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

Required Application Instructions

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts) and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

Food allergy is a common immune-mediated disease that has become a serious health problem in the United States and other developed countries. The estimated prevalence of food allergy ranges from 4 to 8% in children and is approximately 5% in adults. Over the past 2 decades, the prevalence in children has increased substantially. Food allergy is associated with severe and sometimes life-threatening allergic reactions (anaphylaxis). Among certain cohorts of highly allergic children, accidental exposure results in approximately one reaction per subject per year, and 11% of such reactions are severe. It is not possible to predict which individuals are at risk of life-threatening reactions. There is no FDA approved therapy for food allergy; avoidance of food allergens and treatment of food allergy-induced systemic reactions with epinephrine remain the standard of care.

In 2005, NIAID established the Consortium for Food Allergy Research (CoFAR), which was re-competed and renewed in 2010. 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 and the genetics and epigenetics of food allergy.

While there is evidence that genetic traits play a role in food allergy, these factors cannot explain the increase in the prevalence of the disease. Other factors need to be investigated. For example, research on the role of the intestinal microbiome, which could be influencing the induction of tolerance via the gastrointestinal immune system, is needed. It may also be important to examine whether food allergen avoidance, by reducing exposure of the gastrointestinal immune system to antigen, limits the chances for the development of food tolerance.

Through the work of CoFAR and that of other research groups, oral food allergen immunotherapy has shown promise as an approach that can allow the majority of children with food allergy to become desensitized and tolerate substantial amounts of the food they are allergic to. However, oral immunotherapy can cause a relatively high rate of allergic reactions and a number of patients are not able to pass the final oral food challenge that most studies include. Furthermore, there is a small risk for developing eosinophilic esophagitis, 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. In addition, the mechanisms underlying acquisition of desensitization (lack of response to the food during continued exposure to the food), sustained unresponsiveness (lack of response to the food even in the absence of exposure to the food), or acquisition of durable immunologic tolerance are poorly understood, and are all in need of further exploration.

Management of food allergy may benefit from the emergence of a number of immunomodulatory agents that target various aspects of Th2 immunity. Many of those agents are currently in clinical development for other forms of allergic disease, but their testing in food allergy should not be delayed. 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.

Recent evidence indicates that early introduction of allergenic foods in susceptible populations is highly efficacious in preventing food allergy. The Learning Early about Peanut Allergy trial conducted by the NIAID’s Immune Tolerance Network tested strategies to prevent peanut allergy in high-risk infants. This trial demonstrated that, compared to at-risk children who avoided peanut consumption, those who regularly consumed peanut-containing foods beginning at age 4-11 months had an 81% relative reduction at age 5 in the prevalence of peanut allergy. Further investigation of strategies for food allergy prevention, including the underlying mechanisms, is needed.

The Consortium for Food Allergy Research (CoFAR) consists of two distinct entities, the CoFAR Leadership Center (LC) and the CoFAR Clinical Research Units (CRUs). The objectives of the CoFAR LC are to provide scientific strategy and organizational structure to CoFAR for the conduct of ground-breaking research in the areas of prevention, management and understanding of the mechanisms of IgE-mediated food allergy. To advance these objectives, the CoFAR LC will work closely and in collaboration with the CoFAR CRUs to conduct all CoFAR clinical trials and clinical studies. Clinical monitoring, data collection, data management, and statistical support for this effort will be provided by the NIAID-DAIT: Statistical and Clinical Coordinating Center. Standardized biomarker measurements across studies will be conducted by the CoFAR LC through a Central Biomarker Facility. In addition to the biomarker studies conducted by the Central Biomarker Facility, the CoFAR LC will select and support state-of-the-art mechanistic research linked to the CoFAR clinical trials and studies through an Opportunity Fund open to both CoFAR members and outside investigators. The CoFAR LC is expected to develop close interactions between basic scientists and clinical investigators to accelerate the translation of basic research advances into clinical applications. All research developed by the CoFAR LC will involve human subjects. The CoFAR LC will also be responsible for distributing protocol funds to the CoFAR CRUs to conduct CoFAR clinical trials and studies.

The scope of research that the CoFAR LC may conduct includes, but is not limited to, the following:

• Phase I and/or Phase II clinical trial(s) for either treatment or prevention of food allergy. Clinical trials should focus on immune-based approaches such as preventative early allergen exposure, new forms of allergen immunotherapy including immunotherapy in combination with adjuvants, anti-cytokine treatment, or other immunomodulatory agents/approaches.
• Phase III clinical trials will be allowed only following successful completion of a phase II trial.
• Applicants are strongly encouraged to contact NIAID Scientific/Research Contact(s) prior to including such a trial as part of the response to this FOA.
• Birth cohort studies of individuals at high risk vs. low risk of food allergy.
• Cross-sectional or long-term clinical studies in individuals with food allergy.
• The role of the microbiome in the pathogenesis of food allergy.
• Identification of the route of allergen sensitization in food allergy.
• Interactions between immunologic, environmental and genetic or epigenetic factors underlying food allergy.
• Proteomic and/or metabolomic profiling in association with the clinical presentation of food allergy.
• Molecular mechanisms (e.g. analysis of signaling pathways) in association with the clinical presentation of food allergy.
• Mechanisms underlying the severity of allergic reactions and anaphylaxis in food allergy.
• Applicants may submit to both the CoFAR Leadership Center (RFA-AI-15-050) and the CoFAR Clinical Research Units (RFA-AI-15-051). However, an applicant must propose different clinical trials in each of the two applications.

