Part 1. Overview Information

Key Dates

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

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

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

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

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

There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

1. Use the NIH ASSIST system to prepare, submit and track your application online.
2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.
3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Background and Research Scope

Inducing immune tolerance is a primary goal for preventing and treating immune-mediated diseases. Immune tolerance strategies aim to block harmful immune responses while leaving protective immunity intact. Decades of basic immunology research provide a strong foundation for applying such strategies to current and future clinical challenges. The Immune Tolerance Network (ITN) has conducted clinical and mechanistic studies of immune tolerance in the fields of allergy and asthma, autoimmunity, microbiome and immune system interactions, chronic inflammation, and prevention of transplant rejection.

This notice of funding opportunity (NOFO) will support a cross-disciplinary consortium responsible for conducting research in three areas of immune-mediated conditions. Input from clinicians and immunologists, both within and outside the Network, will be important toward the design, development, and conduct of clinical trials and integrated mechanistic studies. The three clinical areas, along with examples of high-priority research topics, include:

Allergic Diseases and Asthma
Allergic diseases and asthma are the most common chronic conditions of children in the United States and are among the leading chronic conditions of adults. Immune tolerance research in this field seeks to prevent or reverse pathogenic immune responses to the allergens that relate to these conditions. Within this clinical area, priority areas of research the ITN will support include: 

• Interventions to prevent disease development or progression or induce durable remission.
• Novel allergen immunotherapy approaches to improve safety, effectiveness, and patient adherence.
• Clinical studies to understand the mechanisms that drive the natural development or loss of tolerance.

Autoimmune Diseases
Approximately 50 million Americans are living with autoimmune diseases, making them among the most common chronic conditions in the United States. New approaches are critically needed to prevent disease and/or restore normal immune function. Within this clinical area, priority areas of research the ITN will support include: 

• Novel antigen-specific/novel therapies that prevent disease progression or modulate autoreactive immune responses.
• Novel strategies, such as co-stimulatory blockade, cytokine modulation, or T regulatory cell induction or administration, to restore immune homeostasis.
• Strategies that involve immune cell depletion or replacement to reset or "re-educate" the immune system to restore immune tolerance.

Transplantation
Organ transplantation saves tens of thousands of lives annually, yet long-term success is challenging, with 10-year graft survival rates ranging from <30% for lung to 60-70% for kidney transplant recipients. Although >49,000 organ transplants were performed in the United States in 2025, there were >81,000 waitlist additions, with >100,000 candidates remaining on waitlists at the end of 2025. Immune tolerance research in transplantation aims to prevent graft rejection and reduce long-term health impacts of immunosuppressive drugs and reduce the need for repeat organ transplantation. Within this clinical area, priority areas of research the ITN aims to support include:

• Innovative approaches to promote donor specific tolerance and/or long-term graft survival, including cell-based therapies and novel biologic agents.
• Innovative approaches to reduce the long-term impact of current transplant therapies, e.g., nephrotoxicity, malignancy, and allosensitization.
• Biomarkers that can risk-stratify patients and predict allograft tolerance.

Functional Areas

The ITN is structured to satisfy the following four functions: Leadership, Clinical Operations, Core Laboratory (or laboratories), and Bioinformatics. These functions are integrally connected to all aspects of the clinical areas of interest. The Network functions as a collaborative unit under the direction of the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)). The functional areas and their overall roles and responsibilities include:

Leadership: The PD(s)/PI(s) will serve as the overall administrative leadership and financial governance of the Network. Leadership is responsible for establishing the Network's research priorities, governance, and quality management, including oversight and evaluation of all Network activities. Leadership is also responsible for the following: 

• Collaborative activities with other clinical networks and clinical research programs.
• Coordination and implementation of the research agenda across the three clinical areas. 
• Establishment and Oversight of Committees, such as:
  • Executive Committee - scientific leadership and implementation of the research agenda
  • Steering Committee - leadership and oversight of the Network functions and recommend changes in direction, scope, or prioritization of the research agenda
• Clinical Research Portal to support:
  • Information regarding status of upcoming and recruiting studies
  • Data collection 
  • Data analysis and tools for ITN investigators and collaborators
  • Public access to ITN data to promote reproducibility and replication research
  • Availability of biorepository samples and information on how these can be accessed by the research community
  • Access to protocol documents, methodologies, and standard operating procedures, as appropriate

Clinical Operations:

• Clinical trial development, implementation, and oversight
• Providing and reviewing documents required for regulatory compliance

Core Laboratory:

• Mechanistic studies
• Laboratory standards and metrics
• Biorepository

Bioinformatics:

• Mechanistic assay validation and analysis
• Integration of clinical and mechanistic data

Resources

In support of the ITN, NIAID serves as the regulatory sponsor for most Network clinical trials conducted under Investigational New Drug (IND) Applications, Investigational Device Exemptions (IDEs), and international equivalents, assuming full sponsor regulatory responsibility and will be responsible for several resources to support clinical trial design, implementation, oversight, and data analysis, to include but not limited to:

