RFA-AI-27-002-Full-Announcement.html

Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES (NIAID)

Funding Opportunity Title

Infectious Diseases Clinical Trials Network (IDCTN) (UM1 Clinical Trial Required)

Activity Code

UM1 Research Project with Complex Structure Cooperative Agreement

Announcement Type

New

Related Notices

Check for any recent Notices of NIH Policy Changes that may impact application requirements.

Funding Opportunity Number (FON)

RFA-AI-27-002

Companion Funding Opportunity

None

Number of Applications

See Part 2, Section III. 3. Additional Information on Eligibility.

Assistance Listing Number(s)

93.855

Funding Opportunity Purpose

The purpose of this notice of funding opportunity (NOFO) is to solicit applications for an Infectious Diseases Clinical Trials Network (IDCTN). The IDCTN, comprised of the Clinical Trial Evaluation Units (CTEUs) and a Network Coordination Center (NCC), supports the evaluation of interventions for emerging and chronic infections. The CTEUs design and implement clinical trials and studies, while the NCC provides the administrative and operational framework for a collaborative, integrated network and engages with experts in the field to solicit and generate clinical trial concepts. The NCC and CTEUs will collaboratively create opportunities to advance investigators early in their careers and those new to the field.

Funding Opportunity Goal(s)

To assist public and private nonprofit institutions and individuals to establish, expand and improve biomedical research and research training in infectious diseases and related areas; to conduct developmental research, to produce and test research materials. To assist public, private and commercial institutions to conduct developmental research, to produce and test research materials, to provide research services as required by the agency for programs in infectious diseases, and controlling disease caused by infectious or parasitic agents, allergic and immunologic diseases and related areas. Projects range from studies of microbial physiology and antigenic structure to collaborative trials of experimental drugs and vaccines, mechanisms of resistance to antibiotics as well as research dealing with epidemiological observations in hospitalized patients or community populations and progress in allergic and immunologic diseases. Because of this dual focus, the program encompasses both basic research and clinical research.

Key Dates

Posted Date

September 01, 2026

Open Date (Earliest Submission Date)

October 10, 2026

November 10, 2026

November 10, 2026

Not Applicable

July 2027

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.

Expiration Date

November 11, 2026

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

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.

Table of Contents

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

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Overview The Infectious Diseases Clinical Trial Network (IDCTN) evaluates therapeutics, vaccines, biologics, diagnostics, and devices targeting infectious diseases, with the goal of treating, and ultimately preventing, emerging and chronic infectious diseases.

The network consists of multiple Clinical Trial Evaluation Units (CTEUs) and only one CTEU with a Network Coordination Center (NCC). A CTEU provides critical domestic infrastructure to support timely conduct of clinical trials. The NCC, through its scientific leadership and clinical trial operational expertise, develops and refines the research agenda of the network, establishes priorities, and reviews concepts to ensure a balanced clinical research portfolio. Clinical trials performed at CTEUs originate from concepts developed by IDCTN.

Note: One (and only one) NCC will be awarded for the entire IDCTN; therefore, inclusion of an NCC within an application is optional. If an NCC is not awarded as part of one CTEU awarded under this notice of funding opportunity (NOFO), the IDCTN in its entirety will not be supported.

Research Areas and Scientific Areas of Interest The scope of the clinical research priorities and clinical trial capabilities (Phase I - IV) across the IDCTN must span the National Institute of Allergy and Infectious Diseases (NIAID) clinical research areas of scientific interest. Each CTEU is not required to have capabilities to support all scientific areas of interest.

A feature of the IDCTN is the formation of multiple scientific working groups that provide expert input into the research areas of scientific interest to the IDCTN. These include:

The clinical trial population scope includes people of varying ages and representative of the U.S. population: healthy volunteers, patients with common outpatient infections (e.g., sexually transmitted infections, respiratory viral infections), and people who are immunocompromised.

Examples of clinical research activities within the scope and scientific areas of interest include, and are not limited to:

Structure of the Clinical Trial Evaluation Unit (CTEU) Each application must propose only one CTEU.