The CoFAR LC will be responsible for oversight and completion of two ongoing CoFAR clinical trials.

• CoFAR 6: Epicutaneous Immunotherapy (EPIT) for Peanut Allergy: A Randomized, Double-Blind, Placebo-Controlled, Phase II Study in Children and Adults (https://www.clinicaltrials.gov/ct2/show/NCT01904604 ). CoFAR 6 is fully enrolled with 75 participants between the ages of 4 and 25 years. CoFAR 6 reached its primary outcome in August, 2015. Currently, CoFAR 6 continues to assess its participants in a follow-up phase on open treatment. Final assessment oral food challenges are expected to be complete by June of 2018, with last patient, last visit (a telephone assessment) in September 2018.
• CoFAR 7: Oral Desensitization to Egg with Subsequent Induction of Sustained Unresponsiveness for Egg-Allergic Children using Baked Egg or Egg Oral Immunotherapy (OIT) (https://www.clinicaltrials.gov/ct2/show/NCT01846208 ). CoFAR 7 is fully enrolled with 92 participants between the ages of 3 and 16 years. Assessment of the primary endpoint is anticipated to be complete in October 2017, with the last patient, last visit (a telephone assessment) in September 2018.
• CoFAR 6 and CoFAR 7 are each supported by: a statistical and data coordinating center that provides clinical monitoring, data management and analysis services; and an NIAID medical officer, an NIAID nurse/project manager, and an NIAID regulatory officer. The CoFAR LC will provide the funds to this center to continue its services for the completion of these two trials and the publication of their results.

This FOA will not support:

• Research conducted in animals or animal cells.
• Research on eosinophilic esophagitis.
• Research on non-IgE mediated diseases such as celiac disease.
• Research on HIV/AIDS.

Applications which include the above topics will be non-responsive and will not be reviewed.

Resources provided by NIAID to the CoFAR

The NIAID-DAIT: Statistical and Clinical Coordinating Center (SACCC) will provide a broad range of clinical research support services, including support for the design and organization of each CoFAR protocol, development of protocol-related materials, data collection, management and quality control, clinical site monitoring, safety monitoring and reporting, data analysis and manuscript development.

NIAID will serve as the Sponsor for the CoFAR clinical trials conducted under Investigational New Drug (IND) Applications with full responsibility for carrying out sponsor regulatory requirements. Under certain circumstances, this role may be delegated by NIAID to another entity (e.g., a collaborating pharmaceutical company).

All clinical trials and clinical studies to be conducted by the CoFAR will be reviewed post award by an NIAID-appointed Asthma and Allergy Data and Safety Monitoring Board (DSMB). In addition, the DSMB will conduct periodic safety reviews.

NIAID will provide for public access, either through ImmPort or through another NIAID resource and all clinical trial, clinical study, biomarker and mechanistic data produced by CoFAR will be made publicly available by NIAID, through the SACCC, at the time of publication of the primary outcome of the study or 18 months after database lock, whichever comes first.

CoFAR Committees

• The CoFAR Investigator Committee: Responsible for review and management of the progress of CoFAR projects including clinical trials and studies.
• The CoFAR Steering Committee: Responsible for advising the LC PD/PI on which clinical projects should be selected for implementation, approving the final clinical protocols, and modifying or adding of protocols as scientifically indicated.

Structure of the CoFAR Leadership Center

The CoFAR LC will consist of the following components:

Overall Research Agenda: This component will be responsible for developing and executing the overall scientific strategic plan of CoFAR, outlining its theme and goals, identifying the most important questions to be answered and indicating how the work of the CoFAR will address these questions and advance the field.

Leadership Complex Component:

Clinical Operations. This section will have the overall responsibility of organizing and administering the clinical projects, which includes development, implementation and management. Training of all CoFAR investigators and staff, both at the CoFAR LC and the CoFAR CRUs, will be the responsibility of this component. This will be done in collaboration with the CoFAR CRUs, the SACCC and with NIAID staff.

Leadership Center Administration. This section will have the responsibility for the administrative oversight, staffing and fiscal management of the CoFAR LC. In addition, the Leadership Center Administration will have responsibility for establishing CoFAR governance and maintaining the CoFAR Investigator and the CoFAR Steering Committees.

Central Biomarker Facility. This section will provide for standardized biomarker assays designed to monitor the effects of therapy on the immune response to the food allergen(s) being targeted, or to establish the phenotype of the participants in all clinical projects. Biomarker assays can be performed at one or more laboratories, at the PD/PI’s discretion but must be centrally coordinated.

Opportunity Fund. This section will include a detailed plan to solicit and review innovative or state-of-the-art mechanistic studies specific for each CoFAR clinical project that will be supported by the CoFAR Opportunity Fund and will be developed in parallel with each clinical project.

Clinical Projects: This component will support the clinical projects that CoFAR may pursue. Clinical projects can be interventional clinical trials or clinical studies. In this FOA, a clinical trial is defined as a research study in humans that evaluates the effects of one or more interventions for the treatment or prevention of IgE-mediated food allergy.

It is anticipated that at least three clinical projects will be implemented during the course of the CoFAR awards. At least two must be clinical trials and the third project may be either a clinical trial or a clinical study. The clinical trials that will be implemented will be chosen from among the trials proposed by the funded CoFAR LC and the funded CoFAR CRUs. The LC PD/PI will decide which clinical projects the CoFAR will conduct based on input from the CoFAR Steering Committee. The Steering Committee will be composed of the PD/PI and two additional members of the LC, as well as the PD/PIs of the funded CRUs, regardless of whether their proposed trials have been selected for implementation. The clinical projects that the CoFAR will conduct will require approval by NIAID, which will consider programmatic priorities in its decision.