• Allergy and Asthma Statistical and Clinical Coordinating Center (AA-SCCC)
• Autoimmune Diseases Statistical and Clinical Coordinating Center (AD-SCCC)
• Transplantation Statistical and Clinical Coordinating Center (T-SCCC)
• Clinical Data and Safety Management Center (CDSMC)
• Clinical Site Monitoring Contract (CSMC)
• Clinical Products Center (CPC)
• Regulatory Management Center (RMC)
• Immunology Database and Analysis Portal (ImmPort)

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

Applications Not Responsive to this NOFO

The following types of applications are not responsive to this NOFO and will not be reviewed:

• Applications that do not cover all three clinical areas

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

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions - Includes all types

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Local Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)

Federal Governments

• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

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

Foreign Organizations/Foreign Collaborations

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

NIH will no longer issue awards (i.e., new, renewal, or non-competing continuation) to domestic or foreign entities that involve foreign subawards/subcontracts. All NIH-funded research involving foreign subawards/subcontracts must be submitted in response to a NOFO that is specifically designated for funded international collaborations. See NIH Grants Policy Statement 16.8 Collaborative International Research Awards.

Applications involving foreign subawards/subcontracts submitted in response to this NOFO will be deemed noncompliant and will not be considered for funding. This policy applies to all monetary international collaborations resulting in foreign subawards/subcontracts, however, it does not preclude unfunded international collaborations or foreign components, funding for foreign consultants, or procurement of unique equipment or supplies from foreign vendors.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the How to Apply - 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. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information

• System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code. Foreign organizations must obtain a NATO Commercial and Government Entity (NCAGE) Code (in lieu of a CAGE code) in order to register in SAM.
  • Unique Entity Identifier (UEI)- A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registrations; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov – Applicants must have an active SAM registration in order to complete the Grants.gov registration.

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

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

All PD(s)/PI(s) must be registered with ORCID. The personal profile associated with the PD(s)/PI(s) eRA Commons account must be linked to a valid ORCID ID. For more information on linking an ORCID ID to an eRA Commons personal profile see the ORCID topic in our eRA Commons online help.

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 their organization to develop an application for 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 How to Apply - Application Guide.

2. Cost Sharing

This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement NIH Grants Policy Statement Section 1.2 Definition of Terms.

3. Additional Information on Eligibility

Number of Applications

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per NIH Grants Policy Statement Section 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NIH Grants Policy Statement 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

Section IV. Application and Submission Information

1. Requesting an Application Package

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

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise (in this NOFO, in a policy notice, or other notice from NIH Guide for Grants and Contracts). Conformance to the requirements in the How to Apply - Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Page Limitations

All page limitations described in the How to Apply – Application Guide and the Table of Page Limits must be followed, with the following additional instructions:

Within the Research Strategy, including the following subsections with the indicated page limits:

Subsection A: Overview of the Immune Tolerance Network – one required - 12 pages
Subsection B: Leadership – one required - 30 pages
Subsection C: Clinical Operations – one required - 30 pages
Subsection D: Core Laboratory – one required - 30 pages
Subsection E: Bioinformatics – one required - 12 pages

The following section supplements the instructions found in the How to Apply – Application Guide and should be used for preparing an application to this NOFO.

SF424(R&R) Cover

All instructions in the How to Apply - Application Guide must be followed.

SF424(R&R) Project/Performance Site Locations

All instructions in the How to Apply - Application Guide must be followed.

SF424(R&R) Other Project Information

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

Facilities and Other Resources

Describe the unique and essential components of the facilities and resources that will be required for:

• Clinical care and research that support the proposed Network activities, including their monitoring and security.
• Reliable and accurate collection and recording of data, and the features of the facilities that will enable curation, secure maintenance, and rapid and secure transfer of all data types between the Network, NIAID, and resources (including research support organizations/entities) provided by NIAID. Describe the resources/plans for management of potential data security breach. 
• Receipt, identification, validation, handling (e.g., aliquot, sample-specific preparation), labeling, storage, tracking, and destruction of biological samples.
• Management and storage of various specimens or reagents, and how the facilities will be monitored and secured based on the nature of the data.

SF424(R&R) Senior/Key Person Profile

All instructions in the How to Apply - Application Guide must be followed.

R&R Budget

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

Include the following:

• A minimum of 3.6 person months per year for the PD/PI. If two or more PD(s)/PI(s) are named, each PD/PI must devote at least 1.8 person months of effort to the project. In the budget justification, provide a detailed apportionment of the PD(s)/PI(s) time to administration, management, and research activities associated with the Network functions.
• One initial Kick-Off Meeting within the first 6 months of the award in the Bethesda, MD area for the PD(s)/PI(s) and key personnel.
• Two ITN Steering meetings per year with the location to be determined by NIAID for the PD(s)/PI(s) and key personnel.