CTEU Administration (required) - The CTEU Administration develops clear governance structures for coordination and collaboration within the IDCTN and with NIAID for development and implementation of clinical trial protocols. It coordinates with NIAID and the NCC to ensure appropriate integration of NIAID-supported resources. The CTEU Administration also identifies and promotes opportunities for investigators at the CTEU that are early in their careers and/or those new to the field.

Clinical Trial Site (required) - The Clinical Trial Site encompasses the requisite infrastructure and personnel which enables the conduct of high-quality clinical research.

Clinic (required) - The CTEU Clinic provides and supports experienced researchers and location(s) for the enrollment of participants and the conduct of other protocol-specified clinical activities.

Clinical Laboratory (required) - The CTEU Clinical Laboratory provides for the conduct of protocol-specific clinical and safety laboratory testing and manages specimens.

Pharmacy (required) - The CTEU Pharmacy manages investigational study product(s) in accordance with applicable regulations and policies.

Research Laboratory (optional) - The CTEU Research Laboratory develops and conducts assays for the analysis of biospecimens for determination of clinical trial outcomes, or other clinical research activities.

IDCTN Collaboration (required) – The CTEU collaborates with the NCC and participates in: committees; annual meetings; and supports investigators early in their careers and/or those new to the field.

Structure of the Network Coordination Center (NCC) (optional) NCC Administration (required if NCC is proposed) - The NCC Administration provides scientific leadership, establishes the operational framework and governance structures and coordinates meetings. It also supports opportunities for the next generation of clinical trialists in infectious disease by establishing a program for investigators early in their career and/or those new to the field.

Governance (required if NCC is proposed) - The NCC establishes the IDCTN research agenda. A Governance Committee, comprised of CTEU PDs/PIs, and in collaboration with NIAID, regularly revises the IDCTN research agenda, identifies scientific priorities and evaluates the portfolio. The highest priority for clinical research is public health emergency declarations.

Scientific Working Groups (required if NCC is proposed) - The NCC is responsible for establishing processes (i.e., scientific working groups [SWGs]) to identify, solicit and review clinical concepts from experts in the field. The NCC also identifies knowledge gaps within specific disease or practice areas and defines corresponding research questions. NIAID subject matter experts, CTEU PDs/PIs, and CTEU key personnel will serve as members on SWGs to develop clinical concepts. Additional subject matter experts needed for concept review and development are identified and supported by the NCC (i.e., product developers, laboratory experts, and statisticians).

Clinical Oversight (required if NCC is proposed) - The NCC establishes processes to provide oversight of IDCTN clinical trials and to manage clinical trials implemented through the IDCTN.

Note: Clinical concepts will be evaluated by NIAID for provision of the appropriate Institute resources for protocol development and clinical trial implementation.

Investigators may contact the Scientific/Research Contact(s) listed in Section VII. Agency Contacts for more information regarding NIAID clinical research policies.

Non-Responsive Applications The following will be considered non-responsive and will not be reviewed:

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

Funding Instrument

Cooperative Agreement: A financial assistance mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this NOFO.

Application Types Allowed

New

Renewal - Renewals of RFA-AI-18-046, RFA-AI-20-021

The OER Glossary and the How to Apply - Application Guide provide details on these application types. Only those application types listed here are allowed for this NOFO.

Clinical Trial?

Required: Only accepting applications that propose clinical trial(s).

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

NAID intends to commit up to $10 million in FY 2027 to fund 7-11 CTEU awards and 1 award for a CTEU that includes an NCC to a single institution under this NOFO.

Award Budget

Budgets for up to $450,000 (direct costs) per year may be requested for CTEU funds. For applications including an NCC, an additional $2,000,000 (direct costs) may be requested for NCC funds. All budgets should reflect the actual needs of the proposed project.

Award Project Period

The project period must be 7 years.

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

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Nonprofits Other Than Institutions of Higher Education

For-Profit Organizations

Local Governments

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.

Required Registrations

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.

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. 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.

Eligible Individuals (Program Director/Principal Investigator)

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.

At least one PD/PI must be a physician (M.D. or D.O. only). An investigator may serve as a PD/PI on only one application. A PD/PI may serve as a collaborator on another application(s) provided there is no scientific overlap.

