Human Subjects and Clinical Trials Information Form. Do not duplicate information requested under the PHS Human Subjects and Clinical Trials Information.
• For clinical trials provide milestones.
• For all mechanistic work (required) describe the scientific question(s) (whether hypothesis-generating or hypothesis-driven research), rationale, biosample selection, assay selection, methodology, and analytic approach. Discuss the feasibility of the work proposed, difficulties that may be encountered, and offer alternative approaches that will be implemented, if needed.
• If a clinical research project incorporates standard biomarker assays, include a concise description of the assays that will be used, including a justification for choosing these assays.
• For multi-visit clinical research projects that are not clinical trials, provide a description of the study design including the procedures and activities that can occur at each visit (schedule of events).

Subsection C: CRC-Specific Research Projects

To improve clarity, applicants are encouraged to organize this subsection using headings to distinguish between different research projects if more than one is proposed.

• Propose a maximum of 2 CoFAR-CRC-specific research projects that are feasible within the constraints of available resources, budget, and period of the award. These projects cannot be clinical trials. Observational studies may be proposed to address clinically important questions or for mechanistic research. Studies using human specimens obtained from relevant ongoing or completed clinical studies or clinical trials (therapeutic or preventive trials included) also may be proposed for mechanistic research. For each proposed project, describe the background and earlier relevant studies and provide the rationale and pertinent information and/or data from preliminary studies that address the need for the project. Outline the hypothesis, objective, and how the proposed outcomes will adequately address the hypothesis. Concisely describe the design of the proposed center-specific project and include the rationale and process for the selection of the participant population (including eligibility criteria and appropriate controls) and schedule of events if relevant. Discuss the project's feasibility, limitations, difficulties that may be encountered, and offer alternative approaches to be implemented, if needed. Include sample size determinations and statistical methodologies.
• Emphasize the impact of the project on a specific food allergy condition, the innovative elements included in the proposed project(s), both in terms of novel hypotheses, as well as in terms of novel study designs.
• Provide a management and staffing plan for the CoFAR-CRC-specific project(s) that includes description of personnel involved in conducting the research, personnel involved in data entry and management and, if applicable, personnel involved in processing and handling of biosamples.
• Describe the biostatistical and monitoring support available for CoFAR center-specific projects.
• Discuss planned laboratory methodologies and provide evidence to demonstrate proof-of-principle, robustness, and/or support feasibility of the planned methodologies.
• For proposed mechanistic studies associated with a CoFAR-CRC-specific clinical research project, describe the rationale, biosample selection, assay selection, methodology and analytic approach.
• Describe the plan to involve junior faculty if applicable.

Letter of Support: Provide a letter of commitment from manufacturers if investigational drug(s) or device(s) are to be provided at no cost. Provide letter(s) of commitment from the principal investigator(s) of any study that will provide samples from a previously conducted or ongoing clinical trial or study.

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.

The following modifications also apply:

• The recipient is expected to make the biological samples, diagnostic products, and other research tools, methods, and materials that they develop under the CoFAR award, available to the research community per policies established by the CoFAR-Steering Committee. Therefore, the Resource Sharing Plan should include a summary of how this will be achieved.

Other Plan(s):

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages.

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

• All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.
• Investigators are expected to share their CoFAR-supported data publicly through ImmPort or other public portals designated by NIAID. Therefore, the Data Management and Sharing Plan should include a summary of how the applicant will manage data submission and interactions with ImmPort, or other NIH-approved public portal.

Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

• No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Although applicants must be prepared for clinical trials, definite plans for such involvement will not be possible at time of application. A Study Record should not be completed.

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Note: Applicants proposing no clinical trials must enter at least one delayed onset study record and check the box "Anticipated Clinical Trial?".

Justification Attachment

All delayed onset studies must provide a justification explaining why information on network-wide clinical research projects will not be available at the time of application. This is because they will need to be considered by the CoFAR Steering Committee, chosen by the CoFAR-LC PD(s)/PI(s) and approved by NIAID.

Section 2- Study Population Characteristics

2.5 Recruitment and retention Plan

• Describe and discuss approaches to improve incorporation of difficult-to-enroll groups such as minorities and infants.

2.7 Study Timeline

Provide a table or graphic representation of a timeline of the proposed center-specific clinical research projects.

Section 3- Protection and Monitoring Plans

3.1 Protection of Human Subjects

3.1.1 Risks to Human Subjects

3.1.1.b Study Procedures, Materials and Potential Risks

For all research projects provide the following information:

• Describe the types of biosamples to be collected and the handling of the biosamples at the collection sites (collection, processing, storage, transportation, and quality control measures to assess and ensure sample integrity); list the research laboratories to be used and describe the selection rationale and the qualifications; describe the methodology(ies) to be used for each proposed assay/test and provide evidence of assay feasibility.
• Describe the source and quantity of samples to be obtained, and potential safety and ethical issues involved in obtaining such samples (for example, blood drawing volume limitations); the availability of the biological samples to be studied; how biological samples will be collected, transported, processed, stored, and distributed and what quality control measures will be used to ensure sample integrity.