CoFAR Protocol Funds:

Additional protocol specific funds will be disbursed by the CoFAR LC to the CoFAR CRUs participating in each of the clinical projects. Protocol funds include (but are not limited to) the following protocol-specific expenses:

• Salary for additional staff or for expanded commitment of core staff.
• Protocol-specific participant screening and recruitment.
• Patient retention.
• Protocol required tests and evaluations.
• Participant reimbursement.
• Equipment and supplies necessary to conduct the clinical trial or clinical study.

For more information see the NIAID Research Funding site Questions and Answers for RFA-AI-15-050 found at the following

http://www.niaid.nih.gov/researchfunding/qa/Pages/RFA-AI-15-050.aspx#

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

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

Non-domestic (non-U.S.) Entities (Foreign Institutions) 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.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons.If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

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

The PD (s)/PI (s) of a CoFAR Leadership Center (RFA-AI-15-050) or the CoFAR Clinical Research Units (RFA-AI-15-051) may be the same individual(s).

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

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

Institutions may submit an application to both the CoFAR Leadership Center (RFA-AI-15-050) and the CoFAR Clinical Research Units (RFA-AI-15-051). However, the same clinical trial cannot be proposed in both RFAs.

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

Applicants can access the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

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

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

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

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

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

The letter of intent should be sent to:

Andrea Wurster, Ph.D.
Telephone: 240-669-5062
Fax: 301-480-2408
Email: [email protected]

Component Types Available in ASSIST	Research Strategy/Program Plan Page Limits
Overall (Use for the Overall Research Agenda)	12 pages
Complex Component (Use for the Leadership Complex Component) A. Clinical Operations B. Leadership Center Administratio C. Central Biomarker Facility D. Opportunity Fund	A. 12 pages B. 12 pages C. 12 pages D. 6 pages
Project (Use for Clinical Projects)	12 pages each

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

The following section supplements the instructions found in the SF424 (R&R) Application Guide, and should be used for preparing a multi-component application.

The application should consist of the following components:

• Overall Research Agenda: required
• Leadership Complex Component (Clinical Operations, Leadership Center Administration, Central Biomarker Facility, Opportunity Fund): required
• Clinical Projects: 2 projects are required, at least 1 of which must be a clinical trial. The second project may be either a clinical trial or a clinical study

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

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

Complete entire form.

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

Follow standard instructions.

Enter primary site only.

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

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

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

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

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

Specific Aims: List the Specific Aims of the Consortium focusing on the overall research agenda.

Research Strategy: In this narrative section, describe and discuss an overview of the proposed scientific strategy and vision of CoFAR.

• Describe and discuss the scientific goals of the application in the context of recent studies and current knowledge in the field of food allergy and the objectives of this FOA.
• Include data pertinent to the development of the Overall Research Agenda and scientific goals.
• Discuss the rationale of each proposed clinical project as it relates to the overall CoFAR Overall Research Agenda and how each clinical project might inform future studies.
• Discuss concepts for potential future studies that may emerge as a result of the findings of each of the proposed clinical projects. Emphasize innovative elements included in the proposed projects, both in terms of novel interventions, as well as in terms of novel study designs (for example, with incorporation of adaptive designs).
• Provide a table or graphic representation of the combined timeline for all proposed Clinical Projects.
• Discuss policies and procedures for the operation of the CoFAR.

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

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

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

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

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

Complete only the following fields:

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

Enter Human Embryonic Stem Cells in each relevant component.

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

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

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

List all performance sites that apply to the specific component.

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

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Leadership Complex Component Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• The PD/PI of the application should also serve as Leadership Complex Component Lead and if multiple PDs/PIs are listed then the contact PD/PI should serve as Leadership Complex Component Lead.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the Clinical Operations, Leadership Center Administration, and Central Biomarker Facility sections and indicate their respective roles.
• Information provided in the biosketches should highlight experience and special skills that qualify the individual for the roles he/she will play. When a Senior/Key person is listed in multiple components, the Biographical Sketch should be included in only one component.
• Multi-Component Lead is not permitted.

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

Applicants must include funding in the budget for the following:

• Clinical Operations, Leadership Center Administration, Central Biomarker Facility, and, a total of $0.5 million per year for the Opportunity Fund.
• Protocol Funds for 5-7 CRUs running 3 clinical protocols. Protocol funds include (but are not limited to) the following protocol specific expenses.
  • Salary for additional staff or expanded commitment of key staff.
  • Participant screening and recruitment.
  • Patient retention.
  • Protocol required tests and evaluations.
  • Participant reimbursement.
  • Equipment and supplies necessary to conduct the clinical trials or clinical study.
• CoFAR 6 and CoFAR 7 (total of $1.8 million for year 1 and $0.5 million for year 2).
• Travel and other expenses for Senior/Key Personnel to attend two (2) CoFAR Program meetings per year in the Rockville, Maryland area to discuss Program Reviews, conduct Strategic Planning activities, and to stimulate CoFAR LC and CoFAR CRU interactions and communications.

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

Specific Aims: List the Specific Aims of the four subsections.

Research Strategy: The Research Strategy consists of the following three clearly labeled subsections:

A- Clinical Operations: In this section, describe the personnel and the procedures and processes that the CoFAR LC will use for the implementation and management of the proposed clinical projects.