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:

• Anticipate initiating a minimum of four new clinical trials per year.
• Assume a balance of new clinical and associated mechanistic studies across the three disease areas over the duration of the award.
• At the time of award, approximately 20 clinical trials and associated mechanistic studies involving an estimated 200 sub-agreements will be ongoing. Details for these clinical trials and studies can be found at www.clinicaltrials.gov. 
• In the budget justification, for all new activities, provide a budget breakout under each group in clearly labeled sections: Leadership, Clinical Operations, Core Laboratory, and Bioinformatics for all proposed activities. Examples of breakout activities include:
  • Design, implementation, and support of clinical trials and mechanistic studies; laboratory functions (including sample collection, storage, and shipping to the biorepository); and bioinformatics functionality and security.
  • Detailed budget for the planning, implementation, and completion of new clinical trials and mechanistic studies. 
  • Detailed budget for the infrastructure and core support functions, including Network personnel, consultants, and related research support resources required to carry out and complete both new and ongoing clinical trials and mechanistic studies.

Outsource costs do not constitute cost sharing as defined in the current NIH Grants Policy Statement and should not be presented as part of the requested budget.

R&R Subaward Budget

All instructions in the How to Apply - Application Guide must be followed.

PHS 398 Cover Page Supplement

All instructions in the How to Apply - Application Guide must be followed.

PHS 398 Research Plan

All instructions in the How to Apply - 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 proposed Network research agenda.

Research Strategy: The Research Strategy section should 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 for integration of the four Network functional areas (Leadership, Clinical Operations, Core Laboratory, and Bioinformatics) and coordination with clinical sites to create a fully integrated, collaborative organization. Provide organizational charts, diagrams or other tools to represent the Network. Discuss how the proposed organization will facilitate decision-making and the ability to complete studies.

Subsection B: Leadership
Describe the functions of leadership and discuss how the organizational structure promotes effective leadership of the overall Network and proposed activities. Provide tables, diagrams, flow charts or organizational charts to reflect the organization of the Network's four functional areas and activities, e.g., Network Executive Committee, Network Steering Committee, or subcommittees proposed. Include the following information:

Network Structure and Governance:
Describe the following:

• General plans for leadership management and oversight of Network activities, including discussions on overall planning, priority setting and decision-making, operational support and resource planning, and coordination for all research projects, including clinical trials and mechanistic studies. Discuss the role of key stakeholders in these decisions.
• Leadership plans to integrate NIAID-provided resources into the overall organizational structure and to minimize duplication of effort within the following: 
  • Clinical Trial Planning, Management, and Coordination 
  • Investigational Product Management
  • Regulatory Compliance 
  • Centralized Data Repository
• Proposed staffing plans for leadership, including lines of authority, and discussion of how the staffing will contribute to effective governance.
• The Network's approach to governance, including establishment of internal committees (e.g., Executive Committee and Steering Committee) and their composition, roles, and responsibilities and decision-making authorities. Do not name potential committee members who are not already key personnel within the application prior to award.
  • Process for selection of individuals to serve on and the structure and function of the committees involved in the governance of the award.
• How project management will be used to develop, record, and monitor individual projects and higher-level program benchmarks, timelines, and contingency plans.
• Plans for communications:
  • Within and across functional areas of the Network. 
  • With contract research organizations or other entities that support ITN activities, NIAID staff, and other stakeholders. 
  • With the scientific community, patient advocacy groups, and the general public. 
• Processes, procedures, and plans, including frequency, of leadership to meet to share scientific and programmatic information, assess scientific progress, and identify new research opportunities and potential avenues of collaboration, both within the Network and with other stakeholders.
• Proposed plans to identify opportunities for collaborations with other federal and private sector research organizations/programs to establish joint sponsorship arrangements that will capitalize on non-Network clinical research resources in furtherance of the research agenda. 
• How leadership will oversee and maximize use of the biorepository samples to advance the Network strategic priorities.

Network Operations:
Describe and/or provide the following:

• Network operations structure, management, and oversight with an emphasis on scientific rigor, efficiency and effectiveness.
• An organizational chart demonstrating the proposed structure for centralized Network operations.
• Plans for the review, award, and management of Network research activities, including monitoring performance and terminating projects as needed.
• The proposed time frames/benchmarks associated with carrying out Network operations.
• Fiscal management plan for administering, tracking, and reporting ITN budgets and activities.
• Plans for managing Network business activities, including staff composition and strategies for effective oversight and cost minimization.
• Plans for ensuring adequate clinical research capacity, including the number of clinical sites, use of social media, and strategies for recruiting and retaining study participants.
• The rationale and plans for soliciting, incorporating, approving, and awarding additional clinical research sites when recruitment for a clinical study is inadequate.
• The biorepository policies and procedures to be followed for sample collection, storage, destruction, distribution including the review, and approval of request for access to samples.

