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 Application Guide and the NOFO) 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.

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

Clinical trials are one strategy NIAID uses to improve prevention, diagnosis, and treatment of infectious, immunologic, and allergic diseases in addition to understanding the mechanisms of these diseases. For additional information about the mission, strategic plan, and research interests of NIAID, applicants are encouraged to consult this NIH website.

Historically, NIAID has supported both the infrastructure and clinical trial networks through a variety of funding mechanisms. NIAID recognizes that additional models of clinical research are important to advance its research mission; therefore, NIAID has established this investigator-initiated clinical trial funding opportunity for clinical trials that cannot or will not be conducted through existing NIAID-supported clinical trial networks or infrastructure. The proposed clinical trial must be ready for implementation, and appropriate documentation must support readiness.

Scope

The NIAID Clinical Trial Implementation Cooperative Agreement supports implementation of clinical trials that address research areas supporting the mission and goals of NIAID and require enhanced oversight.

NIH defines a clinical trial as: "A research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes." For additional details, see NOT-OD-15-015.

A clinical trial that requires enhanced oversight has one or more of the following attributes:

• provision of a non-routine intervention, that is, an intervention that would not otherwise be provided for the condition under study in the local facility where the study is being conducted;
• administration of an unlicensed product; or
• administration of a licensed product for an unapproved indication. 

Any clinical trial that will require a regulatory oversight (such as Investigational New Drug [IND] or Investigational Device Exemption [IDE]) would be considered to require enhanced oversight.

NIAID expects all activities and communications regarding all clinical laboratory testing for study participants to comply with U.S. Code of Federal Regulations (see 42 CFR part 493.2 and 493.3(b)(2)).

The NIAID Clinical Trial Implementation Cooperative Agreement will support the conduct, completion, and analysis of the clinical trial, and related activities, for example:

• training of study personnel
• recruitment and enrollment of study subjects
• data collection, clinical data management, and quality control
• investigational product costs
• laboratory work and data analyses
• study management and oversight
• establishment of committees to manage the complexity of the trial
• preparation of the final study report; and other related post-trial activities
• regulatory activities and site monitoring
• mechanistic studies, if applicable

NIAID reserves the right to specify: 1) whether an IND/IDE application should be submitted to the appropriate regulatory agency; 2) the entity (NIAID, primary recipient, etc.) who will hold the IND/IDE; 3) the requirements for the establishment of a Data Safety Monitoring Board (DSMB)/Safety Monitoring Committee (SMC) or the use of an NIAID-sponsored DSMB/SMC; and 4) the use of other NIAID clinical resources such as a Statistical and Clinical Coordinating Center. Applicants are encouraged to discuss those decisions and requirements with NIAID prior to submission of the application.

Extended Performance Period Rationale

The scope of the proposed clinical trial and related research activities should determine the project period with the expectation that most trials can be completed within 5 years. Examples of factors that may require a project period of 6- or 7-years include:

• nature of condition under study that requires longer follow-up to achieve clinical and mechanistic outcomes
• number and diversity of study sites
• number of participants necessary for study completion
• availability of target population for the study
• known difficulty with participant recruitment and/or retention
• complex regulatory requirements specific to the study

Applications Not Responsive to This NOFO

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

• Applications proposing any of the following clinical trial planning tasks:
  • Development of study design
  • Identification of collaborators and enrollment sites
  • Development of the clinical protocol and informed consent
  • Development of the statistical analysis plan
  • Development of the clinical data management plan
  • Development of the Investigator's brochure or equivalent
• For applications proposing a 6- or 7- year project period:
  • Lack of a study rationale that justifies the need for an extended 6- or 7-year clinical trial
  • Budgeting for a 6- or 7-year clinical trial but lacking a 6- or 7-year milestone plan in the Study Timeline
• Clinical trials that fall outside the mission and research areas of NIAID
• Clinical trials that utilize dedicated resources that are part of an existing NIAID-supported clinical trial network without prior program approval
• Proposing more than one clinical trial in a single application
• DAIT-focused clinical trials on allergic, transplantation, autoimmune, and immune-mediated diseases lacking mechanistic studies

For studies that do not require enhanced oversight, NIAID encourages submission of applications to either NIH Research Project Grant (Parent R01 Clinical Trials Required) PA-25-305 or NIH Research Project Grant (Parent R21 Clinical Trial Required) PA-25-306. Applicants are strongly encouraged to contact the Scientific/Research Contact(s) listed in Section VII. Agency Contacts for questions concerning the classification of the proposed clinical trial.

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

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

Foreign Organizations/International Collaborations

Non-domestic (non-U.S.) Entities (Foreign Organizations) are eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are 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 the 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 Section 1.2 Definition of Terms.