• Present a concise organizational chart of Clinical Operations that the CoFAR LC will conduct. Identify the types of staff associated with each operation and describe their respective roles and responsibilities.
• Describe plans and procedures (not the scientific rationale) for clinical protocol and other clinical document development and how the CoFAR LC will interact with the CoFAR CRUs and the SACCC .
• Describe the process through which the CoFAR LC will choose appropriate CRUs to conduct a particular clinical project.
• Describe the processes through which the CoFAR LC will determine how protocol specific funds will be determined and disbursed to the CoFAR CRUs and how the use of those funds will be monitored.
• Define the role of the CoFAR LC in the organization and implementation of the clinical projects that the CoFAR will conduct including:
  • Development of and adherence to protocol-specific milestones and performance guidelines.
  • Training of CRU investigators and staff in accordance with Federal regulatory requirements, Good Clinical Practice (GCP) guidelines and International Conference on Harmonization (IHC) standards. Include training on: clinical protocol participant screening, recruitment, enrollment and retention; informed consent; assessment and reporting of Adverse Events and Serious Adverse Events; collection of protocol-specific biologic specimens; receipt, storage, packaging, labeling and management of study products; collection, quality control and management of study data; data entry, and creation, maintenance and storage of research records, including Case Report Forms (CRFs), standard operating procedures, manuals of operation, source documents, regulatory files, and subject identification information.
  • Actions to be taken to address problems with recruitment or retention of study participants.
  • Quality control of clinical data collection.
  • Coordination with the SACCC on oversight of collection, transportation, processing, storage and tracking of biologic samples by the CoFAR CRUs, the Central Biomarker Facility and the mechanistic study sites.
  • Actions to be taken to address problems with cGCP adherence.
  • Development of mechanisms for corrective actions including site visits.
  • Interaction with the SACCC on data management, statistical analyses and manuscript preparation.

B-Leadership Center Administration: In this section, describe the administrative structure of the CoFAR LC as it pertains to communications among investigators and between investigators and staff, the handling of its finances and the management of CoFAR governance through its Investigator Committee and Steering Committee.

• Present a concise organizational chart of the administrative structure of the CoFAR Leadership Center Administration. Identify the types of staff associated with each operation and describe their respective roles and responsibilities.
• Provide a detailed plan of the interactions among investigators and between investigators and the Leadership Center Administrative staff with reference to meetings, teleconferences and other communications and explain the role of those interactions in the overall functionality of the CoFAR.
• Describe processes and procedures for the fiscal administration of the CoFAR LC, especially with regard to how protocol-specific funds for the conduct of the clinical projects will be determined, managed and disbursed to the 5- 7 CRUs. Describe the process of establishing consortium agreements.
• Describe how Opportunity Funds for the mechanistic studies will be fiscally administered. Describe the process of establishing consortium agreements.
• Describe the oversight process through which the CoFAR LC will ensure the completion of the CoFAR6 and CoFAR7 clinical trials along with the final publication of the results. Describe plans for efficient IRB review and approval, preferably using federated IRB models.
• Describe plans and procedures for establishing and maintaining the functions of committees responsible for Consortium governance and management, including the CoFAR Investigator Committee and the CoFAR Steering Committee. In discussing the functions of those committees, propose additional activities such as:
  • Developing and implementing policies to ensure the efficient operation and effective management of the functions of the CoFAR, including enforcement of Steering Committee decisions and resolution of disputes and differences of opinion within the Steering Committee.
  • Developing and implementing policies and procedures for the identification, disclosure, reporting and management of potential and actual conflicts of interest for members of the CoFAR LC, CoFAR CRUs or investigators with mechanistic studies supported by the CoFAR Opportunity Fund.
  • Developing and implementing policies and procedures for planning, authorship, preparation, review and final approval of manuscripts resulting from CoFAR-supported studies and for submission of manuscripts for publication in peer-reviewed journals.
  • Developing and implementing policies and procedures for publicizing the accomplishments and the data resulting from CoFAR studies to the scientific and lay communities and other relevant audiences. This includes policies for presentations at scientific meetings and for communications with the press.

• Provide a brief plan for leadership succession if the PD/PI is, for any reason, unable to continue as the leader of the program.

C- Central Biomarker Facility: In this section,

• Discuss general plans to establish and coordinate the functions of the Central Biomarker Facility including services to be provided for incorporation into clinical trials and clinical studies.
• Present a concise organizational chart of the structure of the CoFAR Central Biomarker Facility. Identify the types of staff associated with each operation and describe their respective roles and responsibilities. Biomarker assays can be performed at one or more laboratories, at the PD/PI s discretion, but must be centrally coordinated.
• Describe and justify the standardized biomarkers that will be measured across clinical projects in the context of current knowledge and gaps in this field, discuss the rationale for their selection and provide data supporting the reproducibility and validity of the relevant assays. Biomarkers are not meant to explore new mechanisms, but to document effects of therapy on known biologic phenomena associated with food allergy, to monitor disease progress, and to facilitate comparisons between interventions in terms of biologic effects. Examples of such assays include, but are not limited to, measurement of IgE and IgG levels specific to each allergen and to purified component(s) of each allergen, basophil activation assays, and immune phenotyping of antigen-specific T cells in peripheral blood.
• Describe the methodologies for measuring these biomarkers in sufficient detail to allow assessment of scientific validity. Provide evidence and plans to ensure that assays can be conducted reliably with shipped specimens and address variances due to shipping, storage or site-to-site variability. Describe the complexity of sample processing at the collection site and how variability due to local processing will be reduced and controlled for. Include supporting data, if deemed necessary. Describe how biomarker data will be integrated across the CoFAR clinical studies and what questions they will be used to answer.

