Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	National Institute of Allergy and Infectious Diseases (NIAID)
Funding Opportunity Title	Consortium for Food Allergy Research (U19)
Activity Code	U19 Research Program Cooperative Agreements
Announcement Type	Reissue of RFA-AI-09-039
Related Notices	June 4, 2014 - Notice NOT-14-074 supersedes instructions in Section III.3 regarding applications that are essentially the same.
Funding Opportunity Announcement (FOA) Number	RFA-AI-14-003
Companion Funding Opportunity	None
Number of Applications	Only one application per institution is allowed, as defined in Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.855; 93.856
Funding Opportunity Purpose	This Funding Opportunity Announcement (FOA) solicits applications from single institutions to administer a multi-project multi-institution program, to conduct clinical research and assume the leadership and administrative responsibilities for the Consortium for Food Allergy Research (CoFAR). The selected applicant will continue the mission of the CoFAR, which focuses on immune and other intervention strategies for the prevention and treatment of food allergy, including food allergen-associated severe allergic reactions and anaphylaxis, and food allergen-associated eosinophilic esophagitis. The Consortium will conduct interventional trials with associated mechanistic studies, and observational/natural history and/or genetics studies with associated mechanistic studies, in order to understand better the immunopathogenesis of these conditions.

Posted Date	February 26, 2014
Open Date (Earliest Submission Date)	May 19, 2014
Letter of Intent Due Date(s)	May 19, 2014
Application Due Date(s)	June 19, 2014, by 5:00 PM local time of applicant organization. Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.
AIDS Application Due Date(s)	Not Applicable
Scientific Merit Review	October 2014
Advisory Council Review	January 2015
Earliest Start Date	June 2015
Expiration Date	June 20, 2014
Due Dates for E.O. 12372	Not Applicable

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

Required Application Instructions

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

Part 1. Overview Information
Part 2. Full Text of the Announcement
Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

This FOA solicits applications from single institutions to administer a multi-project multi-institution program, to conduct clinical research and assume the leadership and administrative responsibilities for the Consortium for Food Allergy Research (CoFAR). The selected applicant will continue the mission of the CoFAR, which focuses on the prevention and treatment of food allergy, including food allergen-associated severe allergic reactions and anaphylaxis, and food allergen-associated eosinophilic esophagitis. The Consortium will conduct interventional trials with associated mechanistic studies, and observational/natural history and/or genetics research with associated mechanistic studies, in order to understand better the immunopathogenesis of these conditions.

The CoFAR organization will comprise multiple components to carry out the broad scope of research delineated above. These are:

Administrative Core The Administrative Core will be responsible for the overall scientific leadership and administrative functions of the Consortium and coordination of the other components. This includes naming a supervisor for the Laboratory Program who will be responsible for standardization and quality control for routine clinical laboratory testing and monitoring, in all studies supported under this Consortium. The Administrative Core will have also the responsibility for establishing and maintaining the following committees/groups: Consortium Investigator Committee, Consortium Steering Committee and External Scientific Advisory Group.

Clinical Projects This FOA divides clinical projects into two categories: interventional clinical trials and projects which are not interventional clinical trials; the latter category is referred to as either non-interventional clinical studies or as clinical studies . Applicants should propose 4 required clinical projects, and may propose up to 2 other, optional clinical projects.

Food allergy is a common immune-based disease that has become a serious health problem in the United States and other developed countries. The estimated prevalence of food allergy in children ranges from 4 to 8% and between 1997 and 2011, prevalence has increased 1.5-fold. In addition, recent epidemiologic data suggest that allergy to milk and egg, the most common food allergies in infants, appears to be resolving at an older age than in earlier studies. The onset of most food allergies is during childhood, but some (e.g., crustacean seafood allergy) have onset in adulthood. Food allergy is associated with severe, including life-threatening allergic reactions (anaphylaxis). Indeed, 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. Moreover, of emergency room visits for anaphylaxis, between 13% and 65% are caused by allergic reactions to food allergens. Peanut followed by tree nuts are the most common causes of death from food-induced anaphylaxis. In addition, the severity of food allergy does not correlate with measures of food allergy such as the level of IgE antibody to allergen, indicating that there are many gaps in current knowledge of the mechanisms of food-induced anaphylaxis. Despite these important public health concerns about food allergy, there is no approved therapy except to avoid food allergens and to treat severe allergic reactions with epinephrine.

Eosinophilic esophagitis (EoE) is another increasingly common food-associated disorder characterized clinically by refractory heartburn, dysphagia and food impaction. Food impaction affects between 35 and 55% of adolescents and adults with EoE, and, conversely, EoE is responsible for 39-53% of food impaction episodes in children. EoE is strongly associated with other allergic disorders, including food-associated anaphylaxis, and responds to food avoidance or an elemental diet in many cases; however the mechanisms responsible for this disease or its relationship to food allergy remains unclear.

The need for a separate initiative devoted to human food allergy research was emphasized by two successive NIH expert panels on food allergy in 2003 and 2006. To address this need, in 2005 NIAID established the Consortium for Food Allergy Research (CoFAR), a major clinical network to support food allergy research that is now nationally and internationally recognized for carrying out this research.

The current CoFAR (FY2010-2015) consists of 6 clinical centers. The objectives of the 2010 initiative were to support clinical research and mechanistic studies to prevent and treat food allergy, including food allergen-associated EoE, and to study the genetics of food allergy. In addition CoFAR also supports a single project grant to study the genetics of food allergy.

The CoFAR is conducting, or has completed, the following trials and studies:

• Egg oral immunotherapy trial (ongoing) http://www.clinicaltrials.gov/ct2/show/NCT00461097
• Peanut sublingual immunotherapy trial (ongoing) http://www.clinicaltrials.gov/ct2/show/NCT00580606,
• Egg oral immunotherapy compared to baked egg therapy trial (ongoing CoFAR 7) http://www.clinicaltrials.gov/ct2/show/NCT01846208
• Epicutaneous administration of peanut allergens (ongoing CoFAR6) http://clinicaltrials.gov/ct2/show/NCT01904604
• Rectal administration of mutated peanut allergens pilot trial (completed) http://clinicaltrials.gov/ct2/show/NCT00850668
• An observational study, consisting of a long-standing follow-up on high-risk infants to determine factors which predict loss of egg allergy, loss of milk allergy, and new onset of peanut allergy (ongoing) http://clinicaltrials.gov/ct2/show/NCT00356174.
• A genetic study of subjects with eosinophilic esophagitis (ongoing) http://clinicaltrials.gov/ct2/show/NCT01323803.