Network Evaluation and Improvement:
Describe the following:

• How the overall performance of the Network will be evaluated and improved during the award period.
• Policies, methods, and approaches for evaluating the overall operational performance of the Network, including metrics and assessments of financial management of resources. Include a discussion of metrics that may be used to determine both productivity and quality of the results generated by the Network and how findings will lead to adjustments to Network activities and follow-up evaluations.
• Methods and approaches for monitoring implementation of clinical research.
• The process to review and assess progress and identify risks associated with completion of trials and studies (e.g., early signals obtained from informal benchmarks, soft Go/No-Go juncture points, recruitment, or impact of potential outcome on the scientific field or relevance to clinical practice).
• Processes for the resolution of performance problems and the development of remediation/improvement plans at all levels of the Network functions.
• Research initiatives to attract new, established, and early-in-their-careers investigators to the Network and to promote their continued participation within the Network.

Network Research Agenda:
Describe and/or provide the following: 

• The Network research agenda to advance immune tolerance induction strategies.  Include the following elements:
  • A detailed description of research priorities for clinical trials and mechanistic studies and the rationale for their selection based on significance, soundness and innovation of approaches, strategies, and techniques.
  • How current state-of-the-art research, techniques, approaches, and models help shape the structure, direction, and future activities of the Network research.
  • How the proposed approaches build on prior work in immune tolerance and replicate, reproduce, and advance this research in new directions.
  • The frequency, timing, and plans for reviewing progress and incorporating new information into the research agenda.
• How the concepts for research will be solicited, developed, evaluated, prioritized, and approved for funding by the Network. Provide details of promising investigational approaches across the three main clinical areas of the Network.
• The decision-making process for implementing the Network research agenda including timelines, benchmarks, and solutions to overcome potential obstacles.

Subsection C: Clinical Operations
Describe the following:

• The plans for design and conduct of clinical trials in all three clinical areas of focus. Discuss processes for achieving timely completion, demonstrating awareness and adaptability to unexpected obstacles throughout the study, and identifying factors that could lead to early termination.
• The organizational structure, staffing plans, and lines of authority for the Clinical Operations.
• Demonstrate how this organization provides oversight of the Network's clinical research. 
• Provide tables diagrams, flow charts and organizational charts to connect all operations within Clinical Operations, including pre-study implementation, feasibility assessment, and protocol development. 
• Project management approaches, including metrics and the establishment of timelines and benchmarks for all activities within the purview of the Clinical Operations.
• Processes and procedures to establish effective project management of Clinical Operations activities. Discuss how the Clinical Operations will meet clinical research timelines and benchmarks, plan and manage resources, develop contingency plans and redirect efforts, as needed.
• Communication processes within and between the Clinical Operations, Leadership, and other Network functional areas, including NIAID and resources provided by NIAID.
• Decision-making processes and methods to identify and resolve operational issues.
• Processes and procedures to ensure the efficient and effective review of protocol documents by the single Institutional Review Board (sIRB) of choice.

Study Feasibility Assessment:
Describe the following:

• Processes and procedures for rapidly and accurately assessing the clinical sites considered and approved for participation in Network clinical trials, including the recruitment capabilities, staffing, data services systems, and clinical, laboratory, and pharmacy facilities at each location.
• How additional sites will be proposed, evaluated, and selected for trial or study preparedness if needed.
• The processes for:
  • Identifying actions to improve clinical research capabilities. 
  • Assisting clinical sites in implementing actions.
  • Coordinating clinical site assessment activities and actions with the NIAID clinical site monitoring resources and NIAID staff.
• How site performance will be measured and managed, including processes and procedures to ensure the timely initiation, conduct, and completion of clinical site assessments, and suitable metrics to support discontinuation and replacement of underperforming sites.
• The plans to evaluate the proposed investigational product(s) (IP), including:
  • Availability of IP and quantity needed to complete the clinical trial.
  • How the IP meets Food and Drug Administrating (FDA) and the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) regulatory document requirements, including the proposed protocol's Investigational New Device (IND) Sponsor requirements.
  • Identification of risks, including business risks associated with IP sourced from various entities.

Protocol Development:
Describe the following:

• How the protocol development teams will be assembled to include responsibilities for all areas of protocol development and expertise.
• How clinical research concepts will be developed into protocols and associated documents.
• How decisions at each step in the protocol development process will be made. Include a discussion of the process for fast tracking development of high priority concepts. Provide flow charts/diagrams to present the steps and timelines involved in protocol development, completion, and implementation. Discuss who will be involved at various stages in the development and final approval of clinical trial protocols.
• The plan to design and implement mechanistic studies as an integral component of protocol design.
• Processes to determine the nature and type of biological samples to be collected.
• How performance will be measured and managed, including ensuring adherence to approved protocol timelines.

Protocol Implementation and Oversight:
Describe the following:

• How protocol management plans will be developed, tracked, and monitored. Include a discussion of establishing realistic benchmarks and go/no-go criteria, evaluation of established plans, actual data, and future projections. Include discussion of the development of contingency plans and the processes to adjust project plans including:
  • Protocol readiness for implementation considering preclinical safety data, scientific data, study product availability, fiscal, and human resources.
  • How site readiness and feasibility will be evaluated.
  • Coordination with NIAID regarding sponsor obligations for protocol approval/implementation, clinical site monitoring in clinical trials, methods for monitoring study progress and participant safety.
  • How performance will be measured and managed, including processes and procedures to assess clinical site progress, protocol deviations, corrective action plans, and staff effectiveness and productivity.
  • Plans for the dissemination of results to study participants and the research community.