D. Opportunity Fund: In this section,

• Discuss plans for an Opportunity Fund focusing on 1) how the LC will solicit, within and outside CoFAR, applications for cutting-edge mechanistic studies that will accompany each of the CoFAR clinical projects; 2) how and with what criteria each mechanistic study application will be reviewed and awarded; 3) how open competition and fairness to external and internal applicants will be preserved; and 4) how the Opportunity Fund awardees will collaborate with the CoFAR LC, the CoFAR CRUs and the SACCC in integrating the mechanistic studies into the CoFAR clinical projects.
• Indicate how applications for mechanistic studies will be solicited early in the process of clinical project development so that the Opportunity Fund-supported mechanistic studies can be developed in parallel with clinical project.
• Describe how the CoFAR LC will monitor the progress of the Opportunity Fund awardees and evaluate the overall success of the program.
• Discuss procedures for interacting with the CoFAR CRUs and coordinating implementation of clinical projects through the Opportunity Fund awardees.

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

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

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

Not Applicable

Note Applicable

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

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

Note: Two separate projects are required and one must be a clinical trial. The second project may be either a clinical trial or a clinical study.

SF424 (R&R) Cover (Clinical Projects)

Complete only the following fields:

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

PHS 398 Cover Page Supplement (Clinical Projects)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Clinical Projects)

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

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question. All applicants should mark "no" as vertebrate animal work may not be included as is it non-responsive for this specific RFA.

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

Other Attachments: Provide the following additional materials specified below in support of the application.

Provide a PDF file with the name Staffing Plan . This section should contain the proposed staffing plan for the CRUs to execute the clinical trial or study proposed. The staffing plan should indicate the qualifications and expertise in the field of food allergy research that will be required for each position. Positions may include: clinical staff (nurses and coordinators), dietary/nutrition services staff; pharmacy services staff; other support services, such as social workers or psychology staff; and laboratory technicians for biologic sample processing. Do not name individuals or sites.

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

List all performance sites that apply to the specific component.

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

Note: all performance sites for clinical trials or clinical studies will be through the CoFAR CRUs.

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

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch should be included in only one component. Information provided in the biosketches should highlight the experience and special skills that qualify the investigator for the roles he/she will play in the Clinical Projects.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• Indicate the key personnel who will have leadership responsibility for the project. Multi-Project Lead is not permitted.

Budget (Clinical Projects)

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

Request the budget that the LC will require for its role in the proposed clinical project including the following:

• Salary for additional staff or expanded commitment of key staff for clinical trial/clinical study-specific tasks that are the responsibility of the Leadership Center.

Equipment and supplies to support the conduct of the proposed research.

Protocol Funds for CRUs participating in the proposed multi-center project are to be requested in the Leadership Complex Component.

Do not budget for cost related to:

• IND submissions, if applicable.
• DSMB review.
• Statistical and data management functions.

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

PHS 398 Research Plan (Clinical Projects)

Specific Aims: List the broad, long-range objectives and goals of each proposed clinical project.

Research Strategy: Discuss the project's clinical and biological significance for the field of food allergy and its role in the overall research strategy of the CoFAR. For the proposed clinical project, do not include mechanistic studies as they will be solicited and awarded through the Opportunity Fund. Do not submit a detailed, final clinical protocol; following an award, the final clinical protocol will be developed collaboratively.

• 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 food allergy.
• Describe earlier studies that led to the proposed clinical trial or clinical study and provide information or data from preliminary studies which address the need for and the feasibility of the project.
• Concisely describe the design of the proposed study (include rationale for pivotal choices):
  • Hypothesis;
  • Study objectives (primary, secondary);
  • Primary and secondary outcomes (including biomarkers);
  • Study population with eligibility criteria;
  • Study visit schedule and primary evaluations, including laboratory evaluations;
  • Study duration and study timeline;
  • Key features of a safety monitoring plan including potential risks and measures to mitigate risks. For clinical trials, describe known toxicities of the investigational interventions, as well as any concerns for known or potential toxicities unique to the study population;
  • Summary of the statistical analysis plan and of sample size calculations with description of statistical power. Note that the participation of a SACCC in the functions of the CoFAR does not negate the need for a comprehensive statistical analysis plan in this application.

• Provide a feasibility assessment:
  • Describe the overall experience of the CoFAR LC with the procedures and the population of the proposed study;
  • Provide information on any competing clinical 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;
  • Discuss anticipated problems and propose approaches to overcome or minimize such problems including problems in subject recruitment, enrollment and retention;
  • 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);

If a clinical project incorporates biomarker assays, include a concise description of the following:

• The assays that will be used, including a justification for choosing these assays;
• 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.

Letter of Support: If investigational drug(s) are to be provided by the manufacturer at no cost, provide letter(s) of commitment.

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

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

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

Planned Enrollment Report (Clinical Projects)

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

PHS 398 Cumulative Inclusion Enrollment Report (Clinical Projects)

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

See Part I. Section III.1 for information regarding the requirements for obtaining a Dun and Bradstreet Universal Numbering System (DUNS) Number and for completing and maintaining an active System for Award Management (SAM) registration. Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies) using ASSIST or other electronic submission systems. Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration.

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

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

This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

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

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

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

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

Important reminders:

All PD(s)/PI(s) and component Project Leads must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

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

See more tips for avoiding common errors.

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

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

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

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

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

Does the CoFAR LC address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? If the aims of the CoFAR LC 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?