There have been important recent advances in food allergy research, so it is anticipated that substantial advances in prevention and treatment of food allergy can be made in the future. Experts participating in two NIAID immunotherapy workshops in 2010 and 2012 underscored the importance of continuing to develop and evaluate therapies for food allergy. While preliminary data from clinical trials, mostly of oral immunotherapy, are promising, these experts were unable to identify one immunotherapeutic approach that was clearly superior to other potential approaches. Moreover, there is a subset of patients that has not received any benefits from these therapies and appears to be unable to become desensitized despite repetitive oral administration of allergen. In addition, at least one recent publication has suggested that the duration of benefit from oral immunotherapy may be shorter than anticipated.

The expert panelists acknowledge the need to investigate several mechanistic questions, including whether food allergen immunotherapy achieves only short-term benefits (desensitization) which are reversed when therapy is discontinued or, alternatively, achieves long-term changes in responsiveness to allergen, analogous to tolerance. The mechanisms underlying both desensitization and tolerance are poorly understood and in need of further exploration.

This 2015 FOA will support a single U19 award; it will no longer support U01 applications. The FOA will continue the work of the 2010-2015 Consortium for Food Allergy Research with a focus on clinical trials. The objectives of the CoFAR research program are to: explore the pathophysiology of human IgE-mediated food allergy and the related conditions, IgE-mediated food allergy-associated anaphylaxis and IgE-mediated food allergy-associated EoE, and to develop and evaluate clinical approaches to prevent and treat these diseases, and to use integrated state-of-the-art studies to learn more about the mechanisms of these diseases. Under the CoFAR program, applicants are encouraged to develop close interactions among basic scientists and clinical investigators and accelerate the translation of basic research advances into clinical application. It is expected that the proposed research program will support clinical research (clinical trials, observational/natural history studies, and/or genetic studies) and will include state-of-the-art mechanistic studies that are well-integrated within the trials.

Research Studies

All research involves human subjects, with rare exceptions described below. The applicant should submit clinical and mechanistic study projects with the understanding that the specific studies to be conducted may differ from what is proposed, as a result of peer review, external scientific advisory recommendations, safety reviews by the NIAID Division of Allergy, Immunology and Transplantation Clinical Research Committee (DAIT CRC) and by an independent, NIAID-appointed safety committee, either the Allergy and Asthma Data and Safety Monitoring Board (DSMB) or the Allergy and Asthma Safety Monitoring Committee (SMC), and/or the priorities of NIAID.

The work of the CoFAR will be conducted by the Clinical and the Mechanistic sites with oversight by the Administrative Core.

The Clinical Study Sites must have:

• Ready access to food allergic patient populations to ensure timely screening and enrollment of appropriate study participants;
• Study site leaders with a strong history and experience in successfully designing and conducting clinical studies and trials in food allergy;
• Support personnel and clinical research facilities to execute clinical trial and mechanistic study protocols;
• Capabilities to collect and process the biologic samples required for mechanistic protocols.

The Mechanistic Study Site(s) (these sites may be identical to, or different from, the clinical study sites) must provide:

• Study site leaders with a strong history and experience in conducting cutting-edge, technologically advanced human mechanistic studies;
• Support and technical personnel with immunology, infectious diseases/microbiome, human genetics and molecular biology laboratory experience for research using human biologic samples, and with appropriate GCP/IHC training in handling human biologic samples and;
• Laboratory facilities capable of supporting the research with human biologic specimens.

The clinical and mechanistic studies should not duplicate ongoing or previously completed studies, including CoFAR studies, and should provide new insights into food allergy. The number of Clinical Study Sites participating in a clinical or mechanistic study can range from 1 to all Clinical Study Sites that will participate in the consortium. It is expected that multiple studies will be performed concurrently.

Human subjects research will be either as part of a clinical trial or observational/natural history study or genetic/microbiome study, or for collection of samples for mechanistic studies. Both Interventional Clinical Trials and Clinical Studies projects should include mechanistic studies. Clinical projects that are associated with non-interventional clinical studies may use samples from either new cohorts or from pre-existing cohorts.

Scope of Research for the Clinical Projects

Clinical projects include both interventional clinical trials for prevention or treatment, and clinical studies such as observational studies and genetic studies. Mechanistic studies involve human subjects and are defined as aiming at 1) understanding the mechanisms of disease, and/or 2) understanding the mechanisms of action of a treatment modality, and/or 3) identifying biomarkers that predict disease severity or progression from sensitization to allergy, or that predict the ability of a treatment modality to affect efficacy or safety.

The scope of research for clinical projects and associated mechanistic studies supported by this FOA includes, but is not limited to, the following:

Projects with Interventional Clinical Trials and Associated Mechanistic Studies

Interventional Clinical Trials

• Phase I and/or Phase II clinical trial(s) can be either treatment trials or prevention trials and either single site or multi-site.
• Mechanistic studies using human samples must be included and integrated with the phase I and/or phase II clinical trial.
• Phase III clinical trials will be allowed only following successful completion of a phase II trial. The PD/PI is strongly encouraged to contact NIAID Scientific/Research Contact(s) prior to including such a trial as part of the response to this FOA.
• Mechanistic studies must be included and integrated with the phase III clinical trial.
• Clinical trials to evaluate the safety and efficacy of an intervention on the clinical course of food allergy in allergic subjects. Clinical trials should focus on immune-based approaches (immunotherapy). Current data suggest that specific food allergens must be a major component of the immunotherapy but alternative approaches may be proposed. Trials may involve new delivery routes (oral, sublingual, epicutaneous, other), differing food allergen doses or unique preparations containing food allergens (e.g. food extracts vs. recombinant food allergens), and may test allergens combined with immunomodulatory agents.
• Proposed clinical trials could compare the safety and efficacy of two or more potentially effective therapies for food allergy.
• Trials for primary prevention of food allergy, that is, for prevention of the onset of new food allergy, can be proposed.

Mechanistic Studies

• Evaluate the immunologic, genetic and epigenetic mechanisms underlying therapeutic interventions.
• Determine the mechanisms underlying the efficacy of immunotherapies in inducing desensitization versus tolerance to food allergens.
• Compare two or more potentially effective therapies for food allergy and determine similarities and differences in immunologic changes induced by the therapies.
• Identify biomarkers (i.e, outcome measures that predict therapeutic efficacy and/or adverse reactions).
• Evaluate the mechanisms underlying severe food allergy/anaphylaxis, using defined oral food challenges (OFCs). Such an approach may be feasible in the context of the OFCs currently required as an outcome measure.
• Evaluate the role of the microbiome in immunotherapy-induced changes in allergy.

Projects with Non-Interventional Clinical Studies and Associated Mechanistic Studies

Clinical Studies

• Evaluate the relationships between food allergy and EoE. Studies on EoE must include a focus on IgE-mediated food allergy-associated disease, but these studies may also compare subjects with known food allergy to those without known food allergy.
• Design and conduct studies on birth cohorts of individuals at high risk vs. low risk of food allergy. Include investigations of the role of the microbiome (skin, GI tract, respiratory tract) in the pathogenesis of food allergy.

Mechanistic Studies

• Evaluate the interactions between immunologic, genetic and environmental factors underlying food allergy.
• Evaluate the interactions of the microbiome with genetic and epigenetic components of food allergy.
• Study the genetics and epigenetics of food allergy. Such studies must include replication and/or functional studies.
• Analysis of proteomic and/or metabolomics studies during a clinical study.
• Investigate molecular mechanisms (e.g. analysis of signaling pathways) during a clinical study.

Coordination and Completion of ongoing Clinical Trials (CoFAR6 and CoFAR7)

• CoFAR6 (evaluating safety and efficacy of epicutaneous immunotherapy with peanut)
• CoFAR7 (Egg oral immunotherapy compared to baked egg therapy trial (ongoing)

These are ongoing interventional clinical trials with recruited patient populations who are receiving therapy; the CoFAR Grantee will be required to establish subcontracts with the Institutions currently completing the trials, and to work with the NIAID medical monitor and nurse/project manager to be certain that the studies will be completed.

This FOA will not support:

• Basic research, including animal studies, unless the basic research either provides critical validation (e.g., proof of principle, pre-clinical safety data, pharmacological/toxicological data) for proposed or future clinical projects, or provides interventional clinical trials or non-interventional clinical studies with background data for subsequent human laboratory methodologies.
• Research on non-IgE mediated diseases such as celiac disease.

NIAID Sources of Support: Certain sources of support for the Consortium will be provided by NIAID under separate awards and costs for such sources of support should not be requested in response to this FOA. These are detailed below:

The CoFAR will be supported by a Statistical and Clinical Coordinating Center (SACCC) through an independent NIAID award. The 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 support.

NIAID will serve as the Sponsor for the CoFAR clinical trials conducted under Investigational New Drug (IND) Applications and Investigational Device Exemptions (IDEs) 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 internal NIAID committee, the Division of Allergy Immunology and Transplantation Clinical Research Committee (DAIT CRC) and also by an NIAID-appointed safety committee, either the Asthma and Allergy Data and Safety Monitoring Board (DSMB) or the Asthma and Allergy Safety Monitoring Committee (SMC). In addition, these committees may review interim and final clinical trial data per protocol or ad hoc to ensure the safety of study participants. The DSMB and SMC make recommendations directly to NIAID program staff.

All clinical trial and mechanistic data produced by this consortium will be made publicly available by NIAID, through the SACCC, within 18 months after database lock. 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.

Funding Instrument	Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities.
Application Types Allowed	New Renewal The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	NIAID intends to commit $6.1 million in FY 2015 to fund one award.
Award Budget	Application budgets are not limited but need to reflect the actual needs of the proposed project.
Award Project Period	The scope of the proposed project should determine the project period. The maximum project period is 7 years.

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

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

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

Other

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

Non-domestic (non-U.S.) Entities (Foreign Institutions) 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 and should work with their organizational officials to either create a new account or to affiliate an existing account with the applicant organization’s eRA Commons account. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

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

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

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

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

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

• To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;
• Of an investigator-initiated application that was originally submitted to an RFA but not paid; or
• Of an application with a changed grant activity code.

Applicants 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, 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:

Louis A. Rosenthal, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
6700B Rockledge Drive Room 3246
Bethesda, MD 20817
Telephone: 301-402-8399
Email: [email protected]

Component Types Available in ASSIST	Research Strategy/Program Plan Page Limits
Overall	30 pages
Admin Core	12 pages
Project (Clinical Projects)	12 pages for each project

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

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

The application should consist of the following components:

• Overall: required
• Administrative Core: required
• Clinical Projects: 4 Projects required, and up to 2 additional optional projects

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.

SF424 (R&R) Cover (Overall)

Complete entire form.

PHS 398 Cover Page Supplement (Overall)

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

Research & Related Other Project Information (Overall)

Follow standard instructions.

Project/Performance Site Location(s) (Overall)

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.

Research & Related Senior/Key Person Profile (Overall)

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.

Budget (Overall)

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.

PHS 398 Research Plan (Overall)

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

Research Strategy: This narrative section is an overview that discusses the overall coordination for the development, review, implementation and execution of interventional clinical trials, non-interventional clinical studies and mechanistic studies including integration with the overall Consortium agenda and strategic plan. Applicants should also discuss experience or preliminary data (relevant preliminary data for each project should be included not only here, but also in the description of the individual project) and specifically address how they would accomplish the following:

Interventional Clinical Trials and Non-interventional Clinical Studies: Planning and Implementation: Describe concisely the overall rationale and strategic plan for the clinical program and include plans and procedures for the development, review, implementation and execution of clinical program activities. Address each of the following:

Rationale and strategic plan for the clinical trials/studies:

• Providing an overview of previous clinical trials and clinical studies in food allergy (these can be those done by the applicant, including preliminary data, or those done by other investigators) and what has been learned and identifying existing gaps in knowledge and current challenges in conducting human studies
• Formulating a long-range strategic plan for clinical trials/studies that builds on existing knowledge, addresses current challenges and moves the field in new directions, indicating how each proposed clinical study contributes to the overall strategic plan and how each will inform future studies
• Providing novel approaches in the design of clinical trials aiming at reducing trial duration (e.g. by incorporating adaptive designs)
• Utilizing, wherever possible, standardized study outcomes that facilitate cross-comparisons of clinical trials and studies

Protocol Development:

• Establishing a Protocol Team for each approved study protocol
• Assisting in the development of the clinical trials and clinical studies protocols, under the direction of the Protocol Chair and with the SACCC
• Assisting in the preparation and approval of study forms
• Development of protocol-specific milestones, timelines and performance guidelines for both the protocol development process and for study initiation, execution, completion and analysis of final study data

Clinical Trial/Study Sites:

• Establishing clinical sites in geographic areas of the United States with large relevant food allergic populations
• Identifying a clinical site investigator with responsibility for the conduct, management and oversight of all clinical research activities with clinical expertise in the diagnosis, treatment and management of food allergies and at least 5 years experience in clinical research on food allergies, and experience in the design and conduct of clinical studies
• Identifying the availability of clinical research facilities at the clinical sites such as outpatient clinical research facilities for human subject recruitment, screening, clinical testing, collection of clinical samples and treatment; clinical laboratory facilities for the conduct of protocol-specific laboratory tests, the storage of clinical samples, and the packaging, under appropriate conditions, and shipping of clinical samples to mechanistic sites; and research pharmacy facilities for the receipt, labeling, storage, distribution and inventory of investigational products
• Identifying research pharmacy facilities at the clinical study sites for the receipt, labeling, storage, monitoring, controlled access, inventory, packaging and distribution of investigational products, and for return or disposal of investigational products in accordance with protocol-specific requirements
• Identifying general research facilities at the clinical study sites, including: non-clinical space for contract/subcontract management, data management and study coordination; computers with broadband secure internet access; dedicated office space for clinical and technical staff; and areas for secure storage of confidential study documents with controlled access
• Identifying facilities capable of conducting double-blind food allergen challenges, and that include appropriate safety measures, such as trained nurses, and physicians who can reach the challenge site within 60 seconds of being called
• Demonstrating access to pediatric and adult clinic patients and/or to clinical research databases

Protocol management: directing, monitoring, and managing the implementation of approved clinical studies and trials including the following tasks:

• Assisting the NIAID in the preparation of Investigational New Drug (IND) and Investigational Device Exemption Applications (IDE) applications and ensuring compliance with all regulatory requirements associated with IND/IDE sponsorship
• Preparing Data and Safety Monitoring Plan (DSMP) to ensure adequate data collection and documentation and adequate protection of human subjects commensurate with the anticipated level of risk for each Consortium study in accordance with all applicable Federal regulations and requirements and International Conference Harmonization (ICH) standards for human subjects research
• Assisting in DSMB or SMC review and approval of final clinical protocols and providing interim analyses, progress reports and safety updates and the final safety report and study results to the NIAID DSMB or SMC and the NIAID project scientist/medical officer
• Assisting in the organization and conduct, of protocol-specific training for the participating investigators and the relevant clinical and technical Clinical Trial/Study Site and Mechanistic Study Site staff

Clinical Trial/Study Implementation and Management: assisting with the coordination to execute the following tasks:

• Establishing and implementing 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
• Establishing and implementing 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)
• Establishing and implementing policies and procedures to ensure that all Clinical Trial/Study Sites have the required supply of study materials for study initiation and conduct, and monitor supplies throughout the duration of the study
• Establishing and implementing policies and procedures for the secure transfer of clinical and laboratory data to the central databases of the Consortium SACCC. Note: Training for site personnel in the use of these databases shall be provided by the Consortium SACCC.

Mechanistic Studies associated with the clinical projects: Planning and Implementation

Describe concisely the plans and procedures for the following:

Rationale and strategic plan for proposed mechanistic studies:

• Providing an overview of current knowledge of the immunologic bases of food allergy and mechanisms of food allergy, including mechanisms of desensitization and tolerance
• Providing an overview of previous mechanistic studies in food allergy (these can be those performed by the applicant, including preliminary data, or those performed by other investigators, indicating what has been learned from previous studies
• Identify existing gaps in knowledge and current challenges in conducting human mechanistic studies
• Formulating a long range strategic plan for how the mechanistic studies will address these knowledge gaps and further the field
• Indicating how each of the mechanistic projects contributes to the overall strategic plan and how each will inform future studies
• Incorporating, where possible, standardized mechanistic outcomes to ensure that data can be cross-compared among interventional clinical trials and clinical studies

Mechanistic Study Sites:

• Establishing mechanistic study sites and identifying mechanistic study site leaders
• Providing training in accordance with Federal regulatory requirements, Good Clinical Practice (GCP) guidelines and International Conference on Harmonization (IHC) standards in human subject samples receipt, storage, packaging, labeling and management of study products.
• Providing quality assurance, including laboratory quality assurance, and control of mechanistic studies performance and analysis, including adherence to guidelines of regulatory agencies and for participation in external quality assurance programs; collection, quality control and management of study data; data entry, and creation, maintenance and storage of research records
• Identifying the availability of research facilities including facilities for the conduct of state-of-the-art human sample evaluations, complex bioinformatics analyses; and storage of clinical samples

Protocol Development:

• Assisting in the development of mechanistic studies as parts of the clinical projects that are to be developed and executed
• Assisting in the preparation and approval of mechanistic study forms
• Development of protocol-specific milestones, timelines and performance guidelines for both the protocol development process and for study initiation, execution, completion and analysis of final study data

Protocol Management:

• Directing, monitoring, and managing the implementation of the mechanistic studies

Protocol-specific Training:

Assisting in the organization and conduct of protocol-specific training for the participating investigators and the relevant clinical and technical Clinical Study Site and Mechanistic Study Site staff.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide, with the following 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 Admin Core .

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

SF424 (R&R) Cover (Administrative Core)

Complete only the following fields:

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

PHS 398 Cover Page Supplement (Administrative Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Administrative Core)

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

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

Project Narrative: Do not complete.

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

List all performance sites that apply to the specific component.

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

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

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

Budget (Administrative Core)

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

The Program Director/Principal Investigator (PD/PI) will be required to commit a minimum of 3 person months effort per year to the project.

Applicants are requested to budget for: (1) centralized operational, administrative and fiscal support of the Consortium; and (2) continuation and completion of the EoE database and storage of samples from previous CoFAR studies including the biobank from CoFAR5.

For fiscal year 2015, $2 million total costs and for FY 2016, $1 million total costs of the budget for this FOA must be set aside for the completion of two ongoing clinical trials, CoFAR6 and CoFAR7.

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 (Administrative Core)

Specific Aims: List the Specific Aims of the Administrative Core.

Research Strategy: In this section describe the fiscal, administrative and management responsibilities of the Administrative Core

Applicants should describe plans, processes, and procedures for the following activities:

• Scientific planning and priority setting for Consortium Components.
• Managing and coordinating clinical trials, clinical studies, mechanistic studies and laboratory monitoring/testing.
• Altering or modifying the research agenda based on new scientific developments.
• Recommending funding for priority projects to NIAID.
• Establishing and implementing collaborations with other Federal and non-Federal organizations/institutions for the co-sponsorship of research in areas of mutual interest and collaborations with industry for the evaluation of specific products/approaches. Planning and directing the Consortium s technical, operational, administrative, and fiscal requirements.
• Establishing plans for efficient IRB review (within 30 calendar days of submission) and approval using federated IRB models.
• Establishing plans and procedures to reduce redundancy, delays and excess due to duplicated infrastructure associated with a consortium of clinical and mechanistic sites.
• Establishing and maintaining the functions of committees responsible for Consortium governance and management.
• Providing a brief plan for leadership succession if the PD/PI is, for any reason, unable to continue as the leader of the program.
• Providing coordination and completion of ongoing CoFAR trials (epicutaneous immunotherapy with peanut (CoFAR 6) and a comparison of oral immunotherapy with egg, vs. baked egg (CoFAR7)). Both of these trials began during the 2010-2015 CoFAR.
• Maintaining the registry and biobank of samples for ongoing genetic studies of eosinophilic esophagitis subjects (CoFAR5) (http://clinicaltrials.gov/ct2/show/NCT01323803) and from other protocols from the 2010-2015 CoFAR. The registry currently holds over 90,000 biological specimens, including blood, DNA/RNA, stool and saliva. These are from the approximately 500 subjects in CoFAR5, approximately 500 subjects in CoFAR2, and approximately 200 subjects in other CoFAR studies.
• In conjunction with the SACCC, providing plans for training or verification of training in accordance with Federal regulatory requirements, Good Clinical Practice (GCP) guidelines and International Conference on Harmonization (IHC) standards, including: local Institutional Review Board (IRB) policies/regulations; subject 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.

Committees: Within the governance and management structure, the Administrative Core will have responsibility for establishing and maintaining the following committees/groups:

• Consortium Investigator Committee: The investigator committee includes the PD/PI of the CoFAR, the PD/PI of the Statistical and Clinical Coordinating Center, both clinical and mechanistic investigators at all study sites, and the designated NIAID staff assigned to each project. This committee has teleconferences twice per month, and meets at least twice a year, to review details of planned, ongoing and completed trials. Applicants should describe plans, processes and procedures for this committee to fulfill its role in reviewing the details of planned, ongoing, and completed trials.
• Consortium Steering Committee: The voting members of the Steering Committee include the PD/PI of the CoFAR, the PD/PI of the Statistical and Clinical Coordinating Center, three investigators (either clinical and/or mechanistic) appointed by the PD/PI of the CoFAR, and up to two designated NIAID project scientists. Applicants should describe plans, processes, and procedures for the following activities:
  • Making decisions regarding overall scientific direction, recommending specific studies for NIAID project scientist/medical officer approval, and coordinating and managing approved studies.
  • Developing and implementing policies to ensure the efficient operation and effective management of Consortium functions, including enforcement of Steering Committee decisions and resolution of disputes and differences of opinion within the Steering Committee and between the Steering Committee and the External Scientific Advisory Group.
  • Developing and implementing policies and procedures for the identification, disclosure, reporting and management of potential and actual conflicts of interest for members of the Consortium and the External Scientific Advisory Group.
  • Approval of policies and procedures for the secure transfer of clinical and laboratory data to the central databases of the Consortium Statistical and Clinical Coordinating Center prior to implementation.

Publications and Communications Policy

• Developing and implementing policies and procedures for planning, authorship, preparation, review and final approval of manuscripts resulting from Consortium-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 Consortium sponsored 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.

External Scientific Advisory Group (ESAG)

The recommendations by the ESAG shall be submitted to the Consortium Steering Committee Chairperson. The designated NIAID project scientist will be kept informed as to the outcome of these recommendations. All such recommendations shall be considered advisory and shall not be binding on the decisions made by the Consortium Steering Committee. Applicants should describe plans, processes, and procedures for the following activities:

• Selecting members of the ESAG from institutions that do not include members of the Consortium. The ESAG shall be composed of no less than 3 and no more than 5 clinical and basic science investigators. The ESAG should include expertise in the areas of food allergy pathophysiology, eosinophilic esophagitis, genetics, molecular biology, mucosal immunology and basic immunology, immunotherapeutics, clinical trials, and mechanistic studies in human immunologic diseases. ESAG appointments should be for one year but may be renewed throughout the duration of the Consortium. Proposed ESAG members, with curricula vitae, should be submitted upon request to the NIAID project scientist for review and approval.
• Reviewing and ranking protocols recommended for funding by the Steering Committee based on Consortium needs, scientific merit, innovation and feasibility.
• Reviewing and recommending improvements/modifications to study protocols developed by Protocol Teams prior to final approval by the Steering Committee.
• Reviewing and advising the Steering Committee on the results obtained from studies undertaken by the Consortium.
• Proposing new studies or scientific areas for the Consortium to consider.
• Communicating advisory, non-binding recommendations by the ESAG to the Consortium Steering Committee Chairperson and the NIAID project scientist/medical officer.

For a new application, do NOT contact, recruit, or name potential members. For a renewal application, provide the names of current and former members but do NOT contact, recruit or name potential NEW members.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide, with the following 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 (Administrative Core)

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 (Administrative Core)

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

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

Applicants should propose 4 required clinical projects, and may propose up to 2 additional, optional clinical projects. At least 2 required projects must be interventional clinical trials (either a treatment trial or a primary prevention trial), each with associated mechanistic studies. Of the 2 required interventional clinical trials, at least 1 must focus on research on IgE-mediated food allergy (i.e., not food allergy-associated anaphylaxis or food allergy-associated EoE). The remaining projects (including the 2 optional clinical projects) may be additional interventional clinical trials, or observational/natural history studies or other clinical studies that do not involve treatment or intervention.