For applications proposing to use samples from ongoing or completed clinical research, provide a timeline for the request, transportation and arrival of the biological samples, and the timeline associated with the preparation and use of the biological samples.

3.3 Data and Safety Monitoring Plan

A data and safety monitoring plan will be developed for every study in collaboration with DAIT-NIAID.

3.4 Will a Data and Safety Monitoring Board be appointed for this study?

The DAIT Allergy and Asthma DSMB will be the DSMB for monitoring all clinical research projects that the site will conduct that require monitoring.

Section 4- Protocol synopsis

4.1. Study Design

4.1.a. Detailed Description

For multi-visit studies, provide a description of the study design including the procedures and activities that occur at each visit (schedule of events).

Section 5.1- Other Clinical Trial-related Attachments

Describe the plan to obtain required investigational agents.

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

3. Unique Entity Identifier and System for Award Management (SAM)

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

5. Intergovernmental Review (E.O. 12372)

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.

• Awards issued under this FOA will be incrementally funded awards for project periods of up to seven years.
• Grants awarded under this FOA will be excluded from automatic carryover. All carryovers will require prior approval.
• Grants awarded under this FOA will not be provided with no-cost extension authority of the NIH Standard Terms and Conditions of Award. No extensions will be allowed.
• Progress and financial reporting will be required and reviewed annually.
• All funds must be expended within the approved project period.

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

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

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

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

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

See more tips for avoiding common errors.

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

Applicants are required to follow the instructions for post-submission materials, as described in the policy

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) will not be evaluated at time of review.

For this particular announcement, note the following:

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

Overall Impact

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed). While each application will be evaluated in its entirety based on one overall impact score per application, the CoFAR Clinical Research Projects within each application will also each receive a separate impact score.

Scored Review Criteria

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

Significance

Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? 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 scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

Specific for this FOA

CRC-Clinical Research Functions

• Does the application provide overall convincing evidence that the proposed CoFAR-CRC will be a valuable component of the CoFAR by providing an appropriate clinical research site for the conduct of the CoFAR network-wide clinical trials and studies and through its own proposed center-specific studies?

Investigator(s)

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

With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

Specific for this FOA

CRC Clinical Research Functions

• Do the PD(s)/PI(s) have documented experience of working collaboratively in multi-center clinical trials and/or studies? Do the PD(s)/PI(s) have experience conducting clinical research that involves participants with food allergy? Do the PI and other key personnel devote sufficient effort to the described projects?

CRC-Specific Research Projects

• Are junior faculty members included in key roles in the proposed research projects?

Innovation

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

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed 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 individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Does the application adequately address the following, if applicable

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

Specific for this FOA

CRC Clinical Research Functions

• Do the staff have appropriate and adequate qualifications, training, and expertise in the field of food allergy research?
• Does the application present adequate plans for professional development for CoFAR-CRC investigators and staff in accordance with Federal regulatory requirements, Good Clinical Practice (GCP) guidelines and International Conference on Harmonization (ICH) standards?
• Does the application describe a cohesive structure and range of services to support food allergy clinical research projects under the CoFAR?
• Does the application indicate capacity and readiness to conduct CoFAR network-wide clinical research projects in an expeditious manner?
• Does the proposed CRC offer unique characteristics that will contribute to the CoFAR, such as unique recruitment capabilities and approaches for pediatric and adult patients?
• Is the number of patients with food allergy seen per year in clinics within the applicant's institution adequate to support the CRC's role in conducting the CoFAR network-wide and the center-specific projects?
• Does the application offer satisfactory approaches to recruitment of difficult-to-enroll groups, such as minorities and infants?
• Does the application demonstrate the CRC's ability to work with a single CoFAR-LC IRB and any additional oversight that may be required by the CRC's local IRB?

Network-wide Clinical Research Project

For clinical studies that are not a clinical trial:

• Study Design
  

• Is the design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative, and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Are the study populations (size, gender, age, demographic group) and duration appropriate and well justified? Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available?
• Is the project appropriately designed to conduct the research efficiently? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible? Does the application propose to use existing available resources, as applicable?
• Are milestones described appropriately?
  

• Data Management and Statistical Analysis
  

• Are planned analyses and statistical approach appropriate for the proposed study design? Can the project be completed and analyzed within the period of award?