Specific to this FOA: Are the overall goals and research priorities significant? Does the application demonstrate the potential to lead cutting-edge clinical trials and clinical studies to advance prevention and management strategies and to improve knowledge on the origins and the pathophysiology of IgE-mediated food allergy?

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

Specific for this FOA: Do the PD(s)/PI(s) have documented experience in directing large, complex, integrated, multi-faceted and multi-site clinical trials and clinical studies? Do the PD(s)/PI (s) plan to commit sufficient time to the CoFAR?

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

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the CoFAR LC? 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 CoFAR LC involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?

Specific for this FOA: Is the proposed CoFAR LC comprehensive, well organized, and able to achieve the scientific goals of the CoFAR? Are the Overall Research Agenda and proposed Clinical Projects linked under a strategy that either builds on previous research in the field or stems from a novel, but well justified concept?

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Reviewers will provide one score to reflect their assessment of the likelihood for the Overall Research Agenda to exert a sustained, powerful influence on the research field(s) involved.

Note: Reviewers will consider each of the review criteria below, in the determination of scientific merit of the Overall Research Agenda.

• Is the Overall Research Agenda as a whole scientifically compelling?
• Are the overall goals, as articulated in the Overall Research Agenda, significant and how well do they address key roadblocks to the prevention and treatment of food allergy?
• Does the Overall Research Agenda have a high likelihood of developing critical new knowledge about food allergy in humans?
• Do the PD(s)/PI(s) have appropriate experience developing and conducting clinical research projects?
• Have the PD(s)/PI(s), collaborators, and other researchers provided evidence of successful prior collaborations?
• Does the Overall Research Agenda address incorporation of innovative elements and interventions targeted towards food allergy?
• Is the rationale presented in the Overall Research Agenda sound and is the proposed strategy to inform future studies well-articulated?
• Is the proposed timeline sound and achievable based on the Overall Research Agenda?

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the Leadership Complex Component to exert a sustained, powerful influence on the research field(s) involved.

Note: Reviewers will consider each of the review criteria below, in the determination of scientific merit of the Leadership Complex Component but will not give separate scores for these subcategories.

A- Clinical Operations:

• Are the Clinical Operations of the CoFAR LC clearly described with appropriate staffing, expertise and time commitment?
• Are processes for developing new clinical trial and clinical study concepts and protocols, if the opportunity arises, adequately discussed?
• Is the plan for selection of CRUs to conduct the clinical projects appropriately described?
• Is the role of the CoFAR LC in the organization and implementation of the clinical projects that the CoFAR will conduct adequately discussed and does the application include adequate and appropriate description of:
  • Clinical document development and preparation?
  • The development of and adherence to protocol-specific milestones and performance guidelines?
  • Actions to be taken to address problems with recruitment or retention of study participants?
  • Quality control of clinical data collection?
  • Coordination with the SACCC on oversight of the CoFAR CRUs, the Central Biomarker Facility, any additional laboratory facility used for biomarker measurements and the mechanistic study sites in terms of collection, transportation, processing, storage and tracking of biologic samples.
  • Actions to be taken to address problems with cGCP adherence?
  • Development of mechanisms for corrective actions including site visits?
  • Interaction with the SACCC on data management, statistical analyses and manuscript preparation?

B-Leadership Center Administration:

• Is the administrative structure of the CoFAR LC clearly described?
• Do the PD/PI and other staff members assigned to various responsibilities have appropriate administrative expertise?
• Are the applicants capable of assuming the leadership of the CoFAR and providing responsible oversight of all the clinical projects?
• Is the approach described for overseeing the continuation of CoFAR 6 and CoFAR7 trials likely to lead to timely completion of those trials, along with publication of their final results?
• Does the application describe detailed plans for interactions among investigators and between investigators and the administrative staff and are these plans appropriate for achieving optimal administrative functionality of the CoFAR LC?
• Are the processes and procedures for the fiscal administration of the CoFAR LC clearly described and appropriate?
• Are the plans for IRB review appropriate and efficient?
• Are the plans for establishing and maintaining the committees for Consortium governance and management appropriate?
• Is the leadership succession plan appropriate?

C- Central Biomarker Facility:

• Are the resources or services provided by the Central Biomarker Facility (including procedures, techniques, and quality control) high quality?
• Are the key personnel well qualified and is there an adequate commitment of time? Does the application provide adequate justification for the biomarker selection across clinical projects, including scientific rationale and evidence of validity?
• Are plans for incorporation of the Central Biomarker Facility well integrated into the proposed clinical trials and studies?
• Are the proposed biomarkers appropriate to monitor disease progress and the effects of therapeutic interventions, and to facilitate comparisons between interventions in terms of biologic effects?
• Are the biomarker assays standardized, state-of-the-art and well integrated?

D- Opportunity Fund:

• Do the plans to incorporate an Opportunity Fund have a high likelihood of leading to well integrated, timely, and significant mechanistic studies that will advance the field of food allergy research?
• Are the plans and procedures for soliciting, reviewing, selecting, integrating and monitoring mechanistic studies, to be supported by the Opportunity Fund, acceptable?

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the Clinical Project to exert a sustained, powerful influence on the research field(s) involved.

Note: Reviewers will consider each of the review criteria below, as appropriate for the Clinical Project, in the determination of scientific merit and provide an overall impact score for each Clinical Project.