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

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.

Project Narrative: Do not complete.

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.

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 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.
• Applicants should propose clinical site leaders with a strong history and experience in successfully designing and conducting interventional clinical trials and non-interventional clinical studies in humans and support personnel capable to execute clinical protocols.
• Applicants should propose mechanistic site leaders with a strong history and experience in conducting mechanistic research necessary to carry out the scope of the Consortium’s immunologic research relevant to food allergy immunopathogenesis and immunotherapeutics and technical personnel with immunology and molecular biology laboratory experience for research using human biologic samples, including appropriate GCP/IHC training in handling human biologic samples

Budget (Clinical Projects)

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

Note that application should include a full budget for the entire proposed period of support. Budgets should be based on per patient costs and include the other costs of performing the study (clinical research tests, coordinator and Project Lead time, drug costs if applicable, pharmacy costs, etc.). The costs for mechanistic studies should be included here. The costs for data collection and management, statistical support and monitoring and other costs associated with study management will be covered by the SACCC.

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 in priority order, the broad, long-range objectives and goals of the Project. Concisely describe the hypothesis or hypotheses to be tested.

Research Strategy: Use this section to describe how the proposed research will contribute to meeting the Consortium goals and explain the approach and rationale for selecting the methods to achieve the specific aims. In addition to stating the biological significance of the research, indicate the project's relevance to the primary theme of the application and its role in the overall research strategy of the Consortium. For each project, include any preliminary data that support the proposed research.

Note that all clinical projects must have integrated mechanistic studies. The mechanistic studies must be described within the context of the proposed clinical trial and clinical study project(s). Mechanistic studies presented outside a clinical project are not within the scope of this announcement. It is expected that the mechanistic studies will use state-of-the-art approaches and will evolve in parallel with technological advances. Mechanistic studies will be performed at specialized laboratories with expertise in the appropriate technologies.

It is expected that technologies that accommodate small blood volumes will be used wherever possible for the proposed studies. For clinical studies involving multiple sites, it is expected that state-of-the-art laboratory assays (e.g., basophil activation assays, assays of immune function, immune profiling, etc.) will be performed at a well-equipped central facility at one of the network sites. This central facility requirement is essential to ensure uniform processing of human samples and quality control.

The proposed clinical and mechanistic studies must not exceed the clinical and scientific resources of the applicant’s team of institutions (e.g., the applicant group must be able to recruit the required number of study subjects from within their collaborating institutions).

Clinical Projects (Interventional Clinical Trials and Non-interventional Clinical Studies, with integrated Mechanistic Studies):

The interventional clinical trials and non-interventional clinical studies should be presented in sufficient detail to allow reviewers to judge significance, approach, innovation and environment. Do not submit a detailed, final clinical protocol because, if an award is made, the protocol will be developed collaboratively as a result of initial peer review, external scientific advisory review, DAIT/NIAID CRC review, DSMB or SMC review, according to NIAID priorities.

This Research Strategy section should include the following:

A discussion of the significance of the problem being studied, the need for the clinical trial/clinical study, and the potential impact of the proposed work. For interventional clinical trials, indicate how the trial will improve food allergy clinical status.

A discussion of studies that led to the proposed clinical trial/clinical study and information or data from preliminary studies which address the need for and the feasibility of the project.

A concise description of and rationale for the proposed study design, including how the associated mechanistic studies might inform the conduct of the study.

This should include:

• Study title
• Hypothesis
• Study objectives (primary, secondary; include mechanistic objectives)
• Population
• Study eligibility criteria
• Intervention(s) and comparators (interventional clinical trials only)
  • Include descriptions of the intervention to be tested and the investigational study drugs, potential toxicities and experience in the proposed population. The discussion of toxicities should include known events as well as concerns unique for the population being studied.
  • Plan for provision of investigational drugs with letter(s) of commitment from suppliers, if needed (note additional requirements in appendix).
• Clinical Project design:
  • A description of the protocol to be followed in each arm of the project (where applicable), including a discussion of potential biases or challenges in the protocol and how they will be addressed.
  • Sample size (with justification).
  • Primary and secondary endpoints (include mechanistic endpoints).
  • Anticipated duration of recruitment and of the study as a whole.
  • Preliminary study visit schedule and primary evaluations, including laboratory evaluations.
  • Key features of the safety monitoring plan (interventional clinical trials only)
  • Study duration, including duration of follow-up and contingency plans for any safety-related issues where applicable.
  • Any anticipated Human Subjects issues and how those issues will be resolved.
  • Summary of the statistical analysis plan for the proposed primary endpoint, including a description of the outcome measures and the statistical tests that will be used for data analysis. A more detailed and complete statistical analysis plan will be developed when studies are finalized post-award, with the assistance of the SACCC.
• Feasibility Assessment:
  • Discuss the availability of the overall research population and, for interventional clinical trials, include the standard of care alternatives to trial participation, likelihood of acceptance by study populations of the proposed interventions (e.g. intravenous administration? required hospitalization? high risk to the subjects?).
  • Discuss any competing clinical projects underway in the community and their potential influence on recruitment.
  • Discuss interventions with similar mechanism of action currently under development and their potential influence on the proposed interventional trial.
  • Identify proposed clinical sites; documentation of access to adequate numbers of the types of subjects required and target enrollment for each proposed clinical site.
  • Indicate the investigator’s experience in clinical trials and clinical studies in the proposed study area.
  • Indicate anticipated problems, and proposed approaches to overcome or minimize such problems, for: subject screening, recruitment, enrollment and retention
  • Clinical study timeline.
  • Availability of special services needed to complete the project (e.g. investigational pharmacy for interventional clinical trials).
  • Indicate the availability and costs of the proposed study intervention relative to the total CoFAR budget.
  • Describe the source and quantity of samples to be obtained, and discuss the potential safety and ethical issues involved in obtaining the samples.
  • Describe the routine laboratory services required for the project.

For each mechanistic investigation include a concise description of the following:

• The significance of the mechanistic study(ies), and the potential impact of the results of the study(ies) to inform the clinical project.
• The studies that led to the proposed mechanistic study and information or data from preliminary studies which address the need for and the feasibility of the study.
• The rationale, methodology and analyses to be used to accomplish the goals and specific aims of the mechanistic study and a discussion of how the study will test the hypothesis(es) proposed.
• The availability of the biologic samples to be studied.
• The evidence that the proposed mechanistic studies are feasible, given the availability of biological samples (immune cell subsets, DNA, RNA etc.).
• The participating mechanistic study sites and the investigators and their experience in the proposed study areas.
• How biological samples will be collected, distributed, processed and stored and what quality control measures will be used to ensure sample integrity.
• The availability of special services needed to complete the study (e.g. specialized equipment, high quality bioinformatics support).
• A summary of the statistical tests that will be used for data analysis. A more detailed and complete statistical analysis plan will be developed when studies are finalized post-award, with the assistance of the SACCC.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide, with the following 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.

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.

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

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

For this particular announcement, note the following:

The overarching goal of this FOA is to further clinical and mechanistic research on the prevention and treatment of food allergy, including food allergen-associated severe allergic reactions and anaphylaxis, and food allergen-associated eosinophilic esophagitis. A key feature of the FOA is the integration of clinical protocols with mechanistic studies. In this context, a critical question is whether the applicants have assembled a team of investigators capable of conducting state-of-the-art clinical and mechanistic studies of the immunopathogenesis of food allergies, including food allergen-associated severe allergic reactions and anaphylaxis, and food allergen-associated eosinophilic esophagitis

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

Reviewers will consider each of the review criteria below in the determination of scientific merit, but will not give a separate score for each.

• Have the applicants assembled a team of investigators capable of conducting state-of-the-art clinical and mechanistic studies of the immunopathogenesis of food allergies, including food allergen-associated severe allergic reactions and anaphylaxis, and food allergen-associated eosinophilic esophagitis?
• Is the Consortium as a whole scientifically compelling?
• Are there coordination and synergy of the individual research projects and the core towards the achievements of the central objectives of the Consortium?
• Will the integration of the individual projects into a single consortium be more beneficial than pursuing each project independently?
• Is the leadership plan adequate and appropriate to ensure sufficient communication and coordination among the investigators?
• Are plans for establishing and implementing collaborations with other Federal and non-Federal organizations/institutions for the co-sponsorship of research in areas of mutual interest and collaborations with industry for the evaluation of specific products/approaches adequate?
• Are plans for management of laboratory quality assurance and control adequate?
• Is the administrative and organizational structure appropriate and adequate to the attainment of the objectives?

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

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

Significance

Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or 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?

Have the investigators proposed clinical site leaders with a strong history and experience in successfully designing and conducting interventional clinical trials and non-interventional clinical studies in humans and support personnel capable to execute clinical protocols?

Have the investigators proposed mechanistic site leaders with a strong history and experience in conducting mechanistic research necessary to carry out the scope of the Consortium’s immunologic research relevant to food allergy immunopathogenesis and immunotherapeutics and technical personnel with immunology and molecular biology laboratory experience for research using human biologic samples, including appropriate GCP/IHC training in handling human biologic samples?

Innovation

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

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?

If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?

Do the clinical trials, clinical and mechanistic studies conform to the overall strategic plan outlined in the Research Plan and Administrative Core?

Is the study design for the interventional clinical trials, non-interventional clinical studies and associated mechanistic studies of high quality? Have the investigators demonstrated that they are feasible (including having relevant preliminary data)? Are plans for development, review, implementation, execution and management of interventional clinical trials and non-interventional clinical studies and associated mechanistic studies adequate, including, protocol development, selection and management of clinical and mechanistic study sites?

If animal studies are proposed, do they demonstrate a direct link to ongoing or planned human studies? Do they provide critical validation (e.g., proof of principle, pre-clinical safety data, and pharmacological/toxicological data) for subsequent human research studies, or provide clinical trials or clinical studies with background data for subsequent human laboratory methodologies?

Are state-of-the-art technologies and assays used in the mechanistic studies?

Are adequate statistical analysis plans included?

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?

Are adequate plans in place for training of investigators and staff at Clinical and Mechanistic Study Sites?

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

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

• Is the administrative and organizational structure appropriate to facilitate attainment of the objective(s) of the proposed CoFAR?
• Are the experience, level of commitment, and established competence in organizing multi-project and cores demonstrated, and availability of the Administrative Core Leader and administrative staff adequate to manage the CoFAR program?
• Are the operational activities of the Administrative Core appropriately justified as supporting the research projects?
• Are the plans for coordination, problem identification and resolution, and the organizational structure proposed appropriate and adequate to the attainment of the objective(s) of the proposed program? Does the management plan provide for ongoing formal and informal communications within the CoFAR? Has an administrative structure been proposed that allows for decisions to be made in the absence of the CoFAR Program leader or to replace him/her if the need arises?
• Are the proposed plans to manage subcontracts and fee-for-service activities adequate to assess the quality/appropriateness of the facilities, methods and other resources to be used?
• Are the plans for management (including fiscal) and planning, initiation, implementation, tracking, and monitoring adequate and timely for completion of planned activities?
• Are plans for reducing start-up time of multi-site studies by increasing the efficiency of IRB review using federated IRB models and for reducing redundancy, delays and excess due to duplicated infrastructure associated with a consortium of clinical sites adequate?
• Are plans for establishing and maintaining the functions of committees responsible for governance and management adequate?

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

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Children

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

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

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

Resubmissions

Not Applicable

Renewals

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

Revisions

Not Applicable

As applicable for the components 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

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

Budget and Period of Support

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

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

As part of the scientific peer review, all applications:

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

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

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

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

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

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

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

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

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

Any application awarded in response to this FOA will be subject to the DUNS, SAM Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

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

Cooperative Agreement Terms and Conditions of Award

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 74 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. The PD/PI will establish an Administrative Center composed of the PD/PI and financial and administrative personnel to carry out the following functions:

• Establish and maintain subcontracts with the clinical trials sites and the mechanistic sites.
• 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 a Steering Committee to serve as the governing body of the CoFAR.
• Establish, in consultation with the Steering Committee, an External Scientific Advisory Group (ESAG) composed of no less than 3 and no more than 5 clinical and basic science investigators.
• 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.
• Participate in meetings and teleconferences with key staff to review overall progress and future plans as determined by the NIAID Program Officer.