3. Additional Information on Eligibility

Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

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 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.

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.

SF424(R&R) Senior/Key Person Profile

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

If mechanistic studies are proposed, describe the appropriate expertise within the biosketch of the individual who will have the general responsibility for the scientific and the technical/laboratory aspects of the proposed work. This person may be the application's PD/PI or a single PD/PI in a multi-PD/PI application.

If a platform trial is proposed, describe the appropriate expertise in statistical design and analysis within the biosketch of the individual that will be responsible for the design of the platform trial.

R&R or Modular Budget

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

All applications must request funding needs for the entire trial and data analysis period. In addition to funds required to support clinical trial conduct, the budget should reflect sufficient funds to support independent study monitoring, medical and data monitoring, clinical site monitoring, regulatory submissions, quality management, safety oversight activities. Costs of study agent and/or product, labeling, distribution should also be delineated, if applicable. If parts of the costs of the trial are to be borne by sources other than NIH, these contributions must be presented in detail along with supporting letters signed by individuals who have the authority to make fiduciary commitments on behalf of the institution. 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 or as Estimated Project Funding. NIAID reserves the right to independently procure drug for the study if that offers cost or other advantages to the clinical trial.

Further information concerning budget preparation may be obtained from the Financial/Grants Management Contact(s) listed in Section VII. Agency Contacts.

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:

Each application may propose a single clinical trial that may include more than one intervention. A single platform trial that allows for simultaneous comparison of multiple intervention groups against a single control group or a trial that includes more than one sequential stage is permitted.

All clinical trial planning activities must be completed prior to the time of application submission and investigators must be ready to implement the proposed trial at the time of award.

As applicable, mechanistic studies will be supported as part of the proposed clinical trial. DAIT-focused clinical trials on allergic, autoimmune, and immune-mediated diseases or transplantation must include mechanistic studies.

Prior to initiation, protocols and consent forms may be subject to review by NIAID. Investigators are strongly encouraged to contact the Scientific/Research Contact(s) listed in Section VII. Agency Contacts for more information regarding division-specific clinical protocol templates.

Specific Aims: Specify the primary and major secondary outcomes and endpoints to be measured. Provide a clear explanation of the importance of various outcome measures and endpoints and their relevance to the hypothesis being tested.

Research Strategy: Within the Research Strategy describe the following:

• Studies that led to the proposed clinical trial and information or data from preliminary studies which address the need for and the feasibility of the trial
• Significance of the clinical and mechanistic (if applicable) problem(s) being studied
• How the trial will test the proposed hypothesis(es), and the potential impact of the results of the trial
• A clear rationale for the need of a 6- or 7-year project period that is linked to the clinical trial's specific aims and delineated milestones, if applicable
• Potential biases or challenges in the protocol and how they will be addressed
• Plans for appropriate oversight over the conduct of the trial, including at a minimum the appropriate clinical monitoring independent of the study team, safety monitoring, regulatory compliance plan and approval timelines, and quality management (limit to new details not provided in the Data and Safety Monitoring Plan in Section 3.3 of the PHS Human Subjects and Clinical Trials Information section)
• Demonstrated consideration of ethical issues involving the disease/condition under study
• Activities related to the conduct, completion, and analysis, including statistical approach, of the clinical trial
• Anticipated impediments that could require a revision in the timeline and alternative approaches
• Applications proposing a platform trial must include details about the interventions to be included and contain sufficient detail to assess the totality of planned interventions

Letters of Support: Provide letters of support to document access to or commitment of critical resources, including consortium and/or site participants, cores, laboratories, pharmacies, data management resources, or other collaborators, including sharing of NIH resources, in the case of intramural collaborators. Intramural scientist collaborators are referred to their intramural division contacts for additional guidance on Intramural Scientist Collaboration on Extramural Funded Grants. If co-funding or in-kind support is planned from any source (non-NIH sources or NIH sources), letter(s) of commitment (e.g., type, amount, and source of support), signed by a business official, on organization letterhead, must be included in the Letters of Support section.

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. 

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.

The following modifications apply:

Include the informed consent form(s) and, if applicable, assent form(s).

Complete Clinical Protocol: include a complete protocol as part of the Appendix. Investigators should contact the relevant Scientific/Research Contact(s) listed in Section VII. Agency Contacts to obtain the NIAID Division-specific protocol template for their application. Investigators are urged to address all protocol template elements in a succinct manner. 

Applications that lack the Complete Clinical Protocol are incomplete and will not be reviewed.

Provide the informed consent forms, assent forms and the Complete Clinical Trial Protocol combined in a single PDF file 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.

Section 2 - Study Population Characteristics

2.7 Study Timeline

Include the following:

• Detailed protocol-specific milestones for major project stages and/or activities and completion of the clinical trial. A milestone is defined as a scheduled event in the project timeline, signifying the completion of a major project stage or activity. Discuss the feasibility and appropriateness of achieving and completing milestones on time. Include alternative approaches and contingency plans should there be delays and/or impediments in attaining milestones. Milestones will be negotiated at the time of award, as appropriate
• Include a Gantt chart to describe the timeline for all milestones.
• A timeline for the following general milestones, as applicable
  • Timing of enrollment of 25%, 50%, 75% and 100% of the projected recruitment for all study subjects, including a plan for initial site activation and expected timing of screening/enrollment of first participant
  • Timing of completion of data collection
  • Timing of completion of primary endpoint and secondary endpoint data analyses
  • Completion of clinical study report
  • Completion of regulatory approvals
  • Submission of initial manuscript
• Additional milestones, as applicable, such as personnel training completion, communication and/or submission to U.S. Food and Drug Administration (FDA) or FDA equivalent, DSMB reporting, completion of biospecimen analyses, etc. These milestones will be negotiated at the time of the award, as appropriate
• For clinical trials requesting an extended project period of 6- or 7-years, include a 6- or 7-year milestone plan

Section 3 - Protection and Monitoring Plans

3.3 Data and Safety Monitoring Plan

The Data and Safety Monitoring (DSM) Plan must address the following areas:

• Where the monitoring will occur
• How site(s)/center(s), and participating facilities (labs, pharmacies) will be monitored
• Appropriate oversight for conduct of the trial, including at a minimum the appropriate clinical monitoring independent of the study team, safety monitoring, regulatory submissions and compliance and quality management
• A clinical data management plan describing: (1) database system to be employed, (2) compliance with federal regulations, (3) security and emergency back-up, and (4) quality control of data from clinical sites and laboratories, as appropriate

Applications that lack the DSM Plan are incomplete and will not be peer reviewed.

3.5 Overall Structure of the Study Team

This section must include:

A description of the study organization and administration, including, but not limited to: a description of committee structures needed to manage the complexity of the trial; the role of any internal or external advisory committees; the oversight, responsibilities, and coordination of any sites or cores proposed; and the role of any subawards or service providers for personnel or facilities. Note: If proposing an external advisory committee, then please do not contact potential members prior to award nor propose their names in the application.

Section 4 - Protocol Synopsis

4.5 Will the study use an FDA-regulated intervention?

4.5.a If yes, describe the availability of Investigational Product (IP) and Investigational New Drug (IND)/Investigational Device Exemption (IDE) status

If FDA staff have determined that IND/IDE approval is not required, include a copy of the FDA letter/email stating no IND/IDE is required and the date of the decision.

Section 5 - Other Clinical Trial-related Attachments

5.1 Other Clinical Trial-related Attachments

The following additional documents should be included as attachments:

• Identification and qualifications of clinical trial site(s), pharmacies, and laboratories
• Copies of data collection forms, questionnaires, or other relevant materials, including the Table of Contents of the Manual of Operations (MOPs) and a comprehensive Laboratory Plan
• A plan to implement and monitor Good Clinical Practices (GCP) (see NOT-OD-16-148), Good Laboratory Practices (GLP) and Good Manufacturing Practices (GMP), as appropriate.
• Documentation of availability of study agent(s), as well as plans and support for acquisition, distribution, and administration of study agent(s), including the Investigator's Brochure or equivalent for the study products(s), if applicable
• Documentation of any communications with regulatory authorities, if applicable

If any of these documents requested in Section 5 are not available at the time of submission, substitute a justification for their omission. The Study Timeline included as part of the application should address when these materials will be available, if applicable.

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.

PHS Assignment Request Form

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

Foreign Organizations

Foreign (non-U.S.) organizations must follow policies described in the NIH Grants Policy Statement, and procedures for foreign organizations described throughout the How to Apply- Application Guide.

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.

For project periods of 6- or 7-years, the following are applicable:

• Awards issued under this NOFO will be incrementally funded awards for project periods of up to seven years.
• Multi-year funded cooperative agreements will not be awarded.
• Cooperative agreements awarded under this NOFO will be excluded from automatic carryover – all carryover requests must be approved.
• Cooperative agreements 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 expiration date shown in the Notice of Award. All extensions, including the first extension, will require approval. Please note a 7-year grant does not qualify for a no-cost extension.
• All funds must be expended within the approved project period.

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. 