Subsection D: Core Laboratory (or laboratories)
Describe the following:

• The Core Laboratory organizational structure, including staffing plans to address all areas of specialized needs and lines of authority. Include tables, diagrams, flow charts and organizational charts to include integrating the Core Laboratory within the Network.
• How the Core Laboratory will be involved in the integration of mechanistic studies into the clinical trials.
• Core Laboratory's research approach and expected contributions to the clinical research, including plans for development of new/innovative assays and evaluation of biomarkers.
• How new assays will be assessed and implemented, including how decisions will be made on the use of new and non-FDA approved test methods and procedures for transitioning to new technologies. 
• How laboratories that conduct specialized assays will be selected and evaluated for laboratory readiness and how quality will be assessed and ensured throughout the performance period.
• Discuss the plans for working under current Good Laboratory Practices (cGLP) or current Good Manufacturing Practices (cGMP), including quality management plans, such as quality assurance, quality control, audits and corrective actions.
• How performance will be measured and managed, including processes and procedures to ensure adherence to approved timelines and benchmarks, and the processes for overcoming obstacles.
• The Core Laboratory's capacity to perform testing.
• The Core Laboratory's capacity to provide training on specific assays for Clinical Site and specialized laboratories. 
• How the Core Laboratory will maintain communications and transmit data and assay information between the Core Laboratory and Bioinformatics.
• Biorepository
  • The laboratory data services system used for specimen acquisition, sample identification/deidentification, processing, shipping, tracking, testing, labeling, storage, and retrieval
  • Describe how the security of Personally Identifiable Information associated with clinical specimens will be maintained.
  • The approach for communicating availability of samples to the research community, sharing and distribution of samples, specimens, and other laboratory materials. Address compliance with applicable domestic and international laws and regulations.

Clinical Site Laboratory Capacity and Training:
Describe the following:

• Procedures for interactions among participating clinical site laboratories for performing routine, non-specialized testing, and for collecting, processing and shipping specimens.
• Assessment of methods for data input, assay capacity/throughput, and clinical site training, and processes and procedures for problem resolution.

Subsection E: Bioinformatics
Structure and Governance:
Describe the following:

• The structure, function, and governance of the Bioinformatics Program. Include staffing requirements, lines of authority, project management, timelines and benchmarks, the evaluation of performance, decision-making processes, and identification and resolution of operational issues. Tables, diagrams, flow charts and organizational charts are strongly recommended.
• The communication processes within and between the Bioinformatics Program and other Network functional areas, NIAID, and NIAID resources. 
• How the Bioinformatics Program will develop and incorporate new technologies for data analyses and data visualization, ensuring accuracy, confidentiality and integrity of data transferred among Network members.

Data Services System:
Describe the following:

• Plans for establishing, operating, and maintaining a data services system considering the types and volume of data collected by the Network. 
• The collection, capture, storage, access, query, backup, archiving, exchange, and dissemination of data from mechanistic studies and clinical data from NIAID resources, including but not limited to genetic, cellular, and molecular data. 
• The hardware and software infrastructure requirements for data capture, storage, query and analysis, and disseminating data to investigators, NIAID, and the scientific community.
• Plans for an integrated electronic data repository, including biospecimen identifiers and scientific data for each study participant, and how this will permit rapid and efficient production of analysis-ready files.
• Plans for making de-identified core metadata discoverable using standardized metadata schemas, controlled vocabularies or ontologies, and persistent identifiers (e.g., DOIs, ORCID iDs) to ensure traceability, interoperability, and reuse aligned with the FAIR principles across NIAID-supported resources.
• Procedures for data quality control and verification in collaboration with originating laboratories and NIAID resources.
• System security measures and plans for long-term maintenance and survival of data and the data system.
• A plan for tracking consents for sample use and for sample de-identification and/or destruction when necessary. 

Primary and Secondary Analyses:
Describe the following:

• The range of analysis services offered by the Bioinformatics Program, for example: data analyses, determining sample size, or assistance with manuscript preparation.
• Plans for interacting with investigators, NIAID, and NIAID resources for the development, review, and implementation of proposed studies/sub-studies, including assessing feasibility.
• Relevant statistical methods and study designs for the analysis of mechanistic data and combined mechanistic and clinical data within the context of previous similar analyses performed.

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. 

To document their commitment, include letters in support of the following:

• Study sites and laboratories
• The availability of study agents
• Co-funding of clinical trials from partners, if applicable

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply - Application Guide.

Other Plan(s): 

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

• A Data Management and Sharing Plan (DMS Plan) is required for any NIH-funded or conducted research that will generate scientific data. Applicants must submit the DMS Plan at the time of application using the NIH DMS Plan Format Page. The DMS Plan must address the elements in the structured format. Where the DMS Plan Format Page requires a "Yes or No" response, no additional narrative is allowed.
• All investigators funded under this NOFO will be expected to share their data publicly through the Immunology Database and Analysis Portal (ImmPort)and other public portals approved by NIAID. 

Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the How to Apply - Application Guide.

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

PHS Human Subjects and Clinical Trials Information

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 How to Apply - 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 How to Apply - Application Guide must be followed.

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 How to Apply - 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.

PHS Assignment Request Form

All instructions in the How to Apply - Application Guide must be followed.

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

See Part 2. 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

4. Submission Dates and Times

Part I. 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 Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

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 How to Apply – Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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 Section 7.9.1 Selected Items of Cost.

• Awards issued under this notice of funding opportunity (NOFO) will be incrementally funded awards and may be issued for project periods of up to 7 years. Multi-year funded grants will not be allowed. 
• Grants awarded under this NOFO will not be provided the authority to automatically extend the final budget period one time for up to 12 months beyond the original project period end date shown in the Notice of Award. All extensions, including the first extension, will require prior approval. Please note a 7-year grant does not qualify for a no-cost extension. 
• Progress and financial reporting will be required and reviewed annually. All funds must be expended within the approved project period.

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the How to Apply - 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 form. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this NOFO for information on registration requirements.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization's profile in the eRA Commons and for the System for Award Management. Additional information may be found in the How to Apply - 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. 

Recipients or subrecipients must submit any information related to violations of federal criminal law involving fraud, bribery, or gratuity violations potentially affecting the federal award. See Mandatory Disclosures, 2 CFR 200.113 and NIH Grants Policy Statement Section 4.1.35.

Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to the HHS Office of Inspector Grant Self Disclosure Program at grantdisclosures@oig.hhs.gov. 

Post Submission Materials

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

Section V. Application Review Information

1. Criteria

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

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.

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.

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.

2. Review and Selection Process

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

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

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

Requests for reconsideration of initial peer review will not be accepted for applications submitted in response to this NOFO. 

Applications will be assigned on the basis of established referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this NOFO. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. Funding decisions are based on the core tenets of a unified funding strategy, see ICO Funding Policies and Considerations. Applicants are strongly encouraged to also refer to the ICO-specific funding policies and considerations pages linked therein that build upon the agency-wide framework.

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 Section 2.5.1. Just-in-Time Procedures. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding.

Prior to making an award, NIH reviews an applicant's federal award history in SAM.gov to ensure sound business practices. An applicant can review and comment on any information in the Responsibility/Qualification records available in SAM.gov.  NIH will consider any comments by the applicant in the Responsibility/Qualification records in SAM.gov to ascertain the applicant's integrity, business ethics, and performance record of managing Federal awards per 2 CFR Part 200.206 "Federal awarding agency review of risk posed by applicants."  This provision will apply to all NIH grants and cooperative agreements except fellowships.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement Section 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

A Notice of Award (NoA) is the official authorizing document notifying the applicant that an award has been made and that funds may be requested from the designated HHS payment system or office. The NoA is signed by the Grants Management Officer and emailed to the recipient's business official.

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

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Any pre-award costs incurred before receipt of the NoA are at the applicant's own risk.  For more information on the Notice of Award, please refer to the NIH Grants Policy Statement Section 5. The Notice of Award and NIH Grants & Funding website, see Award Process.

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

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

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

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

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

2. Administrative and National Policy Requirements

The following Federal wide and HHS-specific policy requirements apply to awards funded through NIH:

• The rules listed at 2 CFR Part 200, Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards.
• All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the terms and conditions in the Notice of Award (NoA). The NoA includes the requirements of this NOFO. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities.

All federal statutes and regulations relevant to federal financial assistance, including those highlighted in NIH Grants Policy Statement Section 4 Public Policy Requirements, Objectives and Other Appropriation Mandates.

By applying for or accepting federal funds from HHS, recipients certify compliance with all federal antidiscrimination laws and these requirements and that complying with those laws is a material condition of receiving federal funding streams. Recipients are responsible for ensuring subrecipients, contractors, and partners also comply.

Applicants and recipients are strongly encouraged to refer to the NIH Director's Statement of Priorities, entitled "Advancing NIH's Mission Through a Unified Strategy." 

Recipients are responsible for ensuring that their activities comply with all applicable federal regulations. Pursuant to 2 CFR 200.340, by accepting an NIH award, the recipient agrees that continued funding for the award is contingent upon the availability of appropriated funds, recipient satisfactory performance, compliance with the Terms and Conditions of the award, and may also otherwise be terminated, to the extent authorized by law, if the agency determines that the award no longer effectuates the program goals or agency priorities, in line with 2 CFR 200.340(a)(4).

Pursuant to the Cybersecurity Act of 2015, Div. N, § 405, Pub. Law 114-113, 6 USC § 1533(d), the HHS Secretary has established a common set of voluntary, consensus-based, and industry-led guidelines, best practices, methodologies, procedures, and processes.

Successful recipients under this NOFO agree that:

When recipients, subrecipients, or third-party entities have:

• ongoing and consistent access to HHS owned or operated information or operational technology systems; and
• receive, maintain, transmit, store, access, exchange, process, or utilize personal identifiable information (PII) or personal health information (PHI) obtained from the awarding HHS agency for the purposes of executing the award.

Cybersecurity plans and procedures must at minimum include the following:

• Develop cybersecurity plans and procedures, modeled after the NIST Cybersecurity framework, to protect HHS systems and data:
  • Identify:
    • Develop an inventory of all assets and accounts with access to HHS owned and operated information or operational technology systems or which obtain PII or PHI for the purposes of the award.
  • Protect:
    • Limit access to HHS owned and operated systems to only those in need of access to complete reward activities.
    • Require all staff to complete annual cybersecurity and privacy awareness training. Visit 405(d): Knowledge on Demand (hhs.gov) to obtain free trainings, if needed.
    • Enable multifactor authentication for all employees, subrecipients, and third-party entities to access HHS owned and operated information or operational technology systems.
    • Regularly backup sensitive data and test backups.
  • Detect:
    • Install anti-virus or anti-malware software on all devices, servers, and accounts used to connect to HHS owned and operated systems.
  • Respond:
    • Develop an incident response plan. See Incident-Response-Plan-Basics_508c.pdf (cisa.gov) to learn about developing incident response plans.
    • Have cybersecurity incident reporting procedures that ensure the relevant HHS awarding agencies are notified of a cybersecurity incident within 48 hours of discovery. A cybersecurity incident is defined as an unplanned interruption to a technology service or reduction in the quality of a technology service, or an occurrence that actually or potentially jeopardizes the confidentiality, integrity, or availability of an information system or the information the system processes, stores, or transmits.
  • Recover:
    • Investigate incidents and plug any security gaps identified. 

All activities proposed in your application and budget narrative must align with applicable law, including but not limited to statutes, executive orders, federal regulations and applicable judicial holdings.  Accordingly, discretionary awards shall not be used to fund, promote, encourage, subsidize, or facilitate; racial preferences or other forms of racial discrimination by the recipient, including activities where race or intentional proxies for race will be used as a selection criterion for employment or program participation; denial by the recipient of the sex binary in humans, or the belief that sex is a chosen or mutable characteristic; illegal immigration; or any other initiatives that compromise public safety.  If an application does not align, the application will not receive funding to the extent permitted by law and applicable court orders.

For applications involving substance abuse, the application must not support harm reduction. Please see Updated Funding Guidance for Recipients on Supplies and Services.

For applications involving funding Medication-Assisted Treatment (MAT) or medications for opioid use disorder (MOUD), this funding should be used to provide comprehensive treatment and recovery support services rather than medication-only models for opioid use disorder. Services should include medications, where clinically indicated, in conjunction with psychosocial and other treatment and recovery support services. Funding can also be used to support individualized tapering and discontinuation of medications when clinically indicated. Please see Updated Funding Guidance for Recipients on  MAT/MOUD.

Recipients of both Clinical Trial Required and Clinical Trial Optional awards subject to this term shall report standardized clinical trial activation and enrollment performance data for any interventional clinical trial supported under the award. These metrics are intended to assess trial startup efficiency, site activation, and post-activation performance and to support continuous quality improvement in clinical trial operations (see supplemental guidance). Recipients shall report required data annually at the time of Research Performance Progress Report (RPPR) submission on clinical trial activation and enrollment performance milestone dates as calendar dates; NIH will calculate standardized interval metrics from these dates.

Institutions are expected to maintain capabilities that support efficient clinical trial startup, participant enrollment, and performance monitoring, including streamlined workflows and systems for electronic tracking of milestones.  Recipients are encouraged to implement and evaluate approaches that improve trial efficiency and the participant experience.

As of October 1, 2025, HHS has adopted 2 CFR Part 200, with some modifications included in 2 CFR Part 300. These regulations replace those in 45 CFR Part 75. However, for NIH, under the Consolidated Appropriations Act for FY 2026, (P.L. 119-75, Division B, Title II, Sec. 224), the provisions relating to indirect costs in 45 CFR 75 continue to apply to NIH awards. Consistent with the statute, NIH will not apply updated thresholds outlined within 2 CFR Part 200, at this time.

In administering programs under this and all funding announcements, NIH prioritizes: 

• Research involving rigorous scientific methods, including for studies related to children and adolescents, where NIH is committed to approaches that reflect the highest standards of clinical care and child safety. 
• Biological and physiological integrity: Recognizing the relevance of biological sex to health outcomes, NIH encourages applicants to account for sex-based health factors in program design, data collection, and service delivery where scientifically appropriate.
• NIH will implement these priorities consistent with applicable laws, regulations, court orders, and all required administrative procedures. Applicants are encouraged to describe how their proposed programs align with these priorities in their project narratives. Funded activities must advance NIH's vision of protecting and improving the health and well-being of Americans. The particular focus is on those who are medically vulnerable, or live in areas with limited access to care. NIH's duty is to serve wisely, effectively, and with measurable results that justify every taxpayer dollar invested. 

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 (HHS) grant administration regulations at 2 CFR Part 200, 45 CFR 75 (for indirect cost provisions) and other HHS, PHS, and NIH grant administration policies.

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

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

• The scientific leadership, administration and coordination of all Network activities, including: 
  • Establishing policies and procedures for decision-making that are adaptable to changing research priorities, including selecting and prioritizing proposed clinical trials and mechanistic studies.
  • Establishing procedures and metrics for the assessment of Network progress and productivity in achieving the objectives of the research agenda.
  • Ensuring the participation and appropriate training of investigators participating in Network studies.
  • Establishing and providing standard operating procedures to NIAID within a timeline to be determined after issuance of an award and description of lines of authority and communication within the Network.
  • Implementing procedures for regular assessment of performance, to include processes for the addition, reduction, increase or elimination of Network trial sites and laboratories.
• Participating in the design, conduct, analysis, and publication of clinical trial and mechanistic research findings/results.
• Managing communication between the Network and the single Institutional Review Board (sIRB).
• Leading all Network personnel, consultants and research support services necessary for the continuation and completion of ongoing clinical trials and mechanistic studies being supported by the current Network.
• Ensuring that all operational, administrative, regulatory and site-specific requirements are met, to include submission of required information to NIAID, prior to protocol initiation and that all protocol documents are developed collaboratively with the input of investigators, statisticians, and NIAID staff.
• Chairing the Network Executive Committee and Steering Committee while ensuring the effective implementation of Committee responsibilities.
• Collaborating with NIAID to set Network clinical research priorities in accordance with available NIAID resources.
• Notifying NIAID of any audit specific to this award conducted by regulatory health authorities.
• Developing a plan for sharing archived laboratory specimens obtained during the conduct of Network clinical studies across Network investigators, as well as for external investigators.
• Setting laboratory priorities for mechanistic studies that are based on Network research priorities and integrated into clinical trials.
• Engaging, where appropriate, non-Network expert investigators and laboratories and other supported resources when identifying, evaluating and implementing new tests, reagents and instruments for mechanistic studies of tolerance promoting strategies.
• Managing and reporting the Network associated costs, including oversight of Network resources.
• Recipients will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.

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

• Ensuring Network research efforts align with NIAID's immune tolerance agenda and facilitating coordination with other NIH-supported clinical trial networks and research groups.
• Tracking protocol development, implementation, and study conduct, including monitoring progress of medical, laboratory, and operational aspects of clinical trials.
• Identifying scientific gaps and facilitate exchange of scientific and regulatory information, including during Network meetings.
• Serving as the regulatory sponsor for Network clinical trials conducted under Investigational New Drug (IND) Applications and/or Investigational Device Exemptions (IDEs).
• Providing medical monitoring, project management, and regulatory oversight on the protocol teams as applicable.
• Providing scientific support services for Network clinical trials, including clinical site monitoring, investigational product management, regulatory compliance, and a centralized data repository.
• Participating on Network Executive Committee and Steering Committee as a non-voting member, when applicable. 
• Overseeing clinical site operations to include development of template informed consent documents as well as review of site-specific consents for sIRB submission; operational activation of Network clinical sites; and review and evaluation of site monitoring reports.
• Reviewing submissions of publications.
• Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

• Implementing, monitoring, and updating the clinical research plan for the Network to ensure consistency and relevance with the NIAID scientific priorities.
• Reviewing the Network's research activities and goals on an agreed upon schedule.
• Ensuring the quality and scientific integrity of publications resulting from Network studies.
• Developing, reviewing, and approving Network budgets.
• Clinical trial project management.
• Participation in the presentation of research results, including publications.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between recipients and NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual recipient. This special dispute resolution procedure does not alter the recipient's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and HHS regulation 45 CFR Part 16.

3. Data Management and Sharing

A Data Management and Sharing Plan (DMS Plan) is required for any NIH-funded or conducted research that will generate scientific data. Applicants must submit the DMS Plan at the time of application using the NIH DMS Plan Format Page. The DMS Plan must address the elements in the structured format. Where the DMS Plan Format Page requires a "Yes or No" response, no additional narrative is allowed. 

4. Reporting

When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement Section 8.4.1 Reporting. To learn more about post-award monitoring and reporting, see the NIH Grants & Funding website, see Post-Award Monitoring and Reporting.

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 Section 8.6 Closeout. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 2 CFR Part 200.301.

Section VII. Agency Contacts

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

eRA Service Desk - Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues.

Grants.gov Support Center - Questions regarding Grants.gov registration and services (e.g., Workspace, subscriptions).

National Institute of Allergy and Infectious Diseases (NIAID) 
Email: ITN_UM1@mail.nih.gov

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

National Institute of Allergy and Infectious Diseases (NIAID)
Email: niaidfinancial-grantscontact@mail.nih.gov

Section VIII. Other Information

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

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 2 CFR Part 200.