CRC-Specific Research Projects

• Are the center-specific research project plans realistic and capable of completion within the period of the award?
• Is each of the proposed center-specific projects adequately justified and supported by preliminary data and/or previously published research?
• Is the experimental design of each center-specific project appropriate in terms of outcomes, study population and eligibility criteria, study arms (appropriate controls), study visit schedule and primary evaluations, study duration and study timeline?
• For proposed center-specific mechanistic studies, has a clear rationale justifying the need for each study been presented and has adequate evidence been provided demonstrating the robustness and feasibility of proposed laboratory tests/capabilities?
• Does each center-specific project include an appropriate management plan describing the personnel involved in conducting the research, data entry and management, processing and handling of biosamples?
• Do descriptions of mechanistic studies adequately describe and justify the rationale, biosample and assay selection, methodology and analytic approaches?
• For proposed biosamples in each center-specific project, is there a description of the source and quantity to be obtained, and have potential safety and ethical issues in obtaining such samples (for example, blood drawing volume limitations) been addressed?
• Are described biostatistical and monitoring support capabilities adequate?

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?

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

Specific for this FOA

CRC-Specific Research Projects

Does the application include acceptable evidence for the capabilities of the research laboratories to be used in center-specific projects?

Additional Review Criteria

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Study Timeline

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

Protections for Human Subjects

For research that involves human subjects but does not involve one of the 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 categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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 individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following 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 Animals Section.

Biohazards

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

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

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

Applications from Foreign Organizations

Not Applicable.

Select Agent Research

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

Resource Sharing Plans

Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) will not be evaluated at time of review.

Reviewers will comment on whether the Resource Sharing Plan(s) (i.e., Sharing Model Organisms) or the rationale for not sharing the resources, is reasonable.

Authentication of Key Biological and/or Chemical Resources:

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.

Budget and Period of Support

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

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by National Institute of Allergy and Infectious Diseases, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications will receive a written critique.

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.

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.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. 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.

Section VI. Award Administration Information

1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the recipient's business official.

Recipients 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.

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain applicable clinical trials on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:

• Federalwide Research Terms and Conditions
• Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
• Acknowledgment of Federal Funding

If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex (including gender identity, sexual orientation, and pregnancy). This includes ensuring programs are accessible to persons with limited English proficiency and persons with disabilities. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html

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.

• Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov.
• For information on an institution’s specific legal obligations for serving qualified individuals with disabilities, including reasonable accommodations and making services accessible to them, see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html.
• HHS funded health and education programs must be administered in an environment free of sexual harassment, see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.
• For guidance on administering programs in compliance with applicable federal conscience protection and associated anti-discrimination laws see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.

Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 and 2 CFR Part 200.206 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

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 2 CFR Part 200, 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 recipients 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 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 recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and the NIH as defined below.

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

• Implementing and managing the CoFAR network-wide clinical research projects assigned to the CoFAR-CRC by the CoFAR-LC.
• Participating in the CoFAR Steering Committee meetings and teleconferences and in its subcommittees, as applicable.
• Implementing CoFAR policies and procedures, as established by the CoFAR Steering Committee and the CoFAR-LC.
• Executing and coordinating the scientific activities of the CoFAR-CRC center-specific projects; setting project goals and timelines.
• Reporting progress, presenting data and discussing obstacles related to the CoFAR-CRC center-specific projects with the CoFAR Steering Committee.

Data Sharing Responsibilities

• Recipients are expected to make the biological samples, diagnostic products, and other research tools, methods, data, and materials that they develop under CoFAR-CRC award available to the research community, per policies established by the CoFAR-Steering Committee and consistent with achieving the goals of the program. Informed consent/assent forms utilized in CoFAR-CRC supported clinical trials or studies should reflect this commitment.
• To promote rapid public access to CoFAR-supported data, all CoFAR-CRC investigators are expected to share their CoFAR-supported 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. The PD(s)/PI(s) are responsible for developing data sharing plans to be presented to the NIAID Program Official assigned to the grant for approval. Sharing plans represent a commitment by the recipient to support and abide by the plan. The PD(s)/PI(s) will establish procedures to ensure that all members of CoFAR-CRC and associated scientists conform to the data-sharing plan.
• PD(s)/PI(s) 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 DHHS, PHS, and NIH policies.