• Does the proposed clinical trial or clinical study conform to the overall strategic plan for the CoFAR outlined in the Overall Research Agenda and does it have scientific merit?
• Is the quality, innovation and feasibility of the proposed trial/ study concept likely to advance the treatment or prevention of food allergy?
• Is there a clear question(s) that the clinical trial or clinical study will and can address?
• Is the clinical trial or study adequately justified and supported by preliminary data or previously published research?
• If successful, will the proposed clinical trial improve clinical outcomes of patients with food allergy and will the proposed clinical study improve our knowledge of food allergy?
• Is the experimental design of the clinical project appropriate in terms of primary and secondary outcomes (including biomarkers), study population and eligibility criteria, study arms (appropriate controls), study visit schedule and primary evaluations, study duration and study timeline?
• Are known toxicities of the investigational interventions, as well as any concerns for known or potential toxicities unique to the study population, described?
• Is the safety monitoring plan, including potential risks and measures to mitigate risks, appropriately described?
• Is the summary of the statistical analysis plan and of sample size calculations with description of statistical power adequate and is sample size justifiable?
• Are obstacles for subject recruitment, including competing clinical projects underway in the community, adequately addressed?
• Are other interventions with similar mechanism of action adequately considered?
• Does the application discuss anticipated problems and propose approaches to overcome or minimize such problems?
• Is there a clear description of the source and quantity of samples to be obtained, and potential safety and ethical issues in obtaining such samples (for example, blood drawing volume limitations)?
• Is the impact of the cost of purchasing of investigational drug (if not provided at no cost by the manufacturer) on the overall CoFAR LC budget addressed?
• If applicable, is there evidence of commitment by a manufacturer to provide an investigational drug?
• Is the selection of biomarkers for this clinical project appropriate?
• Are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?

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

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Not Applicable

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

Not Applicable

Not Applicable

Not Applicable

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

Not Applicable

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

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genomic Data Sharing Plan.

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.

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

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

As part of the scientific peer review, all applications:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
• Will receive a written critique.

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

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

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

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

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

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

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

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to 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.

Awardee-selected projects that involve clinical trials or studies involving greater than minimal risk to human subjects require prior approval by NIH prior to initiation.

• The awardee institution will provide NIH with written study protocols that address risks and protections for human subjects in accordance with NIH s Instructions for Preparing the Human Subjects Section of the Research Plan.
• The awardee institution will provide NIH with specific plans for data and safety monitoring, and will notify the IRB and NIH of serious adverse events and unanticipated problems, consistent with NIH DSMP policies.

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Cooperative Agreement Terms and Conditions of Award

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 Parts 75 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

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

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

The PD/PI will provide for the overall management, integration and coordination of all activities of the CoFAR LC. The PD/PI will work within the CoFAR LC structure and CoFAR LC staff to carry out the following functions:

• Establish and maintain consortium agreements with the CoFAR Clinical Research Units (CRUs), the Central Biomarker Facility and with the recipients of the Opportunity Fund awards.
• Develop, implement and manage a process for allocating CoFAR resources for approved studies, including a plan to recommend reallocation of funds to achieve the scientific goals of the CoFAR.
• Establish and operate a CoFAR Investigator Committee and a CoFAR Steering Committee.
• Establish a plan that will ensure that all IRB primary reviews of any multi-center trial or study are conducted within the timeframe negotiated by the NIAID Project Scientist preferably using a federated IRB model.
• Establish and implement policies and procedures for CoFAR CRUs.

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

• NIAID will assign up to two Project Scientists to CoFAR. Project Scientists will provide guidance and support in the design of research activities, will serve as a resource for protocol design and development, will provide scientific/programmatic support during the conduct of the research by participating in the design of the activities, will advise in the selection of sources or resources, and will advise in management and technical performance. The role of NIAID Project Scientists will be to facilitate and not direct activities. It is anticipated that decisions in all activities will be reached by consensus and that the NIAID Project Scientists will participate in this process. In various matters related to clinical study approval and oversight, NIAID Project Scientists will have final decision authority, as described below.
• Protocol Development, Review and Approval: NIAID Project Scientists and other NIAID staff will participate in the development, review, and approval of all CoFAR clinical trials and clinical study protocols. All clinical trials and clinical study protocols, as well as the mechanistic study protocols that will be supported by the CoFAR Opportunity Fund will be reviewed by NIAID and, depending on their level of complexity and risk, will be further reviewed by the DAIT/NIAID Clinical Review Committee and by one of the two DAIT/NIAID Asthma and Allergy Data and Safety Monitoring Board (DSMB) or another monitoring body. Prior to study initiation, all clinical study protocols must be approved by an assigned NIAID Project Scientist who will be the Medical Monitor of the study, as well as by an assigned NIAID Regulatory Officer.
• IND/IDE: NIAID will serve as the IND/IDE sponsor for all CoFAR clinical trials requiring an IND/IDE. As part of NIAID’s IND/IDE sponsor responsibilities, the NIAID Medical Monitor will obtain, through the SACCC, regular reports on adverse events and protocol deviations 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 SACCC, will prepare and submit the final study reports to the FDA. Under certain circumstances, this role may be delegated by NIAID to another entity (e.g., a collaborating pharmaceutical company).
• Clinical Trial Monitoring: NIAID will be responsible for monitoring compliance with good clinical practices, regulatory compliance, accurate protocol implementation, internal quality assurance, and test agent accountability at the CoFAR CRUs. NIAID will convene an independent NIAID Data and Safety Monitoring Board (DSMB) or another monitoring body to review and monitor any protocols deemed to possess more than minimal risks. At NIAID s discretion, the NIAID Medical Monitor may request that the monitoring body convenes ad hoc to review a serious adverse event or a cluster of adverse events or serious adverse events. Furthermore, the NIAID Medical Monitor may request that the SACCC conduct for cause monitoring visits to a CRU. Depending on the seriousness 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 for any of the following reasons: (1) risk to subject safety; (2) the scientific question is no longer relevant or the objectives will not be met; (3) failure to comply with Good Clinical Practices, federal regulations, or Terms and Conditions of Award; (4) occurrence of unforeseen drug safety issues or emergence of data from preclinical studies indicating the presence of unanticipated toxicity; (5) risks that cannot be adequately quantified; (6) failure to remedy deficiencies identified through site monitoring; (7) substandard data; (8) inadequate progress in fulfilling the research plan; (9) slow accrual; or (10) reaching a major study endpoint substantially before schedule and with persuasive statistical significance.
• Scientific and Programmatic Oversight: An NIAID program official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. This stewardship includes monitoring program progress, approving changes and concurring with proceeding into study implementation stage. Release of each yearly funding increment for the CoFAR will be based on a review of progress. NIAID staff may use information obtained from the data for the preparation of internal reports on the activities of the study.
• Coordination with outside entities: In the occasion a company provides investigational materials for a CoFAR study, NIAID will be responsible for entering into Clinical Trial Agreements with that company.
• NIAID will establish an External Scientific Advisory Group (ESAG) composed of clinical and basic science investigators. Members of the ESAG will review and offer input on CoFAR clinical trials and mechanistic studies, both during protocol development and during the analysis of results. ESAG members may be invited to attend some CoFAR Steering Committee meetings. The ESAG will submit its recommendations to the NIAID Project Scientists, who will then inform the CoFAR Leadership PD/PI. Recommendations by the ESAG are advisory.