Prior Consultation with NIAID

Consultation with NIAID staff is strongly encouraged. If requested, NIAID staff will consider whether the proposed clinical trial meets the goals and mission of the Institute and is appropriate to conduct as an investigator-initiated clinical trial. Additionally, NIAID staff will consider the appropriateness of the proposed project period and the readiness of the proposed clinical trial. Consultation with NIAID staff is recommended a minimum of 10 weeks prior to submitting the application.

NIAID staff will not evaluate the technical and scientific merit of the proposed trial; technical and scientific merit will be determined during peer review using the review criteria indicated in Section V of this NOFO. NIAID staff members are also available to work with potential applicants to determine the level of oversight needed for the proposed trial and delineate all documentation that will be needed at the time of application submission. During the consultation phase, if the proposed trial does not meet NIAID's programmatic needs or is not appropriate as an investigator-initiated clinical trial, applicants will be strongly encouraged to consider other NOFOs.

For further information on prior consultation with NIAID program staff, and required documents, applicants are strongly encouraged to contact the Scientific/Research Contact(s) listed in Section VII.

NIAID reserves the right to provide support for clinical trials through other available mechanisms supported by NIAID. If NIAID ascertains that enhanced oversight of this clinical trial is not necessary, then the applicant will be encouraged to consider funding under the Parent R01 Clinical Trial Required (PA-25-305) or Parent R21 Clinical Trial Required (PA-25-306).

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 scored review criteria and additional review criteria (as applicable for the project proposed). An application does not need to be strong in all categories to be judged likely to have a major scientific impact.

Reviewers will consider Factors 1, 2 and 3 in the determination of scientific merit, and in providing an overall impact score. In addition, Factors 1 and 2 will each receive a separate factor score. 

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

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.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:

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

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.

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.

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, 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:

• Conducting the study, including all aspects of the study design, quality control, data management, data analysis and interpretation, preparation of publications, dissemination of data, tools, and technologies, and collaboration with other investigators.
• Ensuring that each clinical site, whether a single institution or a consortium of institutions, will follow the procedures required by the protocol regarding study conduct and monitoring, volunteer management, data collection, data management, and quality control.
• Obtaining prior approval from NIAID/NIH for the support or involvement of any third party in the study.
• Accomplishing negotiated milestones.
• Submitting a clinical close-out plan to NIAID staff within two (2) months of the decision either by NIAID staff or the recipient that an awarded study is no longer feasible. The plan must be approved and signed by the Institutional Signing Official and the PD(s)/PI(s) listed on the award prior to submission.
• 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:

• Maintaining access to data generated under this Cooperative Agreement and periodically reviewing the data and progress.
• Monitoring the progress of the clinical trial, including each participating facility.
• Serving as a resource to provide scientific/programmatic support during the accomplishment of the research by collaborating on the design of the activities, advising the selection of sources or resources (e.g., determining where a particular reagent can be found), providing research resources and reagents available from NIAID recipients and contractors, advising management and technical performance, or participating in the preparation of publications.
• Advising on the progress of study milestones. Progress will be monitored by an internal panel with outside consultants as needed and determined by the NIAID Project Scientist. The schedule for these interim reviews will be based upon the duration of the clinical trial period.
• Assisting in the development, assembly, and submission of all required regulatory documents, e.g., those regarding the use of investigational drugs, to the Food and Drug Administration, if applicable.
• Providing medical monitoring for the clinical trials. Should a pharmaceutical or biotechnology company sponsoring a clinical trial choose to name its own Medical Monitor, then the NIAID Medical Officer will work with the company-assigned Medical Monitor.
• Advising on the adequacy of adverse event management and reporting and having regular communications with the PD(s)/PI(s) and study team, which may include attendance at the safety monitoring (or DSMB) and related committee meetings.
• Participating in the development of study protocols and monitor compliance, enrollment targets, adherence to uniform data collection procedures, ongoing compliance to requirements and the timeliness and quality of data reporting.
• Comparing actual enrollment to the benchmarks and criteria identified in the application. 

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.

NIAID reserves the right to terminate or curtail the study (or an individual award).

Areas of Joint Responsibility include:

• Establishing and participating in a Steering Committee, as applicable, to oversee study operations.
  • The PD/PI, or the contact PD/PI in the case of multi-PD/PI awards, will serve as a voting member of the Steering Committee and will attend all meetings of the Steering Committee.
  • The NIAID Project Scientist may serve as a voting member on the Steering Committee. All NIH staff Steering Committee members will together share one vote in support of the project. 
• Facilitating the conduct of the studies.
• Additional details and responsibilities of the Steering Committee will be negotiated at the time of award or post-award.

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 (or in instances where there is no Steering Committee, a recipient), 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.

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: NIAID_IICT_U01@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.