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

• NIAID Project Scientists will provide guidance and support in the design and implementation of research activities including protocol design and development, study implementation, will advise in the selection of sources or resources, and in management and technical performance. In CoFAR-LC network-wide clinical research projects that include clinical trials and, in some cases, clinical studies, an NIAID-assigned Project Scientist will also have Medical Monitor responsibilities.
• An NIAID Program Official will be responsible for the normal programmatic stewardship of the award and will be named in the award notice.
• Protocol Review and Approval: 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.
• IND/IDE: NIAID will serve as the IND/IDE sponsor for all CoFAR network-wide clinical trials requiring an IND/IDE. As part of NIAID’s IND/IDE sponsor responsibilities, the NIAID Medical Monitor will obtain regular reports on adverse events and protocol deviations from the NIAID-DAIT data management center(s) or the CoFAR-CRC and will review all serious adverse events. NIAID will be responsible for reporting safety information in accordance with FDA requirements. Also, NIAID, in cooperation with the CDSMC and the AA-SCCC, will prepare and submit the final study reports to the FDA. This role may be delegated by NIAID to another entity (e.g., a collaborating pharmaceutical company).
• Clinical Trial Monitoring: NIAID will monitor compliance with good clinical practices, regulatory compliance, accurate protocol implementation, internal quality assurance, and test agent accountability at the CoFAR-CRCs. At NIAID’s discretion, the NIAID Medical Monitor may request that the DSMB convenes ad hoc to review a serious adverse event or a cluster of adverse events or serious adverse events. The NIAID Medical Monitor may request that the CDSMC conduct for-cause monitoring visits to a CoFAR-CRC. Depending on the nature of the problem, such visits may be conducted by the NIAID Medical Monitor and/or NIAID staff. The PD/PI of the CoFAR-LC may be asked to participate in those visits.
• Study Termination: NIAID reserves the right to terminate or curtail a clinical study or clinical trial and/or the involvement of a particular clinical site for any of the following reasons:
  

• Risk to subject safety
• Occurrence of unforeseen safety issues or emerging data indicating a presence of unanticipated toxicity
• Risks that cannot be adequately quantified
• The scientific question is no longer relevant, or the objectives will not be met
• Failure to comply with GCP, federal regulations, or Terms and Conditions of Award
• Failure to remedy deficiencies identified through site monitoring
• Inadequate progress in fulfilling the research agenda
• Slow accrual that may jeopardize study completion within the time frame of the award or negatively influence the scientific validity of the study
• Reaching a major study endpoint substantially before schedule with persuasive statistical significance
• In case an interim statistical analysis indicates futility
  

• Access to Data: The NIAID Project Scientist or designee 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. The original source documentation must be available for external monitoring and discrepancy resolution with the database. NIAID staff may use information obtained from the data for the preparation of internal reports on the activities of the study.

Areas of Joint Responsibility include:

• Protocol Development: The CoFAR-CRC PD(s)/PI(s) will fully develop the center-specific clinical research protocols for the projects supported by this FOA with the participation of NIAID-DAIT program staff at the program staff's discretion. NIAID-DAIT program staff will also decide whether the CoFAR-CRC center-specific protocols will utilize the protocol template used by NIAID.
• Research Activities: Reviewing the CoFAR-CRC's research activities and goals on an agreed upon schedule (but no less than once every year). Promoting, evaluating, and executing opportunities to collaborate with other federal or non-federal research sponsors.
• CoFAR Steering Committee: The purpose of this committee is to advise the CoFAR-LC PD(s)/PI(s) on the network-wide clinical research projects to be conducted, approve the final clinical trial and study protocols and modify or add protocols as scientifically indicated. The overall CoFAR scientific plan will be reviewed and updated yearly. In addition, the Steering Committee will regularly review and advise on the progress of center-specific CoFAR-CRC research projects and will develop and implement policies and procedures for publicizing the accomplishments and the data resulting from CoFAR studies to the scientific and lay communities and other relevant audiences. The CoFAR Steering Committee will include the PD(s)/PI(s) of the CoFAR-LC (who will serve as the Chairperson), a PD/PI from each of the CoFAR-CRCs, the designated Project Leader(s) of the AA-SCCC, and 2 NIAID Project Scientists. All members of the Steering Committee are voting members with the exception of the NIAID Project Scientists. If one individual is the same PD/PI for both a CoFAR-CRC and the CoFAR-LC, s/he will have only one vote.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual recipient. This special dispute resolution procedure does not alter the recipient'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 Part 16.

3. Data Management and Sharing

Note: The NIH Policy for Data Management and Sharing is effective for due dates on or after January 25, 2023.

Consistent with the NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

4. Reporting

When multiple years are involved, recipients 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 RPPR, 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. NIH FOAs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All recipients 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.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

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, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: https://www.era.nih.gov/need-help (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-480-7075

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

Gang Dong, MD PhD
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3508
Email: [email protected]

Poonam Tewary, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-761-7219
Email: [email protected]

Nicole Gormley
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-761-5449
Email: [email protected]

Section VIII. Other Information

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

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 and 2 CFR Part 200.