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

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:

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 sub-sections with the indicated page limits:

Section 1: Clinical Trial Evaluation Unit (CTEU) – Each application must propose one CTEU (sub-sections 1A - 1H) Sub-section 1A. Overview of Clinical Trial Evaluation Unit - required - 6 pages Sub-section 1B. CTEU Administration - required - 12 pages Sub-section 1C. Clinical Trial Site - required - 12 pages Sub-section 1D. Clinic - required - 6 pages Sub-section 1E. Clinical Laboratory - required - 6 pages Sub-section 1F. Pharmacy - required - 6 pages Sub-section 1G. Research Laboratory - optional - 6 pages Sub-section 1H. IDCTN Collaboration - required - 12 pages Section 2: Network Coordination Center (NCC) – Optional; all sub-sections are required in the application if an NCC is proposed - 30 pages maximum in total for sub-sections 2A – 2E Sub-section 2A. Overview of the Network Coordination Center Sub-section 2B. NCC Administration Sub-section 2C. Governance Sub-section 2D. Scientific Working Groups Sub-section 2E. Clinical Oversight

Instructions for Application Submission

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

SF424(R&R) Other Project Information All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

Facilities & Other Resources: Describe each Clinical Trial Site facility identified within the application. All facilities (except Commercial laboratories utilizing a fee-for-service agreement) must be a part of the applicant organization. Describe any proposed laboratory space, which must be located within the applicant organization, within the Research Laboratory, if applicable.

Describe the nature and categories of study product(s) the Pharmacy has experience managing. Include any specialized capabilities of the Pharmacy (e.g., compounding, over-encapsulation) and any certifications for pharmacy facilities. Include any certifications for laboratory facilities.

SF424(R&R) Senior/Key Person Profile All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

Within the biosketches, highlight clinical trial expertise and experience that address the proposed scope and scientific areas of interest. Include in the description the type of study (observational, clinical trials, clinical trial under IND), the duration of the study (in years), and the number of subjects enrolled and retained.

If an NCC is proposed, within the biosketches, describe previous experience with implementation, oversight and overall management of complex projects of this scope. Expand on the specific skills that will contribute to scientific and operational success of the IDCTN.

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

CTEU and NCC funds are considered Core Funds. Do not request funds for support of specific clinical trial protocols (Protocol Funds) in response to this NOFO. Instead, Protocol Funds will be determined and provided as needed, based on the availability of funds.

R&R Subaward Budget

PHS 398 Cover Page Supplement

PHS 398 Research Plan All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

Specific Aims: Describe the specific aims of the CTEU with an emphasis on malaria/neglected tropical diseases, sexually transmitted infections, respiratory infections, enteric diseases, and/or emerging infectious diseases.

Research Strategy: The Research Strategy section should consist of Sub-sections 1A – 1H and Sub-sections 2A – 2E (as applicable).

Section 1: Clinical Trial Evaluation Unit (CTEU) Sub-section 1A: Overview of Clinical Trial Evaluation Unit

Sub-section 1B: CTEU Administration

Sub-section 1C: Clinical Trial Site (one site only)

Sub-section 1D: Clinic

Sub-section 1E: Clinical Laboratory

Sub-section 1F: Pharmacy

Sub-section 1G: Research Laboratory (Optional) If proposed, address the following, as applicable:

Sub-section 1H: IDCTN Collaboration

Section 2: Network Coordination Center (NCC) (Optional) If proposed, address the following, as applicable:

Sub-section 2A: Overview of the Network Coordination Center

Sub-section 2B: NCC Administration

Sub-section 2C: Governance

Sub-section 2D: Scientific Working Groups

Sub-section 2E: Clinical Oversight

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.

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

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:

Applicants must enter at least one delayed onset study record and must check box "Anticipated Clinical Trial?".

Study Title: use: "CTEU Delayed Onset Clinical Trial" All proposed delayed onset studies must provide a justification explaining why information on the clinical research projects will not be available at the time of application. Use the following justification: "Clinical trials supported through this NOFO will be developed and reviewed by the IDCTN, which will be established after award."

PHS Assignment Request Form

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.

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.

Mandatory Disclosure

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 4.1.36.

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.

For this particular NOFO, note the following:

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.

Overall Impact

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).

Scored Review Criteria

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.

Significance

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

In addition, for applications involving clinical trials Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

Investigator(s)

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

With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines?