EXPIRED
National Institutes of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Immune Tolerance Network (UM1 Clinical Trial Required)
UM1 Research Project with Complex Structure Cooperative Agreement
Reissue of RFA-AI-12-043
December 18, 2019 - Notice of Clarification of Funding Restriction Information in RFA-AI-19-068. See Notice NOT-AI-20-018
NOT-OD-19-128, Changes to NIH Requirements Regarding Proposed Human Fetal Tissue Research.
NOT-OD-19-137, Clarifying Competing Application Instructions and Notice of Publication of Frequently Asked Questions (FAQs) Regarding Proposed Human Fetal Tissue Research.
RFA-AI-19-068
None
Only one application per institution is allowed as defined in Section III. 3. Additional Information on Eligibility.
93.855
The purpose of this Funding Opportunity Announcement (FOA) is to solicit applications for the Immune Tolerance Network. The major goal of this Network is to develop tolerogenic approaches for the treatment and prevention of disease in three clinical areas: asthma and allergic diseases; autoimmune diseases; and immune-mediated consequences of allotransplantation. The scope of research to be carried out includes: 1) the design and conduct of clinical trials at all phases to evaluate the safety and efficacy of investigational products and approaches for the induction and maintenance of immune tolerance in humans, 2) the design and conduct of mechanistic studies and the development of tolerance assays as integral components of the clinical trials undertaken, including establishing and directing a consortium of laboratories and one or more biospecimen repositories, and 3) the provision of bioinformatics, data collection, validation and analysis resources. In addition, on a limited basis, the Network may support focused product development and nonclinical studies (e.g., toxicology, pharmacology, pharmacokinetics, etc.) essential for the subsequent evaluation of promising tolerance induction approaches in humans.
December 6, 2019
February 3, 2020
February 3, 2020
March 3, 2020
All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s)
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.
Not Applicable
October 2020
March 4, 2020
Not Applicable
It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.
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
The purpose of this FOA is to solicit applications for the Immune Tolerance Network. The major objective of the Network is to develop tolerogenic approaches for the treatment of disease in three clinical areas: asthma and allergic diseases; autoimmune diseases; and immune-mediated consequences of allotransplantation. The scope of research to be carried out by the Network includes:
1) the design and conduct of clinical trials at all phases to evaluate the safety and efficacy of investigational products and approaches for the induction and maintenance of immune tolerance in humans; 2) the design and conduct of mechanistic studies and the development of tolerance assays as integral components of the clinical trials undertaken; and establishment of biospecimen repositories 3) the provision of services on data management in collaboration with other resources provided by NIAID, bioinformatics analysis, and data sharing in a secure computing environment to support clinical trials and mechanistic studies. The Network may also support limited product development and nonclinical studies (e.g., toxicology, pharmacology, pharmacokinetics, etc.) essential for the subsequent evaluation of promising tolerance induction approaches in humans.
The successful induction of immune tolerance is a major therapeutic goal for the treatment of immune-mediated diseases, including asthma and allergic diseases; autoimmune disorders, such as rheumatoid arthritis and type 1 diabetes; and immune-mediated rejection of transplanted solid organs, tissues, and cells. Tolerance induction strategies aim to selectively block or prevent deleterious immune responses, while leaving protective immunity intact. More than two decades of highly intensive and productive basic research in immunology have provided a solid foundation of knowledge and understanding that will enable the application of promising tolerance induction strategies to the treatment of immune-mediated diseases and transplantation, and enhanced understanding of the underlying mechanisms of disease and therapeutic effect.
Asthma and allergic diseases are among the major causes of illness and disability in the U.S., affecting more than 1 in 5 Americans. Asthma afflicts over 26 million Americans or 7.9 percent of the U.S. population; atopic dermatitis affects up to 20% of children worldwide and, in many of them, it is considered the first step in later development of other allergic conditions, also known as the "atopic march"; allergic rhinitis is estimated to affect 60 million Americans and chronic rhinosinusitis more than 30 million. Food allergy was reported to afflict 5.6 million children under the age of 18 in 2019. In asthma and allergic diseases, the goal of tolerance research is to prevent the development of pathogenic immune responses (mostly Type 2 and IgE-mediated) against aeroallergens and food allergens or to shift such responses towards non-pathogenic states.
Autoimmune diseases are chronic disabling disorders in which immune responses are directed against host cells, tissues, and organs. More than 100 autoimmune diseases have been identified and, for reasons that are not clear, the prevalence of these diseases is rising. Collectively, autoimmune diseases affect approximately 23.5 million people in the U.S., and represent a significant physical, emotional, social, and fiscal burden for patients, their families, and society. These diseases can affect any organ or organ system, and all ages are affected, with onset from childhood to late adulthood. In autoimmune diseases, novel approaches are needed to block deleterious immune responses.
The benefits of organ transplantation, as evidenced by prolonged survival and/or improved quality of life, have been clearly demonstrated for children and adults suffering from a wide range of congenital and acquired diseases. In 2018, 36,527 transplants were performed in the U.S., with approximately 114,000 candidates on the transplant waiting list. Although one-year survival after transplantation has improved markedly for every organ, barriers to long-term graft and patient survival include incompatibility between donor and recipient, acute rejection, chronic graft dysfunction, and complications of long-term use of immunosuppressive drugs. In transplantation, donor-specific immune tolerance - a selective blockade of immune responses directed against the graft - would enable long-term graft survival without the complications and risks of systemic immunosuppressive therapy (e.g., infection, malignancy, and atherosclerosis).
The NIAID has a long-standing commitment to supporting basic, translational and clinical research on immune tolerance with the ultimate goal of developing novel, efficacious therapies for the induction and maintenance of antigen-specific immune tolerance in humans. In 1999, the NIAID awarded a seven-year contract to establish the Immune Tolerance Network - a major program resulting from the scientific planning process, designed to: (1) develop a long-term scientific agenda for clinical trials and mechanistic studies; (2) design and conduct clinical trials at all phases to determine the safety, toxicity and efficacy of tolerogenic treatment strategies for multiple immune system diseases; and (3) design and conduct research to delineate the underlying mechanisms of immune tolerance as an integral part of the clinical trials undertaken by the Network, as well as clinical trials sponsored by other Federal and private sector organizations and companies. In 2007, the contract was recompeted and expanded to include limited nonclinical research and product development, as well as bioinformatics, data collection and analysis. In 2014, the Immune Tolerance Network program was recompeted under a cooperative agreement award.
Since the establishment of this Network in 1999, substantial progress has been made in evaluating diverse tolerogenic products and approaches for a broad range of immune-mediated diseases, enhancing our understanding of underlying mechanisms, and assessing the induction, maintenance and loss of tolerance through multiple assays. Achieving complete and durable tolerance in the setting of established disease has proven to be challenging; hence, studies that provide step-wise advances in achieving over-arching goals have been an important strategy in advancing tolerance research. The Network has initiated 65 clinical trials with associated mechanistic studies: 18 clinical trials in asthma and allergic diseases; 27 clinical trials in autoimmune diseases; and 20 clinical trials in transplantation. It is anticipated that 20 studies will be ongoing at the completion of the current contract and will be continued and completed during the new award period. Additional information about the research activities of the current Network, publications, the status of the studies, as well as information on organizational structure and membership, may be obtained from the Network website here (http://www.immunetolerance.org).
The Network will function as a cross-disciplinary, open consortium with proposed activities for clinical trials and integrated mechanistic studies accepted from investigators both within and outside of the Network and with support provided to Network and non-Network institutions and researchers.
For this FOA, immune tolerance is broadly defined as a clinical phenotype characterized by selective elimination of pathogenic immune responses to relevant antigens (e.g., alloantigens, autoantigens or allergens), with preservation of protective immunity, with no or minimal requirement for ongoing immunosuppression or other immune-based intervention. Approaches may include a variety of mechanisms such as deletion, induction of anergy, immune deviation, sequestration, exhaustion or suppression.
Research Scope: The scope of research to be performed by the Network includes:
Disease-specific Research Priorities: Research priorities within each of the three clinical areas include, but are not limited to, the following:
Allergic Diseases and Asthma
In pursuing the above priorities, research efforts should also be targeted towards improving the effectiveness, safety and patient acceptability of specific allergen immunotherapy using new forms of allergenic products, alternative routes of administration and combination with other immunomodulatory interventions.
Autoimmune Diseases
Innovative, immune-based approaches to restore tolerance, while preserving protective immunity, targeting cell subsets and pathways, including but not limited to:
Transplantation
Innovative tolerogenic approaches to improve long-term graft survival and decrease the adverse immunologic consequences of allotransplantation and pharmacologic immunosuppression, including but not limited to:
The Immune Tolerance Network operates in a coordinated manner across four functional areas: Leadership, Clinical Operations, Core Laboratory, and Bioinformatics. These functional areas are integrally connected to all aspects of the Research Agenda for the prevention and treatment of immune-mediated diseases. The Network functions as a collaborative effort under the direction of the PD(s)/PI(s) with input from key personnel, Network clinical and basic science investigators, Executive and Steering committees, activity-specific subcommittees within the Network and NIAID.
The Leadership Group (LG), led by the PD(s)/PI(s), is responsible for the overall administrative leadership of the Network as well as oversight and evaluation of all Network Activities. The LG is also responsible for the following:
The Clinical Operations Group (COG) provides leadership for the development, implementation, and monitoring of clinical trials, performing clinical site feasibility assessments and other pre-study initiation requirements, development of clinical protocols, study implementation and safety oversight, and ensuring adherence to all standards for FDA, ICH, GMP and other regulatory compliance issues related to clinical trials and biospecimen collection.
The Core Laboratory Group (CLG) is responsible for: 1) designing and implementing mechanistic studies as integral elements associated with the clinical trials; 2) developing and implementing laboratory performance standards and metrics; and 3) implementing procedures for conducting quality assurance and quality control on mechanistic data and samples. In addition, the CLG will accept responsibility for and operate the existing Network repositories as directed, and if needed will establish and operate a repository for clinical specimens generated by Network clinical trials and mechanistic studies, including sample collection methods, tracking, storage, inventory, retrieval and packaging and shipment of specimens in support of the Research Agenda.
The Bioinformatics Group (BG) is responsible for collecting, validating and analyzing mechanistic data, integrating the mechanistic and clinical data, managing all data sources in a secure computing environment to support workflows of clinical trials and mechanistic studies, conducting integration, harmonization and analysis of such data across Network clinical trials and mechanistic studies and providing Web-access to data and analysis results, and sharing data through public repositories and complying with NIH Data Sharing policies and community-based best practices. The BG will also operate a data management system, provide capabilities of analysis and data sharing for mechanistic study data and de-identified clinical data while integrating data sharing with other Division of Allergy, Immunology and Transplantation (DAIT)-supported programs.
The NIAID will provide certain resources to support the design, development, implementation, oversight and monitoring of Network clinical trials, the conduct of mechanistic studies and the analysis of final study data. The Network will cooperate with NIAID to ensure that clinical research complies with all applicable regulatory requirements as well as NIAID policies and procedures. These resources include:
The NIAID will provide funds to the Leadership Group (LG) to support centralized operational, administrative and research-related resources for all Network-affiliated clinical trials and mechanistic studies, including evaluation of proposed research concepts, study design and protocol development, study implementation, oversight and follow-up, and analyses of final integrated study data.
Note: For further information, please visit the following website for general information and questions and answers. https://www.niaid.nih.gov/grants-contracts/questions-answers-rfa-ai-19-068.
See Section VIII. Other Information for award authorities and regulations.
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. See Section VI.2 for additional information about the substantial involvement for this FOA.
New
Renewal
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.
Required: Only accepting applications that propose clinical trial(s)
Need help determining whether you are doing a clinical trial?
NIAID intends to commit $27 million in FY 2021 to fund 1 award.
Recommended application budgets are limited to $23 million per year in direct costs.
The proposed project period must be 7 years.
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.
Higher Education Institutions
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
o Hispanic-serving Institutions
o Historically Black Colleges and Universities (HBCUs)
o Tribally Controlled Colleges and Universities (TCCUs)
o Alaska Native and Native Hawaiian Serving Institutions
o Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)
Nonprofits Other Than Institutions of Higher Education
For-Profit Organizations
Governments
Other
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.
Program Directors/Principal Investigators (PD(s)/PI(s))
All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.
Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
Only one application per institution (normally identified by having a unique DUNS number or NIH IPF number) is allowed.
The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:
The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.
It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.
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:
The letter of intent should be sent to:
Julio Aliberti, PhD
Telephone: 301-761-7322
Fax: 301-480-2310
Email: julio.aliberti@nih.gov
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed with the following additional information:
The Research Strategy must consist of the following subsections with the indicated page limits:
Subsection A: Overview of the Immune Tolerance Network --one required -- 12 pages
Subsection B: Leadership Group -- one required -- 30 pages
Subsection C: Clinical Operations Group -- one required -- 30 pages
Subsection D: Core Laboratory Group -- one required -- 30 pages
Subsection E: Bioinformatics Group -- one required -- 12 pages
The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional information:
Facilities and Other Resources
Clinical Sites and Facilities: Describe the unique and necessary aspects of the facilities to be used for clinical care and clinical research that support the proposed Network research activities. Describe how the facilities will be monitored and secured based on the nature of the research performed therein.
Data Management Facilities: Describe the unique facilities and features of the data management section to support the processes for the reliable and accurate collection and recording of the data, and the features of the facilities that will enable rapid and secure transfer of all data types between the Network and NIAID's supporting awards.
Laboratory Resources and Facilities: Describe the unique and necessary aspects of the facilities related to acquisition, preparation and use of the biological samples to be used for mechanistic research studies. Describe the storage facilities appropriate for various specimens and how the facilities will be monitored and secured based on the nature of the data.
Sample Repository Facilities: Describe the unique and necessary aspects of the facilities needed for the receipt, identification, handling (e.g., aliquot, sample-specific preparation), labeling and storage of the Biological samples. Describe the storage facilities appropriate for various specimens or reagents, and how the facilities will be monitored and secured based on the nature of the data.
Other Attachments: Applicants must provide a Quality Management Plan as described below as a single file attachment for this section.
Quality Management Plan
Provide a full Quality Management Plan including quality control, quality assurance and quality improvement.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional information:
Applicants must budget for the following:
Applicants must request all necessary funds to support the infrastructure and operations of the entire Network. For budgeting purposes, applicants should plan according to the information provided below:
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
Specific Aims: Provide the specific aims for the Network and describe how they support the overall proposed Network Research Agenda.
Research Strategy: The Research Strategy section must consist of a single attachment consisting of subsections A-E, as designated below.
Subsection A. Overview of the Immune Tolerance Network
Describe the overall Network structure and function with respect to advancing immune tolerance induction strategies through clinical trials and integration of studies of underlying mechanisms of the induction, maintenance and loss of tolerance. From a high-level perspective, describe approaches to integrating all Network functional areas (Leadership Group, Clinical Operations Group, Core Laboratory Group and Bioinformatics Group), and plans for coordinating with the clinical sites participating in approved studies to create a fully-integrated, collaborative organization in support of the immediate and long-range goals of the Network research. The use of organizational charts, diagrams or other tools to represent the Network are encouraged. Discuss how the proposed organization will facilitate decision-making and the ability to drive studies through to completion and highlight any innovative aspects for the integration of a large, complex clinical research program.
Subsection B: Leadership Group (LG)
In this subsection, describe the organization of the LG and discuss how the organizational structure promotes effective leadership of the overall Network and proposed activities. Provide tables, diagrams, flow charts or organizational charts as appropriate to reflect the organization of the Network’s four functional areas Leadership (LG), Clinical Operations (COG), Core Laboratory (CLG) and Bioinformatics (BG) and any additional activities, such as executive, steering or subcommittees proposed. Include the following information:
Network Structure and Governance:
Network Operations:
Network Evaluation and Improvement:
Network Research Agenda:
Present the proposed Network Research Agenda to advance immune tolerance induction strategies through clinical trials and to integrate studies of underlying mechanisms of the induction, maintenance and loss of tolerance. Consider the following elements:
Subsection C: Clinical Operations Group (COG)
Study Feasibility Assessment:
Protocol Development:
Protocol Implementation and Oversight:
Subsection D: Core Laboratory Group (CLG)
Quality Management, Evaluation and Improvements:
Communications and Clinical Site Laboratory Capacity/Training:
Subsection E: Bioinformatics Group (BG)
Structure and Governance:
Data Management System:
Primary and Secondary Analyses:
Letters of Support:
The Letters of Support attachment should begin with a table of letter authors, their institutions, and the type of each letter (institutional commitment or resources; collaboration or role in the project; potential or current user of a resource or service proposed in the application).
Provide all appropriate letters of support, including any letters necessary to demonstrate the support of consortium/site participants, cores, laboratories, pharmacies and other collaborators. If parts of the costs of the trial are to be borne by sources other than NIH, these contributions must be presented in detail as part of supporting letters signed by Authorized Organization Representative. These outsource costs do not constitute cost sharing as defined in the current NIH Grants Policy Statement and should not be presented either as part of the requested budget.
To document their commitment, include letters in support of the following:
Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:
Appendix:
Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:
If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.
Study Record: PHS Human Subjects and Clinical Trials Information
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
Although applicants must be prepared for clinical trials, definite plans for such involvement will not be available at the time of application submission. A study record must not be completed.
Delayed Onset Study
Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
All applicants must add and complete the Delayed Onset Study record and must check box "Anticipated Clinical Trial?"
Study Title-- use: "Multiple Delayed-Onset Studies"
Justification Attachment: Indicate each clinical study protocol developed during the project period will be subject to approval through a procedure that involves an initial concept submission and subsequent review by the Immune Tolerance Network. If the concept receives approval, the next stage will be development of the protocol, which also must undergo review and approval prior to implementation through the Immune Tolerance Network.
All instructions in the SF424 (R&R) Application Guide must be followed.
See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov
Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.
Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.
Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.
Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.
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.
Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.
For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.
Important reminders:
All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.
The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.
See more tips for avoiding common errors.
Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.
Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.
Only the review criteria described below will be considered in the review process.
Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.
A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.
Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).
Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.
Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?
Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?
Specific to this FOA:
Is the Network scientifically compelling as a whole? To what extent will the Network Research Agenda address the current state-of-the-art research, techniques, approaches and models, and will it shape the structure, direction and future activities of the Network research? How well does the proposed Research Agenda build on prior work in immune tolerance while advancing the science in new directions? Does the Research Agenda identify current research gaps and opportunities, and prioritize research activities?
Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?
With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?
Specific to this FOA:
Do the PD(s)/PI(s) and the key personnel provide the appropriate balance of leadership and technical expertise necessary to succeed in the implementation of the network? Have the PD(s)/PI(s) committed a sufficient amount of time and effort to the development, implementation and oversight of the network administration, management and research activities?
Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?
Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?
Specific to this FOA:
How well does the Network research agenda incorporate innovative and creative research approaches to the planned research? For example, are there innovative approaches to reach, recruit and retain a diverse and representative population of patients with immune tolerance diseases? Will the proposed innovative approaches significantly influence the immune tolerance community?
Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?
If the project involves human subjects and/or NIH-defined clinical research, are the plans to address
1) the protection of human subjects from research risks, and
2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?
Does the application adequately address the following, if applicable?
Study Design
Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?
Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?
Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?
Data Management and Statistical Analysis
Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?
Specific to this FOA:
Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?
If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?
Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?
If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?
If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?
Specific to this FOA:
Are there adequate, available and appropriate clinical, mechanistic and repository facilities for the clinical care and research required to support the Network? Are the proposed repository facilities and equipment adequate for the scope and volume of work anticipated?
As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.
Study Timeline
Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?
Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?
For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.
For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.
When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.
The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.
Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.
Not Applicable
For Renewals, the committee will consider the progress made in the last funding period.
Not Applicable
As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.
Not Applicable
Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).
Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).
For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.
Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.
Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the National Institute of Allergy and Infectious Diseases , in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.
As part of the scientific peer review, all applications:
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:
After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.
Information regarding the disposition of applications is available in the NIH Grants Policy Statement.
If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.
A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.
Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.
Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.
Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.
ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain applicable clinical trials on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm
Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.
Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).
Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).
All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.
Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.
For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.
In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.
Cooperative Agreement Terms and Conditions of Award
The following special terms of award are in addition to, and
not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB)
administrative guidelines, U.S. Department of Health and Human Services (DHHS)
grant administration regulations at 45 CFR Part 75, and other HHS, PHS, and NIH
grant administration policies.
The administrative and funding instrument used for this program will be the
cooperative agreement, an "assistance" mechanism (rather than an
"acquisition" mechanism), in which substantial NIH programmatic
involvement with the awardees is anticipated during the performance of the
activities. Under the cooperative agreement, the NIH purpose is to support and
stimulate the recipients' activities by involvement in and otherwise working
jointly with the award recipients in a partnership role; it is not to assume
direction, prime responsibility, or a dominant role in the activities.
Consistent with this concept, the dominant role and prime responsibility
resides with the awardees for the project as a whole, although specific tasks
and activities may be shared among the awardees and the NIH as defined below.
The PD(s)/PI(s) will have the primary responsibility for:
NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
NIAID Program Officials and Project Scientists along with other NIH staff will coordinate the activities below and will be identified at the time of award.
Areas of Joint Responsibility include:
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 Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.
A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.
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.
In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.
We encourage inquiries concerning this funding opportunity
and welcome the opportunity to answer questions from potential applicants.
eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred
method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
General Grants Information
(Questions regarding application instructions, application processes, and NIH
grant resources)
Email: GrantsInfo@nih.gov (preferred
method of contact)
Telephone: 301-945-7573
Grants.gov Customer Support (Questions regarding
Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov
Leighton Thomas
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3522
Email: lathomas@niaid.nih.gov
Julio Aliberti, PhD
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-761-7322
Email: julio.aliberti@nih.gov
Tseday Girma
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-747-7388
Email: tseday.girma@nih.gov
Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75 .