Areas of Joint Responsibility between NIH and Awardees include:

• Research Plans. Implementing, monitoring, and updating the clinical research agenda for CoFAR to ensure consistency and relevance with the NIAID scientific priorities.
• Research Activities. Reviewing the CoFAR Leadership’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 Investigator Committee. The purpose of this committee is to review and manage the progress of all projects. This committee will be composed of the PD(s)/PI(s) of the CoFAR LC, the leader of the Central Biomarker Facility, the designated Project Leader of the SACCC, the PD/PI from all CRUs, the investigators of protocol-specific mechanistic studies and the NIAID staff assigned to each CoFAR clinical project.
• CoFAR Steering Committee. The purpose of this committee is to advise the CoFAR LC PD/PI on which clinical projects the consortium will conduct, approve the final clinical trial and study protocols and modify or add protocols as scientifically indicated. The overall scientific plan of CoFAR will be reviewed and updated yearly. In addition, the Steering Committee will develop and implement policies and procedures for publicizing the accomplishments and the data resulting from Consortium sponsored studies to the scientific and lay communities and other relevant audiences. The CoFAR Steering Committee will include the PD/PI of the CoFAR LC (who will also be the Chairperson), two other members of the LC to be chosen by the CoFAR LC PD/PI, a PD/PI from each of the CoFAR CRUs, the designated Project Leader of the SACCC, and 2 NIAID Project Scientists. All members of the Steering Committee are voting members with the exception of the NIAID Project Scientists.

Clinical Study Implementation and Management. The PD/PI of a CoFAR LC will work in coordination with the SACCC, through NIAID, to execute the following tasks related to clinical study implementation and management:

• Establish and implement policies and procedures for study management and continuous oversight to ensure adequate rates of human subject recruitment, timely and accurate data collection, and completion of all studies in compliance with NIH guidelines and Federal regulations, requirements and policies. This will include compliance with clinical site and study monitoring functions carried out by the SACCC for: (i) site initiation visits, when deemed necessary; (ii) routine monitoring visits to the clinical study sites and the mechanistic sites on a protocol-specific basis; and (iii) specialized site visits, when deemed necessary (e.g., research pharmacy and laboratory operations and compliance with protocol-specific requirements, for cause or remedial site visits). This will also include PD/PI compliance with the NIAID-designated Medical Monitor-approved corrective/remedial actions resulting from clinical site and study monitoring activities.
• Establish and implement policies and procedures to ensure the safe and ethical conduct of clinical research in accordance to Federal regulatory requirements, GCP and ICH guidelines and study-specific DSMPs, including the recording and reporting of all Adverse Events (AEs) and Serious Adverse Events (SAEs). This will include policies for the preparation and submission of AE and SAE Reports to the SACCC for initial review and assessment, followed by final assessment and classification by the NIAID-designated Medical Monitor.

All policies and procedures delineated above will be approved by the Consortium Steering Committee prior to implementation.

• Access to Data: The NIAID Project Scientists, the NIAID program official, or designees will have access to all data generated under this cooperative agreement, and may review the data as recorded on the case report forms or in a database. Data must be available for external checking against the original source documentation. All clinical trial, clinical study, biomarker and mechanistic data produced by CoFAR will be made publicly available by NIAID, at the time of publication of the primary outcome of the study or 18 months after database lock, whichever comes first. NIAID will provide the resource for public access, either through ImmPort (https://immport.niaid.nih.gov/immportWeb/home/home.do?loginType=full) or through another NIAID resource. All final manuscripts must be submitted to the NIAID for review in advance of journal submission.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the CoFAR Steering Committee, 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 awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

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

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

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

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

eRA Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
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GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
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Telephone: 301-710-0267

Michael Minnicozzi, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3532
Email: [email protected]

Andrea Wurster, PhD
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-5062
Email: [email protected]

Jorge Machuca
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-2981
Email: [email protected]

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

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.