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

• NIAID will assign one or more Project Scientists to the grant. 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 accomplishment of the research by participating in the design of the activities, will advise in the selection of sources or resources, and will advise in management and technical performance. 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. Up to two NIAID Project Scientists will be designated voting members of the Consortium Steering Committee.
• Protocol Development, Review and Approval: NIAID Project Scientists and other NIAID staff will participate in the development, review, and approval of all clinical trials clinical study and mechanistic study protocols. All clinical trials, clinical study and mechanistic study protocols will be reviewed by NIAID and, depending on their level of complexity and risk, will be further reviewed by the DAIT/NIAID Clinical Research Committee and by the DAIT/NIAID Asthma and Allergy Data and Safety Monitoring Board (DSMB), Safety Monitoring Committee (SMC), 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 Consortium clinical trials requiring an IND/IDE. As part of NIAID’s IND/IDE sponsor responsibilities, the NIAID Medical Monitor will obtain, through the CoFAR 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 Consortium Statistical and Clinical Coordinating Center, will prepare and submit the final study reports to the FDA.
• 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 Clinical Study Sites. NIAID will convene an independent NIAID Data and Safety Monitoring Board (DSMB) or Safety Monitoring Committee (SMC) 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 Consortium Statistical and Clinical Coordinating Center conducts for cause monitoring visits to a Clinical Study Site. Depending on the seriousness of the problem, such visits may be conducted by the NIAID Medical Monitor and/or NIAID project management staff.
• 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 data from preclinical studies indicate a 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 agenda; (9) slow accrual; or (10) reaching a major study endpoint substantially before schedule and with persuasive statistical significance.
• Access to Data: The NIAID Project Scientists 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. Data must be available for external checking against the original source documentation.
• Scientific and Programmatic Oversight: An NIAID program official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. This stewardship includes monitoring program progress, approving changes and concurring in proceeding into study implementation stage. Release of each yearly funding increment for the CoFAR will be based on a review of progress. The Government, via the NIAID program official, will have access to data generated under this Cooperative Agreement and may periodically review the data and progress reports. 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 between NIH and Awardees include:

• Research Plans. Implementing, monitoring, and updating the clinical research plan for the Consortium to ensure consistency and relevance with the NIAID scientific priorities
• Research Activities. Reviewing the Consortium's research activities and goals on an agreed upon schedule (but no less than once every year)

Consortium Investigator Committee

The investigator committee includes the PD/PI of the CoFAR, the PD/PI of the Statistical and Clinical Coordinating Center, both clinical and mechanistic investigators at all study sites, and designated NIAID staff assigned to each project.

Consortium Steering Committee

The voting members of the Steering Committee will include the PD/PI of the U19, the PD/PI of the SACCC, three investigators chosen by the PD/PI of the U19 who are either Clinical Trial Site and/or Mechanistic study site projects leaders and up to two NIAID-designated Project Scientists.

External Scientific Advisory Group (ESAG)

The members of the ESAG will be selected from institutions outside those serving as members of the Consortium The ESAG should include expertise in the areas of food allergy pathophysiology, eosinophilic esophagitis, genetics, molecular biology, mucosal immunology and basic immunology, immunotherapeutics, clinical trials, and mechanistic studies in human immunologic diseases.

Responsibilities of the ESAG will include:

• During protocol development, reviewing and recommending improvements/modifications to study protocols developed by Protocol Teams
• Reviewing and advising the Steering Committee on the results obtained from studies undertaken by the Consortium
• Proposing specific studies and areas of research for Consortium consideration
• The recommendations by the ESAG will be submitted to the Consortium Steering Committee Chairperson and the NIAID Project Scientist.
• The ESAG will meet face-to-face during selected Steering Committee face-to-face meetings. At these meetings, ESAG sessions will be conducted to review study protocols at early stage of development, and major findings from Consortium-sponsored studies. The members of the ESAG may also participate in a joint session with the Consortium Steering Committee to convey and discuss the rationale for the Group’s recommendations. The NIAID Project Scientist may request a meeting with the members of the ESAG in the absence of any Consortium members.
• All ESAG recommendations shall be considered advisory and shall not be binding on the decisions made by the Consortium Steering Committee

Publications and Communications Policy

After the grant award, the Steering Committee will develop and implement policies and procedures for planning, authorship, preparation, review and final approval of manuscripts resulting from Consortium-supported studies and for submission of manuscripts for publication in peer-reviewed journals. All final manuscripts must be submitted to the NIAID for review in advance of journal submission. The respective roles, rights and responsibilities of pharmaceutical and medical device companies providing investigational materials for Consortium-sponsored studies in the publication review process will be specified in Clinical Trial Agreements (CTAs) between NIAID and the company.

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.

Public Access to Data Generated by the Consortium

All clinical trial and mechanistic data produced by this consortium will be made publicly available by NIAID, through the SACCC, within 18 months after database lock. 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.

Protocol-specific Training

Prior to the initiation of any clinical study, the Protocol Chair will organize and conduct, with the support of the Consortium Statistical and Clinical Coordinating Center, protocol-specific training for the participating investigators and the relevant clinical and technical clinical study site and mechanistic site staff. Training will include face-to-face meetings and teleconferences.

Clinical Study Implementation and Management

The PD/PI will work in coordination with the Consortium Statistical and Clinical Coordinating Center to execute the following tasks:

• 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 Consortium Statistical and Clinical Coordinating Center 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 Consortium Statistical and Clinical Coordinating Center for initial review and assessment, followed by final assessment and classification by the NIAID-designated Medical Monitor.
• Establish and implement policies and procedures to ensure that all clinical study sites and mechanistic sites have the required supply of study materials for study initiation and conduct, and monitor supplies throughout the duration of the study.
• Establish and implement policies and procedures for the secure transfer of clinical and laboratory data to the central databases of the Consortium Statistical and Clinical Coordinating Center. Training for site personnel in the use of these databases will be provided by the Consortium Statistical and Clinical Coordinating Center.

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

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 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 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 Non-Competing Continuation Grant Progress Report (PHS 2590 or 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)Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

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

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

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

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

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

Louis A. Rosenthal, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-402-8399
Email: [email protected]

Chernay Mason
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-435-2068
Email: [email protected]

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

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92 .